Acitretin retinoids

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... 

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). 

Contraindications Severely impaired liver or kidney function, chronic abnormal elevated lipid levels, concomitant use of methotrexate ortetracyclines, hypersensitivity to acitretin, etretinate, or other retinoids, sensitivity to parabenz (used as preservative in gelatin capsule)... 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

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... 

METHOTREXATE RETINOIDS-ACITRETIN t methotrexate levels Uncertain Avoid co-administration... 

PORFIMER I. ACE INHIBITORS -enalapril 2. ANALGESICS -celecoxib, ibuprofen, ketoprofen, naproxen 3. ANTIARRHYTHMICS — amiodarone 4. ANTIBIOTICS -ciprofloxacin, dapsone, sulphonamides, tetracyclines 5. ANTICANCER AND IMMUNOMODULATING DRUGS -fluorouracil (topical and oral) 6. ANTIDIABETIC DRUGS-glipizide 7. ANTIMALARIALS -hydroxychloroquine, quinine 8. ANTIPSYCHOTICS -chlorpromazine, fluphenazine 9. CALCIUM CHANNEL BLOCKERS - diltiazem 10. DIURETICS -bumetanide, furosemide, hydrochlorothiazide II. PARA-AMINOBENZOIC ACID (TOPICAL) 12. RETINOIDS-acitretin, isotretinoin 13. SALICYLATES (TOPICAL) t risk of photosensitivity reactions Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy... 

ACITRETIN >- Other immunomodulating drugs. Retinoids below ... 

Vitamin A (retinols) plays a role in epithelial function and the retinoic acid derivative, acitretin (Neotigason, orally), inhibits psoriatic hyperkeratosis over 4-6 weeks. Acitretin should be used in courses (6-9 months) with intervals (3-4 months). It is teratogenic, like the other vitamin A derivatives. Rigorous precautions for use in women of childbearing potential are laid down by the manufacturer and must be followed, including contraception for 2 years after cessation, because the drug is stored in the liver and in fat and released over many months. The plasma t) is 3 months. It can cause other serious toxicity (see Vitamin A, p. 739). Tazarotene, a topical retinoid, is of some benefit in mild psoriasis, but is irritant. 

In 1990, etretinate (Tigason) was replaced by acitretin (Neo-Tigason), an aromatic retinoid, a carboxylic acid metabolite of etretinate (15). It is effective in pustular psoriasis and psoriatic palmoplantar keratoderma and in combination with PUVA or topical therapy (calci-potriol or glucocorticoids) in the treatment of other forms of psoriasis. It has also been used to treat disorders of keratinization (ichthyosis, palmoplantar keratoderma, Darier s disease) and severe cutaneous forms of lichen planus. It prevents new skin carcinomas in patients with xeroderma pigmentosum and those who are immunosuppressed. The main advantage of acitretin is its short half-life of 50 hours, compared with over 80 days for etretinate (16). 

Retinoids are strongly teratogenic (21). Pregnancy should be ruled out and an effective form of contraception must be used for at least 1 month before starting therapy, during therapy, and for at least 1 month (isotretinoin) or 2 years (acitretin) after therapy is stopped. Retinoid-induced teratogenicity has been reviewed (22,23). 

Clinically important, potentially hazardous interactions with acitretin, antacids, bexarotene, cholestyramine, co-trimoxazole, corticosteroids, fish oil supplements, minocycline, retinoids, tetracycline, vitamin A... 

Clinically important, potentially hazardous interactions with acitretin, aluminum hydroxide, amoxicillin, ampicillin, antacids, bacampicillin, betamethasone, bismuth, bromelain, calcium, carbenicillin, cholestyramine, doxacillin, corticosteroids, dairy products, dicloxacillin, didanosine, digoxin, food, glidazide, iron, isotretinoin, methicillin, methotrexate, methoxyflurane, mezlocillin, nafcillin, oxacillin, penicillins, piperacillin, retinoids, rocuronium, strontium ranelate, sucralfate, ticarcillin, vitamin A, zinc... 

Drug Based on the Retinoid Structure Used to Treat Psoriasis (Fig. 8.8). Etrinate is the ethyl ester of acitretin and is active after hydrolysis to the acidic drug. The terminal" half-life after 6 months of etrinate therapy is 120 days. In contrast, the terminal" half-life of acitretin is only 33-96 h. Both drugs are... 

Acitretin, an oral retinoid, is the active metabolite of etretinate and has demonstrated clinical effects similar to etretinate, but with fewer adverse effects. Acitretin is indicated for the treatment of severe psoriasis, including erythrodermic and generalized pustular types, but is more useful as an adjunct in the treatment of plaque psoriasis. In contrast to the fast-acting cyclosporine and methotrexate, acitretin resolves psoriatic lesions more slowly. 

Acitretin has a shorter half-life than etretinate. Its mechanism of action is not completely understood it may achieve benefits by acting on retinoid receptors in the keratinocyte nucleus to correct abnormal cell differentiation. ... 

Radical ion pairs are involved in the photochemical isomerism of P-ionone in the presence of pyrene. trans- -lonone is converted to its radical anion on irradiation in the presence of triphenylphosphine or triethylamine. CIDNP analysis has shown that the radical anions convert to neutral radicals by pro-tonation. Triphenylamine can be used as an electron donating sensitizer for the phototransformations of the enones (75)-(77). Triplet radical ion pairs are formed, which afford the triplet of the enone by back electron transfer, cis-Isomers of the enones are formed. The retinoid acitretin undergoes photo-... 

Acitretin is currently the only retinoid licensed in the United Kingdom for the treatment of psoriasis and is only available for treatment of patients in hospitals. It is given orally and has anti-inflammatory and cytostatic actions. This is useful in inflammatory psoriasis. The half-life of acitretin is about two days. However, there is a high risk of teratogenesis and women must use adequate contraception and stop treatment for two years before conception. 

Abacavir - antiviral Acarbose - oral hypoglycaemic Acipimox - lipid lowering drug Acitretin - oral retinoid psoriasis Acrivastine - antihistamine Acyclovir - antiviral... 

Adtretin is a second-generation retinoid. Acitretin (Soriatane) is the major metabolite of etretinate, an aromatic retinoid that formerly was approved for psoriasis but withdrawn from the market because of its undesirable pharmacokinetics. Acitretin has an elimination half-Ufe of 2 to 3 days. 

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