Lovastatin

Therapy with Lovastatin Tablets USP should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease. Lovastatin Tablets USP should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total-C and LDL-C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk. …

• The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin tablets and should continue on this diet during treatment with lovastatin tablets (see NCEP Treatment Guidelines for details on dietary therapy)
• Lovastatin tablets should be given with meals
• Adult Patients The usual recommended starting dose is 20 mg once a day given with the evening meal
• The recommended dosing range of lovastatin is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day
• Doses should be individualized according to the recommended goal of therapy (see NCEP Treatment Guidelines and CLINICAL PHARMACOLOGY )
• Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE ) should be started on 20 mg/day of lovastatin tablets
• A starting dose of 10 mg of lovastatin may be considered for patients requiring smaller reductions
• Adjustments should be made at intervals of 4 weeks or more
• Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin tablets if cholesterol levels fall significantly below the targeted range
• Dosage in Patients Taking Danazol, Diltiazem, Dronedarone or Verapamil In patients taking danazol, diltiazem, dronedarone or verapamil concomitantly with lovastatin, therapy should begin with 10 mg of lovastatin and should not exceed 20 mg/day (see CLINICAL PHARMACOLOGY , Pharmacokinetics , WARNINGS , Myopathy/Rhabdomyolysis , PRECAUTIONS , Drug Interactions , Other Drug Interactions ). …

• Safety and effectiveness in patients 10 to 17 years of age with heFH have been evaluated in controlled clinical trials of 48 weeks duration in adolescent boys and controlled clinical trials of 24 weeks duration in girls who were at least 1 year post-menarche
• Patients treated with lovastatin had an adverse experience profile generally similar to that of patients treated with placebo
• Doses greater than 40 mg have not been studied in this population. …

A pharmacokinetic study with lovastatin showed the mean plasma level of HMG-CoA reductase inhibitory activity to be approximately 45% higher in elderly patients between 70 to 78 years of age compared with patients between 18 to 30 years of age; however, clinical study experience in the elderly indicates that dosage adjustment based on this age-related pharmacokinetic difference is not needed. …

• Patients should be advised about substances they should not take concomitantly with lovastatin and be advised to report promptly unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing lovastatin (see list below and WARNINGS, Myopathy/Rhabdomyolysis)
• Patients should also be advised to inform other physicians prescribing a new medication that they are taking lovastatin
• It is recommended that liver enzymes be checked before starting therapy, and if signs or symptoms of liver injury occur. …

• Hypersensitivity to any component of this medication
• Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS )
• Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and cobicistat-containing products) (see WARNINGS , Myopathy/Rhabdomyolysis ). …

CYP3A4 Interactions Lovastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin (see CONTRAINDICATIONS , WARNINGS , Myopathy/Rhabdomyolysis , and CLINICAL PHARMACOLOGY , Pharmacokinetics ). …

Myopathy/Rhabdomyolysis Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. The risk of myopathy/rhabdomyolysis is dose related. …

Phase III Clinical Studies In Phase III controlled clinical studies involving 613 patients treated with lovastatin, the adverse experience profile was similar to that shown below for the 8,245 patient EXCEL study (see Expanded Clinical Evaluation of Lovastatin [EXCEL] Study ). Persistent increases of serum transaminases have been noted (see WARNINGS, Liver Dysfunction ). About 11% of patients had elevations of CK levels of at least twice the normal value on one or more occasions. The corresponding values for the control agent cholestyramine were 9 percent. This was attributable to the noncardiac fraction of CK. …

Pregnancy Teratogenic Effects Pregnancy Category X See CONTRAINDICATIONS . Safety in pregnant women has not been established. Lovastatin has been shown to produce skeletal malformations in offspring of pregnant mice and rats dosed during gestation at 80 mg/kg/day (affected mouse fetuses/total: 8/307 compared to 4/289 in the control group; affected rat fetuses/total: 6/324 compared to 2/308 in the control group). …

After oral administration of lovastatin to mice, the median lethal dose observed was > 15 g/m 2 . Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences. A few cases of accidental overdosage have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5 to 6 g. Until further experience is obtained, no specific treatment of overdosage with lovastatin can be recommended. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.