Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Combined oral contraceptives (COCs) consist of two components and these can vary in strength between different preparations (Table 1).
• Oestrogen component: ethinylestradiol (or a prodrug of ethinylestradiol), a synthetic oestrogen.
• Progestogen component: one of the following:
• Levonorgestrel, norethisterone, norethisterone acetate (metabolized to norethisterone), or norgestimate (metabolized to levonorgestrel).
• Desogestrel or gestodene.
• Drospirenone (a derivative of spironolactone). This has anti-androgenic properties and anti-mineralocorticoid activity (unlike most other progestogens).
• COC preparations can be categorized according to:
• The dose/strength of oestrogen:
• Low-strength COCs contain 20 micrograms of ethinylestradiol.
• Standard-strength preparations contain 30–35 micrograms of ethinylestradiol in monophasic COCs and 30–40 micrograms ethinylestradiol in phased preparations.
• Higher-strength preparations with 50 or more micrograms of ethinylestradiol are no longer used.
• The progestogen component: see above.
• How the doses vary over the menstrual cycle:
• Monophasic COCs: the amount of oestrogen and progestogen in each active tablet is constant throughout the cycle.
• Phasic COCs: the amounts of oestrogen and progestogen vary over the cycle.
• Biphasic COCs: contain two different sets of tablets.
• Triphasic COCs: contain three different sets.
• The presence or absence of a pill-free interval:
• Products with 21 pills: most COCs are packaged as calendar strips of 21 active tablets. One tablet is taken daily for 3 weeks; no tablet is taken during the following 7 days.
• Every-day COCs: to aid compliance, some products are packed with 21 active tablets and 7 inert or placebo tablets; a tablet is taken every day of the 28 day cycle.

• Advantages:
• Combined oral contraceptive (COCs) are more effective at preventing pregnancy than barrier methods. For more information, see Effectiveness of contraceptives.
• Sex need not be interrupted to use contraception.
• Menstrual bleeding is usually regular, lighter, and less painful [FFPRHC, 2007b].
• Reduced risk of cancer of the ovary, uterus, and colon (Table 1).
• Reduced severity of acne in some women [Arowojolu et al, 2007].
• Reduced risks of functional ovarian cysts and benign ovarian tumours (Table 1).
• Normal fertility returns after stopping the COC.
• Disadvantages:
• Some women experience temporary adverse effects when they start COCs; these include headaches, nausea, breast tenderness, and mood changes [BNF 53, 2007]. If these do not stop within a few months, changing the type of COC may help.
• Blood pressure may increase [FFPRHC, 2007b].
• The COC does not protect against sexually transmitted infections; people at risk for sexually transmitted infections are advised to use condoms as well.
• Breakthrough bleeding (unexpected bleeding on pill-taking days) and spotting is common in the first few months of use; if this persists, it can be treated. For more information see Unscheduled bleeding.
• They are less effective than long-acting reversible methods of contraception (such as progestogen-only implants or injectables, copper intrauterine devices, levonorgestrel-releasing intrauterine system).
• Risks of some rare but serious conditions are increased [FFPRHC, 2007b]:
• Myocardial infarction (heart attack) and stroke:
• Very small increase in risk. The risk is greatest in women who smoke, and those that are diabetic, have high blood pressure, are very overweight, have migraines with aura, or who have a family history of premature atherosclerotic cardiovascular disease.
• Venous thromboembolism (blood clots):
• Risk may be increased as much as five times, but the absolute risk is very low (less than 1% of the risk of coronary heart disease) and considerably less than the risk of venous thromboembolism in pregnancy.
• The risk is greatest in women with previous thromboembolism and those who require prolonged immobilization.
• Breast cancer:
• There is a possible small increase in risk, which returns to no increased risk within 10 years after stopping the COC.
• Cervical cancer:
• There is a very small increase in risk, which increases with longer duration of COC use.
• Table 1 summarizes risk data for non-smokers who use COCs. Smokers have different baseline risks than non-smokers but are likely to have similar changes in risk.
• For information on avoiding risks, see:
• Surgery or immobilization;
• Advice.
• Benefits which have been claimed for COCs but for which supporting data are inadequate [FFPRHC, 2007b]:
• Benign breast disease: reduced risk.
• Osteoporosis: reduced risk. Although the data are conflicting, no study has found a decrease in bone mineral density.
• Adverse effects which have been claimed for COCs, but for which supporting data are inadequate include:
• Weight gain:
• A Cochrane systematic review found that COCs have no large effect on body weight. However, data were insufficient to determine the effect with any precision [Gallo et al, 2006].
• Loss of libido:
• Studies that have suggested that libido can be lost after taking COCs have received wide publication. However, reviews of the literature find studies in which libido was increased, decreased, or unchanged. Results differ according to study design (retrospective and uncontrolled, prospective and controlled, randomized and controlled) [Davis and Castano, 2004; FFPRHC, 2005c; Schaffir, 2006].
• The Family Planning Association provides useful information leaflets for users of COCs and other contraceptive methods — see www.fpa.org.uk.

To assess a woman's eligibility for use of a combined oral contraceptive (COC):

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Check the woman's blood pressure, weight and body mass index.
• Check the criteria in Combined hormonal methods to ensure that the assessment is complete and that the woman is eligible for a COC.
• Women should not use a COC (UKMEC 4) in the following situations:
• Breastfeeding and less than 6 weeks postpartum.
• Age 35 years or more and smoking 15 or more cigarettes daily.
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension) — UKMEC 3 if less severe (see below).
• Hypertension not adequately controlled (systolic blood pressure equal to, or greater than 160 mmHg, OR diastolic blood pressure equal to, or greater than 95 mmHg).
• Vascular disease, including angina or other ischaemic heart disease, intermittent claudication, hypertensive retinopathy, transient ischaemic attacks, or other cerebrovascular disease.
• Venous thromboembolism (history, or currently receiving treatment).
• High risk of venous thromboembolism (e.g. major surgery with prolonged immobilization, known thrombogenic mutation, Raynaud's disease with lupus anticoagulant).
• Valvular or congenital heart disease if complicated by pulmonary hypertension, atrial fibrillation, or subacute bacterial endocarditis.
• Migraine with aura (any age).
• Current breast cancer.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 3 if less severe.
• Cirrhosis of the liver, decompensated (e.g. ascites, jaundice, encephalopathy, or gastrointestinal haemorrhage).
• Liver tumours — benign (hepatocellular adenoma) or malignant (hepatoma).
• Women should use a COC only after consultation with an expert (UKMEC 3) in the following situations:
• Breastfeeding and between 6 weeks and 6 months postpartum.
• Less than 21 days postpartum and not breastfeeding.
• Age 35 or more years and either smoking less than 15 cigarettes daily, or stopped smoking less than 1 year ago.
• BMI greater than 35 kg/m².
• Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension) — UKMEC 4 if more severe.
• Hypertension adequately controlled (systolic blood pressure less than 159 mmHg, AND diastolic blood pressure less than 94 mmHg).
• Family history of venous thromboembolism in a first-degree relative less than 45 years of age.
• Moderately increased risk of venous thromboembolism (e.g. immobility unrelated to surgery, wheelchair use, debilitating illness).
• Known dyslipidaemia with increased risk of cardiovascular disease.
• Migraine without aura at any age, while already using the COC pill, patch, or ring.
• History of migraine (at least 5 years ago) with aura, at any age.
• Undiagnosed breast mass, carriers of known gene mutations associated with breast cancer (e.g. BRCA1), past history of breast cancer with no recurrence for 5 or more years.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 4 if more severe.
• Gall bladder disease, current or medically treated.
• History of cholestasis related to past COC use.
• Use of liver enzyme–inducing drugs (see Selected concurrent medications).

• The following examinations and laboratory tests are not required to assess eligibility for a combined oral contraceptive (COC):
• Breast, pelvic, or genital examination
• Cervical cytology screening
• Routine laboratory tests, including haemoglobin measurement
• Thrombophilia screening

• These recommendations are based on the guidelines for First prescription of combined oral contraception and the UK medical eligibility criteria for contraceptive use issued by the Faculty of Faculty of Sexual and Reproductive Health Care [FFPRHC, 2007b; FSRH, 2009b].
• The examinations and investigations that are specifically not recommended do not contribute substantially to combined oral contraceptive safety [British Society for Haematology, 2001; FFPRHC, 2007b].

• For a woman receiving her first prescription of a combined oral contraceptive (COC), the recommended first-line option is a monophasic preparation containing 30 micrograms of ethinylestradiol (standard strength) with norethisterone or levonorgestrel (first-line progestogens).
• However, there are no COCs that cannot be used first-line after counselling, and the preference of the woman should be taken into consideration when prescribing a COC.

• Combined oral contraceptives marketed in the UK are listed in Available types.

• Few direct comparative data are available to identify the best, first-line combined oral contraceptives (COCs) [FFPRHC, 2007b].
• The recommendation to offer a monophasic COC containing 30 micrograms of ethinylestradiol combined with norethisterone or levonorgestrel first-line is based on guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2007b]. The guidelines take account of Cochrane systematic reviews and other evidence.
• CKS does not recommend the following as first-line options:
• Biphasic or triphasic COCs:
• This recommendation is based on guidance issued by FFPRHC [FFPRHC, 2007b]. The two relevant Cochrane systematic reviews have been updated since drafting of the FFPRHC guideline, but their conclusions have not changed from the earlier versions.
• Monophasic COCs compared with biphasic COCs: a Cochrane review compared the efficacy, adverse effects, cycle control, and continuity rates of monophasic and biphasic COCs and found no important differences in bleeding patterns between biphasic and monophasic preparations. The strength of the evidence is limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. The authors of the review concluded that because no clear rationale supports the use of biphasic pills, and because extensive evidence is available for monophasic pills, the latter are preferred [van Vliet et al, 2006a].
• Monophasic COCs compared with triphasic COCs: a Cochrane systematic review compared triphasic COCs with monophasic COCs in terms of efficacy, cycle control, and discontinuation owing to adverse effects. Twenty-one trials were found. Meta-analysis was generally not possible because of differences in measuring and reporting the cycle disturbance data and in progestogen type and hormone dosages. The available evidence is insufficient to determine whether triphasic COCs differ from monophasic COCs in effectiveness, bleeding patterns, or discontinuation rates. The authors concluded that because triphasic-pill regimens are more complex and are often more expensive, monophasic pills should be the first-line choice [van Vliet et al, 2006b].
• COCs containing desogestrel and gestodene:
• Norethisterone- and levonorgestrel-containing COCs may have a lower risk of venous thromboembolism than COCs containing desogestrel and gestodene [FFPRHC, 2007b].
• Guidelines from the Department of Health state that, provided women are informed of the very small risks of venous thromboembolism associated with desogestrel and gestodene, the decision about which pill to use should be made jointly by the woman and her doctor or other family planning professional [DH, 1999].
• COCs with 20 micrograms of ethinylestradiol:
• In general, a lower dose of a drug is preferred to a higher dose, if this does not compromise efficacy, because the lower dose usually minimizes adverse effects. Although similar efficacy is found for COCs with 20 and 30 micrograms of ethinylestradiol, women taking 20 micrograms are more likely to have unscheduled bleeding.
• A Cochrane review found no difference in contraceptive effectiveness between COCs containing =< 20 micrograms of ethinylestradiol and those containing > 20 micrograms [Gallo et al, 2005]. However, several COCs containing 20 micrograms of ethinylestradiol resulted in higher rates of early trial discontinuation (overall and due to adverse events, such as irregular bleeding) and increased risk of bleeding disturbances (amenorrhoea/infrequent bleeding; irregular, prolonged, frequent bleeding; or breakthrough bleeding or spotting) than their higher-oestrogen comparison pills.
• Yasmin^® (ethinylestradiol 30 micrograms and drospirenone 3 mg):
• The Scottish Medicines Consortium did not recommend Yasmin^® for use within NHS Scotland because it found no evidence that Yasmin^® is superior to other standard strength COCs with respect to acne, premenstrual symptoms, or well-being, and it is substantially more expensive than alternative products [Scottish Medicines Consortium, 2003a].
• A more recent review found no good evidence to suggest that Yasmin is superior to other COCs (including co-cyprindiol) with regard to acne or premenstrual symptoms [MeReC, 2006]. The review identified a small trial (n = 128) which found Yasmin^® and co-cyprindiol to have a similar effect on reducing median total acne lesion count in those with mild to moderate acne. However, co-cyprindiol is only licensed for severe acne that has not responded to oral antibiotics (or for moderately severe hirsutism). For severe acne, it is not known how effective Yasmin^® would be compared to co-cyprindiol.
• COCs with higher doses of levonorgestrel or norethisterone:
• There is no evidence of any advantages over COCs with lower doses of these progestogens.
• Co-cyprindiol (cyproterone acetate [anti-androgen] and ethinylestradiol):
• Co-cyprindiol is not licensed for use solely as a contraceptive. It should be reserved for selected women requiring treatment for severe acne, those refractory to prolonged antibiotic therapy, and those with moderately severe hirsutism [ABPI Medicines Compendium, 2004a]. Co-cyprindiol is useful in these women who also wish to receive oral contraception [BNF 53, 2007].
• The Committee on the Safety of Medicines warned of the increased incidence of venous thromboembolism in users of co-cyprindiol compared with women who use low dose oestrogen COCs [CSM, 2002].
• For further information on its use in the treatment of acne vulgaris, see the CKS topic on Acne vulgaris.
• Every-day (ED) preparations:
• These are not routinely used in the UK but can be useful to women who have difficulty starting the next packet at the correct time.
• The FFPRHC guidelines recommend as good practice that there are no COCs that cannot be used first-line after counselling and that the preference of the woman should be taken into consideration when prescribing a COC [FFPRHC, 2007b].

