Simvastatin adverse effects

Nefazodone is an inhibitor of the CYP3A4 isoenzyme, so it can raise the level and thus exacerbate adverse effects of many 3A4-dependent drugs. For example, triazolam levels are increased by concurrent administration of nefazodone such that a reduction in triazolam dosage by 75% is recommended. Likewise, administration of nefazodone with simvastatin has been associated with 20-fold increase in plasma levels of simvastatin. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Atorvastatin is an HMG Co-A reductase inhibitor. Pooled data from 21 completed and 23 continuing trials representing 3000 patient-years have shown that constipation, flatulence, dyspepsia, abdominal pain, headache, and myalgia occur in 1-3% of patients. Under 2% of atorvastatin-treated patients discontinued treatment because of an adverse event (1). Serious events in this review amounted to one patient with pancreatitis and one with cholestatic jaundice (1). There were no differences in adverse effects in 177 patients randomized for 52 weeks to either simvastatin or atorvastatin (2). 

Ezetimibe is a selective potent inhibitor of the intestinal absorption of dietary and biliary cholesterol. A total of 432 patients were included in a pooled analysis of two phase-II studies, both lasting for 12 weeks ezetimibe was well tolerated, with an adverse events profile similar to that of placebo (1). In 668 patients who took ezetimibe with simvastatin, the adverse effects were similar to those with simvastatin alone (2). 

In 668 patients ezetimibe was given with simvastatin and adverse effects were similar to those experienced with simvastatin alone (8). 

The adverse effects of statins have been reviewed in the light of the ever increasing dosages that are being used to lower LDL cholesterol to a minimum (2). In another review high doses of atorvastatin and simvastatin were specially emphasized (3). 

Emerging data associate statins with a reduced risk of Alzheimer s disease however, two women had significant cognitive impairment temporally related to statin therapy (18). One took atorvastatin, and the other first took atorvastatin then simvastatin. Cognitive impairment and dementia as potential adverse effects associated with statins has been reviewed (17). 

Hematological adverse effects can occur during treatment with both simvastatin and atorvastatin, according to a brief review (23). They include thrombotic thrombocytopenic purpura and severe thrombocytopenic purpura. 

In a comparison of atorvastatin with pravastatin, of 224 patients taking atorvastatin, two had clinically significant increases in alanine transaminase activity (32). They recovered during the next 4 months, one after withdrawal of atorvastatin and the other after a dosage reduction. Withdrawals due to adverse effects were similar in the two groups. One patient developed hepatitis while taking atorvastatin, but was able to tolerate simvastatin (33). The authors concluded that this adverse effect was not a class effect. Eosinophils in a liver-biopsy specimen pointed to an immunological mechanism. 

Simvastatin is an HMG Co-A reductase inhibitor. Its most serious adverse effect is rhabdomyolysis, which is enhanced by other drugs that inhibit CYP3A4 (1). 

Adverse effects It is noteworthy that during the 5-year trials of simvastatin and lovastatin, only a few adverse effects, related to liver and muscle function, were reported (Figure 21.10). 

LOVASTATIN, SIMVASTATIN PROTEASE INHIBITORS t risk of adverse effects Inhibition of CYP3A4-mediated metabolism of simvastatin Avoid co-administration... 

STATINS GRAPEFRUIT JUICE t levels with simvastatin slight rise with atorvastatin. t risk of adverse effects such as myopathy Constituent of grapefruit juice inhibits CYP3A4-mediated metabolism of simvastatin Patients taking simvastatin and atorvastatin should avoid grapefruit juice... 

The most serious adverse effect of simvastatin is myopathy, which rarely may progress to rhabdomyolysis. Abnormalities of liver function may also occur. These effects are dose-dependent, and a number of drugs and foods may inhibit the metabolism of simvastatin, thereby increasing its toxicity. Examples of these are grapefruit juice and erythromycin, both of which should be avoided in patients taking simvastatin. 

Simvastatin up to 40 mg/day was given to 98 boys and 75 girls, aged 10-17 years, for 48 weeks without any adverse effects beyond a small fall in dehydroepiandrosterone (7). Of special note was the observation that simvastatin had no adverse effects on growth or pubertal development. 

Pharmacists should monitor people who buy simvastatin at least once a year for adverse effects, interactions, changes in risk factors and blood cholesterol levels. 

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