Soriatane (Acitretin)
acitretin
Acitretin Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Severe plaque-type psoriasis | Adults | Monotherapy or combination (UVB/PUVA/cyclosporine/biologics) | FDA Approved |
| Generalised pustular psoriasis | Adults | Monotherapy or combination | FDA Approved |
| Localised pustular psoriasis | Adults | Monotherapy or combination | FDA Approved |
Acitretin is the only systemic retinoid with FDA approval for psoriasis and remains effective as monotherapy. It replaced etretinate (withdrawn 1998) owing to a far shorter elimination half-life (~49 hours vs ~120 days). The drug is positioned for severe psoriasis unresponsive to topical treatments, phototherapy alone, or other systemic agents. In women of childbearing potential, it should be reserved strictly for patients unresponsive to alternative therapies or for whom alternatives are contraindicated, given the extended 3-year post-treatment contraception requirement. Acitretin is particularly effective for pustular and erythrodermic variants and works synergistically with phototherapy to reduce cumulative UV exposure.
NMSC chemoprevention in organ transplant recipients: Reduces incidence of squamous cell carcinomas. Evidence quality: moderate (multiple cohort studies).
Darier disease: Well-established efficacy at lower doses (10–25 mg/day). Evidence quality: moderate.
Pityriasis rubra pilaris (PRP): Considered first-line systemic therapy for severe cases. Evidence quality: moderate (case series, expert consensus).
Lamellar ichthyosis: Improves scaling at 25–50 mg/day. Evidence quality: low.
Lichen planus, lupus erythematosus, Grover disease: Limited evidence from small case series. Evidence quality: very low.
Acitretin Dosing
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Severe plaque psoriasis — monotherapy | 25 mg QD | 25–50 mg QD | 75 mg/day | Titrate based on response and tolerability; 50 mg needed for significant benefit in trials 25 mg/day recommended for maintenance to minimise side effects (Pearce 2006 analysis) |
| Pustular psoriasis — generalised or localised | 25 mg QD | 25–50 mg QD | 75 mg/day | Pustular variants often respond well to retinoid monotherapy Consider higher initial dose (50 mg) for acute generalised pustular flares |
| Combination with phototherapy (UVB or PUVA) | 25 mg QD | 25 mg QD | 50 mg/day | Retinoid pre-treatment may be considered before initiating phototherapy; reduce UV dose significantly Retinoid-thinned stratum corneum increases burn risk; lower UV doses are required (FDA PI) |
| Keratinisation disorders (Darier disease, ichthyosis) — off-label | 10–25 mg QD | 10–25 mg QD | 50 mg/day | Lower doses effective for keratinisation disorders Long-term use; monitor for skeletal changes |
| NMSC chemoprevention in transplant recipients — off-label | 10–25 mg QD | 10–25 mg QD | 25 mg/day | Lowest effective dose for long-term prophylaxis Balance with immunosuppressive regimen; monitor lipids closely |
| Elderly patients (≥65 years) | 10–25 mg QD | Individualise | 50 mg/day | 2-fold higher plasma concentrations observed in elderly Start at the low end of dosing range (FDA PI) |
Acitretin must always be taken with food to optimise absorption (~72% with food vs substantially lower without). Therapeutic response typically emerges after 2–4 weeks, with full effect at 8–12 weeks. Transient worsening of psoriasis may occur early in treatment. Relapses after discontinuation are common; the drug does not provide sustained remission, unlike some biologics. When restarting after relapse, use the same dose-finding approach from the initial course.