• If the woman could be pregnant, delay starting combined oral contraceptives (COCs) until the next menstrual period, or until pregnancy has been ruled out.
• Women not currently using hormonal or intrauterine contraception:
• Start COCs at the beginning of menstruation; ideally on the first day of bleeding, but this can be up to and including day 5 of the cycle.
• Additional contraceptive protection will not be required.
• If this is not possible:
• Start COCs at any other time in the menstrual cycle provided that it is reasonably certain that the woman is not pregnant.
• Advise additional contraceptive protection (such as condoms) for the first 7 days of pill taking.
• Inform the woman that medical advice may differ from that included in the packet of pills.
• Specific advice for women who are amenorrhoeic, postpartum and breastfeeding, postpartum and not breastfeeding, or post-abortion is summarized in Table 1.
• Starting immediately after oral emergency contraception:
• Levonorgestrel emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 7 days of pill taking.
• Ulipristal acetate emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 14 days of pill taking.
• Advise the woman to take a pregnancy test no sooner than 3 weeks after the last episode of unprotected sex.
• Women who have been using a different COC, combined contraceptive patch, or progestogen-only pill:
• The new COC can be started immediately. There is no need to wait for the next menstrual period.
• However, the woman may want to complete the cycle of her current hormonal method, omitting any hormone-free interval (or the inactive pills of 'every day' preparations), before starting the new COC.
• No additional contraceptive protection is needed.
• Women who have been using a progestogen-only injectable:
• The COC should be started when the repeat injection would have been given.
• No additional contraceptive protection is needed if the COC is started less than 14 weeks (98 days) after the injection (outside the terms of the product licence).
• Women who have been using copper intrauterine devices (IUDs) or the levonorgestrel-releasing intrauterine system (IUS):
• The COC is most conveniently begun within 5 days of the start of menstrual bleeding. No additional contraceptive protection is needed. The IUD or IUS can be removed at that time.
• The COC can be started at any other time in the menstrual cycle, provided it is reasonably certain that she is not pregnant. She will need to abstain from sex or use additional contraceptive protection for the next 7 days.
• To provide the extra protection removal of the IUD or IUS could be delayed for at least 7 days.
• The IUD or IUS can be removed immediately unless she has had sexual intercourse in the past 7 days. In which case it should be left in until she has taken at least 7 pills sequentially.

• Explain to the woman that these recommendations may differ from those detailed in the patient leaflet or package insert:
• Manufacturers of combined oral contraceptives (COCs) advise that additional contraceptive protection is required if started between day 2 and day 5 of the menstrual cycle.
• Starting a COC at other times times in the cycle is outside the terms of manufacturers' licences.
• Starting hormonal contraception postpartum: general principles.
• No hormonal method should be started before day 21 unless there are good reasons to do so.
• If a hormonal method is to be used post birth, it can be started on day 21 without the need for any additional contraception.
• If started after day 21, then additional contraception (such as condoms) should be used for 7 days (inconsistency in current FFPRHC guidance with regard to requiring additional contraception between day 21 or 28 will be removed by the end of 2007 [Brechin, Personal Communication, 2007]).
• Table 1 outlines how to start a COC for women who are amenorrhoeic, postpartum, post-abortion or post-miscarriage.

• These recommendations are based on expert opinion from a World Health Organization (WHO) expert working group [WHO, 2004b] and are supported by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005a; FFPRHC, 2007b].
• The WHO expert working group concluded that [WHO, 2004b]:
• The risk of ovulation within the first 5 days of menstruation is acceptably low.
• Ovulation is less reliably suppressed when combined oral contraceptives (COCs) are started after day 5.
• A COC must be used for 7 days to reliably prevent ovulation.
• When switching to a COC from another hormonal method, the need for additional contraceptive protection depends on that method.
• The risk of pregnancy after removal of copper intrauterine devices (IUDs), when there has been intercourse in the current menstrual cycle, is sufficiently high to recommend that the device be left in place until the next menstrual period.
• The recommendations on how long additional contraception should be used if combined hormonal contraception is started immediately after oral emergency contraception is based on the Quick starting contraception guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH) [FSRH, 2010e].

• Arrange follow-up 10–12 weeks after the first prescription of a combined oral contraceptive (COC), and at least every 12 months thereafter.
• At follow up visits:
• Check that the woman is taking the COC correctly and consistently.
• Check her knowledge of what to do if a pill is missed, if she has vomiting or diarrhoea, or if she requires surgery.
• Remind her about possible drug interactions.
• Check her blood pressure.
• Ask about headaches, especially migraine, and any new risk factors — see UK Medical Eligibility Criteria.
• Address any issues or problems she might have:
• The most common problem is unscheduled bleeding.

• These recommendations are based on guidelines published by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2007b], and current UK practice [Guillebaud, 2007].

• A woman who vomits (for any reason) within 2 hours of taking a combined oral contraceptive (COC) should repeat the dose as soon as possible.
• If vomiting or severe diarrhoea persists for more than 24 hours, the woman should follow the instructions for missed pills, counting each day of vomiting and/or severe diarrhoea as a missed pill:
• Additional contraceptive cover is required during the illness and for 7 days afterwards.
• If the illness occurs while taking the last 7 tablets, omit the pill-free period (or inactive tablets) and start the next pill cycle.

• The advice offered by the British National Formulary is more cautious [BNF 53, 2007]:
• 'Vomiting within 2 hours of taking an oral contraceptive or very severe diarrhoea can interfere with its absorption. Additional precautions should therefore be used during (the illness) and for 7 days after recovery. If the vomiting and diarrhoea occurs during the last 7 tablets, the next pill-free interval should be omitted (in the case of everyday [ED] tablets, the inactive ones should be omitted)' [BNF 53, 2007].

• There is concern that vomiting and/or severe diarrhoea can reduce the efficacy of combined oral contraceptives (COCs) by interfering with its absorption [BNF 53, 2007].
• These recommendations are those issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2007b], which reflect those issued by the World Health Organization (WHO) [WHO, 2004a]. The WHO recommendations are based on expert opinion:
• The WHO expert working group found no direct evidence to address the issue of vomiting and/or severe diarrhoea while using COCs [WHO, 2004a].
• Although it is uncertain whether the effect of severe vomiting and/or diarrhoea is sufficient to warrant use of the missed pill regimen, the WHO working group considered the effects of vomiting or diarrhoea to be similar to that of missing pills [WHO, 2004a].

• Restart/catch up with the pill cycle.
• When seven or fewer active COC pills have been missed, the woman should resume taking her pills as soon as possible.
• Restarting. If pills are missed in weeks 1, 2, or 3 of the pack: she should take the last missed pill as soon as possible and continue with the usual pill-taking schedule. Depending on when she remembers, she may take two pills at different times (the moment of remembering and her regular time), or two pills at the same time. For users of everyday COCs: if inactive pills are missed in week 4, she should throw away the missed inactive pills and continue the usual pill-taking schedule.
• Skipping the pill-free interval. If pills are missed in week 3 of the pack: she should finish the active pills in the current pack and then immediately start a new pack (omitting the pill-free interval or discarding any inactive tablets).
• When more than seven active COC pills have been missed, the woman needs to restart the COC as if she had not used it before.
• Assess if contraceptive protection has become unreliable.
• Loss of contraception is most likely if missed pills extend the pill-free (or inactive pill) interval to more than 7 days.
• The fpa (Family Planning Association) and the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), regard contraception as becoming unreliable if:
• Two or more 20-microgram ethinylestradiol pills (Loestrin 20^®, Mercilon^®, Femodette^®) are missed — mnemonic: 'Two for twenty'.
• Three or more 30- or 35-microgram ethinylestradiol pills (all other COCs) are missed — mnemonic: 'Three for thirty'.
• The BNF (British National Formulary) regards:
• Contraception as unreliable if the delay is 24 hours or more (especially the first in the packet).
• Lost if more than 2 COC tablets are missed from the first 7 tablets in a packet.
• If contraceptive protection has become unreliable:
• Advise additional protection, such as condoms or abstinence, until the woman has taken her COC for 7 days in a row.
• Consider emergency contraception. If contraceptive protection has become unreliable and the woman has been sexually active without taking other precautions, consider the possibility of pregnancy and whether emergency contraception would be appropriate — see the CKS topic on Contraception - emergency.

• Recommendations by the fpa and FFPRHC on missed COC pills
• A 'missed pill' is a combined oral contraceptive (COC) pill that is completely omitted from being taken (i.e. 48 hours have elapsed since the last COC pill was taken). The term 'late pill' is no longer used [FFPRHC, 2005a; FFPRHC, 2007b].
• Consider providing information about missed pills when first providing or recommending the COC:
• The fpa (Family Planning Association) provides a useful leaflet with information for users of COCs — see www.fpa.org.uk.
• This information (in tables and in flowchart format) can be printed from guidance on Missed pills from the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005b].
• These missed pill rules do not apply if a woman has missed more than seven consecutive pills [FFPRHC, 2005b].

Experts agree on the need for clear, useful recommendations for managing missed pills, but they disagree on how to formulate recommendations for when missed pills would cause contraception to be lost. CKS has therefore summarized the two most common approaches, that by the fpa (Family Planning Association) and the Faculty of Sexual and Reproductive Healthcare (FSRH), (formerly the Faculty of Family Planning and Reproductive Healthcare [FFPRHC]), and that by the BNF (British National Formulary).

Missed COC pills: recommendations by the fpa and the FFPRHC.

• These 'missed pills rules' are recommended by the Faculty of Family Planning & Reproductive Health Care [FFPRHC, 2005a; FFPRHC, 2005b; FFPRHC, 2007b]. They are largely based on guidelines developed by a World Health Organization (WHO) expert working group [WHO, 2004a]. 
• Ovulation is a rare event after only 7 days of pill taking.
• After taking combined oral contraceptive (COC) pills on 7 consecutive days, at least 7 pills can be missed (such as occurs in the pill-free week) without the need for additional contraception or emergency contraception.
• Consequently, COC pills missed in weeks 2 (days 8–14) and 3 (days 15–21) of pill taking are unlikely to result in a loss of efficacy.
• The advice to use additional contraceptive protection (e.g. condoms) for the first 7 days after resuming the COC is precautionary in case further COC pills are missed.
• It is important to take an active (hormonal) pill as soon as possible when active pills have been missed.
• If COC pills are missed, the chance that pregnancy will occur depends not only on how many pills were missed, but also on when those pills were missed. On the basis of data regarding ovulation, the WHO expert working group determined that missing three or more active (hormonal) pills (or >= two pills for ethinylestradiol pills containing =< 20 micrograms) at any time during the cycle warrants additional precautions. The risk of pregnancy is greatest when active (hormonal) pills are missed at the beginning, or at the end, of the active pills (i.e. when the hormone-free interval is extended).
• Limited evidence on 20-microgram ethinylestradiol pills suggests that there may be a higher risk of pregnancy when these pills are missed than when 30-microgram ethinylestradiol pills are missed. Accordingly, the WHO expert working group recommended a more cautious approach when ethinylestradiol pills containing =< 20 micrograms are missed.
• Field experience from the first edition of the WHO guidelines Selected practice recommendations for contraceptive use highlighted the need for simple 'missed pill' recommendations.

Missed COC pills: recommendations by the BNF.

• The BNF does not explain how its recommendations were derived [BNF 53, 2007].

If a woman has unscheduled intermenstrual bleeding while using a combined oral contraceptive (COC):

• Exclude or manage situations which could compromise the effectiveness of the COC:
• Missed pills: check how the COC is being taken and if any pills have been missed.
• Drug interaction: review if any new prescription or non-prescription medicines, or herbal/natural remedies, have been taken (e.g. antibiotics, St John's wort).
• Vomiting within 2 hours of pill taking: review the cause and duration of vomiting. Check pill taking (e.g. if a second dose of COC was taken).
• Severe diarrhoea: review the cause and duration of severe diarrhoea. Check pill taking (e.g. if additional pills have been taken to compensate for probable malabsorption).
• In all cases, check if additional contraception protection (e.g. condoms) was used.
• Exclude or manage other situations which could result in unscheduled bleeding, such as:
• Sexually transmitted infections.
• Risk of STI if the woman is under 25 years, or has a new sexual partner, or more than one partner in the last year.
• Pregnancy.
• Gynaecological conditions such as cervical cancer. Provided there is consistent and correct use of contraception, speculum examination is warranted:
• For persistent bleeding beyond the first 3 months of use.
• For new symptoms or a change in bleeding after at least 3 months of use.
• If the woman has not participated in a National Cervical Screening programme.
• If requested by the woman.
• After a failed trial of modification of COC treatment (at least 6–8 weeks).
• If there are other symptoms such as pain, dyspareunia, or post coital bleeding. (Note that these symptoms also warrant pelvic examination.)
• Consider the following treatment modifications:
• If the bleeding occurs early in the use of a new COC, encourage persevering for 3 months.
• If the bleeding is intolerable, consider stopping the COC for up to 7 days, and then restarting (and use alternative contraception while protection is lost).
• Changing the type of pill
• If taking 20 micrograms ethinylestradiol, increase to 30 micrograms ethinylestradiol.
• If taking 30 micrograms ethinylestradiol, increase to 35 micrograms ethinylestradiol.
• Increase the dose or changing the type of progestogen may help on an individual basis.
• Changing to another method of contraception.

• These recommendations are based on those issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), which advises clinicians to be aware of the likely causes of unscheduled bleeding in women taking the combined oral contraceptive (COC) [FFPRHC, 2007b; FSRH and RCOG, 2009] and the NHS Clinical Practice Guidance for the Assessment of young women aged 20–24 with abnormal vaginal bleeding [DH, 2010].
• Unscheduled bleeding and ethinylestradiol content:
• The FFPRHC guidance highlighted that unscheduled bleeding was more common in women using combined oral contraceptives (COCs) containing 20 micrograms of ethinylestradiol than in those using COCs containing more than 20 micrograms of ethinylestradiol [FFPRHC, 2007b].
• This was based on a Cochrane review which found that several COCs containing 20 micrograms of ethinylestradiol resulted in higher rates of early trial discontinuation (overall and due to adverse events, such as irregular bleeding), as well as increased risk of bleeding disturbances (both amenorrhoea/infrequent bleeding and irregular, prolonged, or frequent bleeding, breakthrough bleeding, and or spotting) than did the higher-oestrogen comparison pills [Gallo et al, 2005].

• The combined oral contraceptive (COC) should preferably be stopped 4 weeks before major elective surgery, any surgery to the legs, and surgery which involves prolonged immobilization of a lower limb.
• If emergency surgery or immobilization (e.g. fractured leg) is necessary, the COC should be stopped and treatment to prevent thromboembolism should be given.
• Advise the use of another method of contraception that will minimize the risk for venous thromboembolism.
• No precautions are necessary for minor surgery where the duration of anaesthesia and immobilization is short (e.g. laparoscopic sterilization, varicose vein surgery, and tooth extraction).
• The COC should normally be recommenced at the first menses occurring at least 2 weeks after full mobilization. If the woman has used a progestogen-only injectable in the interim, the COC can be restarted before the next injection would be due.

• The risk of venous thromboembolism associated with major surgery depends on the duration of immobilization.
• Major surgery includes operations that last more than 30 minutes. Procedures with a high risk of venous thromboembolism include general and orthopaedic surgery, surgery for trauma, and neurosurgery.

• These recommendations are based on guidance issued by the Faculty of Sexual and Reproductive Health Care (FSRHC), formerly the Faculty of Family Planning and Reproductive Health Care (FFPRHC) [FFPRHC, 2007b; FSRH, 2009b].

