1 Name of Medicine
Pravastatin sodium.
2 Qualitative and Quantitative Composition
Pravastatin-WGR tablets are available in 10 mg, 20 mg, 40 mg and 80 mg.
Excipients of known effect. Sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Pravastatin-WGR is available as yellow capsule shaped biconvex tablets containing 10 mg, 20 mg, 40 mg or 80 mg pravastatin sodium.
The 10 mg tablet (8.8 x 4.4 mm) is engraved ''10'' on one side, the 20 mg tablet (11.0 x 5.5 mm) is engraved ''20'' on one side, the 40 mg tablet (14.0 x 7.0 mm) is engraved ''40'' on one side, the 80 mg tablet (17.6 x 8.8 mm) is engraved ''80'' on one side.
The tablets are supplied in blister packs containing 30 tablets.
4 Clinical Particulars
4.9 Overdose
Symptoms. There has been limited experience with overdosage of pravastatin. To date, there are two reported cases, both of which were asymptomatic and not associated with clinical laboratory test abnormalities. Of these two cases, one occurred in a clinical trial patient who ingested 3 g pravastatin; the other ingested 280 mg pravastatin, as marketed tablets. Both cases also involved overdose of concomitant medications.
Treatment. Should overdose occur, treat symptomatically and institute supportive measures as required.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 16 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. In six genetic toxicology studies performed with pravastatin, there was no evidence of mutagenic potential at the chromosomal or gene level.
Carcinogenicity. In a 2-year oral study of rats, a statistically significant increase in the incidence of hepatocellular carcinomas was observed in male rats given 100 mg/kg daily of pravastatin. This change was not seen in male rats given 40 mg/kg or less, or in female rats at doses up to 100 mg/kg daily. Increased incidences of hepatocellular carcinomas were also observed in male and female mice dosed with pravastatin at 250 and 500 mg/kg daily, but not at 100 mg/kg/day or less. An increased incidence of pulmonary adenomas was seen in female mice dosed at 250 mg/kg/day. The AUC value for the serum concentration of pravastatin at the no effect dose level of 100 mg/kg/day in mice was 2 times higher than that in humans receiving 80 mg pravastatin per day.
The hepatocarcinogenic effect of pravastatin in rats is associated with proliferation of hepatic peroxisomes. Other HMG-CoA reductase inhibitors (simvastatin and lovastatin) also induce hepatic peroxisome proliferation and hepatocellular carcinomas in rats and mice. The clinical significance of these findings is unclear.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure. Pravastatin is one of a new class of lipid-lowering compounds, the HMG-CoA reductase inhibitors, that reduce cholesterol biosynthesis. These agents are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme catalysing the early rate-limiting step in cholesterol biosynthesis, conversion of HMG-CoA to mevalonate.
Pravastatin sodium is an odourless, white to off-white, fine or crystalline powder. It is a relatively polar hydrophilic compound with a partition coefficient (octanol/water) of 0.59 at a pH of 7.0. It is soluble in methanol and water (> 300 mg/mL), slightly soluble in isopropanol, and practically insoluble in acetone, acetonitrile, chloroform, and ether.
Pravastatin sodium is designated chemically as: (3R,5R) -7-[(1S,2S,6S,8S,8aR) -1,2,6,7,8,8a-Hexahydro-6-hydroxy-2-methyl-8-[(S)-2- methylbutyryloxy-1-naphthyl]] -3,5-dihydroxyheptanoic acid, sodium salt, and has the following structure:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSPRASOD.gif CAS number. 81131-70-6.
7 Medicine Schedule (Poisons Standard)
S4 - Prescription only medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/PRAWGRST.gif