Pharmacology
Mechanism of Action
The precise mechanism by which acitretin improves psoriasis is not fully established (FDA PI). As a second-generation aromatic retinoid, acitretin binds to cytosolic retinoic acid-binding protein (CRABP), which transports it to the nucleus where it activates retinoic acid receptors (RAR) and retinoid X receptors (RXR). These receptors modulate gene transcription at retinoic acid response elements (RAREs), resulting in normalisation of keratinocyte proliferation and differentiation. In psoriatic plaques, acitretin exerts an antiproliferative effect that slows the accelerated epidermal turnover, reduces plaque thickness, scaling, and erythema. It also modulates immune signalling by suppressing Th1 and Th17 cytokine pathways, including downregulation of IL-6 and TNF-alpha, contributing to its anti-inflammatory activity.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | ~72% absorbed (with food); Tmax 2–5 h (mean 2.7 h); linear from 25–100 mg | Must take with food; systemic bioavailability ~60% due to first-pass metabolism |
| Distribution | Protein binding >99.9% (albumin); <5% lipoprotein-bound; low Vd relative to etretinate | Minimal adipose storage unlike etretinate; cleared from plasma within ~3 weeks of cessation |
| Metabolism | Isomerisation to 13-cis-acitretin; further chain-shortening and glucuronidation via CYP450; transesterification to etretinate with ethanol | Cis-acitretin accumulates ~6.6-fold at steady state; ethanol converts acitretin to etretinate (t½ ~120 days), extending teratogenic risk |
| Elimination | t½ 49 h (range 33–96 h); cis-acitretin t½ 63 h; feces 34–54%, urine 16–53% | Steady state in ~3 weeks; undetectable (<4 ng/mL) 3 weeks after stopping; 2-fold higher levels in elderly |
Side Effects
Side effect data are derived from FDA PI clinical trials (N = 525 patients, doses 10–75 mg/day) and an extended safety database of 1,289 patients from European trials. Adverse effects are predominantly dose-related and consistent with hypervitaminosis A. Mucocutaneous effects are nearly universal but usually manageable with dose reduction. The overall clinical adverse event rate was 94% during the 8-week double-blind phase, though most events were mild and did not require discontinuation.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Cheilitis (dry/cracked lips) | >75% | Most characteristic retinoid side effect; nearly universal; dose-dependent; manage with emollients and lip balm |
| Hypertriglyceridaemia | 50–75% (66% in trials) | Dose-dependent; can precipitate pancreatitis if severe; monitor fasting lipids at 1–2 week intervals initially |
| Alopecia | 50–75% | More common in women and at doses >17.5 mg/day; reversible on dose reduction or cessation (regrowth in 3–6 months) |
| Skin peeling (palms and soles) | 50–75% | Dose-dependent; reflects retinoid effect on stratum corneum; manage with emollients |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Dry skin (xerosis) | 25–50% | Generalised; use emollients liberally; avoid harsh soaps |
| Hypercholesterolaemia | 25–50% (33% in trials) | Manage per cardiovascular risk guidelines; consider statin if persistent |
| Elevated liver enzymes | 25–50% | Usually mild and transient; marked elevations (>3× ULN) in 1–5%; 3.8% discontinued due to LFTs |
| Nail disorder / fragility | 25–50% | Brittle, slow-growing nails; paronychia possible; reversible |
| Pruritus | 25–50% | May reflect retinoid dermatitis or dry skin; antihistamines and emollients may help |
| Rhinitis / dry nose / epistaxis | 20–30% | Nasal mucosa dryness; petroleum-based nasal gel can reduce nosebleeds |
| Xerophthalmia (dry eyes) | 10–25% | Contact lens intolerance is common; use preservative-free artificial tears |
| Arthralgia | 10–25% | May reflect early musculoskeletal retinoid toxicity; monitor for hyperostosis on long-term use |
| Paresthesia / hyperesthesia | 10–25% | Usually mild; reversible on dose reduction |
| Rigors | 10–25% | Dose-dependent; may improve with dose reduction |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Teratogenicity (severe fetal malformations) | High (Category X) | During or up to 3 years after treatment | Absolute contraindication in pregnancy; 2 forms of contraception required; avoid alcohol (etretinate formation extends risk window) |
| Hepatotoxicity (toxic hepatitis, cirrhosis) | 0.26% overt hepatitis | Variable; weeks to months | Discontinue immediately if hepatotoxicity suspected; investigate with biopsy if indicated; deaths have been reported |
| Pancreatitis (secondary to severe hypertriglyceridaemia) | Rare | Weeks to months | Discontinue if triglycerides rise uncontrollably; maintain triglycerides below threshold with dietary measures and lipid-lowering therapy |
| Pseudotumor cerebri (benign intracranial hypertension) | Very rare | Any time during treatment | Discontinue immediately; urgent neurological referral; papilloedema, headache, nausea, visual disturbance are early signs |
| Skeletal hyperostosis / ligament calcification | 10–25% (long-term use) | Months to years of chronic therapy | Baseline and periodic radiographs for long-term patients; may be irreversible; weigh risk-benefit for prolonged courses |
| Psychiatric effects (depression, suicidal ideation) | Unknown (causal link not established) | Any time | Stop acitretin immediately and refer for psychiatric assessment; reported with other systemic retinoids |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Mucocutaneous intolerance | ~22% | Most common cause; dose reduction often allows continuation |
| Hepatic enzyme elevation | 3.8% | LFTs typically normalise within 2 months of stopping |
| Hyperlipidaemia | <5% | Primarily severe hypertriglyceridaemia unresponsive to dietary or pharmacological intervention |
Nearly all patients on acitretin will experience some degree of mucocutaneous dryness. The most effective strategy is dose reduction rather than discontinuation. Cheilitis responds to frequent application of emollients and lip balm. Dry skin is managed with liberal moisturiser use and avoidance of harsh soaps. For alopecia, reassure patients that hair loss is reversible within 3–6 months of stopping or reducing the dose. Using the lowest effective dose (25 mg/day for maintenance) substantially reduces the burden of mucocutaneous toxicity.
