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42 CPD ACTIVITY FROM PAGE 41 This should be combined with BPO (which doesn’t have to be applied at the same time) to minimise the development of antibiotic resistance of the C. acnes.23 Topical BPO has the added advantage of being anti-inflammatory. However, combining BPO (and other over-the- counter products such as scrubs and facial washes) with topical retinoid or antibiotic treatment is likely to increase the adverse effects of skin dryness and irritation.17,19 Topical retinoids can be used for acne that is more predominantly affected by comedones.10,15 Oral retinoids such as isotretinoin are known teratogens and should be avoided in women who are pregnant or likely to become pregnant.24 Absorption of topical retinoids across human skin is very low and resultant plasma levels are far less than those following oral administration.19 Evidence suggesting topical retinoids are also teratogenic is primarily from case reports; and prospective cohort studies fail to find adverse pregnancy outcomes from topical retinoid use.24 However, due to the very high risk of oral retinoids, topical retinoids are also not recommended before or during pregnancy (particularly the first trimester).25 Women who are concerned they have been exposed to a topical retinoid before or during pregnancy can be assured that the risk is not the same as for oral retinoids, but should be urged to see a doctor as soon as possible to further discuss their risk.25 Topical retinoids commonly cause adverse effects such as scaling, burning and photosensitivity.19,26 It has been suggested that the use of topical retinoids will lead to an acute flare of acne when initiated.17,24 In contrast, others have indicated that the initial irritation that accompanies the use of retinoids can be misinterpreted as a flare of acne.19,27 Patients should be advised that adverse effects won’t persist with continued treatment and be encouraged to continue unless the adverse effects become problematic.24 When starting therapy, applying topical retinoids every other night is recommended to minimise the discomfort before increasing to nightly use.21 In Australia, the topical retinoids approved for use in acne vulgaris include tretinoin cream (0.025 per cent and 0.05 per cent), tazarotene (0.05 per cent and 0.1 per cent) or adapalene (0.1 per cent or 0.3 per cent with or without BPO 2.5 per cent, available as a cream or a gel for dry or oily skin, respectively).10 Data from a meta-analysis involving five randomised controlled trials with 900 patients comparing adapalene 0.1 per cent with tretinoin 0.025 per cent demonstrated equivalent efficacy between the two agents.17 In the adapalene group there was a 57 per cent reduction in total lesion count compared with a 53 per cent reduction with tretinoin.17 However, adapalene appeared to have additional benefits, offering a quicker onset of action and less local irritation compared with tretinoin.17 With the use of adapalene 0.1 per cent, there was a statistically significant reduction in erythema, dryness, scaling and burning sensation compared with the tretinoin group.17 If these measures fail to manage the symptoms, the Therapeutic Guidelines recommends the patient is referred to a specialist for consideration of treatment with isotretinoin. Oral treatment Oral isotretinoin (ITT) is the most effective treatment for severe acne and is the only medicine known to facilitate remission of acne.28 Most patients will no longer have any symptoms within four to six months of treatment, and most of those will have no recurrence of acne.10,15,29 Recently, the indications for ITT have been expanded to include moderate acne refractory to treatment with topical and oral agents with a propensity for scarring.2,10,19 The course of treatment and the expected benefits differ between topical and oral retinoids. The pharmacological effect of ITT interferes with the four main processes of the pathophysiology of acne.30 Isotretinoin exerts its action on the deep follicles and is expected to cause a flare of acne within the first few weeks of treatment.19 These flares often improve with time, or if necessary may require a short course of prednisone.19,31 In Australia, the initiation of treatment with ITT requires specialist dermatologist review.32,33 In contrast, more than half of all prescriptions for ITT in New Zealand in 2012 were provided by GPs as their access was expanded in 2009.34 The dose of ITT is typically initiated at about 0.5mg/kg of bodyweight per day for the first four weeks.19 The target dose is 1mg/ kg for several months until a cumulative dose of 150mg/kg is reached.35 Some patients may benefit from using a lower dose over a longer period as the adverse effect profile of oral ITT is dose dependent (with the exception of teratogenicity).36 Low dose ITT, using 10-20mg daily over a prolonged period, has yielded the same benefits with lower incidence of adverse effects compared with conventional dosing.9,25 A study involving 60 participants compared the efficacy of different dosing regimens of oral ITT over 24 weeks.25 Conventional high dose continuous treatment was compared with low dose continuous therapy and a high dose intermittent regimen.25 The results for those on the intermittent regimen were disappointing. However, there was no appreciable difference in efficacy between high dose and low dose continuous treatment at 24 weeks.25 While ITT often induces remission of acne symptoms, about 10-20 per cent of patients will relapse following an initial course of ITT.19 More recent evidence indicates that the risk of acne recurrence is significantly lower when ITT treatment is adhered to for at least two months after acne symptoms resolve.33,37 It is therefore important that patients are encouraged to continue taking ITT as prescribed even if the symptoms of acne have cleared. The major limitation to the use of oral ITT is its significant adverse effect profile. Due to its targeted action on sebum production, dryness of the lips, mouth, eyes, nose and skin are the most common adverse effects.38 It’s essential that patients are aware of these adverse effects before treatment and use lubricating eye drops, lip balm and skin moisturisers.26 While less common, patients may become more sensitive to sunburn and can use non-comedogenic sunscreens. The most concerning feature of oral ITT therapy is its documented teratogenicity. Teratogenic effects include life threatening foetal malformations, cleft palate, facial dysmorphia and internal organ abnormalities such as cardiovascular and thymus gland dysfunction.15,27 Prescribers must ensure that patients are not pregnant when initiated, during and for one month after finishing treatment. Females of reproductive age should be counselled on the risks and sequelae of pregnancy while on therapy with ITT. The poisons regulation reiterates that prescribers must take steps to confirm negative pregnancy status before starting treatment.39 The use of two forms of contraception (barrier protection and a combined oral contraceptive pill) is highly encouraged, and providing this advice should be clearly recorded in the patient notes.10,19 In a retrospective Australian study over a six-year period, the adverse effects most associated with treatment cessation included cheilitis, mood changes and tiredness.26 Isotretinoin also has an infamous reputation among patients and prescribers of being associated with depression and suicidal ideation.28 The association between acne treatment and psychiatric RETAIL PHARMACY • JUN 2021