Panretin (final drug product)

Hazard statements (CLP)

H360D, H372

Code

Statements

H360D

May damage the unborn child

SECTION 2: Hazards identification

2.1 Classification of the substance or mixture

Regulation (EC) 1272/ Specific Target Organ Toxicity (repeated exposure) - Category 1. Reproductive 2008 [GHS] Toxicity - Category 1B. Directive 67/548/EEC T - R48/24/25; R61 (Repr. Cat. 2) or 1999/45/EC SECTION 2 - HAZARDS IDENTIFICATION …continued

Signal word

Danger None required US Hazard overview Active pharmaceutical ingredient. Can cause damage to the liver, kidney, bone and hematopoietic systems based on human and animal data. Possbile developmental hazard - may cause adverse developmental effects (based on animal data). Possible birth defect hazard - may cause birth defects (based on animal data). SECTION 2 - HAZARDS IDENTIFICATION …continued Note This substance is classified as hazardous according to Directive 67/548/EEC,

CLP CLASSIFICATION

H372 - Causes damage to skin, liver, kidney, bone and hematopoietic systems

Hazard statements

through prolonged or repeated exposure. H360D - May damage the unborn child. CLP/GHS P201 - Obtain special instructions before use. P202 - Do not handle until all safety

Precautionary statements

precautions have been read and understood. P260 - Do not breathe dust. P264 Wash hands thoroughly after handling. P270 - Do not eat, drink or smoke when using this product. P281 - Use personal protective equipment as required. P308 + P313 - If exposed or concerned: get medical advice/attention. P405 - Store locked up. P501 - Dispose of contents/container to location in accordance with local/ regional/national/international regulations.

2.3 Other hazards

Alitretinoin, a derivative of Vitamin A, is a naturally occurring endogenous retinoid used topically to treat skin lesions associated with AIDS-related Kaposi's sarcoma. Alitretinoin may also be given orally to treat severe chronic hand eczema that is unresponsive to other therapies, with a dose range of 10-30 mg/day. Retinoids, such as alitretinoin, modulate expression of specific genes that are involved in a number of vital cellular functions associated with development, growth and maintenance of cells. Following oral administration, the most frequent adverse effects were reversible and included headache, flushing, changes in lipid profiles in blood and thyroid hormone levels. Following topical application, the most common adverse effects included rash, pain, itching, dermatitis, tingling sensations, blistering and edema. Exposure to retinoids has been associated with teratogenic effects and an increased incidence of spontaneous abortions. Although no clinical data specific to alitretinoin were identified, it should be considered teratogenic and/or embryolethal when administered systemically based on developmental effects seen in animal studies at low doses, consistent with the mechanism of action of retinoids. Retinoids have been associated with photosensitivity, typically increased susceptibility to sunburn.