Drug Interactions
Acitretin undergoes isomerisation and CYP450-mediated metabolism. The most clinically critical interaction is with ethanol, which triggers transesterification of acitretin to etretinate—a metabolite with a 120-day half-life that dramatically extends teratogenic risk. No pharmacokinetic interactions were demonstrated with cimetidine, digoxin, phenprocoumon (warfarin class), or glyburide in formal studies (FDA PI).
Monitoring
-
Pregnancy Testing
2 tests before start; monthly during; every 3 months for 3 years after
Routine Sensitivity ≥25 mIU/mL. First test at decision to treat, second during first 5 days of menses before starting. Initiate within 7 days of second negative result. Monthly supply only. -
Liver Function Tests
Baseline; every 1–2 weeks for first 2 months; then every 1–3 months
Routine Includes AST, ALT, GGT, LDH. Discontinue if hepatotoxicity suspected. More frequent monitoring in alcoholics, diabetics, and obese patients. Avoid concurrent hepatotoxic agents. -
Fasting Lipid Panel
Baseline; every 1–2 weeks until stable (4–8 weeks); then every 3 months
Routine Triglycerides elevated in ~66% and cholesterol in ~33% of patients. Discontinue or reduce dose if triglycerides reach dangerous levels. High-risk patients (diabetes, obesity, alcoholism) need more frequent monitoring. -
Complete Blood Count
Baseline; then periodically
Routine Monitor for reticulocytosis and other haematological changes during long-term therapy. -
Blood Glucose
Baseline and periodically in diabetics
Trigger-based Acitretin may alter glucose tolerance; may potentiate sulfonylurea hypoglycaemia. Careful supervision of diabetic patients recommended. -
Skeletal Imaging
Consider baseline and periodic radiographs for long-term therapy
Trigger-based Spinal hyperostosis and ligament calcification reported with chronic retinoid use (10–25% incidence). Particularly relevant for patients on treatment >6 months and paediatric patients (skeletal effects). -
Ophthalmological Assessment
If visual symptoms develop
Trigger-based Night vision changes, blurred vision, dry eyes, and corneal abnormalities have been reported. Decreased contact lens tolerance is common. Stop acitretin and refer for ophthalmological evaluation if visual disturbances occur. -
Psychiatric Assessment
Ongoing awareness
Trigger-based Depression, aggressive feelings, and suicidal thoughts have been reported with systemic retinoids. Causal relationship not established. Discontinue immediately and refer if psychiatric symptoms emerge.
Contraindications & Cautions
Absolute Contraindications
- Pregnancy or intent to become pregnant within 3 years of stopping treatment—Category X; severe fetal malformations documented
- Inability to comply with 2 simultaneous forms of contraception (at least 1 primary method) for 1 month before, during, and 3 years after therapy
- Breastfeeding—acitretin excreted in breast milk
- Concomitant ethanol use (females of childbearing potential)—promotes etretinate formation; contraindicated during treatment and for 2 months after
- Concomitant methotrexate—additive hepatotoxicity risk
- Concomitant tetracyclines—risk of pseudotumor cerebri
- Severe hepatic impairment
- Severe renal impairment
- Chronic severely elevated blood lipids
- Hypersensitivity to acitretin, other retinoids, or excipients
Relative Contraindications (Specialist Input Recommended)
- Women of childbearing potential—prescribe only when all elements of the Do Your P.A.R.T. programme are satisfied; specialist prescribing only
- Pre-existing hyperlipidaemia—may worsen significantly; manage lipids aggressively before and during treatment
- Diabetes mellitus—altered glucose tolerance; may potentiate sulfonylurea effects
- History of depression or psychiatric illness—systemic retinoids have been associated with psychiatric adverse events
Use with Caution
- Elderly patients (≥65 years)—2-fold higher plasma concentrations; start at low doses
- Obesity—increased risk of lipid abnormalities and hepatotoxicity
- Alcoholism—increased hepatotoxicity risk and etretinate formation risk
- Long-term use (>6 months)—skeletal hyperostosis and ligament calcification risk; periodic imaging advisable
- Blood donation—patients must not donate blood during treatment and for at least 3 years after stopping, as acitretin-containing blood could harm a pregnant recipient
Acitretin carries an FDA boxed warning centred on pregnancy prevention. It is a potent teratogen: major human fetal abnormalities have been reported including craniofacial dysmorphia, limb malformations, CNS defects, and cardiovascular malformations. Pregnancy must be avoided for at least 3 years after treatment cessation, with two simultaneous forms of contraception mandatory. Ethanol must not be ingested by women of childbearing potential during treatment or for 2 months after, because alcohol drives conversion of acitretin to etretinate (t½ ~120 days), dramatically extending the teratogenic window. The drug should be prescribed only by clinicians with special competence in severe psoriasis and systemic retinoid use.