• For a woman who is planning to use a combined oral contraceptive (COC):
• Inform her that some drugs (including antibiotics) can reduce the efficacy of the COC, and vice versa:
• These can be prescription drugs or those bought over the counter, as well as natural or herbal remedies that are widely available without restriction.
• Advise the woman to check with a healthcare professional the possibility of drug interaction before starting any drug therapy (including herbal remedies).
• Provide her with verbal and written instruction on additional contraceptive measures to use (e.g. condoms) if the contraceptive effect of COC could be compromised.

• Drugs that may impair the efficacy of the combined oral contraceptive (COC) include:
• Liver enzyme–inducing drugs — for further information see Liver enzyme-inducing drugs.
• Antibiotics (non-liver enzyme–inducing) — for further information see Antibiotics.
• Other significant drug interactions include:
• Lamotrigine — see Lamotrigine.
• Orlistat:
• Although no interactions between COCs and orlistat have been demonstrated in specific studies, orlistat may indirectly reduce the availability of COCs and lead to unexpected pregnancies in some cases [ABPI Medicines Compendium, 2005].
• An additional contraceptive method is recommended if the woman has severe diarrhoea whilst taking orlistat.
• COCs can alter (increase or decrease) serum concentrations of other drugs, such as theophylline and ciclosporin.
• For more information on drug interactions with COCs, see the British National Formulary [BNF 53, 2007].

• These recommendations are based on guidelines published by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005d; FFPRHC, 2007b; FSRH, 2009b].

• Liver enzyme–inducing drugs may reduce the efficacy of combined oral contraceptives (COCs). Commonly encountered drugs include:
• Antibiotics: rifampicin and rifabutin
• Anticonvulsants: carbamazepine, oxcarbazepine, phenytoin, barbiturates, primidone, topiramate.
• Antiretrovirals: particularly non-nucleoside reverse transcriptase inhibitors and ritonavir-boosted protease inhibitors. Drug interactions between certain antiretroviral agents and hormonal contraceptives could alter the safety and effectiveness of both the contraceptives and the anti-retroviral agents. For further information, see antiretrovirals.
• Herbal remedies: St John's wort
• If a liver enzyme–inducing drug is to be used long-term:
• An alternative contraceptive method that is unaffected by enzyme-inducing drugs should be considered, for example, a long-acting reversible method such as depot medroxyprogesterone, levonorgestrel-releasing intrauterine system or a copper intrauterine device (IUD).
• If the woman wishes to use the COC as her primary contraceptive method while taking a liver enzyme–inducing drug, refer to (or consult with) a specialist. A COC regimen with at least 30 micrograms of ethinylestradiol daily should be used, and/or taking the COC without a pill-free interval — these uses are outside the terms of the product license.
• The consistent use of condoms is recommended.
• If a liver enzyme–inducing drug is to be used short term (e.g. 3 weeks):
• Additional contraceptive protection (e.g. condoms) should be used while the liver enzyme–inducing drug is being taken and for at least 4 weeks after stopping it. For women using rifampicin or rifabutin, consider continuing alternative methods for up to 8 weeks after stopping it.
• Emergency contraception should be considered if sexual intercourse has taken place while efficacy of the COC is doubtful and within the past 5 days — see the CKS topic on Contraception - emergency.

• These recommendations are based on guidelines published by the Faculty of Sexual and Reproductive Health Care (FSRHC), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005d; FFPRHC, 2007b; FSRH, 2009b; FSRH, 2010a].
• The situation where a woman is using a combined oral contraceptive (COC) and a liver enzyme–inducing drug is classified as category 3 in the UK Medical Eligibility Criteria for Contraceptive Use. This means the theoretical or proven risks usually outweigh the advantages of using the method. Provision of a method to a woman with a category 3 condition requires expert clinical judgement and/or referral to a specialist contraceptive provider, because use of the method is not usually recommended unless other methods are not available or not acceptable.
• Cytochrome P-450 enzymes can be induced within 2 days of drug treatment. The effects are maximal within 1 week. After discontinuation of the drug, liver enzymes return to function normally in 4 weeks [FFPRHC, 2005d].
• Shortening the hormone-free interval reduces ovarian follicular activity and may lower the risk of contraceptive failure.
• The British National Formulary (BNF) recommends that appropriate contraceptive measures should be used for 4–8 weeks after stopping a liver enzyme–inducing drug [BNF 53, 2007].

• Additional contraceptive precautions are not required during or after courses of antibiotics that do not induce liver enzymes.
• However, women should be advised about the importance of correct contraceptive practice during periods of vomiting or diarrhoea.
• Rifampicin and rifabutin induce liver enzymes. Therefore, if the woman is taking, or needs to take, rifampicin or rifabutin at the same time as a COC, follow the advice for interactions with liver enzyme-inducing drugs.

• These recommendations are based on guidance from the Faculty of Sexual & Reproductive Healthcare (FSRH) [FSRH, 2011].
• Although the UKMEC criteria advise additional precautions with antibiotics that do not induce enzymes [FSRH, 2009b], this was an interim measure until the evidence could be reviewed in detail by the FSRH clinical effectiveness unit.
• Having reviewed the available evidence, the FSRH no longer advises that additional precautions are required to maintain contraceptive efficacy when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less, unless the antibiotics (or the illness) cause vomiting or diarrhoea.

• If the woman is already receiving lamotrigine:
• If she wishes to start a combined oral contraceptive (COC), advise her:
• That a COC containing a minimum of 30 micrograms of ethinylestradiol should be used.
• That seizure control may worsen.
• That the maintenance dose of lamotrigine may need to be increased as much as two-fold, according to clinical response.
• If she wishes to stop a COC, advise her:
• That adverse effects associated with lamotrigine can increase.
• That the maintenance dose of lamotrigine may need to be decreased by as much as 50%, according to clinical response.
• If the woman is already using a COC and wishes to initiate lamotrigine:
• The usual escalation regimen for lamotrigine is recommended.

• The recommendations for adjusting the dose of lamotrigine when starting or stopping a combined oral contraceptive do not apply if the woman is concomitantly taking other drugs which induce lamotrigine metabolism. Such drugs include phenytoin, carbamazepine, phenobarbital, primidone, and rifampicin.
• For further information on the interactions of liver enzyme–inducing drugs with combined oral contraceptives, see Liver enzyme-inducing drugs.

• These recommendations are based on those issued by the Faculty of Sexual and Reproductive Health Care (FSRHC), formerly the Faculty of Family Planning and Reproductive Health Care (FFPRHC) [FSRH, 2009b; FSRH, 2010a], and the manufacturer of lamotrigine [ABPI Medicines Compendium, 2007b].
• Effect of combined oral contraceptives (COCs) on lamotrigine:
• There is evidence from case series and small retrospective studies that although lamotrigine is not thought to induce liver enzymes [FSRH, 2010a]:
• When starting a COC, seizure control can worsen, as combined hormonal contraception increases the clearance of lamotrigine and reduces serum lamotrigine levels.
• Lamotrigine levels are not reduced by combined hormonal contraception, when lamotrigine is given at the same time as sodium valproate.
• When discontinuing a COC, adverse effects can worsen.
• Effect of lamotrigine on hormonal contraceptives:
• The manufacturer of lamotrigine advises that a hormonal contraceptive should be used as the sole method of contraception only if there is no other alternative [ABPI Medicines Compendium, 2007b].
• The FSRH found no evidence to indicate that lamotrigine reduces the effectiveness of hormonal contraceptives (COCs, combined contraceptive patch, or progestogen-only contraceptives) [FSRH, 2010a]:
• The FSRH identified one small prospective study involving 16 women with bipolar disorder using lamotrigine and a COC (containing ethinylestradiol and levonorgestrel). The concentration of ethinylestradiol remained unchanged, and there was no evidence of ovulation despite a small decrease in levonorgestrel concentration.
• The FSRH states that due to the risk of drug interactions, the use of lamotrigine monotherapy with combined hormonal contraception is generally not recommended (risks generally outweigh the benefits) [FSRH, 2010a].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• One combined contraceptive patch (combined hormonal transdermal patch) is available in the UK. This is marketed as Evra^®:
• It is formulated as a 20 cm² patch designed to deliver 203 micrograms of norelgestromin (a progestogen) and 33.9 micrograms of ethinylestradiol (an oestrogen) into systemic circulation per 24 hours for 7 days [ABPI Medicines Compendium, 2009a].

• In general, the advantages, disadvantages, and risks of the combined contraceptive patch are similar to those of the combined oral contraceptive (COC).
• Advantages of the patch compared with COCs:
• The user does not have to think about it every day, only having to remember to replace the patch once a week.
• The patch does not become less effective if the user vomits or has diarrhoea (because the hormones are absorbed through the skin, not through the gastrointestinal tract).
• Disadvantages of the patch compared with COCs:
• It can be seen.
• It irritates the skin in some women.
• It may be detached (partially or fully) from the skin, compromising efficacy.
• It is less effective in women who weigh more than 90 kg.
• The risks of rare but serious adverse effects for users of the patch are similar to those for users of COCs.
• The patch is as effective as COCs at preventing pregnancy — see Effectiveness of contraceptives.
• There is some evidence that, although compliance is improved in patch users compared to those using COC, the use of the patch did not have a significant effect on reducing failure rates.

• A Cochrane systematic review concluded that self-reported compliance was better with the combined contraceptive patch than with combined oral contraceptives (COCs) [Gallo et al, 2003].
• Adverse effects of the combined contraceptive patch compared with COCs [FFPRHC, 2004c]:
• Breast discomfort:
• Breast discomfort was more common with the combined contraceptive patch than with COCs but was significant only in the first two cycles of use: 15.4% compared with 3.5% in cycle one and 6.6% compared with 1.5% in cycle two.
• Most women (85%) who described breast tenderness had only mild to moderate discomfort, and the symptom led to discontinuation in only 1.0% of patch users.
• Site reactions occurred with combined contraceptive patch use in 20.2% of women but led to discontinuation in only 2.6% of women.
• Body weight increased similarly for users of the combined contraceptive patch and users of COCs: +0.4 kg.
• Disruption of bleeding pattern:
• Breakthrough bleeding and spotting with the combined contraceptive patch was similar to that with triphasic COCs.
• Breakthrough bleeding and spotting were more common in cycles one and two with patch use than with COC use. In cycle one, 18.3% of patch users reported breakthrough bleeding and spotting compared with 11.4% of COC users. In cycle three, 10.0% of patch users reported breakthrough bleeding compared with 8.8% of COC users.
• An open-label, non-randomized trial identified good cycle control in 1164 women recruited to use the combined contraceptive patch. Breakthrough bleeding and spotting were reported by 17.5% of women in cycle one; this proportion decreased to 9.2% by cycle 13.
• Metabolic effects:
• Pulmonary embolism was reported in one combined contraceptive patch user, but the patch had been used up until the time of major surgery.
• No clinically significant alterations in laboratory values have been identified with combined contraceptive patch use.

To assess a woman's eligibility for a combined contraceptive patch:

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Check the woman's blood pressure.
• Check the Combined hormonal methods to ensure that the assessment is complete and that the woman is eligible for a patch.
• Women should not use a combined contraceptive patch (UKMEC 4) in the following situations:
• Breastfeeding and less than 6 weeks postpartum.
• Age 35 or more years and smoking 15 cigarettes or more a day.
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension) — UKMEC 3 if less severe.
• Hypertension not adequately controlled (systolic blood pressure equal to, or greater than 160 mmHg, OR diastolic blood pressure equal to, or greater than 95 mmHg).
• Vascular disease, including angina or other ischaemic heart disease, intermittent claudication, hypertensive retinopathy, transient ischaemic attacks, other cerebrovascular disease.
• History of, or current venous thromboembolism on anticoagulants.
• High risk of venous thromboembolism (e.g. major surgery with prolonged immobilization, known thrombogenic mutation, Raynaud's disease with lupus anticoagulant).
• Valvular or congenital heart disease if complicated by pulmonary hypertension, atrial fibrillation, or subacute bacterial endocarditis.
• Migraine with aura (any age).
• Breast cancer (current).
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 3 if less severe.
• Cirrhosis of the liver, decompensated (e.g. ascites, jaundice, encephalopathy, or gastrointestinal haemorrhage).
• Liver tumours — benign (hepatocellular adenoma) or malignant (hepatoma).
• Women should use a combined contraceptive patch only after consultation with an expert (UKMEC 3) in the following situations:
• Breastfeeding and between 6 weeks and 6 months postpartum.
• Postpartum less than 21 days and not breastfeeding.
• Age 35 or more years, and smoking less than 15 cigarettes a day, or stopped smoking less than 1 year ago.
• BMI more than 35 kg/m².
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension) — UKMEC 4 if more severe.
• Hypertension adequately controlled (systolic blood pressure less than 159 mmHg, AND diastolic blood pressure less than 94 mmHg).
• Family history of venous thromboembolism in a first-degree relative less than 45 years of age.
• Moderately increased risk of venous thromboembolism (e.g. immobility unrelated to surgery, wheelchair use, debilitating illness).
• Known dyslipidaemia with increased risk of cardiovascular disease.
• Migraine without aura at any age, while using the combined contraceptive patch.
• Past history (5 years or more) of migraine with aura, at any age.
• Undiagnosed breast mass, carriers of known gene mutations associated with breast cancer (e.g. BRCA1), past history of breast cancer with no recurrence for 5 years or more.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 4 if more severe.
• Gall bladder disease, current or medically treated.
• History of cholestasis, if related to past COC use.
• Use of liver enzyme–inducing drugs (see Selected concurrent medications).

• Contraception for young women and women with learning disabilities:
• Contraception should be seen in terms of the needs of the individual rather than in terms of relieving the anxieties of carers or relatives.
• When a woman with a learning disability is unable to understand and take responsibility for decisions about contraception, carers and other involved parties should meet to address issues around the woman's contraceptive need and to establish a care plan.
• See Considerations for girls under 16.
• The following examinations and laboratory tests are not required to assess eligibility for a combined contraceptive patch:
• Breast, pelvic, or genital examination.
• Cervical cytology screening.
• Routine laboratory tests including haemoglobin measurements.
• Thrombophilia screening.

