Acitretin
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Acitretin: From Severe Keratinisation Disorders to Acne (Disease)
One-Sentence Summary
Acitretin is a second-generation oral retinoid. The Singapore licence records compiled for this report do not state an approved indication. The TxGNN model predicts it may be effective for acne (disease), with 1 clinical trial and 17 publications retrieved. Most of this evidence concerns hidradenitis suppurativa (also called "acne inversa"), not acne vulgaris, so the support is indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence data compiled for this report |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, acitretin is a second-generation oral retinoid. It normalises keratinocyte differentiation and reduces follicular hyperkeratinisation. These effects give plausible biological support for a role in follicular disorders.
Retinoids as a class reduce sebaceous gland activity, and isotretinoin is highly effective in acne. Acitretin has weaker direct sebosuppressive effects than isotretinoin. Its main clinical success has historically been in psoriasis and inherited keratinisation disorders.
The match with the TxGNN "acne" label is partly a nomenclature artefact. The clinical evidence found concerns hidradenitis suppurativa (acne inversa), a different follicular occlusion disorder. It is not acne vulgaris. Teratogenicity with a very long washout (up to 3 years for women of childbearing potential) is a major safety constraint.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07708480 | Phase 4 | Completed | 70 | Randomised comparison of apremilast (30 mg twice daily) vs acitretin (25 mg twice daily) for 12 weeks in moderate-to-severe hidradenitis suppurativa. The primary outcome was IHS4 score. Results are not available, and the condition is not acne vulgaris. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25640693 | 2015 | Guideline | J Eur Acad Dermatol Venereol | European S1 guideline for hidradenitis suppurativa/acne inversa |
| 20874789 | 2011 | Clinical study | Br J Dermatol | Long-term results of acitretin in hidradenitis suppurativa. Earlier case reports described promising results. |
| 12080949 | 2002 | Case report | Cutis | Patient with nodulocystic acne and hidradenitis suppurativa treated with acitretin |
| 41692081 | 2026 | Review | Clin Dermatol | Vitamin A and retinoids in dermatology, including oral acitretin |
| 29234829 | 2018 | Review | Hautarzt | Drug therapy of acne inversa: antibiotics, TNF-α inhibitors |
| 9074840 | 1997 | Review | Drugs | Retinoids in psoriasis, severe acne and related dermatoses, and skin cancer chemoprevention |
| 8573927 | 1995 | Review | Dermatology | Retinoids and sebaceous gland activity. Isotretinoin's anti-acne effect is linked to sebaceous inhibition. |
| 1617858 | 1992 | Review | Clin Pharmacokinet | Pharmacokinetics and efficacy of retinoids in skin diseases. Acitretin is mainly successful in psoriasis. |
| 11586072 | 2001 | Review | Skin Pharmacol Appl Skin Physiol | Mechanisms of retinoid action and future dermatological indications |
| 2112772 | 1990 | Laboratory study | Prostaglandins | Retinoids, including acitretin, inhibit eosinophil LTC4 release, which may contribute to anti-inflammatory effects |
Singapore Market Information
The approved indication text is not recorded for any of the licences.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16829P | ACITRET CAPSULE 25MG | Capsule | Not recorded |
| SIN08392P | NEOTIGASON CAPSULE 25 mg | Capsule | Not recorded |
| SIN15271P | NOVATRETIN CAPSULE 10MG | Capsule | Not recorded |
| SIN16830P | ACITRET CAPSULE 10MG | Capsule | Not recorded |
| SIN08391P | NEOTIGASON CAPSULE 10 mg | Capsule | Not recorded |
A sixth licence, SIN15270P (NOVATRETIN CAPSULE 25MG), is also valid. All six licences are for oral capsules.
Safety Considerations
- Contraindications flagged by the knowledge graph (not label text): liver failure, drug-induced liver injury, pancreatitis, hypertriglyceridemia, diabetes mellitus, diabetic ketoacidosis, obesity, pseudotumor cerebri/intracranial hypertension, vision disorders including night blindness and blindness, hypoalphalipoproteinemia, hyperostosis, substance abuse/dependence, anxiety, neurotic and dysthymic disorders.
- Pregnancy: Acitretin is strongly teratogenic and has a very long washout (up to 3 years for women of childbearing potential).
- Drug Interactions (100 interactions recorded; the main ones are listed):
- Major: doxycycline, minocycline, tetracycline, vitamin A.
- Moderate: sulfonylureas (acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, tolazamide, tolbutamide) and naltrexone.
The package insert warnings and contraindications were not available for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only trial is a Phase 4 study in hidradenitis suppurativa, with no results available, and nearly all the literature concerns that condition or other retinoids rather than acne vulgaris. Acitretin's weaker sebosuppressive effect, the teratogenicity risk and the long washout make it an unlikely choice over isotretinoin without direct evidence.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA, and approved indication text for the Singapore licences
- Mechanism of action data
- Direct controlled evidence in acne vulgaris, or a clear decision to treat hidradenitis suppurativa as a separate indication
- Results of NCT07708480
- A pregnancy-prevention and monitoring plan covering liver function, lipids and ocular effects
Other predicted indications: The remaining nine predictions (ranks 2–10) have no direct evidence and should be held. These are pediatric systemic lupus erythematosus, fetal erythroblastosis, familial cutaneous telangiectasia with oropharyngeal cancer predisposition, complement component 4a deficiency, subacute bacterial endocarditis, familial acanthosis nigricans, prolapse of lacrimal gland, familial localised heat urticaria and Sjögren syndrome. Several are implausible: fetal erythroblastosis (teratogenic risk), endocarditis (no antimicrobial activity) and lacrimal gland prolapse (acitretin causes dry eye). The Sjögren syndrome literature concerns Sjögren-Larsson syndrome, a different inherited ichthyosis disorder.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.