Alitretinoin

Alitretinoin (9-cis-retinoic acid) is a naturally occurring endogenous retinoid that binds to and activates all known intracellular retinoid receptor subtypes (RARα, RARβ, RARγ, RXRα, RXRβ and RXRγ). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells.

• 1.1 Kaposi’s Sarcoma PANRETIN GEL is indicated for topical treatment of cutaneous lesions in adults with AIDS related Kaposi’s sarcoma (KS). Limitations of Use: PANRETIN GEL is not indicated when systemic anti-KS therapy is required (including more than 10 new KS lesions in the prior month, symptomatic lymphedema, symptomatic pulmonary KS, or symptomatic visceral involvement) [see Clinical Studies ( 14.1 )] .

• PANRETIN GEL is contraindicated in patients with a known hypersensitivity to retinoids or to any of the ingredients of the product.contraindicated

PANRETIN GEL is for topical use only. Do not use occlusive dressings with PANRETIN GEL. Apply PANRETIN GEL twice daily to coat the entire cutaneous Kaposi sarcoma lesions. Gradually increase the application frequency up to four (4) times a day as tolerated. Continue PANRETIN GEL as long as patient is deriving benefit. Reduce application frequency for application site toxicity. Interrupt treatment for severe irritation; may resume at a reduced application frequency once symptoms improve. Avoid application of gel to normal skin and do not apply on or near mucosal surfaces. Wash hands after application unless gel is applied to Kaposi sarcoma lesions on the hands. Allow gel to dry for three to five minutes before covering with clothing. • Apply to the affected lesions twice daily; increase to 4 times daily as tolerated. ( 2 ) • For topical use only. ( 2 )

• Embryo-Fetal Toxicity : Can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception. ( 5.1 . 8.1 , 8.3 ) • Photosensitivity : Minimize exposure to sunlight and sunlamps. ( 5.2 ) • DEET toxicity : Do not use DEET-containing products ( 5.3 ) 5.1 Embryo-Fetal Toxicity Based on data from animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo-lethal at exposures 5 times the estimated daily human topical dose. Advise women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with PANRETIN GEL and for 1 week after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] . 5.2 Photosensitivity Retinoids as a class have been associated with photosensitivity. Advise patients to minimize exposure of treated areas to sunlight and sunlamps during the use of PANRETIN GEL. 5.3 Toxicity with DEET-Containing Products Animal toxicology studies showed increased DEET toxicity when DEET was included as part of the formulation. Advise patients to not use PANRETIN GEL concurrently with products that contain DEET (N,N-diethyl-m-toluamide), a common component of insect repellent products.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Photosensitivity [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (> 5%) at the application site are rash, pain, paresthesia, pruritis, exfoliative dermatitis, edema, and skin disorders. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Advanz Pharma (US) Corp. at 1-877-370-1142 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PANRETIN GEL was assessed in two multicenter, prospective, randomized, double-blind, vehicle-controlled trials (Trial 1 and Trial 2) in patients with cutaneous lesions of AIDS-related KS [see Clinical Studies ( 14.1 )] . In a pooled analysis of both trials, the most common adverse reactions in ≥ 5% of patients were rash, pain, paresthesia, pruritis, exfoliative dermatitis, edema, and skin disorder. In Trial 1, severe local skin adverse reactions (erythema and edema with or without vesiculation) occurred in 10% of patients during the first 12 weeks of treatment (versus 0% in the vehicle control). Adverse reactions led to withdrawal from the study in 7% of patients.

• Pregnancy : Can cause fetal harm ( 8.1 ) • Lactation: Advise not to breastfeed ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo lethal at exposures at least 5 times the estimated daily human topical dose ( see Data ). There are no data on the use of PANRETIN GEL in pregnant women. Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Oral administration of alitretinoin to pregnant rabbits during the period of organogenesis resulted in early resorptions, post-implantation loss, and fetal defects (limb, craniofacial, fused sternebrae) at doses ≥ 0.5 mg/kg/day (approximately 5 times the estimated daily human topical dose based on body surface area, assuming complete systemic absorption of alitretinoin, when PANRETIN GEL is administered as a 60 g tube over 1 month in a 60 kg human).

Metabolism

The range of 9-cis-retinoic acid plasma concentrations in patients with cutaneous lesions of AIDS-related KS after multiple daily applications of PANRETIN GEL for up to 60 weeks was similar to the range of circulating, naturally occurring 9-cis-retinoic acid plasma concentrations in untreated healthy participants. Elimination Metabolism 9-cis-retinoic acid is metabolized to 4-hydroxy-9-cis-retinoic acid and 4-oxo-9-cis-retinoic acid by CYP2C9, 3A4, 1A1, and 1A2.

