ZOCOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOCOR (ZOCOR).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Increases hepatic LDL receptor expression, enhancing clearance of LDL from plasma.
| Metabolism | Extensively metabolized via CYP3A4; active metabolite (beta-hydroxyacid). Also undergoes glucuronidation and oxidation. |
| Excretion | Approximately 13% renal, 60% biliary/fecal as metabolites; parent drug and active metabolites. |
| Half-life | Terminal elimination half-life of simvastatin is approximately 2 hours for the parent drug, but for the active metabolite (simvastatin acid), it is about 1.9 hours. Clinical context: Due to extensive first-pass metabolism, the effective half-life for HMG-CoA reductase inhibition is longer (approximately 4-6 hours), supporting once-daily dosing in the evening. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Mean volume of distribution is about 0.9 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral bioavailability of simvastatin is less than 5% due to extensive first-pass metabolism; however, the active metabolite (simvastatin acid) has an oral bioavailability of approximately 5%. |
| Onset of Action | Oral: Reductions in LDL cholesterol are detectable within 2 weeks, with maximal effect observed after 4-6 weeks of continuous therapy. |
| Duration of Action | LDL cholesterol reduction persists for the duration of daily dosing. After discontinuation, lipid levels return to baseline within several weeks. Clinical notes: Once-daily dosing is sufficient due to prolonged suppression of hepatic cholesterol synthesis. |
| Action Class | HMG CoA inhibitors (statins) |
| Brand Substitutes | StayHappi Simvastatin 20mg Tablet, Simastin 20mg Tablet, Simvastol 20mg Tablet, Simlip 20mg Tablet, Simlup 20mg Tablet, Starstat 40mg Tablet, Zosta 40mg Tablet, Simvotin 40 Tablet, Simvatic 40 Tablet, Sim 10mg Tablet, Biosim 10mg Tablet, Stn 10mg Tablet, Simvas 10mg Tablet, Satin 10mg Tablet, Colors Syrup, Eclor 125mg Premix Syrup, Mytex 125mg Syrup, Sporicef 125mg Syrup, Acticlor 125mg Syrup |
5-40 mg orally once daily in the evening; initial dose 10-20 mg, maximum 40 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: contraindicated; CrCl 30-80 mL/min: no adjustment required but use cautiously. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. Child-Pugh class A: no adjustment; Child-Pugh class B or C: contraindicated. |
| Pediatric use | Heterozygous familial hypercholesterolemia (age 10-17): 10-40 mg orally once daily in the evening; start at 10 mg, adjust at 4-week intervals. |
| Geriatric use | Initiate at lower end of dosing range (5-10 mg) due to increased risk of myopathy; monitor renal function (CrCl) and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOCOR (ZOCOR).
| Breastfeeding | Contraindicated in breastfeeding. Simvastatin is excreted into human breast milk; M/P ratio not reported. Potential for serious adverse effects in nursing infant, including disruption of lipid metabolism. Use not recommended during breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy. HMG-CoA reductase inhibitors may cause fetal harm when administered to pregnant women. There are reports of congenital anomalies following intrauterine exposure to statins. Risk of skeletal and neurological defects. First trimester exposure may increase risk of spontaneous abortion; second and third trimester exposure may increase risk of fetal abnormalities. Discontinue therapy immediately if pregnancy occurs. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to simvastatin or any component of the formulation","Active liver disease or unexplained persistent elevations of serum transaminases","Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products)","Concomitant use with gemfibrozil, cyclosporine, or danazol","Pregnancy and breastfeeding","Concomitant use of large doses (>1 g/day) of niacin in Chinese patients"]
| Precautions | ["Risk of myopathy/rhabdomyolysis, especially with concurrent use of CYP3A4 inhibitors (e.g., cyclosporine, gemfibrozil, azole antifungals, macrolide antibiotics, protease inhibitors, grapefruit juice)","Hepatic enzyme elevations; monitor liver function before and during therapy","Avoid use in patients with active liver disease or unexplained persistent transaminase elevations","Use caution in patients with predisposing factors for myopathy (e.g., renal impairment, hypothyroidism, age >65, female sex)"] |
Loading safety data…
| Fetal Monitoring | Not indicated due to contraindication. If inadvertent exposure, monitor fetal development via ultrasound. Perform liver function tests (ALT, AST) and creatine kinase (CK) as clinically indicated. Monitor maternal lipid levels if therapy is resumed postpartum. |
| Fertility Effects | No human data on fertility effects. In animal studies, simvastatin did not impair fertility at clinically relevant doses. However, statins may theoretically affect steroidogenesis and gametogenesis; no clinical evidence of significant impairment. |