24 HR lovastatin 20 MG Extended Release Oral Tablet

INDICATIONS AND USAGE 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. Primary Prevention of Coronary Heart Disease In individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C, and below average HDL-C, Lovastatin Tablets USP are indicated to reduce the risk of: - Myocardial infarction - Unstable angina - Coronary revascularization procedures (See CLINICAL PHARMACOLOGY , Clinical Studies in Adults .) Coronary Heart Disease Lovastatin Tablets USP are indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels. Hypercholesterolemia Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Lovastatin Tablets USP are indicated as an adjunct to diet for the reduction of elevated total-C and LDL-C levels in patients with primary hypercholesterolemia (Types IIa and IIb 2 ), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate. 2 Classification of Hyperlipoproteinemias Lipid Elevations Type Lipoproteins elevated major minor I chylomicrons TG ↑→C IIa LDL C — IIb LDL, VLDL C TG III (rare) IDL C/TG — IV VLDL TG ↑→C V (rare) chylomicrons, VLDL TG ↑→C IDL = intermediate-density lipoprotein. Adolescent Patients With Heterozygous Familial Hypercholesterolemia Lovastatin Tablets USP are indicated as an adjunct to diet to reduce total-C, LDL-C and apolipoprotein B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with heFH if after an adequate trial of diet therapy the following findings are present: 1. LDL-C remains > 189 mg/dL or 2. LDL-C remains > 160 mg/dL and : • there is a positive family history of premature cardiovascular disease or • two or more other CVD risk factors are present in the adolescent patient General Recommendations Prior to initiating therapy with lovastatin, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total-C, HDL-C, and TG. For patients with TG less than 400 mg/dL (< 4.5 mmol/L), LDL-C can be estimated using the following equation: LDL-C = total-C - [0.2 x (TG) + HDL-C] For TG levels > 400 mg/dL (> 4.5 mmol/L), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In hypertriglyceridemic patients, LDL-C may be low or normal despite elevated total-C. In such cases, Lovastatin Tablets USP are not indicated. The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below: NCEP Treatment Guidelines: LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes and Drug Therapy in Different Risk Categories Risk Category LDL Goal (mg/dL) LDL Level at Which to Initiate Therapeutic Lifestyle Changes (mg/dL) LDL Level at Which to Consider Drug Therapy (mg/dL) CHD CHD, coronary heart disease or CHD risk equivalents (10 year risk > 20%) < 100 ≥ 100 ≥ 130 (100 to 129: drug optional) Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of < 100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory. 2+ Risk factors (10 year risk ≤ 20%) < 130 ≥ 130 10 year risk 10 to 20%: ≥ 130 10 year risk < 10%: ≥ 160 0 to 1 Risk factor Almost all people with 0 to 1 risk factor have a 10 year risk < 10%; thus, 10 year risk assessment in people with 0 to 1 risk factor is not necessary. < 160 ≥ 160 ≥ 190 (160 to 189: LDL-lowering drug optional) After the LDL-C goal has been achieved, if the TG is still ≥ 200 mg/dL, non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category. At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge if the LDL-C is ≥ 130 mg/dL (see NCEP Treatment Guidelines above). Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the total-C be used to monitor therapy. Although Lovastatin Tablets USP may be useful to reduce elevated LDL-C levels in patients with combined hypercholesterolemia and hypertriglyceridemia where hypercholesterolemia is the major abnormality (Type IIb hyperlipoproteinemia), it has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL or IDL (i.e., hyperlipoproteinemia types I, III, IV, or V). *** The NCEP classification of cholesterol levels in pediatric patients with a familial history of hypercholesterolemia or premature cardiovascular disease is summarized below: Category Total-C (mg/dL) LDL-C (mg/dL) Acceptable < 170 < 110 Borderline 170 to 199 110 to 129 High ≥ 200 ≥ 130 Children treated with lovastatin in adolescence should be re-evaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C.

DOSAGE AND ADMINISTRATION 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 ). Dosage in Patients Taking Amiodarone In patients taking amiodarone concomitantly with lovastatin tablets, the dose should not exceed 40 mg/day (see WARNINGS , Myopathy/Rhabdomyolysis and PRECAUTIONS , Drug Interactions , Other Drug Interactions ). Adolescent Patients (10 to 17 Years of Age) With Heterozygous Familial Hypercholesterolemia The recommended dosing range of lovastatin is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Pediatric Panel Guidelines 4 , CLINICAL PHARMACOLOGY , and INDICATIONS AND USAGE ). Patients requiring reductions in LDL-C of 20% or more to achieve their goal 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. 4 National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics . 89(3):495-501. 1992. Concomitant Lipid-Lowering Therapy Lovastatin tablets are effective alone or when used concomitantly with bile-acid sequestrants (see WARNINGS , Myopathy/Rhabdomyolysis and PRECAUTIONS , Drug Interactions ). Dosage in Patients With Renal Insufficiency In patients with severe renal insufficiency (creatinine clearance < 30 mL/min), dosage increases above 20 mg/day should be carefully considered and, if deemed necessary, implemented cautiously (see CLINICAL PHARMACOLOGY and WARNINGS , Myopathy/Rhabdomyolysis ).

