Panretin

Posology Panretin therapy should only be initiated and maintained by specialist physicians experienced in the treatment of patients with KS. Men Patients should apply Panretin to cutaneous KS lesions using sufficient gel so as to cover each lesion with a generous coating.

Frequency of application Patients should initially apply Panretin twice a day to cutaneous KS lesions. The application frequency can be increased stepwise to three or four times a day according to individual lesion tolerance, allowing no less than two weeks between dose increases.

The frequency of application should be adjusted for each lesion independently. If application site toxicity occurs, the application frequency can be reduced as described below. There are no data on the efficacy of Panretin applied less frequently than twice daily.

Local dermal irritation may be graded according to the five-point scale shown in Table 1. Medicinal product no longer authorised 3 Table 1 Grading of local dermal irritation GRADE DEFINING CLINICAL SIGNS 0 = No reaction None 1 = Mild Definite pink to red coloration 2 = Moderate Increased redness, possible oedema 3 = Severe Very red, with oedema, with or without vesiculation 4 = Very severe Deep red, swelling and oedema with or without signs of bullae formation and necrosis Table 2 Adjustment guidelines for treatment-limiting toxicity LOCAL DERMAL IRRITATION (Graded per Table 1) TREATMENT ADJUSTMENTS Grade 0, 1 or 2 No action required except continued monitoring.

Grade 3 Treatment frequency for that lesion should be reduced or suspended. When dermal irritation improves to Grade 0 or 1, treatment may be restarted at twice daily, increasing every two weeks as tolerated. Grade 4 As for Grade 3 irritation.

However, treatment should not be restarted if Grade 4 toxicity occurred at an application frequency of less than twice a day. Duration of application It is recommended that Panretin should be applied to lesions for an initial period of up to 12 weeks.

Treatment of lesions that have not shown a decrease in area and/or height by week 12 should be discontinued. For those lesions that have shown a decrease in height and/or area by week 12, applications may be continued providing that there is continued improvement or at least maintenance of the response and that the product continues to be tolerated.

Adverse events associated with the use of Panretin gel in AIDS-related KS occurred almost exclusively at the site of application. The dermal toxicity typically begins as erythema; with continued application of Panretin gel erythema may increase and oedema may develop.

Dermal toxicity may become treatment-limiting, with intense erythema, oedema, and vesiculation. 1% of patients experienced adverse drug reactions at the application site. Table 3 shows the following application-site drug-related adverse reactions were reported during clinical studies in patients with KS.

The frequency of adverse events are classified as very common (≥1/10), common (≥1/100 to <1/10), and uncommon (≥1/1,000 to <1/100). Medicinal product no longer authorised 6 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

1%. The incidence of drug-related skin disorder, skin ulcer, pain and rash appeared to be greater in patients applying Panretin gel four times daily than in those applying it less frequently. However, the incidence of other equally common drug-related adverse events such as pruritus, oedema, exfoliative dermatitis and dry skin did not appear to increase as a function of the frequency of application.

The incidence of mild/moderate rash (all events regardless of causality) was less in patients treated for less than 16 weeks than in those treated for 16 weeks or more (mild, 33% v 63%; moderate, 29% v 43%). The incidence of severe skin rash was independent of the duration of treatment (10% in both cases).

2). Only two serious adverse reactions were reported (sepsis and cellulitis in the same patient). The adverse events seen with Panretin gel are similar to those seen with other topical retinoids. It is unlikely that the undesirable systemic side effects associated with oral retinoids will be observed with the use of Panretin gel because the range and frequency of quantifiable 9-cis-retinoic acid plasma levels concentrations after application of the medicinal product were comparable to the range and frequency of quantifiable plasma concentrations of circulating, naturally occurring 9-cis-retinoic acid in untreated individuals.

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. However, patients must be cautioned to minimise exposure of treated areas to sunlight or other ultraviolet (UV) light.

3). It is recommended that daily dietary intake of vitamin A should not exceed the Recommended Dietary Intake value. Alitretinoin may cause harm to the foetus. 6) and until one month after cessation of treatment.

1. 6).  Women planning a pregnancy.  Treatment of KS lesions in close proximity to other skin disorders.