• These recommendations for assessing a woman before starting a combined contraceptive patch are based on guidelines issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC):
• New product review: norelgestromin/ethinyl oestradiol transdermal contraceptive system (Evra) [FFPRHC, 2004c]
• First Prescription of Combined Oral Contraception [FFPRHC, 2007b]:
• Because the risks for users of the combined contraceptive patch are similar to those for users of combined oral contraceptives (COCs), guidelines and evidence on the use of COCs largely applies to the patch (the exceptions are obvious and mainly relate to the differences in absorption routes).
• UK medical eligibility criteria for contraceptive use (UKMEC) [FSRH, 2009b].
• The examinations and investigations that are specifically not recommended do not contribute substantially to the safety of women using combined hormonal contraceptives [British Society for Haematology, 2001; FFPRHC, 2007b].
• Obesity as a contraindication to use of the contraceptive patch:
• The manufacturer of the contraceptive patch warns that contraceptive efficacy may be decreased in women who weigh 90 kg or more, but does not discuss BMI.

When the combined contraceptive patch is best started depends on the woman's situation:

• New users who have not been using hormonal contraception and have not recently delivered or had an abortion:
• Advise the woman to start using the patch at the beginning of menstruation, ideally on the first day — this is the only licensed use:
• The patch can also be started up to and including day 5 of the cycle, without additional contraceptive protection being required.
• If it is not possible or practical to start the combined contraceptive patch by day 5 of the menstrual cycle:
• Start the patch at any other time in the menstrual cycle, provided that it is reasonably certain that the woman is not pregnant.
• Advise additional contraceptive protection (e.g. condoms) for the first 7 days of wearing the patch.
• Starting immediately after oral emergency contraception:
• Levonorgestrel emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 7 days of use.
• Ulipristal acetate emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 14 days of use.
• Advise the woman to take a pregnancy test no sooner than 3 weeks after the last episode of unprotected sex.
• After abortion or miscarriage:
• No additional contraceptive method is needed if the patch started within 7 days of an abortion or miscarriage before 24 weeks of gestation:
• In the case of miscarriage at or after 24 weeks gestation, manage as for postpartum women who are not breastfeeding.
• An additional contraceptive method (e.g. condoms) is required for 7 days if the patch is started more than 7 days after abortion.
• Postpartum women who are not breastfeeding (including any pregnancy over 24 weeks gestation):
• No additional contraceptive method is needed if the patch started on day 21 after delivery as recommended.
• An additional contraceptive method (e.g. condoms) is required for 7 days if the patch is started more than 21 days after delivery.
• Advise the woman that these recommendations may differ from that stated in the package insert:
• The only licensed time for starting the patch is the first day of the menstrual cycle. Initiation at any other time is an unlicensed use.

• These recommendations are based on guidelines published by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2004c; FFPRHC, 2005a], which were adapted from guidelines developed for the World Health Organization by an expert working group [WHO, 2004b].
• Recommendations about unlicensed uses of the combined contraceptive patch are inconsistent with recommendations in the British National Formulary [BNF 53, 2007]. These recommendations can be found in FFPRHC guidelines on the use of contraception outside the terms of the product licence [FFPRHC, 2005a].
• The recommendations on how long additional contraception should be used if combined hormonal contraception is started immediately after oral emergency contraception is based on the Quick starting contraception guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH) [FSRH, 2010e].

• Apply the combined contraceptive patch weekly for 3 consecutive weeks; no patch is applied during the fourth week. The next week starts a new cycle.
• Apply the patch to clean, dry, lotion-free, healthy, hairless skin:
• Suitable patch sites are the upper outer arm, upper torso (excluding breast), buttock, or lower abdomen.
• Use a different site when changing a patch, as this will avoid skin irritation.
• Discard used patches safely according to the manufacturer's instructions in the packet.

• To prevent interference with the adhesive properties of the patch, do not apply make-up, creams, lotions, powders, or other topical products to the skin area where the patch is placed.
• Used patches should be discarded carefully in accordance with the manufacturer's instructions, as used patches contain substantial quantities of the active ingredients.

• These recommendations are based on those issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2004c] and the manufacturer of Evra^® patches [ABPI Medicines Compendium, 2007a].

• Review the woman no longer than 3 months after she starts to use the contraceptive patch, to ensure correct use and that there are no problems.
• Depending on the woman's wishes and anticipated use of the patch, arrange for up to 1 year's supply following this, before requiring a new prescription. Women with specific medical conditions may need more frequent follow-up.
• Advise the woman that she should return at any time if she has any problems.

• These recommendations are pragmatic and are based on those issued for combined oral contraceptives, because both formulations are combined hormonal contraceptives — see Follow-up.
• The contraceptive patch's current status as a Black Triangle drug is an additional reason to review the woman no longer than 3 months after she starts to use it.

• The patch is very adherent and is designed for use in the shower, bath, sauna, and hot tub, and during exercise (including swimming).
• If the patch detaches, the recommended actions depend on how long it has been off. A partially detached patch is treated the same as one that has completely detached.
• If the patch has been off for less than 48 hours:
• Reapply it as quickly as possible, if it is still sticky.
• If it is not sticky, it may not work as a contraceptive; in this case, apply a new patch. Do not use sticking plaster, tape, or bandage to hold the old patch in place.
• No additional contraception is required.
• Continue to use the patch as normal and change it on the normal change day.
• If the patch has been off for 48 hours or longer, or if the time it detached is uncertain:
• Start a whole new patch cycle by applying a new patch as soon as possible. This is now week 1 of the patch cycle. It is also the new day of the week for changing patches and for starting new patch cycles.
• Additional contraception (e.g. condoms or abstinence) is advised for the next 7 days.
• If unprotected sexual intercourse has taken place in the past 5 days, emergency contraception should be considered — see the CKS topic on Contraception - emergency.

• These recommendations are based on those of the fpa (Family Planning Association) [Belfield et al, 2006].
• More rigorous recommendations (24 hour threshold) are made by the manufacturer of Evra^® patches [ABPI Medicines Compendium, 2007a].
• Some experts base their (different) recommendations more closely on the pharmacology and physiology of hormonal contraceptives [Guillebaud, 2007].

• If the woman forgets to take the patch off at the end of week 1 or week 2:
• If the delay in changing the patch is less than 48 hours:
• Replace the old patch with a new one as soon as possible.
• Continue to use the patch as normal, changing it on the usual change day.
• No additional contraceptive protection is required.
• If the delay in changing the patch is 48 hours or more:
• Replace the old patch with a new one as soon as possible.
• This is now week 1 of a new patch cycle. It is also a new day of the week for changing patches and starting new cycles.
• An additional method of contraception (e.g. condoms, abstinence) is advised for the next 7 days.
• If unprotected sexual intercourse has taken place in the previous 5 days, emergency contraception should be considered — see the CKS topic on Contraception - emergency.
• If the woman forgets to take the patch off at the end of week 3:
• Take the patch off as soon as possible.
• Start the new patch cycle on the usual start day.
• If the woman forgets to put on a new patch at the end of the patch-free week:
• If the delay in starting the new patch is less 48 hours:
• Put a new patch on as soon as possible.
• This is now week 1 of a new patch cycle. It is also the new day of the week for changing patches and starting new cycles.
• No additional contraception is required.
• If the delay in starting the new patch is 48 hours or longer:
• Put a new patch on as soon as possible.
• This is now week 1 of a new patch cycle. It is also the new day of the week for changing patches and starting new cycles.
• An additional method of contraception (e.g. condoms, abstinence) is advised for the next 7 days.
• If unprotected sexual intercourse has taken place in the previous 5 days emergency contraception should be considered — see the CKS topic on Contraception - emergency.

• These recommendations are based on those of the manufacturer of the combined contraceptive patch (Evra^®) [ABPI Medicines Compendium, 2007a].

• The efficacy of the combined contraceptive patch can be reduced by liver enzyme–inducing drugs (including the antibiotics rifampicin and rifamycin) and non-liver enzyme–inducing antibiotics.
• Precautions to be taken are the same as for women taking a combined oral contraceptive. For details, see:
• Advice
• Liver enzyme-inducing drugs
• Antibiotics
• Lamotrigine

• Interactions of the combined contraceptive patch with lamotrigine are similar as for combined oral contraceptives (COCs):
• When women using lamotrigine start using COCs, seizure control can worsen.
• When women using lamotrigine discontinue COCs, the adverse effects associated with lamotrigine can increase.
• The manufacturer of lamotrigine warns that other hormonal contraceptives may have similar interactions with lamotrigine, although this has not been studied [ABPI Medicines Compendium, 2007b].
• For further information, see Lamotrigine.

• These recommendations are based on guidelines from the Faculty of Sexual and Reproductive Health Care (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2004c; FFPRHC, 2005d; FFPRHC, 2007b; FSRH, 2010a].
• No good specific data are available to guide the use of the combined contraceptive patch by women using liver enzyme inducers or antibiotics [FFPRHC, 2004c]. Recommendations therefore follow those for women using combined oral contraceptives.
• The Summary of Product Characteristics for the combined contraceptive patch suggests that barrier contraception should be used in addition to the patch when liver enzyme–inducing drugs are used, or that an alternative method should be considered [ABPI Medicines Compendium, 2007a].
• The situation where a woman is using a combined contraceptive patch and a liver enzyme–inducing drug is classified as a category 3 condition in the UK Medical Eligibility Criteria for use of combined hormonal methods. With category 3 conditions, the theoretical or proven risks usually outweigh the advantages of using the method. Provision of a method to a woman with a UKMEC category 3 condition requires expert clinical judgement and/or referral to a specialist contraceptive provider because use of the method is not usually recommended unless other methods are not available or not acceptable.

The management of these problems is similar to that for women using a combined oral contraceptive (COC). For more information see:

• Unscheduled bleeding
• Surgery or immobilization

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• There is one combined contraceptive vaginal ring currently available in the UK. This is marketed as NuvaRing^®, which is a flexible, latex-free, transparent, and colourless to almost colourless vaginal ring, with an outer diameter of 54 mm and a cross-sectional diameter of 4 mm.
• It contains 11.7 mg etonogestrel (a progestogen) and 2.7 mg ethinylestradiol (an oestrogen). The ring releases etonogestrel and ethinylestradiol at an average amount of 120 micrograms and 15 micrograms respectively per 24 hours, over a period of 3 weeks [ABPI Medicines Compendium, 2009b].
• It is a Black Triangle product (i.e. subject to intensive monitoring by the Medicines and Healthcare products Regulatory Agency [MHRA]).

To assess a woman's eligibility for a combined contraceptive vaginal ring:

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Advise the woman that the combined contraceptive vaginal ring does not protect against HIV or AIDS, or other sexually transmitted diseases.
• Check the woman's blood pressure.
• Check the criteria in Combined hormonal methods to ensure that the assessment is complete and that the woman is eligible for a vaginal ring. The restrictions applying to the combined contraceptive vaginal ring are identical to those applying to the combined oral contraceptive (COC) and combined patch.
• Women should not use a combined vaginal ring (UKMEC 4) in the following situations. Should any of the conditions appear for the first time during the use of the combined contraceptive vaginal ring, it should be removed immediately:
• Breastfeeding and less than 6 weeks postpartum.
• Age 35 or more years and smoking 15 cigarettes or more a day.
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension) — UKMEC 3 if less severe.
• Hypertension not adequately controlled (systolic blood pressure equal to, or greater than 160 mmHg, OR diastolic blood pressure equal to, or greater than 95 mmHg).
• Vascular disease, including angina or other ischaemic heart disease, intermittent claudication, hypertensive retinopathy, transient ischaemic attacks, other cerebrovascular disease.
• History of, or current venous thromboembolism on anticoagulants.
• High risk of venous thromboembolism (e.g. major surgery with prolonged immobilization, known thrombogenic mutation, Raynaud's disease with lupus anticoagulant).
• Valvular or congenital heart disease if complicated by pulmonary hypertension, atrial fibrillation, or subacute bacterial endocarditis.
• Migraine with aura, at any age.
• Current breast cancer.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 3 if less severe.
• Cirrhosis of the liver, decompensated (e.g. ascites, jaundice, encephalopathy, or gastrointestinal haemorrhage).
• Liver tumours — benign (hepatocellular adenoma) or malignant (hepatoma).
• Specifically relating to the combined contraceptive vaginal ring, it should not be used if a woman has:
• Undiagnosed vaginal bleeding.
• Known or suspected malignant conditions of the genital organs, if sex steroid-influenced.
• Prolapse of the uterine cervix, cystocele and/or rectocele, or severe or chronic constipation (may cause difficulty with ring insertion, or increase the risk of losing it).
• Hypersensitivity to the active substances and excipients of the combined contraceptive vaginal ring.
• Women should use a combined contraceptive vaginal ring only after consultation with an expert (UKMEC 3) in the following situations:
• Breastfeeding and between 6 weeks and 6 months postpartum.
• Postpartum less than 21 days and not breastfeeding.
• Age 35 or more years, and stopped smoking for less than 1 year, or smoking less than 15 cigarettes a day.
• BMI greater than 35 kg/m².
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension) — UKMEC 4 if more severe.
• Hypertension adequately controlled (systolic blood pressure less than 159 mmHg, AND diastolic blood pressure less than 94 mmHg).
• Family history of venous thromboembolism in a first-degree relative less than 45 years of age.
• Moderately increased risk of venous thromboembolism (e.g. immobility unrelated to surgery, wheelchair use, debilitating illness).
• Known dyslipidaemia with increased risk of cardiovascular disease.
• Migraine without aura, at any age, while using the combined vaginal ring.
• Past history (at least 5 years ago) of migraine with aura, at any age.
• Undiagnosed breast mass, carriers of known gene mutations associated with breast cancer (e.g. BRCA1), past history of breast cancer with no recurrence for 5 years or more.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease — UKMEC 4 if more severe.
• Gall bladder disease, current or medically treated.
• History of cholestasis related to past COC use.
• Use of liver enzyme–inducing drugs (see Selected concurrent medications).

• Contraception for young women and women with learning disabilities:
• Contraception should be seen in terms of the needs of the woman rather than in terms of relieving the anxieties of carers or relatives.
• When a woman with a learning disability is unable to understand and take responsibility for decisions about contraception, carers and other involved parties should meet to address issues around the woman's contraceptive needs and to establish a care plan.
• See Considerations for girls under 16 regarding legal and ethical issues, but note that the combined contraceptive vaginal ring's safety and efficacy has only been established in women aged 18 to 40 years.
• The following examinations and laboratory tests are not required to assess eligibility for a combined contraceptive vaginal ring:
• Breast, pelvic, or genital examination.
• Cervical cytology screening.
• Routine laboratory tests including haemoglobin measurements.
• Thrombophilia screening.