WARNINGS 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. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily. There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents. All patients starting therapy with lovastatin, or whose dose of lovastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing lovastatin. Lovastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with lovastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy. Many of the patients who have developed rhabdomyolysis on therapy with lovastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. Lovastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Lovastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy. The risk of myopathy/rhabdomyolysis is increased by concomitant use of lovastatin with the following: Strong inhibitors of CYP3A4: Lovastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of cytochrome P450 3A4 (CYP3A4). Certain drugs which inhibit this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or cobicistat-containing products. Combination of these drugs with lovastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with lovastatin should be suspended during the course of treatment (see CONTRAINDICATIONS ; PRECAUTIONS , Drug Interactions ). Gemfibrozil: The combined use of lovastatin with gemfibrozil should be avoided. Other lipid-lowering drugs (other fibrates or ≥ 1 g/day of niacin): Caution should be used when prescribing other fibrates or lipid-lowering doses (≥ 1 g/day) of niacin with lovastatin, as these agents can cause myopathy when given alone. The benefit of further alterations in lipid levels by the combined use of lovastatin with other fibrates or niacin should be carefully weighed against the potential risks of these combinations. Cyclosporine: The use of lovastatin with cyclosporine should be avoided. Danazol, diltiazem, dronedarone, or verapamil with higher doses of lovastatin: The dose of lovastatin should not exceed 20 mg daily in patients receiving concomitant medication with danazol, diltiazem, dronedarone, or verapamil. The benefits of the use of lovastatin in patients receiving danazol, diltiazem, dronedarone, or verapamil should be carefully weighed against the risks of these combinations. Amiodarone: The dose of lovastatin should not exceed 40 mg daily in patients receiving concomitant medication with amiodarone. The combined use of lovastatin at doses higher than 40 mg daily with amiodarone should be avoided unless the clinical benefit is likely to outweigh the increased risk of myopathy. The risk of myopathy/rhabdomyolysis is increased when amiodarone is used concomitantly with higher doses of a closely related member of the HMG-CoA reductase inhibitor class. Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with lovastatin coadministered with colchicine, and caution should be exercised when prescribing lovastatin with colchicine (see PRECAUTIONS , Drug Interactions ). Ranolazine: The risk of myopathy, including rhabdomyolysis, may be increased by concomitant administration of ranolazine. Dose adjustment of lovastatin may be considered during coadministration with ranolazine. Prescribing recommendations for interacting agents are summarized in Table VII (see also CLINICAL PHARMACOLOGY , Pharmacokinetics ; PRECAUTIONS , Drug Interactions ; DOSAGE AND ADMINISTRATION ). Table VII: Drug Interactions Associated With Increased Risk of Myopathy/Rhabdomyolysis Interacting Agents Prescribing Recommendations Strong CYP3A4 inhibitors, e.g.: Contraindicated with lovastatin Ketoconazole Itraconazole Posaconazole Voriconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Boceprevir Telaprevir Nefazodone Cobicistat-containing products Gemfibrozil Avoid with lovastatin Cyclosporine Danazol Do not exceed 20 mg lovastatin daily Diltiazem Dronedarone Verapamil Amiodarone Do not exceed 40 mg lovastatin daily Grapefruit juice Avoid grapefruit juice Liver Dysfunction Persistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatin for at least one year in early clinical trials (see ADVERSE REACTIONS). When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases usually appeared 3 to 12 months after the start of therapy with lovastatin, and were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity. In the EXCEL study (see CLINICAL PHARMACOLOGY , Clinical Studies in Adults ), the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in postmarketing experience with lovastatin, symptomatic liver disease has been reported rarely at all dosages (see ADVERSE REACTIONS ). In AFCAPS/TexCAPS, the number of participants with consecutive elevations of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (> 3 times the upper limit of normal), over a median of 5.1 years of follow-up, was not significantly different between the lovastatin and placebo groups (18 [0.6%] vs. 11 [0.3%]). The starting dose of lovastatin was 20 mg/day; 50% of the lovastatin treated participants were titrated to 40 mg/day at Week 18. Of the 18 participants on lovastatin with consecutive elevations of either ALT or AST, 11 (0.7%) elevations occurred in participants taking 20 mg/day, while 7 (0.4%) elevations occurred in participants titrated to 40 mg/day. Elevated transaminases resulted in discontinuation of

CONTRAINDICATIONS 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 Error! Hyperlink reference not valid. ). Pregnancy and lactation (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid. ). 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. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as lovastatin to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, lovastatin is contraindicated during pregnancy and in nursing mothers. Lovastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, lovastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see Error! Hyperlink reference not valid. ).

