Lovastatin study

Lovastatin Study Groups I through IV (1993). Arch. Intern. Med. 153, 1079-1087. 

In the first clinical studies with lovastatin, pte-dmg semm cholesterol values of 150—300 mg/dL were shown to be decreased as much as 25% with a dosage of 15 mg twice daily for just over a week (149). Whereas the dmg shows few adverse side effects, gastrointestinal disturbances, including diarrhea and abdominal pain, ate the most common. 

Over the last decade, several studies in tens of thousands of patients have revealed that lowering cholesterol, specifically lowering LDL cholesterol with statins, is effective for both primary and secondary prevention of IHD-related events. Statins shown to decrease morbidity and mortality associated with IHD include lovastatin, simvastatin, pravastatin, and atorvas-tatin.22,23 A recent meta-analysis showed that the risk of major adverse cardiac events is reduced by 21% with the use of statins in patients at high risk for IHD-related events.23... 

Some patients, in particular those with genetic forms of hypercholesterolemia (Table 9-2), will require three or more drugs to manage their disorder. Regimens using a statin, resin, and niacin were found to reduce LDL cholesterol up to 75%.42 These early studies were conducted with lovastatin, so larger reductions would be expected with the more potent statins available today. 

The answer is a. (Hardman, pp 885-8870 Lovastatin should not be used in patients with severe liver disease. With routine use of lovastatin, serum transaminase values may rise, and in such patients the drug may be continued only with great caution. Lovastatin has also been associated with lenticular opacities, and slit-lamp studies should be done before and one year after the start of therapy There is no effect on the otic nerve. The drug is not toxic to the renal system, and reports of bone marrow depression are very rare There is a small incidence of myopathy, and levels of creatinine kinase should be measured when unexplained muscle pain occurs. Combination with cyclosporine or clofibrate has led to myopathy There is no danger in use with bile acid sequestrants. 

There is interest in the use of lipid-lowering agents, especially the 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, to prevent AD. Pravastatin and lovastatin, but not simvastatin, were associated with a lower prevalence of AD. Further study is needed before these agents can be recommended for this use. 

The medication costs in this study are for branded Lovastatin and generic niacin. For niacin, the cost was taken to be Medicaid s reimbursement for multiple-source drugs. The actual measure was slightly below the average wholesale price but was above the lowest wholesale prices quoted. For Lovastatin, costs were estimated using the 1994 average wholesale price. 

The statins may lower the risk of CHD by decreasing inflammation, an important component of atherogene-sis. Lovastatin decreased elevated plasma levels of C-reactive protein, a marker for cellular inflammation, and acute coronary events in patients with relatively low plasma cholesterol levels. Recent studies also suggest that use of statins may decrease the risk of stroke, dementia, and Alzheimer s disease and may improve bone... 

Noa, M., R. Mas, and R. Mesa. A comparative study of policosanol vs lovastatin on intimal thickening in rabbit cuffed carotid artery. Pharmacol Res 2001 43(1) 31-37. 

Note that the warnings in the labeling about interactions with lovastatin, atorvastatin, and pimozide are based on extrapolation from clinical studies with simvastatin and cisapride. 

Erectile dysfunction has been reported in 12% of 339 men treated with fibrate derivatives or statins, compared with 5.6% of similar patients not taking these drugs (62). The mechanism is unknown and should be confirmed in randomized studies. A class effect has been suggested by the case of a 57-year-old man who had impotence after taking lovastatin for 2 weeks and also when he later tried pravastatin (63). 

Physicians should check for lipid-lowering drugs before treating elderly individuals with itraconazole (73). Susceptibility to this interaction varies from statin to statin, in that simvastatin is more affected than pravastatin (74). Concomitant use of simvastatin with itraconazole should be avoided, and the same holds true for atorvastatin (75). In another study, the blood concentration of fluvastatin was not significantly increased, whereas that of lovastatin was (76). 

Laties AM, Shear CL, Lippa EA, Gould AL, Taylor HR, Hurley DP, Stephenson WP, Keates EU, Tupy-Visich MA, Chremos AN. Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin. Am J Cardiol 1991 67(6) 447-53. 

In a double-blind study, 209 healthy adults were randomized to placebo or lovastatin 20 mg/day for 6 months (4). Placebo-treated subjects improved between baseline and post-treatment periods on neuropsychological tests in all performance domains (neuropsychological performance, depression, hostility, and quality of life), consistent with the effects of practice on test performance, whereas those treated with lovastatin improved only on tests of memory recall. Comparisons of the changes in performance between placebo and lovastatin showed small but significant differences for tests of attention... 

The effects of co-administration of oral diltiazem, a potent inhibitor of CYP3A, on the pharmacokinetics of lovastatin have been evaluated in a randomized study in 10 healthy volunteers (10). Lovastatin is oxidized by CYP3A to active metabolites. Diltiazem significantly increased the oral AUC and maximum serum concentration of lovastatin, but did not alter its half-life. The magnitude of the increase of plasma concentration of lovastatin suggested that caution is necessary when coadministering diltiazem and lovastatin. 

In another study by the same investigators, 10 healthy volunteers were randomized in a two-way, crossover study either to oral lovastatin or to intravenous diltiazem followed by oral lovastatin. Intravenous diltiazem did not significantly affect the pharmacokinetics of lovastatin (oral AUC, Cmax, tmax, or half-life), suggesting that the interaction does not occur systemically and is primarily a first-pass effect (11). Drug interactions with diltiazem may therefore become evident when a patient is changed from intravenous to oral dosing. 

The effects of itraconazole 100 mg on the pharmacokinetics of lovastatin 40 mg have been studied in a randomized, placebo-controlled, crossover study in 10 healthy volunteers (16). Itraconazole, even in this low dosage, greatly increased plasma concentrations of lovastatin and its active metabolite, lovastatin acid, and increased the Cmax of lovastatin about 15-fold and the total AUC by more than 15-fold similarly, the Cmax and total AUC of lovastatin acid were increased about 12-fold and 15-fold respectively. 

Based on case reports or small studies, the potential for drug interactions between macrolides and lovastatin should be considered (17). 

Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, Gould AL, Hesney M, Higgins J, Hurley DP, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med 1991 151(1) 43—9. 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

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