PRAVACHOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRAVACHOL (PRAVACHOL).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased hepatic LDL receptor expression and reduced plasma LDL cholesterol.
| Metabolism | Metabolized by the liver, primarily via sulfation; minor renal excretion; not significantly metabolized by CYP3A4. |
| Excretion | Approximately 70% of an oral dose is excreted in feces, primarily as metabolites, with about 20% recovered in urine. Biliary excretion is a major route for parent drug and metabolites. |
| Half-life | The terminal elimination half-life of pravastatin is approximately 1.8 hours, but clinical LDL-cholesterol lowering effects persist beyond this due to sustained HMG-CoA reductase inhibition. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution is about 0.5 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is 17% due to extensive first-pass hepatic extraction. Food decreases the rate but not the extent of absorption. |
| Onset of Action | Significant reduction in total cholesterol and LDL-cholesterol is observed within 1 week of oral administration, with maximal effect seen after 4 weeks. |
| Duration of Action | The lipid-lowering effect persists for the duration of therapy; upon discontinuation, cholesterol levels return to baseline within several weeks. |
10-80 mg orally once daily, with or without food, typically in the evening.
| Dosage form | TABLET |
| Renal impairment | For CrCl <30 mL/min: initial dose 10 mg orally once daily, maximum 20 mg orally once daily. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. Use with caution in Child-Pugh class A; avoid in Child-Pugh class B or C. |
| Pediatric use | For heterozygous familial hypercholesterolemia: 8-13 years: 20 mg orally once daily; 14-18 years: 40 mg orally once daily. Maximum 40 mg/day. |
| Geriatric use | Start at lower end of dosing range (10-20 mg orally once daily) due to increased risk of myopathy and drug accumulation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRAVACHOL (PRAVACHOL).
| Breastfeeding | Pravastatin is excreted into human milk in low amounts; M/P ratio not well characterized. Due to potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated. |
| Teratogenic Risk | Pravastatin is contraindicated in pregnancy. First trimester: Limited human data suggest no significant increase in major malformations, but animal studies show fetal toxicity. Second and third trimesters: Cholesterol is essential for fetal development; HMG-CoA reductase inhibition may cause fetal harm. Postmarketing reports include congenital anomalies, skeletal abnormalities, and low birth weight. |
■ FDA Black Box Warning
Not FDA approved for use in children younger than 8 years; Safety and effectiveness not established.
| Serious Effects |
["Active liver disease or unexplained persistent elevations of liver enzymes","Hypersensitivity to pravastatin or any component","Pregnancy and breastfeeding"]
| Precautions | ["Risk of myopathy/rhabdomyolysis, especially with concurrent use of cyclosporine, gemfibrozil, or niacin","Hepatic enzyme elevations; monitor liver function tests","Increased risk of diabetes mellitus","Caution in patients with predisposing factors for renal failure or hypothyroidism"] |
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| Fetal Monitoring | Monitor hepatic function (ALT, AST) at baseline and periodically. Assess lipid profile. In pregnancy, if inadvertent exposure occurs, monitor fetal growth and development via ultrasound. |
| Fertility Effects | No specific effects on fertility reported in human studies. Animal studies show no impairment of fertility at clinically relevant doses. |