ACITRETIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACITRETIN (ACITRETIN).
Retinoid that binds to and activates retinoic acid receptors (RARs), thereby modulating gene expression involved in cell differentiation, proliferation, and keratinization.
| Metabolism | Metabolized in the liver via isomerization and glucuronidation; major metabolite is cis-acitretin; also forms etretinate (in presence of ethanol) which has a longer half-life. |
| Excretion | Primarily via feces (approximately 70%) as unchanged drug and metabolites; renal excretion accounts for about 20% (mostly as glucuronide conjugates and oxidative metabolites). |
| Half-life | 50 hours (range 33–96 hours); clinically, due to accumulation, the effective half-life after multiple doses is approximately 50 hours, requiring a 5-week washout before donation or pregnancy. |
| Protein binding | ≥99.9% bound primarily to albumin; also binds to lipoproteins. |
| Volume of Distribution | Approximately 2.4 L/kg (range 0.9–3.8 L/kg) indicating extensive tissue distribution, particularly in skin, liver, and adipose tissue. |
| Bioavailability | Oral bioavailability is approximately 60% (range 30–90%) when taken with food; absorption is enhanced by a high-fat meal. |
| Onset of Action | Oral: 4–8 weeks for initial improvement in psoriasis; full effect may require 2–3 months. |
| Duration of Action | Duration of therapeutic effect after discontinuation: several weeks to months; however, drug levels decline slowly with terminal half-life of 50 h, and clinical improvement may persist for weeks. |
10-25 mg orally once daily for initial 2-4 weeks, then 25-50 mg once daily as maintenance; maximum 50 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment guidelines; use with caution in severe renal impairment (eGFR <30 mL/min) due to potential accumulation. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh class A or B): reduce starting dose by 50% and monitor closely. |
| Pediatric use | Not recommended for use in children due to risk of pseudotumor cerebri and premature epiphyseal closure; only use if clearly needed with extreme caution at 0.5-1 mg/kg/day (max 35 mg/day). |
| Geriatric use | No specific dose adjustment; initiate at low end of dosing range (10-25 mg/day) due to potential age-related renal and hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACITRETIN (ACITRETIN).
| Breastfeeding | Contraindicated during breastfeeding. Acitretin is excreted in human milk in concentrations that may cause adverse effects in the infant. M/P ratio not established; do not breastfeed while on therapy and for at least 3 years after stopping. |
| Teratogenic Risk | Acitretin is a potent human teratogen with high risk of major congenital malformations (CNS, cardiovascular, craniofacial) and increased spontaneous abortion risk if used during pregnancy. Contraindicated in women of childbearing potential without two forms of contraception. Pregnancy must be avoided for at least 3 years after discontinuation due to prolonged teratogenic risk from metabolic conversion to etretinate. |
■ FDA Black Box Warning
ACITRETIN IS TERATOGENIC. FEMALES OF CHILDBEARING POTENTIAL MUST NOT BE PREGNANT AT THE INITIATION OF THERAPY AND MUST AVOID PREGNANCY FOR AT LEAST 3 YEARS AFTER DISCONTINUATION. CONTRAINDICATED IN PREGNANT OR NURSING WOMEN.
| Serious Effects |
["Pregnancy or potential pregnancy","Breastfeeding","Severe hepatic impairment","Concomitant use of methotrexate or tetracyclines","Hypersensitivity to acitretin or other retinoids"]
| Precautions | ["Hepatotoxicity: monitor liver enzymes","Pancreatitis: especially in patients with hypertriglyceridemia","Pseudotumor cerebri: with concomitant tetracyclines","Hyperlipidemia: monitor triglycerides and cholesterol","Ocular effects: decreased night vision, corneal opacities","Musculoskeletal: hyperostosis, premature epiphyseal closure"] |
| Food/Dietary | Take with a fatty meal to enhance absorption. Avoid alcohol (ethanol) due to risk of forming etretinate, a teratogenic metabolite. No other significant food interactions. |
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| Fetal Monitoring | Women of childbearing potential require negative pregnancy test before initiation, monthly pregnancy tests during therapy, and every 3 months for 3 years after discontinuation. Monitor liver function tests, serum lipids, and renal function at baseline and periodically. Watch for signs of pseudotumor cerebri. |
| Fertility Effects | No known direct impairment of fertility in males or females at therapeutic doses. However, teratogenic risk necessitates strict pregnancy prevention. Use of effective contraception is mandatory during and for 3 years after treatment. |
| Clinical Pearls | Acitretin is a second-generation retinoid used for severe psoriasis. It is teratogenic and contraindicated in pregnancy. Women of childbearing potential must use contraception for 3 years after discontinuation due to storage in adipose tissue. Monitor liver function and lipids monthly for first 3-6 months. Avoid concurrent use with methotrexate due to hepatotoxicity risk. May cause pseudotumor cerebri; report headache, visual changes. Dose adjustment needed in renal impairment. |
| Patient Advice | Do not become pregnant while taking acitretin or for 3 years after stopping; use two reliable forms of contraception. · Avoid alcohol completely; acitretin is formed from etretinate, and alcohol can form a teratogenic metabolite. · Report any severe headache, nausea, or visual disturbances immediately. · Do not donate blood during treatment or for 3 years after stopping. · Expect dry lips, skin, and eyes; use moisturizers and lip balm. · Avoid vitamin A supplements to prevent toxicity. · Take with food to improve absorption. |