Alitretinoin

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Alitretinoin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Overview

Alitretinoin is a Dermatological Agent that is FDA approved for the treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Common adverse reactions include Rash, Application site pain, Pruritus, Exfoliative dermatitis, Skin disorder, Edema, Paresthesia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • Panretin® gel is indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Panretin® gel is not indicated when systemic anti-KS therapy is required (e.g., more than 10 new KS lesions in the prior month, symptomatic lymphedema, symptomatic pulmonary KS, or symptomatic visceral involvement). There is no experience to date using Panretin® gel with systemic anti-KS treatment.

Dosage

  • Panretin® gel should initially be applied two (2) times a day to cutaneous KS lesions. The application frequency can be gradually increased to three (3) or four (4) times a day according to individual lesion tolerance. If application site toxicity occurs, the application frequency can be reduced. Should severe irritation occur, application of drug can be temporarily discontinued for a few days until the symptoms subside.

Sufficient gel should be applied to cover the lesion with a generous coating. The gel should be allowed to dry for three to five minutes before covering with clothing. Because unaffected skin may become irritated, application of the gel to normal skin surrounding the lesions should be avoided. In addition, do not apply the gel on or near mucosal surfaces of the body.

A response of KS lesions may be seen as soon as two weeks after initiation of therapy but most patients require longer application. With continued application, further benefit may be attained. Some patients have required over 14 weeks to respond. In clinical trials, Panretin® gel was applied for up to 96 weeks. Panretin® gel should be continued as long as the patient is deriving benefit.

Occlusive dressings should not be used with Panretin® gel.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alitretinoin in adult patients.

Non–Guideline-Supported Use

  • Hand eczema, chronic (Moderate to Severe), Refractory to treatment[1][2]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Alitretinoin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alitretinoin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Alitretinoin in pediatric patients.

Contraindications

  • Panretin® gel is contraindicated in patients with a known hypersensitivity to retinoids or to any of the ingredients of the product.

Warnings

  • Pregnancy

Panretin® gel could cause fetal harm if significant absorption were to occur in a pregnant woman. 9-cis-Retinoic acid has been shown to be teratogenic in rabbits and mice. An increased incidence of fused sternebrae and limb and craniofacial defects occurred in rabbits given oral doses of 0.5 mg/kg/day (about five times the estimated daily human topical dose on a mg/m2 basis, assuming complete systemic absorption of 9-cis-retinoic acid, when Panretin® gel is administered as a 60 g tube over 1 month in a 60 kg human) during the period of organogenesis. Limb and craniofacial defects also occurred in mice given a single oral dose of 50 mg/kg on day eleven of gestation (about 127 times the estimated daily human topical dose on a mg/m2 basis). Oral 9-cis-retinoic acid was also embryocidal, as indicated by early resorptions and post-implantation loss when it was given during the period of organogenesis to rabbits at doses of 1.5 mg/kg/day (about 15 times the estimated daily human topical dose on a mg/m2 basis) and to rats at doses of 5 mg/kg/day (about 25 times the estimated daily human topical dose on a mg/m2 basis). Animal reproduction studies with topical 9-cis-retinoic acid have not been conducted. It is not known whether topical Panretin® gel can modulate endogenous 9-cis-retinoic acid levels in a pregnant woman nor whether systemic exposure is increased by application to ulcerated lesions or by duration of treatment. There are no adequate and well-controlled studies in pregnant women. If Panretin® gel is used during pregnancy, or if the patient becomes pregnant while taking it, the patient should be apprised of the potential hazard to the fetus. Women of child-bearing potential should be advised to avoid becoming pregnant.

Precautions

  • Panretin® gel is indicated for topical treatment of Kaposi's sarcoma. Patients with cutaneous T-cell lymphoma were less tolerant of topical Panretin® gel; five of seven patients had 6 episodes of treatment-limiting toxicities—grade 3 dermal irritation—with Panretin® gel (0.01% or 0.05%).

Information for Patients

Please see accompanying "PATIENT'S INSTRUCTIONS FOR USE"

Photosensitivity Retinoids as a class have been associated with photosensitivity. There were no reports of photosensitivity associated with the use of Panretin® gel in the clinical studies. Nonetheless, because in vitro data indicate that 9-cis-retinoic acid may have a weak photosensitizing effect, patients should be advised to minimize exposure of treated areas to sunlight and sunlamps during the use of Panretin® gel.

