Simvastatin dosage

Homozygous familial hypercholesterolemia-The recommended dosage is 40 mg/day in the evening or 80 mg/day in 3 divided doses of 20 mg, 20 mg, and an evening dose of 40 mg. Use simvastatin as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) in these patients or if such treatments are unavailable. 

Elderly In patients older than 70 years of age, the AUC of lovastatin, pravastatin, and simvastatin is increased. Pravastatin does not need dosage adjustment. The safety and efficacy of atorvastatin, rosuvastatin, and lovastatin extended-release in patients 70 years of age and older were similar to those of patients younger than 70 years of age. Elderly patients (65 years of age and older) demonstrated a greater treatment response in respect to LDL-C, total-C and LDL/HDL ratio than patients younger than 65 years of age. 

Dose The recommended usual starting dose is 10 mg ezetimibe/20 mg simvastatin daily. Initiation of therapy with 10 mg ezetimibe/10 mg simvastatin daily may be considered for patients requiring less aggressive LDL-C reductions. Patients who require a larger reduction in LDL-C (more than 55%) may be started at 10 mg ezetimibe/40 mg simvastatin daily. After initiation or titration of ezetimibe/simvastatin, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed. 

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. 

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). 

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. 

Healthy volunteers were given protease inhibitors and statins, and the authors concluded that simvastatin should be avoided and that atorvastatin could be used with caution in people taking ritonavir and saquinavir (111). Dosage adjustment of pravastatin may be necessary with co-administration of ritonavir and saquinavir. Pravastatin does not alter the pharmacokinetics of nelfinavir, and thus appears to be safe for co-administration. 

In two cases, rhabdomyolysis was caused by itraconazole in heart transplant recipients taking long-term ciclosporin and simvastatin (48,49). To avoid severe myopathy, ciclosporin concentrations should be monitored frequently and statins should be withdrawn or the dosage should be reduced, as long as azoles need to be prescribed in transplant recipients. Patients need to be educated about signs and symptoms that require immediate physician intervention. 

St John s wort 1. Atorvastatin 2. Simvastatin 3. Lovastatin 1 blood levels and lipid-lowering effect Induction of metabolizing CYP3A4 enzymes, which metabolize simvastatin Avoid concomitant use if possible. Monitor response to simvastatin closely. Avoid sudden changes of the herb dosage... 

Another spectrophotometric method used the derivative method. Rajput and Raj [19] developed a first-order derivative zero-crossing method to analyze ezetimibe in combination with simvastatin. This method was further applied to determine ezetimibe in combination with lovastatin. The first derivation method also applied to determine ezetimibe in combination with rosuvastatin [20]. Besides the first-derivative method, second- and third-derivative methods were also reported for defermining ezetimibe as a single compound in its dosage form [21]. Flowever, the third-derivative method yielded the lowest limits of defecfion and quantitation relative to other methods used in this research. The maximum wavelength also remained constant regardless of fhe derivative method applied. 

Simvastatin Potentiation (233,234) Unknown Adjust dosage Monitor INR... 

They suggest that a dosage reduction of the statin should be considered during concurrent use. The manufacturer of posaconazole (also a CYP3A4 inhibitor) contraindicates its use with simvastatin or lovastatin. ... 

Metabolism Of considerable importance is the consistency with which small but important increments in the incidence of new diabetes mellitus have been reported in patients taking statins. This adverse effect was noted in the early Heart Protection Study with simvastatin (although it was not statistically significant) and in the ASCOT Trial with atorvastatin in both trials the hazard ratio for type 2 diabetes was 1.15 [31 ]. Atorvastatin at different dosages (10-80 mg/day) compared with placebo reduced insuhn sensitivity significantly within 2 months as glycemia increased. 

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