Panretin

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.

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.

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.

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.

Panretin^® gel 0.1% contains alitretinoin and is intended for topical application only. The chemical name is 9-

Chemically, alitretinoin is related to vitamin A. It is a yellow powder with a molecular weight of 300.44 and a molecular formula of C₂₀H₂₈O₂. It is slightly soluble in ethanol (7.01 mg/g at 25^oC) and insoluble in water. Panretin^® gel is a clear, yellow gel containing 0.1% (w/w) alitretinoin in a base of dehydrated alcohol USP, polyethylene glycol 400 NF, hydroxypropyl cellulose NF, and butylated hydroxytoluene NF.