Adverse Reactions

Clinical Trials Experience

  • The safety of Panretin® gel has been assessed in clinical studies of 385 patients with AIDS-related KS. Adverse events associated with the use of Panretin® gel in patients with AIDS-related KS occurred almost exclusively at the site of application. The dermal toxicity begins as erythema; with continued application of Panretin® gel, erythema may increase and edema may develop. Dermal toxicity may become treatment-limiting, with intense erythema, edema, and vesiculation. Usually, however, adverse events are mild to moderate in severity; they led to withdrawal from the study in only 7% of the patients. Severe local (application site) skin adverse events occurred in about 10% of patients in the U.S. study (versus 0% in the vehicle control). Table 2 lists the adverse events that occurred at the application site with an incidence of at least 5% during the double-blind phase in the Panretin® gel-treated group and in the vehicle control group in either of the two controlled studies. Adverse events were reported at other sites but generally were similar in the two groups.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Alitretinoin in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Patients who are applying Panretin® gel should not concurrently use products that contain DEET (N,N-diethyl-m-toluamide), a common component of insect repellent products. Animal toxicology studies showed increased DEET toxicity when DEET was included as part of the formulation.

Although there was no clinical evidence in the vehicle-controlled studies of drug interactions with systemic antiretroviral agents, including protease inhibitors, macrolide antibiotics, and azole antifungals, the effect of Panretin® gel on the steady-state concentrations of these drugs is not known. No drug interaction data are available on concomitant administration of Panretin® gel and systemic anti-KS agents.

Drug/Laboratory Test Interactions No interference with laboratory tests has been observed.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): D

  • Panretin® gel could cause fetal harm if significant absorption were to occur in a pregnant woman. 9-cis-Retinoic acid has been shown to be teratogenic in rabbits and mice. An increased incidence of fused sternebrae and limb and craniofacial defects occurred in rabbits given oral doses of 0.5 mg/kg/day (about five times the estimated daily human topical dose on a mg/m2 basis, assuming complete systemic absorption of 9-cis-retinoic acid, when Panretin® gel is administered as a 60 g tube over 1 month in a 60 kg human) during the period of organogenesis. Limb and craniofacial defects also occurred in mice given a single oral dose of 50 mg/kg on day eleven of gestation (about 127 times the estimated daily human topical dose on a mg/m2 basis). Oral 9-cis-retinoic acid was also embryocidal, as indicated by early resorptions and post-implantation loss when it was given during the period of organogenesis to rabbits at doses of 1.5 mg/kg/day (about 15 times the estimated daily human topical dose on a mg/m2 basis) and to rats at doses of 5 mg/kg/day (about 25 times the estimated daily human topical dose on a mg/m2 basis). Animal reproduction studies with topical 9-cis-retinoic acid have not been conducted. It is not known whether topical Panretin® gel can modulate endogenous 9-cis-retinoic acid levels in a pregnant woman nor whether systemic exposure is increased by application to ulcerated lesions or by duration of treatment. There are no adequate and well-controlled studies in pregnant women. If Panretin® gel is used during pregnancy, or if the patient becomes pregnant while taking it, the patient should be apprised of the potential hazard to the fetus. Women of child-bearing potential should be advised to avoid becoming pregnant.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Alitretinoin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Alitretinoin during labor and delivery.

Nursing Mothers

  • It is not known whether alitretinoin or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions from Panretin® gel in nursing infants, mothers should discontinue nursing prior to using the drug.

Pediatric Use

  • Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

  • Inadequate information is available to assess safety and efficacy in patients age 65 years or older.

Gender

There is no FDA guidance on the use of Alitretinoin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Alitretinoin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Alitretinoin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Alitretinoin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Alitretinoin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Alitretinoin in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Alitretinoin in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Alitretinoin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Alitretinoin in the drug label.

Pharmacology

There is limited information regarding Alitretinoin Pharmacology in the drug label.

Mechanism of Action

Structure

File:Alitretinoin01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Alitretinoin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Alitretinoin in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to assess the carcinogenic potential of 9-cis-retinoic acid have not been conducted. 9-cis-Retinoic acid was not mutagenic in vitro (bacterial assays, Chinese hamster ovary cell HGPRT mutation assay) and was not clastogenic in vitro (chromosome aberration test in human lymphocytes) nor in vivo (mouse micronucleus test).

Clinical Studies

There is limited information regarding Clinical Studies of Alitretinoin in the drug label.

How Supplied

Storage

There is limited information regarding Alitretinoin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Alitretinoin in the drug label.

Precautions with Alcohol

  • Alcohol-Alitretinoin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Ruzicka T, Lynde CW, Jemec GB, Diepgen T, Berth-Jones J, Coenraads PJ; et al. (2008). "Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial". Br J Dermatol. 158 (4): 808–17. doi:10.1111/j.1365-2133.2008.08487.x. PMID 18294310.
  2. ↑ Bissonnette R, Worm M, Gerlach B, Guenther L, Cambazard F, Ruzicka T; et al. (2010). "Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema". Br J Dermatol. 162 (2): 420–6. doi:10.1111/j.1365-2133.2009.09572.x. PMID 19906075.
  3. ↑ Empty citation (help)
  4. ↑ "http://www.ismp.org". External link in |title= (help)

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