Concurrent use with methotrexate is contraindicated due to additive hepatotoxicity risk, including fatal cases reported with the related compound etretinate. Hepatotoxicity can occur with acitretin alone (0.26% overt hepatitis in 1,877 patients), with two cases of biopsy-confirmed toxic hepatitis in European trials. This warning is in the FDA WARNINGS section, separate from the boxed warning above, but is equally critical for prescribing decisions.
Patient Counselling
Purpose of Therapy
Acitretin is prescribed for severe psoriasis that has not responded adequately to other treatments. It works by slowing the abnormally rapid growth of skin cells and reducing inflammation. It is taken as a capsule once daily with your main meal, and you may begin to see improvement after 2–4 weeks, with full effect typically after 8–12 weeks.
How to Take
Take the capsule with your main meal to help your body absorb the medication properly. Swallow the capsule whole. If you miss a dose, skip it and take your next dose at the usual time—do not double up. Do not share this medication with anyone else. Store at room temperature, protected from light and humidity.
Sources
- Stiefel Laboratories / GSK. SORIATANE (acitretin) capsules. Full prescribing information. Revised 2017. accessdata.fda.gov Primary source for all dosing, pharmacokinetic, contraindication, and boxed warning data in this monograph.
- SORIATANE (acitretin) capsules. Revised label 2023 (s029). accessdata.fda.gov Most recent FDA label revision confirming unchanged dosing, safety profile, and teratogenicity warnings.
- DailyMed. Acitretin capsule label. National Library of Medicine. dailymed.nlm.nih.gov Structured FDA label providing pharmacokinetic tables (half-life 49 h, Tmax 2.7 h, elimination data).
- Gupta AK, Goldfarb MT, Ellis CN, Voorhees JJ. Side-effect profile of acitretin therapy in psoriasis. J Am Acad Dermatol. 1989;20(6):1088–1093. doi:10.1016/S0190-9622(89)70138-4 Original dose-ranging study (10–75 mg/day, 38 patients) establishing dose-dependent mucocutaneous adverse effect profile.
- Pearce DJ, Klinger S, Ziel KA, et al. Low-dose acitretin is associated with fewer adverse events than high-dose acitretin in the treatment of psoriasis. Arch Dermatol. 2006;142(8):1000–1004. doi:10.1001/archderm.142.8.1000 Re-analysis of phase 3 trials confirming that 25 mg/day produces fewer adverse events than higher doses while maintaining clinical benefit.
- Carretero G, Ribera M, Belinchón I, et al. Guidelines for the use of acitretin in psoriasis. Actas Dermosifiliogr. 2013;104(7):598–616. doi:10.1016/j.adengl.2013.01.001 Comprehensive guideline covering dosing strategy, combination therapy approaches, monitoring protocols, and special populations.
- Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020;82(6):1445–1486. doi:10.1016/j.jaad.2020.02.044 AAD-NPF guideline positioning acitretin among systemic nonbiologic therapies for moderate-to-severe psoriasis.
- Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs. 1997;53(3):358–388. doi:10.2165/00003495-199753030-00003 Comprehensive review of retinoid pharmacology covering receptor binding, gene regulation, and clinical applications in dermatology.
- Dogra S, Yadav S. Acitretin in psoriasis: an evolving scenario. Int J Dermatol. 2014;53(5):525–538. doi:10.1111/ijd.12365 Review addressing the evolving role of acitretin including combination strategies and off-label dermatological applications.
- Larsen FG, Jakobsen P, Knudsen J, et al. The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients. J Clin Pharmacol. 1991;31(4):344–349. doi:10.1002/j.1552-4604.1991.tb03715.x Key PK study in 12 psoriasis patients establishing half-life range (mean 47.1 h) and cis-acitretin accumulation characteristics.
- Geiger JM, Baudin M, Saurat JH. Acitretin. In: Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. 2nd ed. Elsevier; 2007:289–310. Textbook chapter providing detailed safety data from the 525-patient clinical trial programme and the 1,877-patient European hepatotoxicity assessment.
- Rollman O, Vahlquist A. Oral retinoids (“aromatic retinoid”) therapy for psoriasis: pharmacokinetic review. Drugs. 1988;36(5):535–554. doi:10.2165/00003495-198836050-00002 Early pharmacokinetic review establishing the rationale for replacing etretinate with acitretin based on elimination half-life differences.