PANRETIN

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE 1.1 Kaposi’s Sarcoma PANRETIN GEL is indicated for topical treatment of cutaneous lesions in adults with AIDS related Kaposi’s sarcoma (KS). Limitations of Use: PANRETIN GEL is not indicated when systemic anti-KS therapy is required (including more than 10 new KS lesions in the prior month, symptomatic lymphedema, symptomatic pulmonary KS, or symptomatic visceral involvement) [see Clinical Studies ( 14.1 )] . PANRETIN GEL is a retinoid indicated for the topical treatment of cutaneous lesions in adults with AIDS-related Kaposi’s sarcoma (KS). Limitations of Use : PANRETIN GEL is not indicated when systemic anti-Kaposi’s sarcoma therapy is required. Dosage and administration 2 DOSAGE AND ADMINISTRATION PANRETIN GEL is for topical use only. Do not use occlusive dressings with PANRETIN GEL. Apply PANRETIN GEL twice daily to coat the entire cutaneous Kaposi sarcoma lesions. Gradually increase the application frequency up to four (4) times a day as tolerated. Continue PANRETIN GEL as long as patient is deriving benefit. Reduce application frequency for application site toxicity. Interrupt treatment for severe irritation; may resume at a reduced application frequency once symptoms improve. Avoid application of gel to normal skin and do not apply on or near mucosal surfaces. Wash hands after application unless gel is applied to Kaposi sarcoma lesions on the hands. Allow gel to dry for three to five minutes before covering with clothing. • Apply to the affected lesions twice daily; increase to 4 times daily as tolerated. ( 2 ) • For topical use only. ( 2 ) Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Embryo-Fetal Toxicity : Can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception. ( 5.1 . 8.1 , 8.3 ) • Photosensitivity : Minimize exposure to sunlight and sunlamps. ( 5.2 ) • DEET toxicity : Do not use DEET-containing products ( 5.3 ) 5.1 Embryo-Fetal Toxicity Based on data from animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo-lethal at exposures 5 times the estimated daily human topical dose. Advise women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with PANRETIN GEL and for 1 week after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] . 5.2 Photosensitivity Retinoids as a class have been associated with photosensitivity. Advise patients to minimize exposure of treated areas to sunlight and sunlamps during the use of PANRETIN GEL. 5.3 Toxicity with DEET-Containing Products Animal toxicology studies showed increased DEET toxicity when DEET was included as part of the formulation. Advise patients to not use PANRETIN GEL concurrently with products that contain DEET (N,N-diethyl-m-toluamide), a common component of insect repellent products. Pregnancy 8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo lethal at exposures at least 5 times the estimated daily human topical dose ( see Data ). There are no data on the use of PANRETIN GEL in pregnant women. Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Oral administration of alitretinoin to pregnant rabbits during the period of organogenesis resulted in early resorptions, post-implantation loss, and fetal defects (limb, craniofacial, fused sternebrae) at doses ≥ 0.5 mg/kg/day (approximately 5 times the estimated daily human topical dose based on body surface area, assuming complete systemic absorption of alitretinoin, when PANRETIN GEL is administered as a 60 g tube over 1 month in a 60 kg human). Early resorptions and post-implantation loss also occurred in rats administered oral alitretinoin at doses ≥5 mg/kg/day (approximately 25 times the estimated daily human topical dose based on body surface area). Limb and craniofacial defects also occurred in mice administered oral alitretinoin on day 11 of gestation at single doses ≥50 mg/kg (approximately 127 times the estimated daily human topical dose based on body surface area).