Niacin/Simvastatin drug interactions

# Drug Interactions
No drug interaction studies were conducted with SIMCOR. However, the following interactions have been noted with the individual components of SIMCOR:
Simvastatin

## Strong CYP3A4 Inhibitors, Cyclosporine, or Danazol
Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4.  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.
Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of SIMCOR . Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated . If treatment with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with SIMCOR must be suspended during the course of treatment.
Although not studied clinically, voriconazole has been shown to inhibit lovastatin metabolism in vitro (human liver microsomes). Therefore, voriconazole is likely to increase the plasma concentration of . It is recommended that dose adjustment of SIMCOR be considered during concomitant use of voriconazole and SIMCOR to reduce the risk of myopathy, including rhabdomyolysis .
Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated .

## Verapamil or Diltiazem
The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of verapamil or diltiazem with doses of  exceeding 10 mg. Because all doses of SIMCOR contain  in excess of 10 mg, concomitant use of these drugs is contraindicated .

## Lipid-Lowering Drugs That Can Cause myopathy When Given Alone
Gemfibrozil: Contraindicated with SIMCOR . Other fibrates: Combined use with SIMCOR should be avoided .

## Amlodipine or Ranolazine
The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amlodipine or ranolazine .

## Propranolol
In healthy male volunteers there was a significant decrease in mean Cmax, but no change in AUC, for  total and active inhibitors with concomitant administration of single doses of  and propranolol. The clinical relevance of this finding is unclear. The pharmacokinetics of the enantiomers of propranolol were not affected.

## Digoxin
Concomitant administration of a single dose of digoxin in healthy male volunteers receiving  resulted in a slight elevation (less than 0.3 ng/mL) in digoxin concentrations in plasma (as measured by a radioimmunoassay) compared to concomitant administration of placebo and digoxin. Patients taking digoxin should be monitored appropriately when SIMCOR is initiated.

## Coumarin Anticoagulants
In normal volunteers and hypercholesterolemic patients,  20-40 mg/day modestly potentiated the effect of coumarin anticoagulants since the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteers and patients, respectively. With other reductase inhibitors, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting SIMCOR and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of SIMCOR is changed or discontinued, the same procedure should be repeated.

## Colchicine
Cases of myopathy, including rhabdomyolysis, have been reported with  coadministered with colchicine, and caution should be exercised when prescribing SIMCOR with colchicine .
niacin

## Aspirin
Concomitant use of aspirin may decrease the metabolic clearance of niacin. The clinical relevance of this finding is unclear.

## Antihypertensive Therapy
niacin may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.

## Bile Acid Sequestrants
An in vitro study was carried out investigating the niacin-binding capacity of colestipol and cholestyramine. About 98% of available niacin was bound to colestipol, with 10 to 30% binding to cholestyramine. These results suggest that 4 to 6 hours, or as great an interval as possible, should elapse between the ingestion of bile acid-binding resins and the administration of SIMCOR.

## Other
Nutritional supplements containing large doses of niacin or related compounds may potentiate the adverse effects of SIMCOR.