• These recommendations for assessing a woman before starting a combined contraceptive vaginal ring are based on guidelines issued by the Faculty of Sexual and Reproductive Health Care (FSRH) UK medical eligibility criteria for contraceptive use (UKMEC) [FSRH, 2009b], New product review: combined vaginal ring (NuvaRing^®) [FSRH, 2009a], and the Summary of Product Characteristics for the NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• There is currently a lack of direct data on the safety of hormones delivered by the vaginal route [FSRH, 2009a]. Because the risks for users of the combined contraceptive vaginal ring are assumed to be similar to those for users of combined oral contraceptives (COCs), guidelines and evidence on the use of COCs largely applies to the ring (the exceptions are obvious and mainly relate to the differences in absorption routes).
• The examinations and investigations that are specifically not recommended to assess eligibility do not contribute substantially to the safety of women using combined hormonal contraceptives [British Society for Haematology, 2001; FFPRHC, 2007b].

• In general, the advantages, disadvantages, and risks of the combined contraceptive vaginal ring are similar to those of the combined oral contraceptive (COC).
• Advantages of the ring compared with COCs include:
• The woman does not have to think about it every day, only having to remember to remove the ring after 3 weeks and replace it a week later, each month.
• The ring does not become less effective if the woman vomits or has diarrhoea (because the hormones are absorbed through the vaginal mucosa, not through the gastrointestinal tract).
• Disadvantages of the ring compared with COCs include:
• It may occasionally cause vaginal irritation and vaginitis in some women.
• It may occasionally cause a foreign body sensation in the vagina or coital problems.
• It may become broken during use, or may be expelled, compromising efficacy.
• It may very rarely be inserted inadvertently in the urethra and possibly end up in the bladder.
• The risks of rare but serious adverse effects for users of the ring are thought to be similar to those for users of COCs.
• The most frequently reported undesirable effects in clinical trials of the ring are headache, vaginal infections and vaginal discharge, affecting 5–6% of women.
• The ring appears to be at least as effective as COCs at preventing pregnancy — see Effectiveness of contraceptives.

• Information about the advantages, disadvantages, adverse effects, and risks of the combined contraceptive vaginal ring are based on the Summary of Product Characteristics for NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b] and a Faculty of Sexual and Reproductive Healthcare review [FSRH, 2009a].
• The adverse effects identified are based on spontaneous reporting, and exact frequencies are not yet available on the basis of current data.
• The vaginal route has the advantage that it avoids first-pass metabolism and gastrointestinal interference with drug absorption.
• Serum concentrations of ethinylestradiol from NuvaRing^® are lower than that from the combined oral contraceptive, which results in lower systemic exposure to ethinylestradiol from NuvaRing^®. It is not yet known whether this results in any clinical benefits.

When the combined contraceptive vaginal ring is best started depends on the woman's situation:

• New users who have not been using hormonal contraception and have not recently delivered or had an abortion:
• Advise the woman to insert the ring ideally on the first day of menstruation.
• The ring can also be started up to and including day 5 of the cycle, but additional barrier contraception is also
• Starting immediately after oral emergency contraception:
• Levonorgestrel emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 7 days of use.
• Ulipristal acetate emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 14 days of use.
• Advise the woman to take a pregnancy test no sooner than 3 weeks after the last episode of unprotected sex.
• Changing from a combined hormonal contraceptive:
• The woman should insert the ring at the latest on the day following the usual tablet-free, patch-free, or placebo tablet interval of her previous combined hormonal contraceptive.
• If she has been using her previous method consistently and correctly, and if it is reasonably certain that the woman is not pregnant, she may switch from her previous combined hormonal contraceptive on any day of the cycle.
• Changing from a progestogen-only method (e.g. progestogen-only pill, implant, injectable, or levonorgestrel-releasing intrauterine system):
• The woman may switch on any day from the progestogen-only pill, implant or levonorgestrel-releasing intrauterine system on the day it is removed, or injection when the next injection is due, and additional barrier contraception should be used for the first 7 days of use.
• Note: as there is a small theoretical risk of implantation of a previously fertilized egg once the levonorgestrel-releasing intrauterine system (or other intrauterine device) is removed, women should be additionally advised to abstain from intercourse or use another method of contraception for at least 7 days before planned removal.
• After miscarriage up to 24 weeks:
• If the ring is started within 7 days of the miscarriage no additional contraceptive method is needed. If started after 7 days, additional barrier contraception is advised for 7 days.
• After miscarriage after 24 weeks:
• Women should insert the ring 21 days after the miscarriage.
• After first-trimester abortion:
• No additional contraceptive method is needed if the ring is started immediately (within 24 hours).
• If an immediate switch is not desirable, the ring can also be started up to and including day 5 of the cycle, but additional barrier contraception is also recommended for the first 7 days of ring use. In the meantime, she should be advised to use an alternative contraceptive method.
• Postpartum women who are not breastfeeding, or after second-trimester abortion:
• Women should insert the ring 21 days after delivery or second-trimester abortion.
• If starting after this time, additional barrier contraception is also recommended for the first 7 days of ring use. If intercourse has already occurred, pregnancy should be excluded, or she should wait for her first menstrual period, before starting the ring.

• These recommendations are based on the Summary of Product Characteristics for NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b], and guidelines published by the Faculty of Sexual and Reproductive Healthcare [FSRH, 2009a].
• It is noted that there is no specific information in the Summary of Product Characteristics regarding starting the combined contraceptive vaginal ring after miscarriage. The recommendations given are based on a pragmatic approach to what is considered standard practice in guidelines published by the Faculty of Sexual and Reproductive Healthcare on combined oral contraception [FFPRHC, 2002; FFPRHC, 2007b].
• The advice to abstain from intercourse or use another method of contraception for at least 7 days before planned levonorgestrel-releasing intrauterine system (or other intrauterine device) removal is based on recommendations from the Faculty of Sexual and Reproductive Healthcare's guidance on intrauterine contraception [FSRH, 2007].
• The recommendations on how long additional contraception should be used if combined hormonal contraception is started immediately after oral emergency contraception is based on the Quick starting contraception guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH) [FSRH, 2010e].

• The woman herself can insert the combined contraceptive vaginal ring. Instruct her to insert one ring vaginally and leave it in the vagina continuously for 3 weeks. She should remove the ring after 3 weeks of use on the same day as the ring was inserted. A new ring is inserted after a 7 day ring-free break, which then starts a new cycle.
• To insert the ring, the woman should find a comfortable position (standing with one leg up, squatting, or lying down). The ring should be compressed and inserted high into the vagina until it feels comfortable — the exact position is not critical for the ring to provide effective contraception.
• Women should be advised to check the presence of the ring regularly.
• The ring may be kept in during tampon use and sexual intercourse (but may be removed for no more than 3 hours if intercourse is uncomfortable with the ring in situ).
• The ring can be removed by hooking the index finger under the ring or grasping it between the index and middle finger.
• The used ring should be discarded by placing it in its sachet and disposing of with normal household waste.

• These recommendations are based on those issued by the Faculty of Sexual & Reproductive Healthcare (FSRH) [FSRH, 2009a] and the manufacturer of NuvaRing^®combined vaginal ring [ABPI Medicines Compendium, 2009b].

• Prior to dispensing, the combined contraceptive vaginal ring should be stored in a refrigerator (2°C–8°C) for up to 36 months.
• After dispensing:
• The ring can be stored at room temperature, but should not be stored above 30°C.
• The ring should be inserted up to 4 months from the date of dispensing or the expiry date, whichever comes first.

• These recommendations are based on the Summary of Product Characteristics for NuvaRing^®combined vaginal ring [ABPI Medicines Compendium, 2009b].

• Review the woman no longer than 3 months after she starts to use the combined contraceptive vaginal ring, to ensure correct use and that there are no problems.
• Check that the woman is using the ring correctly and consistently.
• Check her knowledge of what to do if she is late removing the ring or late reinserting a new ring.
• Remind her about possible drug interactions.
• Check her blood pressure.
• Ask about headaches, especially migraine, and any new risk factors — see UK Medical Eligibility Criteria.
• Address any issues or problems she might have, such as unscheduled bleeding.
• Depending on the woman's wishes and anticipated use of the ring, repeat scripts may be arranged for up to a year following this. Note: due to the shelf life of the ring, it is recommended that women are supplied with up to 3 rings at a time, and each ring should be inserted within 4 months of the date of dispensing.
• Women with specific medical conditions including an observed rise in blood pressure using the ring may need more frequent follow-up.
• Advise the woman that she should return at any time if she has any problems, including any new headache symptoms.

• The recommendations for follow-up and review are based on a pragmatic approach to what is considered standard practice for combined hormonal contraception.
• The recommendations for dispensing are in line with Summary of Product Characteristics for NuvaRing^® combined vaginal ring, and guidance from the Faculty of Sexual and Reproductive Healthcare [ABPI Medicines Compendium, 2009b; FSRH, 2009a].

Lengthened ring use

• If the ring has been left in place for up to 4 weeks (rather than the recommended 3 weeks), contraceptive efficacy is not reduced. Advise the woman to remove the ring and insert a new ring after one ring-free week.
• If the ring has been left in place for more than 4 weeks (rather than the recommended 3 weeks), contraceptive efficacy may be reduced. Advise the woman to rule out pregnancy and consider emergency contraception (if appropriate) before inserting a new ring.
• If a woman has not used the ring as recommended and has no withdrawal bleed in the ring-free week, advise her to rule out pregnancy before inserting a new ring.

Lengthened ring-free interval

• Advise the woman to insert a new ring as soon as she remembers.
• Advise her to use additional barrier contraception for the next 7 days.
• If the woman had sexual intercourse in the ring-free interval, advise her to rule out pregnancy and consider emergency contraception (if appropriate) before inserting a new ring.

• These recommendations are based on the Summary of Product Characteristics for NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• The longer the ring-free interval the higher the risk of pregnancy.
• A study has shown that intrauterine concentrations of contraceptive steroids with the vaginal ring are similar to the levels in women who use the combined oral contraceptive. There are currently no reports of the clinical outcomes of pregnancies exposed to the vaginal ring.

• Advise the woman to check the presence of the ring regularly (for example, pre-coitally) as there are reports that it may be expelled if it is not inserted properly, while removing a tampon, during sexual intercourse, or in severe or chronic constipation.
• Prolonged expulsion may lead to contraceptive failure and/or breakthrough bleeding.
• Deliberate removal of the ring is not recommended.
• If the ring is removed or expelled and left outside the vagina for less than 3 hours, contraceptive efficacy is not reduced. The ring should be rinsed with cool to lukewarm water and reinserted as soon as possible, within 3 hours.
• If the ring is expelled and left outside the vagina for more than 3 hours, contraceptive efficacy may be reduced. The following advice depends on which week of use this has occurred in.
• If this has occurred during the first or second week of use, the woman should reinsert the ring as soon as she remembers. Additional barrier contraception should be used until the ring has been in the vagina continuously for 7 days. Assess the need for emergency contraception.
• If this has occurred during the third week of use, the woman should discard the ring, and either:
• Insert a new ring immediately, which will start a new cycle. Advise her that breakthrough spotting or bleeding may occur.
• Have a withdrawal bleed, and insert a new ring no later than 7 days from when the previous ring was expelled.

• These recommendations are based on the Summary of Product Characteristics of the NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• The longer the time the ring has been out of the vagina, and the closer this is to the ring-free interval, the higher the risk of pregnancy.

• If the ring is found to be broken during use, advise the woman to remove it, reinsert a new ring as soon as possible, and use additional barrier contraception for the next 7 days (a woman would not be aware of any symptoms if a ring breaks, but she would notice it was broken when it was removed).
• If it is suspected that unprotected sexual intercourse has taken place in the previous 5 days, emergency contraception should be considered — see the CKS topic on Contraception - emergency.

• These recommendations are based on the Summary of Product Characteristics of NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• There is no specific advice regarding when the risk of pregnancy should be considered following the discovery of a broken ring, so clinical judgement should be used to decide when emergency contraception should be considered.

• If pregnancy occurs with a combined contraceptive vaginal ring in situ, the ring should be removed.

• This recommendation is based on the Summary of Product Characteristics of NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• A study has shown that intrauterine concentrations of contraceptive steroids with the vaginal ring are similar to the levels in women who use the combined oral contraceptive. There are no reports of the clinical outcomes of pregnancies exposed to the vaginal ring currently.

• If irregular bleeding (spotting or breakthrough bleeding) occurs after previously regular cycles while the ring has been used as recommended, then consider other non-hormonal causes. Consider excluding pregnancy and refer the woman according to clinical judgement.
• Some women do not experience a withdrawal bleed in the ring-free week.
• If the ring has been used as recommended, it is unlikely the woman is pregnant.
• If the ring has not been used as recommended prior to the first missed withdrawal bleed, or if there are two missed withdrawal bleeds, advise the woman that pregnancy should be ruled out before use of the ring is continued.

• These recommendations are based on the Summary of Product Characteristics of NuvaRing^® combined vaginal ring [ABPI Medicines Compendium, 2009b].
• A large comparative study of a combined oral contraceptive (levonorgestrel with ethinylestradiol) and NuvaRing^® combined contraceptive vaginal ring over 13 cycles found low incidences of breakthrough spotting or bleeding for the ring (2-6.4%), with most bleeding occurring during the ring-free interval.

• The efficacy of the ring may be reduced by liver enzyme-inducing drugs, and non-liver enzyme-inducing antibiotics (excluding amoxicillin and doxycycline which do not appear to be affected).
• If a woman is taking a liver enzyme-inducing drug, advise her to use additional barrier contraception for the duration of treatment and for 28 days after its discontinuation, or choose another method of contraception. If the drug treatment runs beyond the 3 weeks of her cycle, advise her to insert the next ring immediately without a ring-free week.
• If a woman is taking non-liver enzyme-inducing antibiotics (excluding amoxicillin and doxycycline), advise her to use additional barrier contraception for the duration of treatment and for 7 days after their discontinuation. If the drug treatment runs beyond the 3 weeks of her cycle, advise her to insert the next ring immediately without a ring-free week.
• Specifically relating to the vaginal ring:
• Vaginally administered spermicide has no effect on the efficacy or safety of the ring.
• Antifungal drugs do not appear to affect the efficacy of the ring, but miconazole may cause increased release of ethinylestradiol and etonogestrel from the ring, resulting in higher serum levels of these hormones.
• Antifungal ovules may increase the risk of ring breakage.
• For more information on potential drug interactions, see:
• Advice on drug interactions with COCs.
• Liver enzyme-inducing drugs
• Antibiotics
• Lamotrigine

• These recommendations are based on the Summary of Product Characteristics (SPC) for NuvaRing^® combined vaginal ring, and a Faculty of Sexual and Reproductive Healthcare review [ABPI Medicines Compendium, 2009b; FSRH, 2009a; FSRH, 2010a].
• Ethinylestradiol and etonogestrel are metabolized in the liver, so drugs that induce liver enzymes may reduce the contraceptive efficacy of the ring.
• In clinical trials, use of the ring with amoxicillin and doxycycline did not significantly affect the pharmacokinetics of ethinylestradiol and etonogestrel. Evidence is lacking for other antibiotics, therefore the SPC recommends the use of additional barrier contraception when using non-liver enzyme-inducing antibiotics (except amoxicillin and doxycycline) and for 7 days after their discontinuation.

