Acitretin dosing

Acitretin is an oral retinoid that is likely safer than methotrexate or cyclosporine, especially when considering continuous use over many years.21 The initial dose is 25 mg/day which can be increased to a maximum of 75 mg/day if needed.17 When acitretin is used concurrently with phototherapy (ReUVB or RePUVA), there appears to be a synergistic treatment effect, and the number and duration of phototherapy sessions needed to achieve clearance is reduced.21 RePUVA is a well-established... 

Sulfasalazine is an antiinflammatory agent that inhibits 5-lipoxygenase. It is used selectively as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. When used alone, it is not as effective as methotrexate, PUVA, or acitretin. However, it has a relatively high margin of safety. The usual oral dose is 3 to 4 g/day for 8 weeks. Its adverse effects are similar to other sulfonamide antibiotics. 

Sequential therapy involves rapid clearing of psoriasis with aggressive therapy (e.g., cyclosporine), followed by a transitional period in which a safer drug such as acitretin is started at maximal dosing. Subsequently, a maintenance period using acitretin in lower doses or in combination with UVB or PUVA can be continued. 

Unlike isotretinoin, acitretin (Soriatane) is not primarily sebosuppressive. Rather, it promotes normalization of dysregulated keratinocyte proliferative activity in the epidermis and is also antiinflammatory. Oral absorption is optimal when acitretin is taken with a fatty meal peak levels are reached approximately 3 hours after ingestion, while steady-state plasma levels are achieved after approximately 3 weeks of daily dosing. The mean terminal elimination half-life of the parent compound is 49 hours. However, when consumed with ethanol, acitretin may be transesterifled to form etretinate, a retinoid that is stored in adipose tissue, resulting in a much longer half-life (3-4 months or longer). 

Acitretin is most useful for the treatment of severe psoriasis, particularly the pustular and erythrodermic variants. Psoriatic nail changes and arthritis also may respond. Combining the drug with ultraviolet light therapy (Re-UVB, in the case of ultraviolet B radiation, or Re-PUVA, with psoralen plus ultraviolet A radiation) permits the use of lower doses of both acitretin and ultraviolet radiation. Other conditions for which the drug may be especially useful include congenital and acquired hyperkeratotic disorders, such as the ichthyoses and palmoplantar keratodermas, and severe lichen planus. 

Retinoids, topical as well as systemic, have been tried in EHK but were often found to be irritating. Nonetheless some patients are improved by oral acitretin,39 but the dose must be kept low in order to avoid the epidermolytic side effect of the drug. If correctly used, topical tretinoin and tazarotene may also be effective in some patients with EHK (Figure 8.7). Interestingly, the response to retinoid therapy seems to be partially determined by which keratin gene (Kl, K2e, or K10) is mutated patients with K2e and K10 mutations have the best response probably because they tolerate a retinoid-induced down-regulation of K2e expression better than other patients.40 However the... 

Medicines related to vitamin D are also effective but an unwanted side effect of the early ones was to cause the body to retain too much calcium, which is detrimental. More than 1500 different compounds have been synthesised to try and find one that would act on the psoriasis without raising the level of calcium in the blood. Calcipotriol cream was the one that performed best and is now widely used. Another chemical, etretinate, was introduced in 1975 and found to be just as effective. It was eventually superseded by acitretin when it was discovered that the body converted etretinate to acitretin and it was the latter which was the active agent. Acitretin is now the prescribed drug and it is very effective with three quarters of those treated reporting noticeable improvement and for about a third of patients their psoriasis cleared up completely. Psoriasis can also be treated with successive oral doses of methoxsalen followed by UV irradiation of the affected area. 

Fig. 3 (A) Relationship between dose and Cmax for acitretin. (B) Relationship between dose and AUC for acitretin. (From Ref.P l.)...

