Page 89 - Retail Pharmacy November/Decemeber 2020

88 CPD ACTIVITY FROM PAGE 87 with product strength. Adapalene 0.3% has been shown to have superior efficacy compared with adapalene 0.1%, particularly in patients with higher acne lesion counts. Therefore, while trial of adapalene 0.1% is highly recommended for suitable patients, referral for consideration of adapalene 0.3% is warranted if results are insufficient or if the patient has a high lesion count at presentation.6 While traditional approaches have used adapalene to treat comedonal acne, its anti-comedogenic and anti-inflammatory activity means it should be recommended for patients with comedonal and/or inflammatory acne. The degree of improvement with adapalene is most marked in patients who present with more severe baseline acne.6 Clinical trials consistently show that topical adapalene is more effective than placebo at reducing total acne lesion count (TALC) after 12 weeks treatment. A head-to-head trial showed that topical tretinoin 0.05%, adapalene 0.3% and adapalene 0.1% reduced TALC by 76.7 per cent, 66.4 per cent and 57.8 per cent respectively, compared with only 21.8 per cent for placebo.7 Combination therapy Comparative data for the different topical retinoids is limited. While it does seem that adapalene 0.3% is more effective than 0.1% for moderate-severe baseline acne cases, the difference is marginal for milder cases. However, high quality clinical trials consistently indicate that combination therapy is more effective than retinoid monotherapy.8 The efficacy of adapalene 0.1% can be improved by combining it with a topical agent that complements the retinoid mechanism of action, eg, benzoyl peroxide 2.5%, azelaic acid 15-20% and/ or topical antibiotics such as erythromycin and clindamycin. Fixed combination products make therapy less complicated and help to address poor adherence.9 The benefit of combination therapy is that several parts of the acne development cascade can be targeted at the same time. The most often studied combination is adapalene 0.1% + benzoyl peroxide 2.5%. Benzoyl peroxide is bactericidal against C. acnes via generation of free radicals. It’s also anti-inflammatory and has mild anti- comedogenic properties. It also helps to address the growing concern of C. acnes antibiotic resistance. To date, no cases of benzoyl peroxide or azelaic acid resistance have been reported, but it’s estimated that more than 50 per cent of C. acnes strains around the world are resistant to antibiotics, particularly topical macrolides.8,10 While once a major part of acne therapy, resistance and concerns over long-term use of oral antibiotics in general, means they are now less commonly used for acne management. However, combination topical therapy plus an oral antibiotic is still used for severe acne. Oral tetracyclines tend to be preferred over macrolides due to the prevalence of macrolide resistance, but also because tetracyclines such as doxycycline have the added benefit of being anti-inflammatory.8 Studies have shown that topical benzoyl peroxide is more effective and acts faster against C. acnes than topical antibiotics. Adapalene has been shown to promote the absorption of benzoyl peroxide into the follicle. This is advantageous as there is little difference in efficacy between 2.5% and 10% benzoyl peroxide, but the higher strength is more irritating on the skin. The fixed combination product promotes the absorption of benzoyl peroxide but is well tolerated.8 Not only have clinical trials shown that the fixed combination of adapalene and benzoyl peroxide is more effective then retinoid monotherapy, the combination is also more effective than the sum of the individual benefits of each, further demonstrating the advantages of the complementary mechanisms of the combination.8 As acne is a chronic condition, there is a high risk of relapse. Depending on tolerability, topical adapalene can be used for maintenance therapy after the initial treatment period has ended. Combination adapalene and benzoyl peroxide is effective at preventing relapse and has been shown to be safe to use in the long term (eg, up to 12 months). Adding a topical macrolide for eight weeks may further reduce the risk of relapse.8 Safety and tolerability of topical retinoids and combination products The safety of topical adapalene is well documented in adults and children aged 12 years and over (not in those aged under 12 years). The most common adverse effects are local and include erythema, scaling, dryness, pruritus and burning. These are usually mild and peak after two weeks of use, decreasing in severity until week 12. Clinical trial indicated that adverse effects caused by adapalene 0.1% occurred in 10.3 per cent of users compared with 4.7 per cent in those using a placebo vehicle. The risk of adverse effects approximately doubles with adapalene 0.3%. The adapalene formulation may also affect the incidence of adverse effects, with adapalene formulated into microspheres being better tolerated than regular gel. Adapalene 0.1% is consistently better tolerated than tretinoin 0.025% in clinical trials.10 According to the Therapeutic Goods Administration’s ‘Prescribing medicines in pregnancy’ database, adapalene is category D (drugs that have caused, or are suspected to have caused, or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details).11 This is related to the fact that oral retinoids are known teratogens. Evidence that topical retinoids cause a retinoid-like embryopathy is based on case reports including one that led to therapeutic abortion in a mother who was treated with adapalene gel perinatally. However, a multicentre prospective study including 235 women exposed to a topical retinoid didn’t show a risk of major birth defects greater than baseline. This is supported by other epidemiological data.10 Pharmacists can reassure pregnant women exposed to topical retinoids before conception and during the first trimester that the risk of adverse pregnancy outcomes is low, and refer them to their pregnancy care physician for review. The Therapeutic Guidelines strongly advise against the intentional use of topical retinoid in this population.3 It’s not known whether topical adapalene is excreted in breast milk. The potential for risk of adapalene use in breastfeeding women should be balanced against the benefit to the mother. Contact of the baby with the maternal application site should be avoided. The most common adverse effect of benzoyl peroxide is skin irritation, including erythema, burning and peeling. Irritation is highly correlated with benzoyl peroxide concentration. Tolerability of the 2.5% and 5% strengths is comparable, but 10% causes about 2.5 times more irritation. Considering there is little difference in efficacy increasing from 2.5% to 10%, the marked increase in skin irritation of the 10% strength limits its clinical utility. Wash-off formulations may help address skin irritation.10 Skin irritation is also the most common adverse effect of azelaic acid, while some patients may also experience a flare in their acne at the start of treatment.10 The adverse effect profile of topical treatments for acne is an important consideration, as it’s known that RETAIL PHARMACY • NOV/DEC 2020