CLINICAL PHARMACOLOGY The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL-C and low high-density lipoprotein cholesterol (HDL-C) are both associated with coronary heart disease. However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (total-C) and LDL-C in the lower end of this range. Lovastatin has been shown to reduce elevated LDL-C concentrations. LDL is formed from very low-density lipoprotein (VLDL) and is catabolized predominantly by the high affinity LDL receptor. The mechanism of the LDL-lowering effect of lovastatin may involve both reduction of VLDL-C concentration, and induction of the LDL receptor, leading to reduced production and / or increased catabolism of LDL-C. Apolipoprotein B also falls during treatment with lovastatin. Lovastatin is a specific inhibitor of HMG-CoA reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol. Pharmacokinetics Lovastatin is a lactone which is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a strong inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of lovastatin. Following an oral dose of 14 C-labeled lovastatin in man, 10% of the dose was excreted in urine and 83% in feces. The latter represents absorbed drug equivalents excreted in bile, as well as any unabsorbed drug. Plasma concentrations of total radioactivity (lovastatin plus 14 C-metabolites) peaked at 2 hours and declined rapidly to about 10% of peak by 24 hours postdose. Absorption of lovastatin, estimated relative to an intravenous reference dose, in each of four animal species tested, averaged about 30% of an oral dose. In animal studies, after oral dosing, lovastatin had high selectivity for the liver, where it achieved substantially higher concentrations than in non-target tissues. Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable. In a single dose study in four hypercholesterolemic patients, it was estimated that less than 5% of an oral dose of lovastatin reaches the general circulation as active inhibitors. Following administration of lovastatin tablets the coefficient of variation, based on between-subject variability, was approximately 40% for the area under the curve (AUC) of total inhibitory activity in the general circulation. Both lovastatin and its β-hydroxyacid metabolite are highly bound (> 95%) to human plasma proteins. Animal studies demonstrated that lovastatin crosses the blood-brain and placental barriers. The major active metabolites present in human plasma are the β-hydroxyacid of lovastatin, its 6′-hydroxy derivative, and two additional metabolites. Peak plasma concentrations of both active and total inhibitors were attained within 2 to 4 hours of dose administration. While the recommended therapeutic dose range is 10 to 80 mg / day, linearity of inhibitory activity in the general circulation was established by a single dose study employing lovastatin tablet dosages from 60 to as high as 120 mg. With a once-a-day dosing regimen, plasma concentrations of total inhibitors over a dosing interval achieved a steady state between the second and third days of therapy and were about 1.5 times those following a single dose. When lovastatin was given under fasting conditions, plasma concentrations of total inhibitors were on average about two-thirds those found when lovastatin was administered immediately after a standard test meal. In a study of patients with severe renal insufficiency (creatinine clearance 10 to 30 mL/min), the plasma concentrations of total inhibitors after a single dose of lovastatin were approximately two-fold higher than those in healthy volunteers. In a study including 16 elderly patients between 70 to 78 years of age who received lovastatin 80 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18 to 30 years of age (see PRECAUTIONS , Geriatric Use ). Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for lovastatin and lovastatin acid is presumably due, in part, to inhibition of CYP3A4. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Strong inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy (see WARNINGS , Myopathy/Rhabdomyolysis and PRECAUTIONS , Drug Interactions ). Lovastatin is a substrate for cytochrome P450 isoform 3A4 (CYP3A4) (see PRECAUTIONS , Drug Interactions ). Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study 1 , 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with and 30 and 90 minutes following a single dose of 80 mg lovastatin on the third day. This regimen of grapefruit juice resulted in a mean increase in the serum concentration of lovastatin and its β-hydroxyacid metabolite (as measured by the area under the concentration-time curve) of 15 fold and 5 fold, respectively [as measured using a chemical assay — high performance liquid chromatography]. In a second study, 15 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 40 mg lovastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [using an enzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 1.34 fold and 1.36 fold, respectively, and of lovastatin and its β-hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry — different from that used in the first 1 study] of 1.94 fold and 1.57 fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on lovastatin pharmacokinetics has not been studied. 1 Kantola, T, et al., Clin Pharmacol Ther 1998; 63(4):397-402. TABLE I: The Effect of Other Drugs on Lovastatin Exposure When Both Were Coadministered Number of Subjects Dosing of Coadministered Drug or Grapefruit Juice Dosing of Lovastatin AUC Ratio Results based on a chemical assay. (with/without coadministered drug) No Effect = 1.00 Lovastatin Lovastatin acid Lovastatin acid refers to the β-hydroxyacid of lovastatin. Gemfibrozil 11 600 mg BID for 3 days 40 mg 0.96 2.80 Itraconazole The mean total AUC of lovastatin without itraconazole phase could not be determined accurately. Results could be representative of strong CYP3A4 inhibitors such as ketoconazole, posaconazole, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone. 12 200 mg QD