• The management of women using the ring who will be undergoing planned surgery or prolonged immobilization is similar to that for women taking the combined oral contraceptive. For more information, see Surgery or immobilization.

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Five progestogen-only pills are licensed in the UK [BNF 53, 2007]:
• Desogestrel (Cerazette^®) — 28 tablets per pack
• Etynodiol diacetate (Femulen^®) — 28 tablets per pack
• Levonorgestrel (Norgeston^®) — 35 tablets per pack
• Norethisterone (Micronor^®, Noriday^®) — 28 tablets per pack
• There is no 7-day pill-free period as with the combined oral contraceptive.

• Advantages:
• The progestogen-only pill (POP) is very effective when taken correctly and is more effective than barrier methods of contraception. See Effectiveness of contraceptives.
• Sex need not be interrupted to use contraception.
• There are no serious adverse effects.
• It can be used by women for whom the combined oral contraceptive (COC) is not suitable:
• Women who are breastfeeding.
• Older women (35 or more years of age).
• Heavy smokers (15 or more cigarettes daily).
• Hypertension.
• Valvular heart disease.
• Diabetes mellitus with complications, or duration of diabetes greater than 20 years.
• Migraine without aura, or history of migraine with aura.
• Major surgery, as well as surgery affecting the legs.
• Normal fertility returns when the POP is stopped.
• Disadvantages:
• For contraceptive cover to be reliably maintained, pills must be taken at the same time each day: within 3 hours, except for the desogestrel-only pill, Cerazette^®, which must be taken within 12 hours.
• Temporary adverse effects are experienced by some women when they first start a POP (e.g. spotty skin, headaches) [BNF 53, 2007]. Women may be advised that there is no evidence of a causal association between progestogen-only pill use and weight change or depression [FSRH, 2008b].
• Menstrual irregularities (oligomenorrhoea and menorrhagia) are common [BNF 53, 2007]. Although they tend to resolve with time, there is no way of predicting who will continue to have erratic bleeding, and who will become amenorrhoeic. As a general guide [FSRH, 2008b]:
• 20% of women will become amenorrhoeic.
• 40% will bleed regularly.
• 40% will have erratic bleeding.
• May be less effective in women who weigh more than 70 kg (except for the desogestrel-only pill, Cerazette^®) [FFPRHC, 2007c].
• Functional ovarian cysts develop in some women. POP use is associated with a roughly 30% higher risk of developing spontaneously reversible ovarian retention cysts — risk is lower for Cerazette^® [Robinson and Kubba, 1997].
• The POP does not protect against sexually transmitted infections; people at risk for sexually transmitted infections are advised to use condoms as well.
• Risks of some rare but serious conditions are increased:
• Ectopic pregnancy: small increased risk (for POPs excluding Cerazette^®) [Furlong, 2002]. But the absolute risk is lower than that if not using contraception.
• Breast cancer: the risk of breast cancer may be increased in POP users. A meta-analysis of cohort and case-control studies showed a trend similar to that for COCs, but the results were not statistically significant, possibly because the studies had small sample sizes and were under-powered [Collaborative Group on Hormonal Factors in Breast Cancer, 1996a; Collaborative Group on Hormonal Factors in Breast Cancer, 1996b]. The Committee on Safety of Medicines has advised that the possible small increase in the risk of breast cancer should be weighed against the benefits [CSM, 1998].
• Adverse effects which have been claimed for POPs, but for which supporting data are inadequate:
• Loss of libido:
• Reviews of the literature find studies in which libido was increased, decreased, or unchanged when taking oral contraceptives. Results differ according to study design (retrospective and uncontrolled, prospective and controlled, or randomized controlled) [Davis and Castano, 2004; Schaffir, 2006].

To assess a woman's eligibility for use of a progestogen-only pill (POP):

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Check the woman's blood pressure, weight and body mass index (BMI).
• Check the UK Medical Eligibility Criteria to ensure that the assessment is complete and that the woman is eligible for a POP:
• She should not use a POP (UKMEC 4) if she currently has breast cancer.
• She should use a POP only after consultation with an expert (UKMEC 3) in the following situations:
• Stroke or transient ischaemic attack, while using the POP.  
• Ischaemic heart disease while using the POP.
• History of breast cancer and no evidence of recurrence for 5 years.
• Cirrhosis of liver: severe (decompensated).
• Liver tumours: benign (hepatocellular adenoma) and malignant (hepatoma).
• Systemic lupus erythematosus, with positive (or unknown) antiphospholipid antibodies.
• Use of liver enzyme–inducing drugs (for further information, see Selected concurrent medications).
• Breast and cervical examinations, routine blood tests, and thrombophilia screening are not required to assess eligibility for a POP.

• Contraception for young women and women with learning disabilities:
• Contraception should be seen in terms of the needs of the individual rather than in terms of relieving the anxieties of carers or relatives.
• When a woman with a learning disability is unable to understand and take responsibility for decisions about contraception, carers and other involved parties should meet to address issues around the woman's contraceptive need and to establish a care plan.
• See Considerations for girls under 16.
• The following examinations and laboratory tests are not required to assess eligibility for a progestogen-only pill (POP):
• Breast, pelvic and genital examination.
• Cervical cytological screening.
• Routine laboratory tests including haemoglobin measurements.
• Thrombophilia screening.

• These recommendations for assessing a woman before starting a progestogen-only pill (POP) are based on the UK medical eligibility criteria for contraceptive use issued by the Faculty of Sexual and Reproductive Health Care [FSRH, 2009b].
• The examinations and investigations that are specifically not recommended do not contribute substantially to safety of the combined oral contraceptive [British Society for Haematology, 2001; FFPRHC, 2007b].

• Any licensed progestogen-only pill (POP) may be used first-line.
• However, rules about missed pills differ between products, and this may affect their acceptability.
• If the woman weighs more than 70 kg, then consider the desogestrel-only pill, Cerazette^®, as the first line option.
• Irregular bleeding (particularly in the first few months) may be more of a problem with the desogestrel-only pill than with other POPs.

• There has been some debate over whether the desogestrel-only contraceptive pill (Cerazette^®) should be preferred over older progestogen-only pills [DTB, 2003]. However, the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), has not recommended that any one POP be preferred over another [FFPRHC, 2003]. The FFPRHC concluded that:
• One randomized trial found that a 75-microgram desogestrel pill inhibited ovulation in 97% of cycles. Thus, on theoretical grounds, we would expect the desogestrel pill to be more effective than existing progestogen-only pills (POPs). Although Pearl indices (measures of contraceptive failure rates) from a clinical trial comparing desogestrel to a levonorgestrel POP were not significantly different, the study was small and statistically underpowered. Therefore, an evidence-based recommendation cannot be made that the desogestrel-only pill differs from other POPs in terms of efficacy, nor that it is similar to combined oral contraceptives (COCs) in this respect.
• In the same randomized trial above, incidence of adverse effects was similar in desogestrel and levonorgestrel users. Overall discontinuation rates were high: 44.8% for the desogestrel group and 39.4% for the levonorgestrel group. Discontinuation rates due to abnormal bleeding however were similar: 22.5% for desogestrel and 18% for levonorgestrel. However, variable bleeding was almost twice as common in desogestrel users than levonorgestrel users in the first 2-4 months of use. Bleeding problems decreased with increasing duration of use. By 11-13 months of use, almost 50% of women using desogestrel had infrequent bleeding or amenorrhoea compared to 10% in the levonorgestrel group.
• An evidence-based recommendation can be made that the desogestrel-only pill is similar to other POPs in terms of adverse effects and acceptability.
• The desogestrel-only pill is not recommended as an alternative to COCs in routine practice, but it provides a useful alternative for women who require or wish oestrogen-free contraception.
• Previously, the FFPRHC on reviewing the available evidence concluded that POPs may be less effective in women who weigh more than 70 kg (except for the desogestrel-only pill, Cerazette^®) [FFPRHC, 2007c]. However, a more recent review of the data concluded that current evidence does not support the unlicesend use of two traditional progestogen-only pills per day for women weighing more than 70 kg [FSRH, 2008b].
• The Scottish Medicines Consortium advises that the use of Cerazette^® should be restricted to those individuals who cannot tolerate oestrogen containing contraceptives or in whom those preparations are contraindicated [Scottish Medicines Consortium, 2003b].

Women who are starting to use a progestogen-only pill (POP):

• Exclude pregnancy.
• If the woman is not amenorrhoeic and not breastfeeding:
• Start the POP at the beginning of menstruation — ideally on the first day (licensed use), but this can be up to and including day 5 of the cycle (unlicensed use).
• Additional contraceptive protection will not be required.
• If this is not possible:
• Start the POP at any other time in the menstrual cycle, provided that it is reasonably certain that a woman is not pregnant (unlicensed use).
• Advise additional contraceptive protection (such as condoms) for the first 48 hours of pill taking.
• If starting immediately after oral emergency contraception:
• Levonorgestrel emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 2 days of use.
• Ulipristal acetate emergency contraception used — advise additional contraception (condoms or avoidance of sex) for the first 9 days of use.
• Advise the woman to take a pregnancy test no sooner than 3 weeks after the last episode of unprotected sex.
• If the woman is amenorrhoeic:
• Start the POP at any time, provided that it is reasonably certain that a woman is not pregnant (unlicensed use).
• Advise additional contraceptive protection (such as condoms) for the first 48 hours of pill taking.
• If the woman is postpartum and not breastfeeding:
• Contraception is not required before day 21 postpartum.
• Ideally, start the POP on day 21 postpartum for immediate contraceptive protection — this is the only licensed use for postpartum women.
• However, the POP can be started before day 21 if requested.
• If started after day 21, advise additional contraceptive protection (such as condoms) for the first 48 hours of pill taking.
• If the woman is postpartum and breastfeeding:
• Start on or before day 21 postpartum for immediate contraceptive protection.
• If started after day 21, advise additional contraceptive protection (such as condoms) for the first 48 hours of pill taking.
• These are unlicensed uses.

• Explain to the woman that these recommendations may differ from those provided in the patient leaflet or package insert.
• For details of licensed uses and recommended unlicensed uses, see Table 1.
• 'Breastfeeding' means 'fully or nearly fully breastfeeding' during the day and at night.

• These recommendations are based on guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2005a; FSRH, 2008b].
• The FFPRHC concluded that:
• The risk of ovulation when starting a progestogen-only pill (POP) within the first 5 days of menstruation is acceptably low because the POP has a rapid contraceptive effect on cervical mucus.
• Suppression of ovulation is less reliable when starting after day 5.
• The recommendations on how long additional contraception should be used if the progestogen-only pill is started immediately after oral emergency contraception is based on the Quick starting contraception guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH) [FSRH, 2010e].
• Recommendations in FFPRHC guidelines on 'The use of contraception outside the terms of the product licence' [FFPRHC, 2005a] have been quoted when these differ from recommendations in the FFPRHC guidelines 'Selected practice recommendations' [FFPRHC, 2002]. The differences are minor and related to starting a POP in the postpartum period.

Women who are changing to a progestogen-only pill (POP) from:

• Another hormonal method:
• The woman can start a POP immediately, provided that she has been using her hormonal method consistently and correctly, or if it is otherwise reasonably certain that she is not pregnant.
• There is no need to wait for the next menstrual period.
• An injectable progestogen-only contraceptive:
• The woman should start a POP when the repeated injection would have been given.
• No additional contraceptive protection is needed.
• A non-hormonal method other than a copper intrauterine device (IUD):
• The woman can start a POP within 5 days of the start of menstrual bleeding.
• No additional contraceptive protection is needed.
• The woman can also start at any other time, if it is reasonably certain that she is not pregnant.
• If it has been more than 5 days since menstrual bleeding started, the woman will need to abstain from sex or use additional contraceptive protection (such as condoms) for the next 48 hours.
• A copper IUD or levonorgestrel-releasing IUS:
• The POP is most conveniently begun within 5 days of the start of menstrual bleeding.
• No additional contraceptive protection is needed.
• The IUD can be removed at this time.
• The woman can also start a POP at any other time, if it is reasonably certain that she is not pregnant. Because the POP will become effective only after 48 hours, the IUD or IUS should not be removed before this if:
• She has been sexually active in the past 7 days, or
• She requires interim protection from the IUD or IUS.

• These recommendations are based on guidance issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FSRH, 2008b].
• the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), considered the risk of ovulation when starting progestogen-only pills (POPs) within the first 5 days of menstruation to be acceptably low.
• Suppression of ovulation was considered to be less reliable when starting after day 5.
• An estimated 48 hours of POP use was deemed necessary to achieve the contraceptive effects on cervical mucus.
• There was some concern about the risk of pregnancy when removing an intrauterine device within a cycle where there has already been intercourse. That concern led to the recommendation that the device be left in place until the next menstrual period.

• Arrange follow up 10–12 weeks after the first prescription of a progestogen-only pill (POP) and then at least every 12 months thereafter, provided there are no problems.
• At the follow-up visit:
• Check that the woman is taking the POP correctly and consistently.
• Check her knowledge of what to do if a pill is missed.
• Remind her about possible drug interactions.
• Review for any new risk factors — see UK Medical Eligibility Criteria.
• Address any issues or problems she might have. The most common problems are:
• Breast tenderness. This is usually transient; if it is persistently troublesome, consider changing to another POP, or to another contraceptive method.
• Irregular menstrual bleeding.

• These recommendations are pragmatic and based on expert opinion [Guillebaud, 2007].

• A woman who vomits (for any reason) within 2 hours of taking a progestogen-only pill (POP) should repeat the dose as soon as possible.
• If she is now more than 3 hours late (or 12 hours for desogestrel), continues to vomit or has very severe diarrhoea, the woman should follow the instructions for missed pills.
• If vomiting or severe diarrhoea persists for more than 24 hours, the woman should follow the instructions for missed pills, counting each day of vomiting and/or severe diarrhoea as a missed pill:
• Additional contraceptive cover is required during the illness and for 48 hours afterwards.

• These recommendations may differ from those detailed in the patient leaflet or package insert.

