Alitretinoin Monograph for Professionals - Drugs.com

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# Alitretinoin

Brand name: Panretin
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
VA class: DE600
Chemical name: (2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid
Molecular formula: C20H28O2
CAS number: 5300-03-8

Medically reviewed by Drugs.com on Jan 24, 2022. Written by ASHP.

## Introduction

A vitamin A derivative; naturally occurring endogenous retinoid with topical antineoplastic activity.

## Uses for Alitretinoin

### AIDS-related Kaposi’s Sarcoma

Treatment of cutaneous lesions associated with AIDS-related Kaposi’s sarcoma.

Not recommended for treatment of systemic AIDS-related Kaposi’s sarcoma, characterized by ≥10 new lesions in the prior month, symptomatic lymphedema, symptomatic pulmonary Kaposi’s sarcoma, or symptomatic visceral disease.

No clinical experience to date in patients receiving systemic therapy for Kaposi’s sarcoma.

## Alitretinoin Dosage and Administration

### Administration

#### Topical Administration

Apply topically to skin.

Wait 20 minutes after bathing or showering before applying gel; avoid use of occlusive dressings or wrappings.

Avoid contact with healthy skin or mucous membranes (e.g., eyes, nostrils, mouth, lips, vagina, tip of penis, rectum, anus); irritation may occur.

Allow gel to dry for 3–5 minutes before covering treated area with clothing.

If possible, do not bathe, shower, or swim for at least 3 hours after application.

If application-site toxicity occurs, reduce application frequency.

If severe irritation occurs, discontinue temporarily until manifestations subside.

### Dosage

#### Adults

##### AIDS-related Kaposi’s Sarcoma

###### Topical

Initially, apply twice daily in sufficient amounts (to cover only affected areas). May increase application frequency gradually to 3 and then 4 times daily, according to individual lesion tolerance.

In some patients, appreciable response occurred only after ≥14 weeks of therapy.

Continue therapy as long as the patient derives benefit (has been applied for up to 175 weeks in clinical trials).

Detailed Alitretinoin topical dosage information

## Cautions for Alitretinoin

### Contraindications

- Known hypersensitivity to retinoids or any ingredient in the formulation.

### Warnings/Precautions

#### Warnings

##### Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals receiving oral alitretinoin. No reproduction studies in animals with topical alitretinoin.

No adequate and well-controlled studies in humans. Avoid pregnancy during therapy. If used during pregnancy, apprise of potential hazard to the fetus.

#### Sensitivity Reactions

##### Photosensitivity

Retinoids associated with photosensitivity; in vitro data indicate alitretinoin may have weak photosensitizing effect.

Minimize exposure of treated areas to natural or artificial (e.g., sunlamps) sunlight.

#### Major Toxicities

##### Dermatologic Effects

Possible severe local skin reactions (e.g., intense erythema, edema, vesiculation). Patients with cutaneous T-cell lymphoma exhibit less tolerance to these effects than those with Kaposi’s sarcoma.

#### Specific Populations

##### Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

##### Lactation

Not known whether alitretinoin or its metabolites are distributed into milk; discontinue nursing due to risk in nursing infants.

##### Pediatric Use

Safety and efficacy not established in children <18 years of age.

##### Geriatric Use

Insufficient clinical experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

### Common Adverse Effects

Rash, pruritus, exfoliative dermatitis, skin disorders (excoriation, cracking, scabbing, crusting, drainage, eschar, fissure, oozing ), pain, paresthesia, edema.

## Interactions for Alitretinoin

Metabolized by CYP2C9, CYP3A4, CYP1A1, and CYP1A2.

No data available on interactions between topical alitretinoin and systemically administered drugs for Kaposi’s sarcoma.

### Specific Drugs

Drug | Interaction | Comments
--- | --- | ---
Antifungals, azoles | No clinical evidence of interactions during concomitant use | Unknown effect on steady-state concentrations of azole antifungals
Antiretroviral agents (including protease inhibitors) | No clinical evidence of interactions during concomitant use | Unknown effect on steady-state concentrations of antiretroviral agents
Diethyltoluamide (DEET) | Increased DEET toxicity observed in animals | Avoid concomitant use
Macrolide antibiotics | No clinical evidence of interactions during concomitant use | Unknown effect on steady-state concentrations of macrolide antibiotics

Alitretinoin topical drug interactions (more detail)

## Alitretinoin Pharmacokinetics

### Absorption

#### Bioavailability

Not substantially absorbed systemically following topical application.

Following repeated, multiple-daily-dose topical applications of alitretinoin (9-cis-retinoic acid) in patients with cutaneous lesions associated with Kaposi’s sarcoma, plasma concentrations of 9-cis-retinoic acid were similar to those of naturally occurring 9-cis-retinoic acid found in healthy untreated patients.

### Distribution

#### Extent

Not known whether alitretinoin or its metabolites are distributed into milk.

### Elimination

#### Metabolism

Alitretinoin metabolized to 4-hydroxy-9-cis-retinoic acid and 4-oxo-9-cis-retinoic acid by CYP2C9, CYP3A4, CYP1A1, and CYP1A2 in vitro; major circulating metabolite in vivo following oral alitretinoin is 4-oxo-9-cis-retinoic acid.

#### Elimination Route

Principally by metabolism; no unchanged drug excreted in urine.

#### Half-life

1.3–2.4 hours following oral administration.

## Stability

### Storage

#### Topical

##### Gel

25°C (may be exposed to 15–30°C).

## Actions

- Binds to and activates both intracellular retinoic acid receptors (RAR) (e.g., RARα, RARβ, RARγ) and retinoid X receptors (RXR) (e.g., RXRα, RXRβ, RXRγ) that appear to enhance gene transcription.

- Exact mechanism of action in Kaposi’s sarcoma not fully elucidated; appears to affect expression of genes that inhibit cell proliferation, induce cell differentiation, and trigger apoptosis in both healthy and cancer cells.

- In vitro, alitretinoin appears to inhibit Kaposi’s sarcoma cell growth.

## Advice to Patients

- Provide patients with a copy of manufacturer’s patient information.

- Describe risk of photosensitivity and associated precautions.

- Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Necessity of advising women to avoid pregnancy during therapy.

- Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

- Importance of informing patients of other important precautionary information. (See Cautions.)

## Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Alitretinoin
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer
--- | --- | --- | --- | ---
Topical | Gel | 0.1% w/w | Panretin (with dehydrated alcohol) | Ligand

AHFS DI Essentials™. © Copyright 2023, Selected Revisions February 1, 2005. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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## More about alitretinoin topical

- Check interactions
- Side effects
- Dosage information
- During pregnancy
- Drug class: miscellaneous topical agents
- En español

### Patient resources

- Drug Information
- Alitretinoin Topical (Advanced Reading)

### Professional resources

#### Other brands

Panretin

### Related treatment guides

- Kaposi's Sarcoma

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