Norvir Tablets

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies in mice and rats have been carried out on ritonavir. In male mice, at levels of 50, 100 or 200 mg per kg per day, there was a dose dependent increase in the incidence of both adenomas and combined adenomas and carcinomas in the liver. Based on AUC measurements, the exposure at the high dose was approximately 0.3-fold for males that of the exposure in humans with the recommended therapeutic dose (600 mg twice-daily). There were no carcinogenic effects seen in females at the dosages tested. The exposure at the high dose was approximately 0.6-fold for the females that of the exposure in humans. In rats dosed at levels of 7, 15 or 30 mg per kg per day there were no carcinogenic effects. In this study, the exposure at the high dose was approximately 6% that of the exposure in humans with the recommended therapeutic dose. Based on the exposures achieved in the animal studies, the significance of the observed effects is not known.

Mutagenesis

However, ritonavir was found to be negative for mutagenic or clastogenic activity in a battery of in in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli, the mouse lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human lymphocytes.

Impairment of Fertility

Ritonavir produced no effects on fertility in rats at drug exposures approximately 40% (male) and 60% (female) of that achieved with the proposed therapeutic dose. Higher dosages were not feasible due to hepatic toxicity.

Norvir Tablets, 100 mg Ritonavir

NORVIR (ritonavir) tablets are white film-coated ovaloid tablets debossed with the "a" logo and the code NK.

Bottles of 30 tablets each (NDC 0074-3333-30).

Recommended Storage

Store at or below 30°C (86°F). Exposure to temperatures up to 50°C (122°F) for seven days permitted. Dispense in original container or USP equivalent tight container (60 mL or less). For patient use: exposure of this product to high humidity outside the original or USP equivalent tight container (60 mL or less) for longer than 2 weeks is not recommended.

NORVIR Oral Solution, 80 mg per mL Ritonavir

NORVIR (ritonavir) oral solution is an orange-colored liquid, supplied in amber-colored, multi-dose bottles containing 600 mg ritonavir per 7.5 mL marked dosage cup (80 mg per mL).

240 mL bottles (NDC 0074-1940-63).

Recommended Storage

Store at room temperature 20°-25°C (68°-77°F). Do not refrigerate. Shake well before each use. Use by product expiration date.

Product should be stored and dispensed in the original container.

Avoid exposure to excessive heat. Keep cap tightly closed.

NORVIR Oral Powder, 100 mg Packet

NORVIR (ritonavir) oral powder is beige/pale yellow to yellow, supplied in packets containing 100 mg of ritonavir.

30 foil/laminate, child-resistant packets per carton (NDC 0074-3399-30).

Recommended Storage

Store at or below 30°C (86°F).

Commonly reported side effects of ritonavir include: asthenia, diarrhea, hypertriglyceridemia, increased gamma-glutamyl transferase, nausea, vomiting, and unpleasant taste. Other side effects include: abdominal pain, dyspepsia, fever, hyperlipidemia, increased serum alanine aminotransferase, peripheral paresthesia, dysgeusia, and oral paresthesia. See below for a comprehensive list of adverse effects.