MEVACOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEVACOR (MEVACOR).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Reduces hepatic cholesterol synthesis, leading to increased LDL receptor expression and enhanced clearance of LDL from plasma.
| Metabolism | Primarily hepatic via CYP3A4 isoenzyme; significant first-pass metabolism. |
| Excretion | Lovastatin is primarily excreted via the biliary/fecal route (approximately 80-85% of the absorbed dose) as metabolites. Renal excretion accounts for about 10% of the administered dose, mostly as metabolites; less than 5% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of lovastatin is approximately 1-2 hours for the parent drug. However, the active metabolite (lovastatin acid) has a half-life of about 1.7-2.6 hours. Despite the short half-life, the duration of HMG-CoA reductase inhibition is prolonged due to enterohepatic recirculation and tissue distribution. Once-daily dosing is effective for LDL-C reduction. |
| Protein binding | Lovastatin and its active metabolite are extensively bound to plasma proteins, with binding >95% for the parent drug and >92% for lovastatin acid. The primary binding protein is albumin. |
| Volume of Distribution | The apparent volume of distribution (Vd) for lovastatin is approximately 0.3-0.6 L/kg, indicating distribution into tissues, but predominantly into the liver (the primary site of action). High Vd reflects extensive tissue binding. |
| Bioavailability | Oral bioavailability of lovastatin is low, approximately 5% for the parent drug due to extensive first-pass metabolism in the liver. The active metabolite (lovastatin acid) is formed via hydrolytic metabolism. Food increases absorption, so it is recommended to be taken with the evening meal. |
| Onset of Action | With oral administration, a significant reduction in LDL cholesterol is typically observed within 2-4 weeks of starting therapy, with maximal effect seen at 4-6 weeks. |
| Duration of Action | The duration of HMG-CoA reductase inhibition following a single oral dose extends beyond the plasma half-life due to enzyme inhibition and drug accumulation in the liver. Clinically, the lipid-lowering effect persists over the 24-hour dosing interval, allowing once-daily administration. Maximal LDL reduction is sustained with continued therapy. |
10-80 mg orally once daily in the evening.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; if GFR <30 mL/min, start at 5 mg/day and increase cautiously. |
| Liver impairment | Contraindicated in active liver disease or unexplained transaminase elevations; Child-Pugh Class A/B: use with caution, no specific dose adjustment; Child-Pugh Class C: contraindicated. |
| Pediatric use | For heterozygous familial hypercholesterolemia: 10-20 mg orally once daily in the evening for ages 10-17; adjust based on response. |
| Geriatric use | Start at lower end of dosing range (10 mg/day) due to increased risk of myopathy; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEVACOR (MEVACOR).
| Breastfeeding | Contraindicated. Excreted into human milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants, including interference with cholesterol biosynthesis. |
| Teratogenic Risk | Pregnancy Category X. Contraindicated in all trimesters due to risk of fetal skeletal muscle damage, CNS abnormalities, and cardiac defects. Case reports of limb defects, cleft palate, and fetal death. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Fainting Skin rash Angioedema swelling of deeper layers of skin |
| Serious Effects |
["Active liver disease","Unexplained persistent elevations of serum transaminases","Hypersensitivity to any component of the product","Pregnancy","Lactation"]
| Precautions | ["Myopathy/rhabdomyolysis risk increased with high doses or concomitant use of CYP3A4 inhibitors","Hepatic enzyme elevations; monitor liver function tests","Avoid use in patients with active liver disease or unexplained persistent transaminase elevations","Use caution in patients with predisposing factors for renal failure"] |
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| Monitor hepatic function (ALT, AST), creatine kinase (CK) if muscle symptoms; fetal ultrasound for growth and anomalies if inadvertent exposure occurs. |
| Fertility Effects | No direct clinical data; animal studies show no impairment of fertility. Theoretical concern due to cholesterol synthesis inhibition on steroid hormone production. |