• There is concern that vomiting and/or severe diarrhoea can reduce the efficacy of progestogen-only pills (POPs) by interfering with its absorption [BNF 53, 2007].
• These recommendations follow guidelines issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FSRH, 2008b]. The FFPRHC guidelines reflect those issued by the World Health Organization (WHO) [WHO, 2002; WHO, 2004a]. The WHO recommendations are based on expert opinion:
• The WHO expert working group found no direct evidence to address the issue of vomiting and/or severe diarrhoea while using POPs [WHO, 2004a].
• Although it is uncertain whether the effect of severe vomiting and/or diarrhoea is sufficient to warrant use of the missed pill regimen, the WHO working group considered the effects of vomiting or diarrhoea to be similar to that of missing pills [WHO, 2004a].

• Check which progestogen-only pill (POP) the woman is taking and the time since the last pill was taken.
• For the desogestrel pill (Cerazette^®): a pill is missed if she is more than 12 hours late (i.e. more than 36 hours since taking the last pill).
• For any other progestogen-only pills: a pill is missed if she is more than 3 hours late (i.e. more than 27 hours since taking the last pill).
• If the woman has missed any POPs, she should:
• Take a POP as soon as possible.
• Continue taking the pills daily, one each day. This may mean taking two pills in 24 hours: the missed pill and the next one at the usual time.
• Use additional contraceptive protection for the next 48 hours, unless she is less than 6 months postpartum, fully breastfeeding, and amenorrhoeic.
• Consider emergency contraception if unprotected sexual intercourse has taken place while contraceptive protection from the POP is doubtful. See the CKS topic on Contraception - emergency.

• For the desogestrel pill (Cerazette^®), the manufacturer advises that contraceptive protection may be reduced if more than 36 hours have elapsed between two tablets [ABPI Medicines Compendium, 2004b].

• These recommendations are based on guidance issued by the World Health Organization [WHO, 2004a] and are supported by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005b; FSRH, 2008b]:
• The World Health Organization expert working group considered the inconsistent or incorrect use of pills to be a major reason for unintended pregnancy and highlighted the importance of taking the progestogen-only pill at approximately the same time each day [WHO, 2004a]:
• An estimated 48 hours of progestogen-only pill use was deemed necessary to achieve the contraceptive effects on cervical mucus.

• Interactions:
• Liver enzyme–inducing drugs can affect the efficacy of the progestogen-only pill (POP). Commonly encountered liver enzyme–inducing drugs are:
• Antibiotics: rifampicin and rifabutin.
• Anticonvulsants: carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate.
• Herbal remedies: St John's wort.
• Antiretrovirals: drug interactions between certain antiretroviral agents and hormonal contraceptives could alter the safety and effectiveness of both the hormonal contraceptives and the antiretroviral agents. See antiretrovirals.
• Antibiotics that do not induce liver enzymes (i.e. all antibiotics except rifampicin and rifamycin) do not reduce the effectiveness of POPs.
• Precautions:
• The woman should check with a healthcare professional whether a drug interaction could be problematic before she starts using any drug or herbal remedy.
• The woman may choose to continue with the POP if she is receiving a short course of an interacting drug, but she should use additional contraception (e.g. condoms) whilst taking the drug and for 4 weeks after finishing the course.
• Women receiving long-term courses of drugs that continue to interact with hormonal contraception should consider an alternative contraceptive method for which interaction is not a problem:
• Suitable alternative contraception methods include progestogen-only injectables, levonorgestrel-releasing intrauterine system, and a copper intrauterine device (IUD).
• If she is unable or unwilling to use an alternative or additional method, refer to (or consult with) a specialist.
• Emergency contraception should be considered if sexual intercourse has taken place in the past 5 days and the efficacy of the POP is doubtful. See the CKS topic on Contraception - emergency.

• For further information on choosing an appropriate contraceptive for women prescribed a liver enzyme–inducing drug, see Selected concurrent medications.

• This advice is based on guidelines from the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2005d; FFPRHC, 2006a; FSRH, 2010a].
• Although the interaction of rifampicin or certain anticonvulsants with progestogen-only pills (POPs) is not harmful to women, it is likely to reduce the effectiveness of POPs.
• Evidence is insufficient to be certain that increasing the hormone dose of POPs will ensure effective contraception with long-term use of liver enzyme–inducing drugs.
• Limited data suggest that potential drug interactions between many antiretroviral agents and hormonal contraceptives may alter the safety and effectiveness of both the hormonal contraceptives and the antiretroviral agents.
• There is evidence that progestogen-only methods are not affected by lamotrigine.

• Many women experience irregularities in menstruation while using a progestogen-only pill (POP). Nevertheless, exclude or manage situations which could compromise the effectiveness of the POP:
• Missed pills: check how the POP is being taken and if any pills have been missed.
• Drug interactions: review if any new prescription or non-prescription medicines, or herbal/natural remedies, have been taken (e.g. antibiotics, St John's wort).
• Vomiting within 2 hours of pill taking: review the cause and duration of vomiting. Check pill taking (e.g. if a second dose of POP was taken).
• Severe diarrhoea: review the cause and duration of severe diarrhoea. Check pill taking (e.g. if additional pills have been taken to compensate for probable malabsorption).
• Exclude or manage other situations which could result in unscheduled bleeding, such as:
• Sexually transmitted infections.
• Risk of STI if the woman is under 25 years, or has a new sexual partner, or more than one partner in the last year.
• Pregnancy.
• Gynaecological conditions such as cervical cancer. Provided there is consistent and correct use of contraception, speculum examination is warranted:
• For persistent bleeding beyond the first 3 months of use.
• For new symptoms or a change in bleeding after at least 3 months of use.
• If the woman has not participated in a National Cervical Screening programme.
• If requested by the woman.
• After a failed trial of modification of POP treatment (at least 6–8 weeks).
• If there are other symptoms such as pain, dyspareunia, or post coital bleeding. (Note that these symptoms also warrant pelvic examination.)
• If the above causes of menstrual irregularities have been excluded, the irregularity can be assumed to be caused by the POP.
• Although bleeding may settle with time, there is no evidence to indicated which women may become amenorrhoeic or which women may experience irregular bleeding, or for how long. As a general guide:
• 2 in 10 women will become amenorrhoeic; this is most likely in older women.
• 4 in 10 women will have regular bleeding.
• 4 in 10 women will have irregular bleeding.
• Frequent or prolonged bleeding may be managed by trying another POP or by changing to another contraceptive method.
• If amenorrhoea does occur, the woman can continue with the POP, once pregnancy has been excluded.

• These recommendations are based on guidelines from the Faculty of Sexual and Reproductive Healthcare, the Royal College of Obstetricians and Gynaecologists, and the Department of Health [FSRH, 2008b; FSRH and RCOG, 2009; DH, 2010].
• The advice on early recognition of genito-urinary cancer is based on guidance from the National Institute for Health and Clinical Excellence [NICE, 2005].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Two progestogen injectables are currently available in the UK [BNF 53, 2007]:
• Depot medroxyprogesterone acetate, 150 mg (Depo-Provera^®) [ABPI Medicines Compendium, 2004c]:
• This is given every 12 weeks by deep intramuscular injection.
• It is licensed for long-term use, but the risks and benefits of its use must be re-evaluated after 2 years.
• Norethisterone enantate, 200 mg (Noristerat^®) [ABPI Medicines Compendium, 2004e]:
• This is given every 8 weeks by deep intramuscular injection.
• It is licensed only for short-term use (two injections).

• Advantages:
• Very effective: when given at the recommended intervals, less than 2 in 1000 women will become pregnant with each year's use:
• Depot medroxyprogesterone acetate (Depo-Provera^®) is more effective than norethisterone enantate (Noristerat^®).
• Users do not have to think about contraception for as long as the injection lasts — 12 weeks for depot medroxyprogesterone acetate and 8 weeks for norethisterone enantate.
• Sex need not be interrupted to use contraception.
• Can be used when breastfeeding.
• Not affected by other medicines.
• May reduce heavy painful periods and help with premenstrual symptoms.
• Can be used in situations where combined oral contraceptives are not recommended, such as:
• Migraine without aura, past history of migraine with aura.
• Concomitant use of antibiotics/drugs/herbal preparations that induce liver enzymes.
• Can be used by women with a body mass index greater than 35 kg/m².
• May reduce the frequency of seizures in women with epilepsy.
• May reduce the risk of endometrial cancer.
• Disadvantages:
• Not rapidly reversible. After stopping use of progestogen-only injectables:
• There could be a delay of up to 1 year in the return of normal fertility.
• Menstruation can take several months to return to normal.
• Do not protect against sexually transmitted infections.
• Risks and possible adverse effects:
• Altered bleeding:
• Amenorrhoea is likely during use of progestogen-only injectables. It is more likely with depot medroxyprogesterone acetate than norethisterone enantate, is more likely as time goes by, and is not harmful.
• The most common reason for discontinuation is an altered bleeding pattern, including persistent bleeding: up to 50% of women stop using depot medroxyprogesterone acetate within 1 year.
• Prolonged and sometimes heavy bleeding is experienced by less than 10% of users.
• Irregular bleeding may continue for some months after stopping the injections.
• Increase in body weight — up to 2–3 kg over 1 year:
• Not all women put on weight, and some lose weight.
• Overweight women may be at increased risk of gaining weight.
• There is no evidence of a causal association between the use of progestogen-only injectable contraceptives and mood change or headache.
• Loss of bone mineral density with long-term use (more than 1 year):
• The effect is small and largely recovers when depot medroxyprogesterone acetate is stopped.
• There is no evidence that depot medroxyprogesterone acetate increases the risk of fracture.
• Women who wish to continue using depot medroxyprogesterone acetate for longer than 2 years should be supported in their decision making: review their clinical situation and discuss the balance between the benefits and potential risks.
• Because of the possible effect on bone mineral density, progestogen-only injectables are best avoided by adolescents and women with risk factors for osteoporosis (e.g. age over 40 years, longterm use of systemic corticosteroids). They may be given if other methods are not suitable or acceptable.
• Women should also be warned that additional drugs such as carbamazepine, phenytoin, primidone and sodium valproate are associated with decreased bone mineral density. Strategies to protect against bone mineral density loss such as diet and exercise should be discussed with at-risk women.
• Unknown effects:
• There is no good evidence on possible changes in libido, mood changes, or headache.
• The risk for breast cancer may be slightly increased, but there is uncertainty about the validity of the data.
• There is no evidence of congenital malformation to the fetus if pregnancy occurs during use of depot medroxyprogesterone acetate.

• This information is based on guidance published by the National Institute for Health and Clinical Excellence and the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2004d; National Collaborating Centre for Women's and Children's Health, 2005; FFPRHC, 2006a; FSRH, 2008c; FSRH, 2010a].
• The evidence relates primarily to depot medroxyprogesterone acetate, and is assumed to apply to norethisterone enantate.

To assess a woman's eligibility for use of a progestogen-only injectable:

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection, and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Assess the risk for osteoporosis.
• Check the woman's blood pressure.
• Check the UK Medical Eligibility Criteria to ensure that the assessment is complete and that the woman is eligible for a progestogen-only injectable.
• Women should not use a progestogen-only injectable (UKMEC 4) in the following situations:
• Current breast cancer.
• Women should use a progestogen-only injectable only after consultation with an expert (UKMEC 3) in the following situations:
• Multiple risk factors for arterial cardiovascular disease (e.g. older age, smoking, diabetes, and hypertension).
• Vascular disease, including angina or other ischaemic heart disease, intermittent claudication, hypertensive retinopathy, stroke or transient ischaemic attack.
• Unexplained vaginal bleeding: before evaluation.
• History of breast cancer and no evidence of recurrence for 5 years.
• Diabetes with nephropathy, neuropathy, retinopathy, or other vascular disease.
• Cirrhosis of liver: severe (decompensated).
• Liver tumours: benign (hepatocellular adenoma) and malignant (hepatoma).
• Systemic lupus erythematosus with positive (or unknown) antiphospholipid antibodies, or with severe thrombocytopenia if considering initiating depot medroxyprogesterone acetate.
• If the woman is at increased risk for osteoporosis, she should consider alternatives to depot medroxyprogesterone acetate.

• Contraception for young women and women with learning disabilities:
• Contraception should be seen in terms of the needs of the individual rather than in terms of relieving the anxieties of carers or relatives.
• When a woman with a learning disability is unable to understand and take responsibility for decisions about contraception, carers and other involved parties should meet to address issues around the woman's contraceptive need and to establish a care plan.
• See Considerations for girls under 16.
• Risk factors for osteoporosis:
• Treatment with corticosteroids.
• Low body mass index (< 19 kg/m²).
• Family history of maternal hip fracture before age 75 years.
• Medical disorders independently associated with bone loss (e.g. chronic inflammatory bowel disease, rheumatoid arthritis, hyperthyroidism, coeliac disease).
• Conditions associated with prolonged immobility.
• The following examinations and laboratory tests are not required to assess eligibility for a progestogen-only injectable:
• Bone mineral density tests (also not required for the recommended re-evaluation after 2 years use of depot medroxyprogesterone acetate).
• Breast, pelvic, or genital examination.
• Cervical cytology screening.
• Routine laboratory tests, including haemoglobin measurements.
• Thrombophilia screening.

• These recommendations for assessing a woman before starting a progestogen-only injectable are based on the UK medical eligibility criteria for contraceptive use issued by the Faculty of Sexual and Reproductive Health Care [FSRH, 2009b] and guidance issued by the National Institute for Health and Clinical Excellence on the use of long-acting reversible contraceptives [National Collaborating Centre for Women's and Children's Health, 2005].
• The recommendations are also based on guidelines issued by the Medicines and Healthcare products Regulatory Agency (MHRA), and the Faculty of Sexual and Reproductive Health Care on the use of depot medroxyprogesterone acetate and norethisterone enantate injections [FFPRHC, 2002; CSM, 2004; FFPRHC, 2004e].

• If the woman requires long-acting contraception for a few months (i.e. short-term use), depot medroxyprogesterone acetate (Depo-Provera^®) and norethisterone enantate (Noristerat^®) are options.
• If the woman requires long-acting contraception for an extended period (i.e. more than 16 weeks), depot medroxyprogesterone acetate (Depo-Provera^®) is recommended.

• Examples of when short-term contraception is useful for a woman include:
• When her partner is waiting for confirmation that his vasectomy has been successful.
• When she is waiting for tubal ligation.

• Norethisterone enantate (Noristerat^®) is licensed for up to two injections, 8 weeks apart [ABPI Medicines Compendium, 2004e].
• Depot medroxyprogesterone acetate (Depo-Provera^®) injections can be repeated every 12 weeks. The license does not restrict the duration of use (apart from recommending that the risks and benefits of continued use be reviewed after 2 years) [ABPI Medicines Compendium, 2004c].

