PRAVASTATIN SODIUM
Clinical safety rating: avoid
Contraindicated (not allowed)
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Lowers LDL cholesterol, triglycerides, and increases HDL cholesterol by upregulating hepatic LDL receptor expression.
| Metabolism | Partially metabolized by CYP3A4 (minor pathway); primarily undergoes hepatic metabolism via glucuronidation and sulfation. Active metabolite: 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor (minor activity). |
| Excretion | Primarily biliary (60% as unchanged drug and metabolites), with approximately 20% renal excretion; fecal elimination accounts for about 70% of total clearance. |
| Half-life | Terminal elimination half-life is 1.3-2.6 hours; despite short half-life, HMG-CoA reductase inhibition persists longer due to effective hepatic extraction and enterohepatic recirculation. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.46-0.5 L/kg, indicating distribution primarily into extracellular fluid and tissues. |
| Bioavailability | Oral bioavailability is 18% (range 14-21%) due to extensive first-pass hepatic extraction. |
| Onset of Action | Oral: reduction in LDL-C seen within 1-2 weeks; maximal effect at 4 weeks. |
| Duration of Action | Duration of lipid-lowering effect persists for 24 hours with once-daily dosing; clinical trials show sustained LDL-C reduction over long-term administration. |
10-40 mg orally once daily; initiate at 10-20 mg and titrate based on response.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: initial dose 10 mg once daily, maximum 20 mg once daily. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations; Child-Pugh class A: no adjustment; Child-Pugh class B or C: use with caution, no specific dose guidelines. |
| Pediatric use | Children 8-13 years: 10-20 mg orally once daily; adolescents 14-18 years: 10-40 mg orally once daily; for heterozygous familial hypercholesterolemia. |
| Geriatric use | Elderly patients: initiate at lower end of dosing range (10 mg once daily) due to increased risk of myopathy; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Not significantly metabolized by CYP450 enzymes fewer interactions Can cause myopathy and rhabdomyolysis.
| Breastfeeding | Pravastatin is excreted in human milk at low levels; M/P ratio is approximately 0.4-0.5 based on limited data. Due to potential for adverse effects in nursing infants (e.g., interference with lipid metabolism), breastfeeding is not recommended during treatment. Alternative therapies with established safety in lactation should be considered. |
| Teratogenic Risk | Pravastatin is contraindicated in pregnancy due to potential fetal harm. HMG-CoA reductase inhibitors decrease synthesis of cholesterol and possibly other mevalonate derivatives essential for fetal development. First trimester exposure may be associated with congenital anomalies including CNS and limb defects. Second and third trimester exposure may cause fetal toxicity including skeletal abnormalities, growth restriction, and organ malformation. The drug should be discontinued immediately upon pregnancy recognition. |
■ FDA Black Box Warning
No FDA black box warning for pravastatin.
| Common Effects | Headache |
| Serious Effects |
["Active liver disease or unexplained persistent elevations of serum transaminases","Hypersensitivity to pravastatin or any component of the formulation","Pregnancy","Lactation"]
| Precautions | ["Risk of myopathy/rhabdomyolysis; increased with concurrent use of cyclosporine, fibrates, macrolide antibiotics, azole antifungals, or niacin","Hepatic enzyme elevations; monitor liver function tests","Contraindicated in active liver disease or unexplained persistent transaminase elevations","Use with caution in patients with severe renal impairment (CrCl <30 mL/min)","Avoid during pregnancy and breastfeeding; pregnancy category X"] |
Loading safety data…
| Fetal Monitoring | Monitor liver function tests (ALT, AST) at baseline and periodically during therapy due to risk of hepatotoxicity. Assess renal function (serum creatinine, BUN) in patients with risk factors. Obtain lipid profiles before initiation, at 4-6 weeks after starting therapy, and then periodically. In pregnant women with accidental exposure, perform fetal anatomic ultrasound if exposure occurred during first trimester. |
| Fertility Effects | No significant adverse effects on fertility have been reported in animal studies. However, by reducing cholesterol levels, statins may theoretically impact steroid hormone synthesis. In premenopausal women with hypercholesterolemia, no consistent evidence of impaired fertility has been observed in clinical studies. |