Tacrolimus
| Evidence Level: L2 | Predicted Indications: 2 |
Table of Contents
Tacrolimus: From Atopic Eczema to Seborrheic Dermatitis
One-Sentence Summary
Tacrolimus is a calcineurin inhibitor, originally used to treat atopic eczema (atopic dermatitis). The TxGNN model predicts it may be effective for Seborrheic Dermatitis, with 2 clinical trials (one completed Phase 3 and one completed Phase 4) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atopic eczema / atopic dermatitis |
| Predicted New Indication | Seborrheic dermatitis |
| TxGNN Prediction Score | 0.9926 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, tacrolimus is a calcineurin inhibitor. It blocks T-cell activation and the release of pro-inflammatory cytokines. This is the pathway behind its established use in atopic dermatitis.
Seborrheic dermatitis is a chronic, relapsing inflammatory skin disease of the face and scalp. It involves an inflammatory response to Malassezia yeast. Atopic dermatitis and seborrheic dermatitis share an inflammatory, T-cell-driven component, so calcineurin inhibition is a plausible way to treat both. Tacrolimus may also have indirect effects on Malassezia-related inflammation. The very high TxGNN score is consistent with this rationale.
Note on the evidence level: the completed Phase 3 trial supports the topical ointment form specifically. A strict reading of the L1 rule (at least two completed Phase 3 RCTs) is not met for seborrheic dermatitis, because the second trial is Phase 4. The evidence is therefore placed at L2 here, a conservative reading of one completed Phase 3 trial plus supportive Phase 4 and published clinical data.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02004860 | Phase 3 | Completed | 120 | Tacrolimus ointment (Protopic) as maintenance treatment of severe seborrheic dermatitis on the adult face, aiming to reduce relapses and steroid use |
| NCT01591070 | Phase 4 | Completed | 104 | Proactive once- or twice-weekly 0.1% tacrolimus ointment to keep adult facial seborrheic dermatitis in remission and reduce exacerbations |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26512166 | 2015 | RCT/Clinical study | Annals of Dermatology | Maintenance therapy of facial seborrheic dermatitis with 0.1% tacrolimus ointment |
| 27804089 | 2017 | Systematic Review | American Journal of Clinical Dermatology | Systematic review of topical treatments for facial seborrheic dermatitis |
| 19222250 | 2009 | Review | American Journal of Clinical Dermatology | Role of topical calcineurin inhibitors in seborrheic dermatitis: pathophysiology, safety and efficacy |
| 24171300 | 2013 | Clinical trial | Annals of Parasitology | Sertaconazole 2% cream compared with tacrolimus 0.03% cream in 60 patients with seborrheic dermatitis |
| 19213227 | 2009 | Review | Journal of Drugs in Dermatology | Current status and therapeutic horizons for facial seborrheic dermatitis |
| 31476936 | 2019 | Review | Journal of Cutaneous Medicine and Surgery | Off-label use of topical calcineurin inhibitors in dermatologic disorders |
| 17685874 | 2007 | Review | Expert Opinion on Investigational Drugs | New roles for topical tacrolimus beyond atopic dermatitis |
| 15461548 | 2004 | Review | Expert Opinion on Pharmacotherapy | Tacrolimus ointment for atopic dermatitis and other inflammatory skin diseases |
| 11770914 | 2001 | Review | Seminars in Cutaneous Medicine and Surgery | Future directions for topical tacrolimus and pimecrolimus, including seborrheic dermatitis |
| 39219446 | 2024 | Systematic Review / Network Meta-analysis | Clinical and Experimental Allergy | Cochrane review of topical anti-inflammatory treatments for eczema (indirect for this indication) |
India Market Information
The approved indication text is not recorded for these licences. The 20 valid single-ingredient licences are mostly oral capsules, plus one ointment (Tames Forte) and one prolonged-release capsule (Advagraf).
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 221068 | Tames Forte Ointment (Ampra Pharmaceuticals) | Tube of 10 gm ointment | Not recorded |
| 2091 | Advagraf 1mg Capsule PR (Astellas Pharma) | Strip of 10 prolonged-release capsules | Not recorded |
| 219172 | Takfa 0.25 Capsule (Intas Pharmaceuticals) | Strip of 10 capsules | Not recorded |
| 220926 | Tacrolim 1mg Capsule (Dr Reddy’s Laboratories) | Strip of 10 capsules | Not recorded |
| 190385 | Rengraf 0.5mg Capsule (Abbott) | Strip of 10 capsules | Not recorded |
Only one topical product (Tames Forte Ointment) is registered, and the other registrations are oral capsules. The predicted indication relies on topical use, so the topical supply and its approved labelling need to be confirmed.
Safety Considerations
- Contraindications / disease associations (from the knowledge graph, not label text): hypertension, long QT syndrome, torsades de pointes, liver failure, kidney disease, epilepsy, diabetes mellitus, hyperglycaemia, diabetic ketoacidosis, active infections (including herpes simplex and herpes zoster), cancer, lymphoma, progressive multifocal leukoencephalopathy and posterior leukoencephalopathy syndrome. Many of these relate to systemic immunosuppressive use and may apply less to topical use.
- Drug Interactions: 868 interactions were found. Major-level examples include amphotericin B, loperamide, mesalazine, omeprazole and balsalazide. Moderate-level examples include acarbose, famotidine, rabeprazole, hydrocortisone, metformin, pioglitazone, dexamethasone and aprepitant.
- Cancer risk with topical use: a 2023 systematic review and meta-analysis (PMID 36370744) examined cancer risk with topical calcineurin inhibitors, a safety concern that should be part of any monitoring plan.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 trial and a completed Phase 4 study of tacrolimus ointment in facial seborrheic dermatitis, plus a published clinical study and several reviews, support the TxGNN prediction. The mechanism is consistent with its use in atopic dermatitis. The evidence is limited by the small trials and the lack of a second Phase 3 RCT.
To proceed, the following is needed:
- Review of the Phase 3 (NCT02004860) and Phase 4 (NCT01591070) results, and ideally a second confirmatory RCT
- The package insert warnings and contraindications for the India products, which are not yet available
- Confirmation of topical ointment availability and labelling in India, since most registrations are oral capsules
- Detailed mechanism of action data
- A safety monitoring plan covering infection risk, long-term cancer risk, and interactions with concomitant drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.