Zocor (Simvastatin) Contraindications and Precautions
- breast-feeding
- cholestasis
- hepatic disease
- hepatic encephalopathy
- hepatitis
- jaundice
- pregnancy
- rhabdomyolysis
- alcoholism
- children
- elderly
- electrolyte imbalance
- endocrine disease
- females
- hypotension
- infection
- myopathy
- organ transplant
- renal disease
- renal failure
- renal impairment
- seizure disorder
- surgery
- trauma
Zocor (Simvastatin) Contraindications and Precautions
Simvastatin is absolutely contraindicated in patients with active hepatic disease (including cholestasis, hepatic encephalopathy, hepatitis, jaundice) or unexplained persistent elevations in serum aminotransferase concentrations. In addition, patients should minimize alcohol intake while receiving simvastatin therapy, and simvastatin should be avoided in patients with alcoholism. Liver function tests should be performed at the start of simvastatin therapy, and thereafter when clinically indicated. Before titrating to the 80 mg dose, liver function tests (LFTs) should be measured, and then repeated 3 months after dosage titration, and periodically thereafter (e.g., semiannually) for the first year of treatment with the higher dosage.
Simvastatin should be discontinued immediately in any patient who develops myopathy, elevations in CPK, or signs of rhabdomyolysis. Simvastatin should be used with caution in organ transplant patients receiving immunosuppressant therapy such as cyclosporine because of an increased risk of rhabdomyolysis and renal failure (see Drug Interactions). The risk of developing myopathy is increased when HMG-CoA reductase inhibitors are used in combination with CYP3A4 inhibitors or drugs which have an independent risk of myopathy (see Drug Interactions). The manufacturer suggests a lower maximum dosage of simvastatin when used with some drugs (e.g., amiodarone, cyclosporine, gemfibrozil, verapamil) known to increase the risk of myopathy (see Dosage). Simvastatin may be contraindicated in conditions that can cause decreased renal perfusion since renal failure is possible if simvastatin-induced rhabdomyolysis occurs. Predisposing conditions include renal disease or renal insufficiency, hypotension, acute infection, endocrine disease, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Although pharmacokinetic data are lacking for simvastatin in patients with renal failure or renal impairment, data for a related HMG-CoA reductase inhibitor (lovastatin) suggest the need for cautious dosage escalation in such patients (see Dosage). In patients with severe renal impairment (CrCl 10 - 30 ml/min), the plasma concentrations of total inhibitors after a single dose of lovastatin are approximately two-fold higher than those in healthy volunteers.
Some elderly patients may be more sensitive to the effects of the usual adult dosage of simvastatin; dosage should be individualized to achieve serum lipoprotein goals. A pharmacokinetic study with simvastatin showed the mean plasma level of HMG-CoA reductase inhibitory activity to be approximately 45% higher in patients aged 70 - 78 compared with patients aged 18 - 30 years. However, long-term therapy with 20 - 80 mg/day PO has been used safely in elderly patients in clinical trials, with no differences in safety compared to younger patients. In the 4S trial and the Heart Protection Study, 23% and 52% of the patients, respectively, were elderly. The were no differences in the cardiovascular or stroke protection benefits of simvastatin between older and younger patients in these clinical outcome trials.
Simvastatin is classified as FDA pregnancy category X and is contraindicated for use during pregnancy, because of the potential effects of HMG-CoA reductase inhibitors on cholesterol pathways. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Treatment should be immediately discontinued as soon as pregnancy is recognized. In a prospective review of about 100 pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidence of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. However, atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Simvastatin should only be administered to females of child-bearing potential, including female adolescents at least 1 year post-menarche, when such patients are highly unlikely to conceive and have been informed of the potential hazards. Females should be counseled regarding appropriate methods of contraception while on therapy.
Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. Because of the ability of HMG-CoA reductase inhibitors to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, simvastatin is contraindicated for use during breast-feeding.
Simvastatin is FDA-approved for use in high risk hypercholesterolemic adolescents and children aged >= 10 years. Simvastatin is not recommended for children < 10 years. Simvastatin may be used as an adjunct to diet in adolescents and children >= 10 years (including girls at least 1 year post-menarche) when either: 1) the LDL remains >= 190 mg/dl, or 2) the LDL remains >= 160 mg/dl and there is an increased risk for cardiovascular disease (e.g., positive family history of premature cardiovascular disease or >= 2 other risk factors are present). The long-term efficacy of statin therapy in childhood to reduce morbidity and mortality later in adulthood has not been established. In one small study, 16 children < 17 years old received a mean simvastatin dose of 16 mg daily for 2 years. LDL-cholesterol was decreased by 37% and HDL-cholesterol increased by 22.5%. No adverse effects or effects on growth were reported. Adolescent females should be counseled regarding appropriate methods of contraception while on therapy.
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