Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External:
Panretin: 0.1% (60 g)
Pharmacology
Mechanism of Action
Alitretinoin is a naturally occurring endogenous retinoid that binds to and activates intracellular retinoid receptors (RAR and RXR subtypes); this results in altered expression of the genes controlling cellular differentiation and proliferation in normal and neoplastic cells, inhibiting the growth of Kaposi sarcoma
Pharmacokinetics/Pharmacodynamics
Absorption
Not extensive
Use: Labeled Indications
Kaposi sarcoma: Topical treatment of cutaneous lesions in AIDS-related Kaposi sarcoma.
Limitations of use: Alitretinoin is not indicated when systemic therapy is necessary (eg, >10 new Kaposi sarcoma lesions in previous month, symptomatic visceral involvement, symptomatic pulmonary Kaposi sarcoma, symptomatic lymphedema). There is no experience in using alitretinoin (topical) in combination with systemic treatment for Kaposi sarcoma.
Contraindications
Known hypersensitivity to alitretinoin, other retinoids, or any component of the formulation
Dosage and Administration
Dosing: Adult
Kaposi sarcoma: Topical: Initial: Apply gel twice daily to cutaneous lesions; may gradually increase application frequency to 3 or 4 times daily based on lesion tolerance. Continue as long as deriving clinical benefit; response may be observed within 2 weeks of initiation, but typically a longer period is required (>14 weeks); in clinical trials, therapy lasted up to 96 weeks.
Dosing: Adjustment for Toxicity
Application site irritation: May reduce the frequency of administration if application site toxicity occurs.
Grades 0, 1, or 2 dermal irritation: No dosage adjustment necessary (Walmsley 1999).
Grade 3 dermal irritation: Reduce dosing frequency to once daily (Bodsworth 2001) or reduce frequency or withhold treatment for up to 2 weeks and restart when irritation improves to grade 1 or lower (Walmsley 1999).
Grade 4 dermal irritation: Discontinue treatment until irritation improves to grade 1 or lower within 2 weeks and then restart at less than once daily for 2 weeks before increasing application frequency. If grade 4 irritation occurs less than once daily, do not restart treatment (Walmsley 1999).
Administration
Topical: Apply sufficient gel to cover lesion(s) with a generous coating; allow gel to dry 3 to 5 minutes after application before covering with clothing. Do not cover alitretinoin application site with occlusive dressings. Avoid applying gel to normal skin surrounding lesions. Do not apply to any lesions on or near mucosal surfaces.
Storage
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
Drug Interactions
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Tetracyclines: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Avoid combination
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Pain (≤34%), paresthesia (3% to 22%)
Dermatologic: Skin rash (25% to 77%), pruritus (8% to 11%)
1% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), dermatological disease (≤8%)
Warnings/Precautions
Concerns related to adverse effects:
- Dermal irritation: Application site irritation and pain have been reported, including grade 3 dermal irritation; may require dosage reduction.
- Photosensitivity: Alitretinoin may be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Products containing DEET: Do not use concurrently with topical products containing DEET (eg, insect repellant); an increase in DEET toxicity has been observed.
Pregnancy
Pregnancy Considerations
Alitretinoin may cause fetal harm if significant absorption occurs in a female who is pregnant.
Females of reproductive potential should avoid becoming pregnant during treatment with topical alitretinoin.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber burning or numbness feeling, edema, or severe skin irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
