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).

• People with venous leg ulcers have high rates of skin sensitivity to allergens. Common allergens may be present in products used for venous leg ulcers, as listed in Table 1.

• For ulcers with low amounts of exudate, use a low-adherent dressing such as a knitted viscose primary dressing (e.g. NA dressings^®, Tricotex^®).
• For ulcers with heavy exudate, use an alginate dressing (e.g. Kaltostat^®, Sorbsan^®), polyurethane foam dressing (e.g. Allevyn lite^®, Lyofoam^®), or a hydrocolloid dressing (Aquacel^®, ActivHeal Hydrocolloid^®).
• For ulcers that require desloughing use a ready-mixed hydrogel (e.g. ActivHeal Hydrogel^®, Granugel^®).
• Occlusive hydrocolloid (ActivHeal Hydrocolloid^®) may be useful for painful ulcers.
• Low-adherent, alginate, and foam dressings may be preferred because they can be left in place for 7 days. Hydrogel and hydrocolloid dressings require more frequent changes (every 3 days).
• Dressings which are not recommended include:
• Adhesive bordered dressings.
• Dressings that contain topical antibiotics or lanolin.

• These recommendations are based on published expert opinion, systematic reviews, and randomized controlled trials [Simon et al, 2004; Jones et al, 2006; RCN, 2006].
• There is no evidence that dressings such as hydrogel, hydrocolloid, alginate, or polyurethane foam have an additional effect on wound healing over that achieved by low-adherent dressings under multilayer compression bandaging [Simon et al, 2004; RCN, 2006].
• Low adherent dressings (e.g. NA dressings^®, Tricotex^®):
• Low-adherent dressings remain on the surface of a wound for several days, allowing exudate to pass through to an absorbent secondary dressing. Underneath high compression bandages, a knitted viscose dressing will suffice in producing a microenvironment that promotes granulation. The absorbent layer above the dressing can be easily changed with minimal disturbance to the wound surface [Jones et al, 2006].
• Hydrogel dressings (e.g. ActivHeal Hydrogel^®, Granugel^®):
• Hydrogel dressings consist of a matrix of insoluble polymers with up to 96% water content, enabling them to donate water molecules to the wound surface and to maintain a moist environment at the wound bed. They promote wound debridement by rehydration of non-viable tissue thus facilitating autolytic debridement of the wound, and may be useful for maintaining a moist wound environment in dry, sloughy wounds [Jones et al, 2006].
• Hydrocolloid dressings (e.g. ActivHeal Hydrocolloid^®):
• Hydrocolloid dressings consist of a wafer constructed from a thin layer of polyurethane film (which is impermeable to water and microorganisms) with an adhesive that contains gelatine, pectin, and carboxymethylcellulose. Wound exudate combines with the ingredients of the adhesive to form a gel, which promotes moist wound healing [Jones et al, 2006].
• Aquacel^® is a hydrofibre dressing made from modified carmellose fibres that resemble alginate dressings. It is not occlusive.
• Foam dressings (e.g. Allevyn lite^®, Lyofoam^®):
• Foam dressings transmit moisture vapour and oxygen and provide thermal insulation to the wound bed. Polyurethane foams consist of two or three layers, including a hydrophilic wound contact surface and a hydrophobic backing, making them highly absorbent. They facilitate uniform dispersion of exudate throughout the absorbent layer and prevent exterior leakage (strike-through) due to the presence of a semi-permeable backing [Jones et al, 2006].
• Alginate dressings (e.g. Kaltostat^®, Sorbsan^®):
• Alginate dressings are produced from alginic acid found in a family of brown seaweed (Phaeophyceae). They partly dissolve on contact with wound fluid to form a hydrophilic gel, as a result of the exchange of sodium ions (in wound fluid) for calcium ions (in the dressing). Alginates can absorb 15–20 times their own weight of fluid, making them suitable for highly exuding wounds. They should not be used, however, on wounds with little or no exudate as they will adhere to the healing wound surface, causing pain and damaging healthy tissue on removal [Jones et al, 2006].
• Dressings not recommended:
• People with venous leg ulcers are prone to contact sensitivity particularly from lanolin and topical antibiotics.
• Dressings with adhesive borders are not recommended because dressings under high-compression multilayer bandages do not tend to slip.

• The choice of multi-layer bandage system is based on the person's ankle circumference.
• Four-layer, 3-layer, or 2-layer compression bandaging may be used.
• Use 4-layer or 3-layer compression bandaging when the person is immobile.
• Use 2-layer compression bandaging for someone who is ambulant.
• Compression therapy should always be applied by a healthcare professional trained in venous ulcer management.

