Etretinate Methotrexate

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)... 

A case of severe hepatitis has been attributed to the combination of methotrexate with etretinate (134), a finding that was not explained by a pharmacokinetic interaction between the two drugs (135). 

Beck HI, Foged EK. Toxic hepatitis due to combination therapy with methotrexate and etretinate in psoriasis. Dermatologica 1983 I67(2) 94-6. 

Larsen FG, Nielsen-Kudsk F, Jakobsen P, Schroder H, Kragballe K. Interaction of etretinate with methotrexate pharmacokinetics in psoriatic patients. J Clin Pharmacol 1990 30(9) 802-7. 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, carbamazepine, carbimazole, cyclosporine, daclizumab, diuretics, etoposide, etretinate, grapefruit juice, indomethacin, isoniazid, itraconazole, ketoconazole, licorice, live vaccines, methotrexate, naproxen, oral contraceptives, pancuronium, phenobarbital, phenytoin, rifampicin, troleandomycin... 

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. 

Methotrexate, an anti-cancer drug, slows cellular growth and is prescribed to decrease the acceleration of epidermal cell growth in severe psoriasis. Etretinate (Tegison) is used for severe pustular psoriasis when other medications have failed. Etretinate has an anti-inflammatory effect and inhibits keratinization and prohferation of the epithehal cells. 

Although the concurrent use of methotrexate with etretinate can be successfui, the incidence of severe fiver toxicity appears to be considerabiy increased. The serum ieveis of methotrexate may be increased by etretinate. 

A man was given a 48-hour infusion of methotrexate 10 mg every week, for chronic discoid psoriasis but when he was also given etretinate 30 mg... 

Severe toxic hepatitis has been reported in a number of cases when both etretinate and methotrexate were given. " It may take several months to develop. In one clinic, signs of liver toxicity were seen in 2 out of 10 patients given both drugs, but there was no evidence of liver toxicity in 531 patients given methotrexate alone or in 110 patients given etretinate alone. ... 

Although methotrexate and etretinate have been used together with success for psoriasis, the risk of severe drug-induced hepatitis seems to be very considerably increased. One author says that he has decided not to use this combination in future. Concurrent use should clearly be undertaken with great care. Etretinate has been largely superseded by acitretin (a metabolite of etretinate, which has a shorter half-life) but some consider that the combination of methotrexate and acitretin should also be avoided. ... 

Zachariae H Dangers of methotrexate/etretinate combination therapy Ltwee/ (1988) i, 422... 

Zachariae H Methotrexate and etretinate as concurrent therapies in the treatment of psceiasis ArchDennatol(m4) 120,155. 

Ad s JD. Coicurrent methotrexate and etretinate ther y for psoriasis. Arch Dermatol (1983) 119,793. 

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