Women who are currently not using any hormonal contraceptives or a copper intrauterine device (IUD), and are:

• Having menstrual cycles and are not postpartum, post-abortion, or post-miscarriage:
• The woman can have the first injection up to and including day 5 after the start of menstrual bleeding:
• No additional contraceptive protection is needed.
• She can also have the first injection after day 5, if it is reasonably certain that she is not pregnant.
• This use is unlicensed.
• She must abstain from sex or use additional contraceptive protection (such as condoms) for the next 7 days.
• Amenorrhoeic:
• The woman can have the first injection at any time, if it is reasonably certain that she is not pregnant (this is an unlicensed use).
• She must abstain from sex or use additional contraceptive protection (such as condoms) for the next 7 days.
• Postpartum:
• Principles of starting hormonal contraception postpartum:
• No method should be started before day 21 unless there are good reasons to do so.
• If a hormonal method is to be used post birth, it can be started on day 21 without the need for any additional contraception.
• If started after day 21, then additional contraception should be used for 7 days.
• Postpartum and not breastfeeding:
• Depot medroxyprogesterone acetate can be used immediately after birth. However, if depot medroxyprogesterone acetate is started in the puerperium, there is a risk of prolonged heavy bleeding. Therefore, if practical delay starting it until 3 weeks after birth. Otherwise, start within the first 5 days.
• Norethisterone enantate can be used immediately after birth.
• Breastfeeding (primarily or fully) and less than 6 weeks postpartum:
• Use of depot medroxyprogesterone acetate is not recommended, unless other, more appropriate methods are not available or not acceptable; this is an unlicensed use. If, because of the risk of pregnancy, it must be used before 6 weeks postpartum, it should ideally be delayed until at least day 21 postpartum.
• Norethisterone enantate can be used immediately after birth, although breastfeeding should be withheld from neonates with severe or persistent jaundice requiring medical treatment.
• Breastfeeding (primarily or fully) and 6 weeks to 6 months postpartum, and amenorrhoeic:
• The woman can have her first injection at any time.
• If she is fully or nearly fully breastfeeding, no additional contraceptive protection is needed.
• Breastfeeding, more than 6 weeks postpartum, and menstrual periods have returned:
• The woman can have the first injection as advised for other women having menstrual cycles.
• Post-abortion or post-miscarriage:
• The woman can receive an injection immediately after miscarriage (unlicensed use) or abortion (unlicensed use for depot medroxyprogesterone acetate):
• If started on the day of surgical, or the second part of a medical, abortion (induced or spontaneous at less than 24 weeks), no additional contraceptive method is required.
• If started more than 5 days after abortion (unlicensed use), an additional contraceptive method is required for 7 days.

• These recommendations are those issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2005a; FSRH, 2008c] and are in line with those issued by the National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's and Children's Health, 2005].

A woman who is switching to a progestogen-only injectable from:

• Another hormonal method — excluding the levonorgestrel-releasing intrauterine system (IUS):
• The woman can have the first injection immediately, if she has been using her hormonal method consistently and correctly (unlicensed use), or if it is reasonably certain that she is not pregnant. There is no need to wait for the next menstrual period.
• If her previous method was another injectable, she should have the new progestogen-only injectable no later than when the original repeated injection would have been given.
• No additional contraceptive protection is needed.
• A non-hormonal method other than a copper intrauterine device (IUD):
• The woman can have the first injection immediately, if it is reasonably certain that she is not pregnant. There is no need to wait for the next menstrual period.
• If she is within 5 days of the start of menstrual bleeding, no additional contraceptive protection is needed.
• If it has been more than 5 days since menstrual bleeding started (unlicensed use), she must abstain from sex or use additional contraceptive protection (such as condoms) for the next 7 days.
• A copper IUD or the levonorgestrel-releasing intrauterine system (IUS):
• The woman can have the first injection within 5 days after the start of menstrual bleeding:
• No additional contraceptive protection is needed.
• The IUD or IUS can be removed at that time.
• The woman can also start at any other time (unlicensed use), if it is reasonably certain that she is not pregnant.
• The IUD or IUS may be removed 7 or more days later.
• It may be removed earlier provided that she has not been sexually active in the past 7 days and that additional precautions are taken for the next 7 days.
• If she is amenorrhoeic or has irregular bleeding, she can have the injection as advised for other amenorrhoeic women.

• These recommendations are based on guidelines published by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2005a].
• the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), considered that an injection given up to day 7 of the menstrual cycle results in a low risk of an ovulatory cycle that could lead to pregnancy.
• The need for additional contraceptive protection among those switching from another hormonal method will depend on the previous method used.
• There was some concern about the risk of pregnancy when removing an intrauterine device within a cycle where there has already been intercourse. That concern led to the recommendation that the device be left in place until the next menstrual period.
• Whereas an estimated 48 hours of use of the progestogen-only pill (POP) was deemed necessary to achieve contraceptive effect on cervical mucus, the time required for progestogen-only injectables to exert such an effect was uncertain.

• For women using norethisterone enantate, arrange for the second injection to be given in 8 weeks.
• For women using depot medroxyprogesterone acetate, arrange repeat injections at 12-week intervals:
• There is a two-week 'window of safety' if the repeat injection is late.
• At the follow-up visit:
• Check the woman's knowledge of what to do if is she is late.
• Review for any new risk factors — see the UK Medical Eligibility Criteria.
• Address any issues or problems she might have. The most common problems are:
• Weight gain.
• Irregular menstrual bleeding: see Advice on menstrual irregularity.
• If problems arise, change to another method (if this is what she wants or needs), or repeat the injection, or change to the other type of injectable.

• These recommendations are based on expert opinion [Guillebaud, 2007] and informed by guidelines from the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2006a].

• Up to 14 days late (i.e. up to 98 days since the last injection):
• Repeat the injection.
• No additional contraception is needed.
• More than 14 days late (i.e. more than 98 days since the last injection):
• Exclude pregnancy before repeating the injection:
• Use an additional contraceptive method for 7 days after giving the injection.
• If pregnancy cannot be excluded immediately:
• Consider if emergency contraception is indicated (see the CKS topic on Contraception - emergency).
• Advise alternative methods, and delay repeating the injection until there is a negative pregnancy test at least 3 weeks after the last unprotected sex.
• After the injection, continue with alternative contraception for 7 more days.

• Table 1 shows the differences between the licensed and unlicensed uses of progestogen-only injectables.

• These recommendations follow guidelines issued by the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC) [FFPRHC, 2002; FFPRHC, 2005a], which are developed from guidance issued by a World Health Organization (WHO) expert working group [WHO, 2004a].
• The basis of the WHO recommendations are [WHO, 2004a]:
• The expert working group considered the risk of ovulation to be minimal within 2 weeks after the time for a repeated injection (3 months for depot medroxyprogesterone acetate and 2 months for norethisterone enantate).
• The mechanisms of action, the medical eligibility criteria, and the adverse-effects of depot medroxyprogesterone acetate and norethisterone enantate are similar. Therefore it is safe to stop using one and start using the other.
• Whereas an estimated 48 hours of progestogen-only pill use was deemed necessary to achieve contraceptive effect on cervical mucus, the time required for progestogen-only injectables to exert such an effect was uncertain.
• Where recommendations are sometimes inconsistent, CKS has followed the FFPRHC guidelines. For example:
• The Summary of Product Characteristics for depot medroxyprogesterone acetate regards a delay of more than 5 days in repeating the injection as compromising the reliability of contraception [ABPI Medicines Compendium, 2004c]. However, the FFPRHC would regard a delay of up to 2 weeks as not affecting reliability of contraception [FFPRHC, 2005a].
• The Summary of Product Characteristics for depot medroxyprogesterone acetate recommends 14 days of additional contraceptive protection when the repeated injection is more than 5 days late [ABPI Medicines Compendium, 2004c]. However, the FFPRHC recommend 7 days [FFPRHC, 2005a].

• Advise that many women experience irregularities in menstruation while using a progestogen-only injectable:
• A few women have very heavy or prolonged bleeding. This can be managed by:
• Treating with a combined oral contraceptive (either cyclically or continuously) for up to 3 months.
• Treating with mefenamic acid 500 mg twice or three times a day for 5 days.
• Changing to another contraceptive method.
• Some women experience prolonged amenorrhoea; this is most likely in older women and, with forewarning, is usually accepted.
• Exclude or manage other situations which could result in unscheduled bleeding, such as:
• Sexually transmitted infections.
• Risk of STI if the woman is under 25 years, or has a new sexual partner, or more than one partner in the last year.
• Pregnancy.
• Gynaecological conditions such as cervical cancer. Provided there is consistent and correct use of contraception, speculum examination is warranted:
• For persistent bleeding beyond the first 3 months of use.
• For new symptoms or a change in bleeding after at least 3 months of use.
• If the woman has not participated in a National Cervical Screening programme.
• If requested by the woman.
• After a failed trial of modification of treatment.
• If there are other symptoms such as pain, dyspareunia, or post coital bleeding. (Note that these symptoms also warrant pelvic examination.)

• For more information on treating heavy bleeding, see the CKS topic on Menorrhagia.

• These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's and Children's Health, 2005] and guidelines published by the Faculty of Sexual & Reproductive Healthcare and the Royal College of Obstetricians and Gynaecologists [FSRH and RCOG, 2009] and the Department of Health [DH, 2010].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• From mid-October 2010, Nexplanon^® will replace Implanon^® as the only progestogen-only implant licensed for use in the UK.
• Nexplanon^® and Implanon^® are bioequivalent (both contain 68 micrograms etonogestrel and have the same release rate). Both are inserted subdermally under the skin in the inner part of the upper arm.
• Both are designed to provide contraception for 3 years.
• The main differences are that Nexplanon^® is radio-opaque, and has a different application device and insertion technique (training is required).
• However, UK family planning clinics continue to see women requesting the removal of implants, such as Norplant^® (discontinued from the UK market in 1999) and Jadelle^® (used in other countries). These implants are designed to provide contraception for 5 years.

[National Collaborating Centre for Women's and Children's Health, 2005; FSRH, 2010d; MSD, 2010]

The following advice applies to both Nexplanon^® and Implanon^® [FSRH, 2010d].

• Advantages:
• The implant is very effective: over 3 years, fewer than 1 in 1000 women will become pregnant:
• No pregnancies have been reported in clinical trials, but pregnancies have occasionally occurred in practice, usually because of operator error or method failure [National Collaborating Centre for Women's and Children's Health, 2005].
• Users do not have to think about contraception for 3 years.
• Sex need not be interrupted to use contraception.
• Can be used when breastfeeding.
• Normal fertility returns as soon as the implant is removed.
• Can be used in women in whom combined oral contraceptives (and other medicines with oestrogens) are not recommended, such as migraine without aura or history of migraine with aura.
• May reduce the risk of endometrial cancer.
• Not associated with any serious adverse effects. There is evidence that contraceptive implants have no adverse effects on [National Collaborating Centre for Women's and Children's Health, 2005]:
• Blood pressure.
• Venous thromboembolism.
• Risk factors for cardiovascular disease.
• Bone mineral density.
• Diabetes.
• Effective in women of all weights [National Collaborating Centre for Women's and Children's Health, 2005].
• However, the manufacturer advises earlier replacement of the implant in 'heavier women' [ABPI Medicines Compendium, 2006].
• Disadvantages:
• Most women will have changes in menstrual bleeding, and bleeding patterns are likely to remain irregular [National Collaborating Centre for Women's and Children's Health, 2005]:
• 20% of women will have no bleeding, and almost 50% of women will have infrequent, frequent, or prolonged bleeding.
• Bleeding problems result in almost 33% of women having their implant removed within 2 years.
• Irregular bleeding associated with implant-use can be treated with mefenamic acid or ethinylestradiol.
• Acne may develop (but it may also improve) in some women [National Collaborating Centre for Women's and Children's Health, 2005].
• Contraceptive efficacy likely to be reduced in women using liver enzyme–inducing drugs [FFPRHC, 2006a].
• An implant does not protect against sexually transmitted infections.
• Fitting and removing the implant requires a minor surgical procedure and may cause some pain, bruising, itching, or irritation.
• The surgical procedure can rarely (less than 1 in 100 women) cause such problems as an abscess, scarring, and migration or expulsion of the implant [National Collaborating Centre for Women's and Children's Health, 2005].
• Changes in weight, mood, libido, or headaches are commonly reported by women using progestogen-only implants. However, research has not shown that these problems, which are common in the general population, are associated with the implant [National Collaborating Centre for Women's and Children's Health, 2005].
• Other problems cause about 6% of women to have their implant removed within 2 years [National Collaborating Centre for Women's and Children's Health, 2005].
• Risks:
• No association with any serious adverse effects. In particular:
• There is no evidence that the risk of acquiring a sexually transmitted infection (including HIV) is increased.
• There is no evidence of a teratogenic effect; however, if a woman becomes pregnant and continues with the pregnancy, the implant should be removed [National Collaborating Centre for Women's and Children's Health, 2005].

To assess a woman's eligibility for a progestogen-only implant:

• In young women and women with special needs, assess their competence to decide, and support them in making their own decisions about contraception.
• Exclude pregnancy.
• Assess the woman's risk for sexually transmitted infection and, when appropriate, advise testing, promote safer sex, and/or refer for counselling.
• Check the woman's blood pressure.
• Check the UK Medical Eligibility Criteria to ensure that the assessment is complete and that the woman is eligible for a progestogen-only implant:
• Women should not use a progestogen-only implant (UKMEC 4) if they currently have breast cancer.
• Women should use a progestogen-only implant only after consultation with an expert (UKMEC 3) in the following situations:
• Stroke or transient ischaemic attack, while using an implant.
• Current and history of ischaemic heart disease, while using an implant.
• Unexplained vaginal bleeding, before evaluation.
• History of breast cancer and no evidence of recurrence for 5 years.
• Cirrhosis of liver: severe (decompensated).
• Liver tumours: benign (hepatocellular adenoma) and malignant (hepatoma).
• Systemic lupus erythematosus: positive (or unknown) antiphospholipid antibodies.
• Use of liver enzyme–inducing drugs (see Selected concurrent medications).

• Contraception for young women and women with learning disabilities:
• Contraception should be seen in terms of the needs of the individual rather than in terms of relieving the anxieties of carers or relatives.
• When a woman with a learning disability cannot understand and take responsibility for decisions about contraception, carers and other involved parties should meet to address issues around the woman's contraceptive need and to establish a care plan.
• See Considerations for girls under 16.
• The following examinations and laboratory tests are not required to assess eligibility for a progestogen-only implant:
• Breast, pelvic, or genital examination.
• Cervical cytology screening.
• Routine laboratory tests, including haemoglobin measurements.
• Thrombophilia screening.