Alitretinoin

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Alitretinoin is a prescription gel medication used topically (on the skin) to treat lesions resulting from Kaposi Sarcoma (KS). KS is a cancer of the cells lining the blood vessels which is commonly seen in patients with HIV/AIDS. Alitretinoin is a first generation member of the retinoid family, which also includes retinol, retinal, tretinoin (retinoic acid or Retin-A), and isotretinoin. The retinoids are related to Vitamin A.

Cutaneous brown Kaposi's sarcoma lesions located over the medial left ankle and foot. Source: CDC

Contents

Other Names

Uses

Alitretinoin gel is used to treat skin lesions in patients with AIDS-related Kaposi's sarcoma (KS). The gel is applied directly to the skin lesions, and is not used when treatment with internal (oral) anti-KS treatment is required (more than 10 new lesions in the past month, symptomatic KS in the lungs, or internal KS with symptoms). Use of the gel does not prevent new KS lesions from appearing.

How Alitretinoin Is Taken

Alitretinoin is manufactured as a 0.1% gel. It is initially applied to KS lesions twice a day. The dosage can be increased to three or four times a day as tolerated. If side effects occur, the frequency of application should be decreased.

The gel should be applied liberally and allowed to dry for several minutes. The skin around the KS lesions should be avoided.

Response to treatment has been seen in as few as two weeks in some patients, however, longer treatment periods may be required.

How it Works

Alitretinoin is a retinoid, a class of drugs related to vitamin A. Retinoids play a role in regulating normal cell growth and cell death. Alitretinoin binds to retinoid receptors inside the cell and activates the receptors. The receptors then are able to regulate the expression of genes that control cell differentiation and growth in both normal and abnormal cells. In this way, alitretinoin is able to inhibit the growth of Kaposi sarcoma cells. [1]

Benefits

A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients in 1999 and showed 35% of patients treated with alitretinoin 0.1% gel had a positive response, compared 18% of patients treated with vehicle gel (placebo). The alitretinoin gel was well tolerated and side effects were mainly reversible with reduced frequency of application or discontinuation of the drug. [2]

Side Effects

Side effects with the use of alitretinoin occur mainly at the site where it is applied. If side effects occur, they are usually mild to moderate, although severe adverse reactions occur in 10% of patients using the gel. Side effects may be lowered with a decrease in the frequency of application.

Possible side effects can include:

  • Rash (e.g., scaling, irritation, redness)
  • Pain (e.g., burning)
  • Itching
  • Flaking, peeling of the skin
  • Cracking, scabbing, crusting, drainage or oozing
  • Stinging, tingling
  • Swelling, inflammation

Risks

Interactions

When being treated with Panretin gel, patients should not use products that contain N,N-Diethyl-meta-toluamide (DEET), a common ingredient of insect repellents, because Panretin gel increases the toxicity of DEET.

Precautions

  • Anyone who has have ever had an allergic reaction to medicines containing retinoids should not use Panretin gel.
  • Anyone who becomes pregnant while taking Panretin gel should contact their health care provider immediately. Panretin gel can cause harm to an unborn child. Women of child-bearing age should avoid becoming pregnant while using Panretin gel. The gel should not be used when breastfeeding.
  • Alitretinoin should not be used near openings of the body (e.g., the eyes, nostrils, mouth, or lips).
  • Retinoids increase in the skin's sensitivity to sunlight. Sun and tanning beds should be avoided while using the drug.

History

Alitretinoin gel is marketed in the United States by Ligand Pharmaceuticals under the brand name Panretin . It received FDA approval on February 2nd, 1999.

Alternatives

  • The antiviral drug docosanol may be an effective treatment for Kaposi's sarcoma lesions in HIV type 1-infected patients. [3]
  • Imiquimod 5% cream appears to be an effective topical treatment for KS lesions, but only in HIV negative patients. [4]

Research

  • Recent studies have examined the efficacy of oral alitretinoin in the treatment of severe chronic hand dermatitis. [5]. [6] [7] [8]
  • Although it appears to be an effective therapy, oral alitretinoin is still an investigative drug at this time.

Clinical Trials

A list of ongoing Clinical Trials is available at ClinicalTrials.gov: alitretinoin trials

References

  1. U. S. Food and Drug Administration. alitretinoin gel prescribing information
  2. Walmsley S, Northfelt DW, Melosky B, Conant M, Friedman-Kien AE, Wagner B. Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group. J Aquir Immune Defic Syndr. 1999 Nov 1;22(3):235-46. Abstract
  3. Scolaro MJ, Gunnill LB, Pope LE, Khalil MH, Katz DH, Berg JE. The antiviral drug docosanol as a treatment for Kaposi's sarcoma lesions in HIV type 1-infected patients: a pilot clinical study. ADIS Res Hum Retroviruses. 2001 Jan 1;17(1):35-43. Abstract
  4. Célestin Schartz NE, Chevret S, Paz C, et al. Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A phase I to II, open-label trial in 17 patients. J Am Acad Dermatol. 2008 Apr;58(4):585-91. Epub 2008 Feb 20. Abstract
  5. ClinicalTrials.gov. Efficacy and Safety of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
  6. ClinicalTrials.gov. Safety and Efficacy of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
  7. ClinicalTrials.gov. Follow-up Efficacy and Safety of Alitretinoin in Severe Chronic Hand Dermatitis
  8. Ruzicka T, Larsen FG, Galewicz D, et al. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004 Dec;140(12):1453-9. Abstract

External Links

MedlinePlus Drug Information: Alitretinoin

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