Oral bioavailability of etretinate is approximately 40%. Milk and lipids increase the absorption. Etretinate is converted significantly to the free acid on the first pass through the liver. The free acid (acitretin) is also active. After a single dose, the half-life of etretinate is 6 to 13 hours, but after long-term therapy, the half-life is 120 days. Etretinate s high lipid character results in storage in adipo.se tis.sue. from which it is relea.sed slowly. After discontinuation of therapy, etretinate can be detected for up to I year. 

Acitretin has the advantage of a shorter half-life. 2 hours after a single dose and 50 hours after multiple doses. It is. however, more susceptible to conversion to 13-ci.t-etretin. Thus, it appears that the e.stcr provides metabolic stability. 

Acitretin is indicated for the treatment of severe psoriasis. The initial dose is 25 to SO mg in a single dase with food. Because of.significant variation in pharmacokinetics and efficacy. however, the maintenance dose should be individualized. Initial response may occur in 2 weeks, but maximal response requires 2 to 5 months. Because of significant adverse effects a.ssociaied with its use. acitretin should be reserved for patients who do nut respond to other therapies or whose clinical condition contraindicates the use of other treatments. 

Acitretin has shown good results when combined with other psoriatic therapies, including PUVA and UVB, cyclosporine, and methotrexate. The combination of acitretin and PUVA is highly effective and provides faster and more complete clearance, as well as allowing a decrease in the doses of both agents, thereby limiting the risk of adverse effects. ... 

An initial recommended dose of acitretin is 25 to 50 mg once daily, with therapy continued until lesions have resolved. A dosage of 50 mg/day is typically required for plaque psoriasis, and even at this relatively high dose, acitretin is only moderately effective. It is better tolerated when taken in conjunction with a meal. 

McKenna, D.B. and Murphy, G.M. (1999) Skin cancer chemoprophylaxis in renal transplant recipients 5 years of experience using low-dose acitretin. The British Journal of Dermatology, 140, 656-660. 

Side effects of acitretin include dryness of mucous membranes and skin with localized exfoliation of the palms and plantar surface of the feet, skin and nail erosion and transient thinning of hair. These effects are dose-dependent and reversible. Longer-term adverse effects include ossification of ligaments and raised plasma triglycerides and cholesterol levels. Acitretin should not be taken in combination with methotrexate because of toxicity to the liver. 

The manufacturers of acitretin say that the concurrent use of vitamin A should be avoided. In the UK they advise no more than 4000 to 5000 units daily, which is the recommended daily allowance, and in the US they advise doses of no more than the minimum recommended daily allowance. Similarly, the manufacturers of isotretinoin say that vitamin A should be avoided. ... 

Acitretin is also available for use in psoriasis, although there is no consensus on its optimum effective dose with acceptable side effects. A randomised, double-blind, parallel-group, dose ranging study (three fixed doses in adult patients) was carried out [2 ]. This investigation included patients of either gender (age range, 18-65 years) with severe chronic plaque-type psoriasis. 

Acitretin 35 mg/day was observed to be more efficacious compared to 25 mg/day and 50 mg/day dosing, whereas its safety profile is better than 50 mg/day dosing in the management of severe-plaque-type psoriasis in adult patients. 

Dogra S, Jain A, Kawar AJ. Efficacy and safety of acitretin in three fixed doses of 25,35 and 50 mg in adult patients with severe plaque type psoriasis a randomized, double-blind, parallel group, dose ranging study. J Eur Acad Dermat Ven 2013 27(3) e305-ll. 

In a series of other dermatoses oral retinoids have been applied with varying clinical efficacy. Etretinate/acitretin were found effective in (i) lichen planus [50] including oral manifestations of lichen mucosae oris with papillomatous and erosive/bullous lesions, (ii) cutaneous variants of lupus erythematosus [11], particularly the hyperkeratotic lesions of chronic-discoid lupus erythematosus, and (iii) lichen sclerosus et atrophicans [7]. Both lichen planus and lichen mucosae oris were also shown to respond to low-dose oral tretinoin. Complete remission was observed in 13/18 patients [65]. The beneficial effect of retinoids in these entities underlines their immunomodulatory dermal action. Prurigo nodularis may be another entity responding well to systemic retinoid therapy. 

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