• Three-layer and 4-layer compression consists of three or four levels of bandage, applied from the base of the toes to the knee (over a contact dressing) in the following order:
• Sub-compression wadding bandage.
• Light support bandage, such as cotton crepe bandage.
• Light compression bandage, such as knitted elastomer and viscose bandage.
• Cohesive bandage (a bandage that adheres to itself to prevent movement of dressing).
• Two-layer compression is the application of a short-stretch (inelastic) bandage over a sub-compression wadding bandage. Shoes can be worn if 2-layer compression bandaging has been applied.

• This recommendation is based on published expert opinion [Enoch et al, 2006].

• Advise the person to remove the compression if they notice any adverse effects (such as numbness, tingling, pain, or dusky toes) and seek advice [Enoch et al, 2006].

• Compression stockings should be put on first thing in the morning before getting out of bed.

• Three different classes of stockings or graduated compression hosiery are available.

• Compression hosiery is available in two lengths, 'below the knee' and 'thigh length'. A range of styles and colours are available. Hosiery may have an open or closed toe. For open-toed hosiery, a heel may or may not be present.
• Socks are available, as are suspenders for use with thigh-length stockings.

• After a venous leg ulcer has healed, prescribe below knee, high-compression stockings (class III) if the person can tolerate them and there are no contraindications.
• If the person cannot tolerate class III stockings, prescribe the highest level of compression that can be tolerated, such as class II stockings.

• These recommendations are based on published expert opinion and systematic reviews [RCN, 2006].
• The use of compression stockings reduces venous ulcer recurrence rates and is cost effective. Class III stockings are associated with lower recurrence rates than class II stockings.
• Below-knee compression hosiery is associated with increased compliance [Enoch et al, 2006].

• Flucloxacillin should not be taken by people who have true penicillin allergy. However, gastrointestinal adverse effects alone (i.e. nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin [BNF 54, 2007].
• Flucloxacillin has been associated with an increased risk of hepatic disorders, namely hepatitis and cholestatic jaundice.
• The Committee on Safety of Medicines (CSM) advises that hepatic reactions may very rarely occur up to 2 months after treatment with flucloxacillin has ceased. Risk factors include treatment for more than 14 days and increasing age. The dose and route of administration do not appear to affect this risk.

• Flucloxacillin is usually well tolerated but nausea, vomiting, or diarrhoea can sometimes occur.
• Some people are allergic to penicillin antibiotics (including flucloxacillin). Advise that if the person gets a rash; swelling of the face, hands, or feet; or feels short of breath, they should stop taking the flucloxacillin and seek urgent medical advice.
• Antibiotics may cause the combined oral contraceptive pill to fail during the first few weeks of treatment. Advise women to use additional contraception (such as condoms) during the course of antibiotic 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].

• Consider using clarithromycin in people who have have a history of gastrointestinal effects when taking erythromycin. Clarithromycin is usually associated with milder gastrointestinal adverse effects [BNF 54, 2007].
• Possible enhanced effect of aminophylline or theophylline, and carbamazepine (due to cytochrome P450 enzyme inhibition). Consider using clarithromycin (or azithromycin) in preference to erythromycin as it causes only modest increases in levels [Baxter, 2006]. Check levels if toxicity is suspected (e.g. palpitations, nausea, headache), or 48 hours after starting concurrent treatment with erythromycin.
• Possible enhanced effect of carbamazepine (due to cytochrome P450 enzyme inhibition). Consider using azithromycin instead (no interaction reported). Alternatively, consider reducing the dose of carbamazepine by 30–50% during treatment with erythromycin or clarithromycin, and advise people to report symptoms of toxicity (e.g. dizziness, diplopia, ataxia, confusion) [Baxter, 2006].
• Possible enhanced effect of warfarin. Reduce warfarin dose by 50% (especially in people over 60 years of age, who clear warfarin slowly) and monitor weekly for up to 3 weeks after stopping.
• Possible QT-interval prolongation. If possible, avoid giving erythromycin or clarithromycin if the person is already taking a drug that can potentially prolong the QT interval (e.g. anti-arrhythmics, antipsychotics, tricyclic antidepressants) or if the person has hypokalaemia which also increases the risk of QT prolongation [Baxter, 2006].
• Increased risk of myopathy in people taking atorvastatin or simvastatin (due to cytochrome P450 enzyme CYP3A4 inhibition) [CSM, 2004]. Stop atorvastatin or simvastatin for the duration of erythromycin or clarithromycin treatment [ABPI Medicines Compendium, 2009], or advise people to report muscle symptoms if atorvastatin or simvastatin need to be continued [Baxter, 2006]. Alternatively, consider using azithromycin instead (as it is reported to have little effect on cytochrome P450 enzymes) but advise people to report muscle symptoms [Sweetman, 2005].

• Erythromycin, and less commonly clarithromycin, may cause gastrointestinal adverse effects (e.g. nausea, vomiting, diarrhoea) [BNF 54, 2007].
• Antibiotics 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].