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. |
| Molecular Weight | 404.54 |
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 | Contraindicated due to risk of fetal developmental abnormalities (cholesterol synthesis essential for fetal development). |
| 2nd trimester | Contraindicated; can cause fetal harm as cholesterol and other mevalonate derivatives are critical for fetal development. |
| 3rd trimester | Contraindicated; may cause neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for MEVACOR (MEVACOR).
| Placental transfer | Crosses placenta in animal studies; human data limited but presumed to cross due to low molecular weight. |
| Breastfeeding | Excreted into human milk in small amounts; potential for serious adverse effects in nursing infants; manufacturer advises to discontinue nursing or discontinue drug. |
| Lactation Rating |
■ 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 diseaseUnexplained persistent elevations of serum transaminasesPregnancyLactationHypersensitivity to any component
| 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 |
| Food/Dietary | Grapefruit juice inhibits CYP3A4 and increases lovastatin levels, increasing risk of myopathy/rhabdomyolysis; avoid concurrent intake. High-fat meals enhance absorption; take with evening meal to optimize efficacy. |
Loading safety data…
| L5 (Contraindicated) |
| 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 | 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. |
| Clinical Pearls | MEVACOR (lovastatin) is a prodrug that requires CYP3A4 metabolism; avoid coadministration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, erythromycin, clarithromycin, protease inhibitors, nefazodone, grapefruit juice). Titrate dose based on LDL-C response; start at 20 mg daily with evening meal. Monitor liver function tests at initiation and as clinically indicated; contraindicated in active liver disease or unexplained transaminase elevations. Increased risk of myopathy/rhabdomyolysis with concurrent fibrates (especially gemfibrozil), niacin (>1 g/day), and CYP3A4 inhibitors. Use cautiously in patients with renal impairment. |
| Patient Advice | Take this medication with the evening meal to enhance absorption and reduce side effects. · Avoid consuming grapefruit or grapefruit juice while taking this drug, as it can increase the risk of side effects. · Report unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise. · Do not take over-the-counter niacin or other cholesterol-lowering medications without consulting your healthcare provider. · Inform your doctor about all other medications, including herbal supplements and over-the-counter drugs. · Adhere to a heart-healthy diet and exercise regimen as prescribed by your healthcare provider. · Adverse effects may include headache, abdominal pain, and nausea; contact your doctor if severe or persistent. |