Investigation of the interaction with other drugs was carried out only in adults. Interactions with other lipid-lowering drugs, which can lead to an increased risk of myopathy / rhabdomyolysis Fibrates The risk of myopathy, including rhabdomyolysis, is increased during simultaneous use of simvastatin with fibrates. The combined use of gemfibrozil resulting in increased plasma concentrations of simvastatin, so their combined use is contraindicated. There are no data on increasing myopathy risk with concomitant use of simvastatin and fenofibrate. Controlled primobolan only cycle studies of interaction with other fibrates has not been carried out. Nicotinic acid There are few reports about the development of myopathy / rhabdomyolysis with concomitant use simvastatin and niacin in lipid-lowering doses (more than 1 g / day). fusidic acid The risk of myopathy is increased, while the use of fusidic acid with statins, including simvastatin. If you can not, for whatever reasons, to avoid the simultaneous use of simvastatin with fusidic acid, it is recommended to consider the possibility to delay treatment with simvastatin. If necessary, they simultaneous application of patients should be monitored carefully. Recommendations on the use of interacting drugs are given in the table.
Simvastatin is a substrate . Strong inhibitors increase the risk of myopathy and rhabdomyolysis by increasing the inhibitory activity reductase inhibitor in plasma during treatment with simvastatin. Such inhibitors include itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, protease inhibitors (such as nelfinavir), boceprevir, telaprevir, and nefazodone. Concomitant use of simvastatin with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin , protease inhibitor (such as nelfinavir), and nefazodone is contraindicated. If you can not, for whatever reasons, to avoid the combined use of simvastatin with the above mentioned drugs, it is necessary to delay treatment with simvastatin to the end of treatment with these preparations. It should be used with caution simvastatin with certain less potent inhibitors of :. Fluconazole, verapamil or diltiazem Fluconazole Rare primobolan only cycle cases have been reported of rhabdomyolysis associated with the concurrent use of simvastatin and fluconazole.cyclosporine Concomitant use of cyclosporine and simvastatin. Danazol The risk of myopathy / rhabdomyolysis is increased by concomitant use of danazol particularly with higher doses of simvastatin.amiodarone The risk of myopathy and rhabdomyolysis is increased by concomitant use of amiodarone with high doses of simvastatin. In clinical studies, the development of myopathy were detected in 6% of patients treated with simvastatin 80 mg in conjunction with amiodarone. Consequently, the simvastatin dose should not exceed 20 mg daily in patients treated with both medication with amiodarone, unless the clinical benefits outweigh the risk of myopathy and rhabdomyolysis.
Blockers “slow” calcium channel blockers verapamil The risk of myopathy and rhabdomyolysis is increased by concomitant use of verapamil with simvastatin doses greater than 40 mg. The simvastatin dose should not exceed 10 mg daily in patients who use the drug concurrently with verapamil, unless the clinical benefits outweigh the risk of myopathy and rhabdomyolysis. Diltiazem The risk of myopathy and rhabdomyolysis is increased by concomitant use of diltiazem with simvastatin 80 mg. With simultaneous use of simvastatin 40 mg with diltiazem risk of myopathy was not increased. The dose of simvastatin should not exceed 10 mg daily in patients who use the drug at the same time with diltiazem, unless the clinical benefits outweigh the risk of myopathy / rhabdomyolysis. Amlodipine Patients applying both amlodipine with simvastatin at a dose of 80 mg might be at higher risk of developing myopathy. With primobolan only cycle simultaneous use of simvastatin 40 mg amlodipine risk of myopathy was not increased. With simultaneous use of simvastatin with amlodipine, the simvastatin dose should not exceed 20 mg per day if the clinical benefits outweigh the risk of myopathy / rhabdomyolysis. Lomitapid The risk of myopathy / rhabdomyolysis is increased when applied simultaneously lomitapida with simvastatin.
Other interactions Grapefruit juiceGrapefruit juice contains one or more components which inhibit the isoenzyme may increase plasma concentrations of drugs metabolized isoenzyme . When used in a conventional amount of juice (one glass of 250 ml per day), this minimal effect (13% increase in the activity reductase inhibitors by evaluating the area under the curve “concentration-time”) and has no clinical significance. However, grapefruit juice consumption in very large volumes (more than 1 liter per day) greatly increases the plasma level of activity of primobolan only cycle reductase inhibitor simvastatin during therapy.In this connection it is necessary to avoid the consumption of grapefruit juice in large quantities. Colchicine There myopathy / rhabdomyolysis on the development of communication, while the use of colchicine and simvastatin in patients with renal insufficiency. Patients applying both these drugs should be under medical supervision. Rifampicin Because rifampicin is a potent inducer of the isoenzyme of CYP3A4, patients continuously receiving the drug (for example, in the treatment of tuberculosis), perhaps the lack of efficacy of simvastatin (failure to achieve target cholesterol concentrations plasma).effects of simvastatin on the pharmacokinetics of other drugs simvastatin exerts no inhibitory effects on the isoenzyme . Therefore, it is suggested that simvastatin did not affect the plasma concentration of compounds metabolized isoenzyme . Digoxin has been reported that, while the use of digoxin and simvastatin significantly increased plasma concentrations of the first, so you should carefully observe patients taking digoxin, especially at the beginning of therapy with simvastatin. Indirect anticoagulants in two clinical studies, one of which was conducted in healthy volunteers, and the other – in patients with hypercholesterolemia, simvastatin 20-40 mg / day modestly enhanced the effect of coumarin anticoagulants.
The international normalized ratio , increased from in healthy volunteers and patients, respectively. Patients who use coumarin anticoagulants, prothrombin time primobolan only cycle should be determined before treatment and, in the future, often determine the initial phase of treatment with simvastatin, to ensure that no significant changes . After establishing a stable value , it can be controlled through the time intervals recommended for patients taking coumarin anticoagulants. If you change the dose of simvastatin or interruption of treatment, monitoring frequency should be increased. The occurrence of bleeding or change in patients who do not use anticoagulants, not associated with the use of simvastatin.
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