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).

• Pregnancy:
• Co-amoxiclav and erythromycin may be given during pregnancy.
• Metronidazole: despite theoretical safety concerns, a number of epidemiological studies have shown no conclusive evidence that metronidazole use during pregnancy causes an increased risk of malformations, stillbirths, or low birth-weight infants.
• Tetracyclines are not suitable for use during pregnancy, as they are deposited in the teeth and bones of the developing fetus.
• Breastfeeding:
• Co-amoxiclav and erythromycin may be given to women who are breastfeeding.
• Short courses (7 days) of doxycycline and oxytetracycline may be used during breastfeeding.
• A single course (7 days) of oral metronidazole 200 mg or 400 mg three times a day may be used during breastfeeding.

[NTIS, 1999; Schaefer, 2001; UKMiCentral, 2004; BNF 53, 2007]

• Cholestatic jaundice may rarely occur during or shortly after the use of co-amoxiclav [CSM, 1997]. This is more common in men, in people over the age of 65 years, and with longer courses of treatment (over 14 days).

• Common adverse effects include a metallic taste and gastrointestinal irritation (in particular nausea and vomiting). These are more common at higher doses.
• Some people taking oral metronidazole experience disulfiram-like reactions to alcohol (flushing, increased respiratory rate, increased pulse rate). Although there is no conclusive evidence to support an interaction between metronidazole and alcohol, people taking metronidazole should be advised of the possible consequences of drinking alcohol [Baxter, 2006].

• Common adverse effects include gastrointestinal disturbances (e.g. nausea, vomiting, diarrhoea), especially at higher doses. Gastrointestinal adverse effects are less common with clarithromycin than with erythromycin [BNF 55, 2008].
• Erythromycin and clarithromycin can increase the plasma levels of certain other drugs (e.g. theophylline, carbamazepine) and can potentiate the effects of warfarin. A dose reduction may be required in these circumstances.
• Advise the person to seek medical advice if symptoms of toxicity to these drugs occur during treatment with erythromycin or clarithromycin.
• If a person is taking additional medication that may interact with erythromycin or clarithromycin, an alternative macrolide (azithromycin) may be considered [BNF 53, 2007].
• If erythromycin or clarithromycin is taken with a statin, there is an increased risk of myopathy. Advise the person to stop the statin whilst the macrolide is being taken.
• Erythromycin and clarithromycin may cause the combined oral contraceptive pill or patch to fail during the first few weeks of treatment [Baxter, 2006]. Advise women to use additional contraception during the course of treatment and for 7 days afterwards. If this 7-day period runs beyond the end of the pack of contraceptive pills, advise the woman to start a new pack without a break (omitting any inactive tablets) [FFPRHC, 2005; FFPRHC, 2007].

• Tetracyclines should not be used in in children under 12 years of age, as they are deposited in the teeth and bones of the developing child.
• Tetracyclines may cause oral contraceptives to fail and women should be advised to use additional contraception during the course and for at least 7 days afterwards. If the 7 days run beyond the end of the packet, a new packet should be started without a break, omitting any of the inactive tablets [Baxter, 2006].
• Benign intracranial hypertension is a rare but important adverse effect of tetracyclines. If a person taking a tetracycline develops headache and visual disturbances, the tetracycline should be stopped.
• Doxycycline may cause photosensitivity reactions: advise the person to avoid exposure to direct sunlight or to sunlamps.