• Feb 2, 1999NDANDA020886Advanz Pharma

1. 1Off Label Use2320%
2. 2Drug Ineffective2219%
3. 3Drug Intolerance97.7%
4. 4Headache97.7%
5. 5Hypercholesterolaemia86.8%
6. 6Treatment Failure86.8%
7. 7Vomiting86.8%
8. 8Product Use In Unapproved Indication76.0%
9. 9Cough65.1%
10. 10Diarrhoea65.1%
11. 11Drug Eruption65.1%
12. 12Fatigue65.1%
13. 13Localised Infection65.1%
14. 14Nausea65.1%
15. 15Pain In Extremity65.1%

Recent PubMed references pinned to Alitretinoin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Comparative Efficacy of Monotherapies for Chronic Hand Eczema: A Network Meta-Analysis Study.
  Journal of cosmetic dermatology · 2025 · Gupta AK, Bamimore MA, Talukder M, et al.
  PMID 41277505DOI 10.1111/jocd.70552
• Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial.
  Lancet (London, England) · 2025 · Giménez-Arnau AM, Pinter A, Sondermann W, et al.
  PMID 40252681DOI 10.1016/S0140-6736(25)00001-7
• Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.
  Health technology assessment (Winchester, England) · 2024 · Wittmann M, Smith IL, Brown ST, et al.
  PMID 39364555DOI 10.3310/TWQC0141
• Comparative Study of Efficacy Between Cyclosporine and Alitretinoin in Patients With Chronic Hand Eczema.
  Dermatitis : contact, atopic, occupational, drug · 2024 · Jang JH, Joh HC, Song CH, et al.
  PMID 37870578DOI 10.1089/derm.2023.0113
• Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells.
  The Journal of biological chemistry · 2023 · Yoo HS, Moss KO, Cockrum MA, et al.
  PMID 37714463DOI 10.1016/j.jbc.2023.105255
• Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro.
  Toxicology · 2023 · Kubickova B, Martinkova S, Bohaciakova D, et al.
  PMID 36805303DOI 10.1016/j.tox.2023.153461
• Human Plasma Metabolomics Identify 9-cis-retinoic Acid and Dehydrophytosphingosine Levels as Novel biomarkers for Early Ventricular Fibrillation after ST-elevated Myocardial Infarction.
  Bioengineered · 2022 · Luo J, Shaikh JA, Huang L, et al.
  PMID 35094641DOI 10.1080/21655979.2022.2027067
• Alitretinoin in the treatment of cutaneous T-cell lymphoma.
  Cancer medicine · 2021 · Kaemmerer T, Stadler PC, Helene Frommherz L, et al.
  PMID 34435474DOI 10.1002/cam4.4237

The 10 most recently updated of 21 ClinicalTrials.gov registrations naming Alitretinoin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema
  Completed · Phase 3 · Interventional · 513 enrolled · LEO Pharma
  NCT05259722updated 2025-05-09
• Safety and Efficacy of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
  Completed · Phase 3 · Interventional · 250 enrolled · Basilea Pharmaceutica
  NCT00309621updated 2023-05-10
• Alitretinoin in the Treatment of Chronic Hand Eczema
  Completed · Phase 3 · Interventional · 150 enrolled · Basilea Pharmaceutica
  NCT00519675updated 2023-05-10
• Follow-up Efficacy and Safety of Alitretinoin in Severe Chronic Hand Dermatitis
  Completed · Phase 3 · Interventional · 300 enrolled · Basilea Pharmaceutica
  NCT00124436updated 2023-05-10
• Efficacy and Safety of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
  Completed · Phase 3 · Interventional · 1,035 enrolled · Basilea Pharmaceutica
  NCT00124475updated 2023-05-10
• Dupilumab in Severe Chronic Hand Eczema
  Unknown · Phase 2 · Interventional · 30 enrolled · University Medical Center Groningen
  NCT04512339updated 2022-08-23
• Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for Treating Patients With Multidrug-resistant TB and Patient With Both Multidrug-resistant TB and COVID-19
  Unknown · Phase 2 · Interventional · 250 enrolled · Kafrelsheikh University
  NCT05077813updated 2021-10-14
• Investigating the Potential Role of a Novel Quadrate Combination Therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic Acid and Cannabidiol ( Selective Cyp 26 Inhibitor) for Treating Early Breast Cancer.
  Unknown · Phase 3 · Interventional · 160 enrolled · Mahmoud Ramadan mohamed Elkazzaz
  NCT05016349updated 2021-08-23
• Efficacy and Safety of a Retinoid in the Treatment of Severe Chronic Hand Eczema
  Completed · Phase 3 · Interventional · 599 enrolled · Stiefel, a GSK Company
  NCT00817063updated 2020-04-27
• Alitretinoin vs Cyclosporine in Severe Recurrent Vesicular Hand Eczema
  Unknown · Phase 3 · Interventional · 76 enrolled · University Medical Center Groningen
  NCT03026946updated 2019-02-26

Frequently asked questions

How does Alitretinoin work?

Alitretinoin (9-cis-retinoic acid) is a naturally occurring endogenous retinoid that binds to and activates all known intracellular retinoid receptor subtypes (RARα, RARβ, RARγ, RXRα, RXRβ and RXRγ). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells.

What is Alitretinoin used for?

According to FDA labeling, Alitretinoin carries indications including: 1.1 Kaposi’s Sarcoma PANRETIN GEL is indicated for topical treatment of cutaneous lesions in adults with AIDS related Kaposi’s sarcoma (KS). Limitations of Use: PANRETIN GEL is not indicated when systemic anti-KS therapy is required (including more than 10 new KS lesions in the prior month, symptomatic lymphedema, symptomatic pulmonary KS, or symptomatic visceral involvement) [see Clinical Studies ( 14.1 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Alitretinoin?

Alitretinoin is classified as Agents for dermatitis, excluding corticosteroids, Retinoids for cancer treatment, Retinoid, Receptor Interactions, Decreased Transcription to RNA.

What are the brand names for Alitretinoin?

Alitretinoin is marketed under brand names including Panretin.

What are the contraindications for Alitretinoin?

Alitretinoin labeling lists contraindications including: PANRETIN GEL is contraindicated in patients with a known hypersensitivity to retinoids or to any of the ingredients of the product.. Always consult the full prescribing information and a clinician.