There are limited data on drug overdose. The most likely and the main symptom of overdose is a marked reduction in blood pressure. Should be supportive therapy buy primobolan depot in case of overdose and the development of symptomatic hypotension.
Interaction with other medicinal products
The probability of interaction of aliskiren with other medicinal products is low. There were no clinically significant interaction with aliskiren acenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide 5-mononitrate, irbesartan, digoxin, ramipril and hydrochlorothiazide.
In the application of aliskiren with one of the following drugs may change its Cmax or AUC: valsartan (28% reduction), metformin (28% reduction), amlodipine (29% increase), cimetidine (19% increase).
Since the combined use of aliskiren has no significant effect on the pharmacokinetics of atorvastatin, valsartan, metformin, amlodipine, while the appointment or change dosages Rasileza above drugs is required.
Interaction at the level of cytochrome P450. Aliskiren does not inhibit cytochrome P450 isoenzymes ) or induces of isoenzyme. Because aliskiren is metabolized to a minor extent by cytochrome P450 isozymes, a clinically significant effect on the bioavailability of Rasileza drugs that are inducers or inhibitors of cytochrome P450 metabolized or with its participation, it is unlikely.
Interaction at the level of P-glycoprotein (Pgp), encoded by genes MDRl / Mdrla / lb. Since pilot studies it was found that the P-glycoprotein (membrane transporter molecules) plays an important role in the absorption of regulation and distribution of aliskiren may alter the pharmacokinetics of the latter, while use of substances inhibiting Pgp (depending on the degree of inhibition). Not found significant buy primobolan depot interactions of aliskiren with mild to moderately active Pgp-inhibitors, such as atenolol, digoxin, amlodipine, and cimetidine.
In an application with an active inhibitor of Pgp-atorvastatin (80 mg / day) at steady state observed increase in AUC and C max of aliskiren (dose 300 mg / day) for 50%.
At the same time taking an active Pgp-inhibitor ketoconazole (200 mg) and aliskiren (300 mg) was observed increase in plasma concentration of the latter (AUC and Cmax) by 80%. In experimental studies simultaneous reception ketoconazole aliskiren resulted in increased absorption of the latter in the gastro-intestinal tract and reducing its elimination in bile. Changes in plasma concentrations of aliskiren in the plasma while the use of ketoconazole or atorvastatin concentrations are expected in the range defined by increasing the dose of aliskiren in 2 times. In controlled clinical studies have demonstrated the safety of the drug at a dose of 600 mg and increasing the maximum recommended therapeutic dose of 2 times.
In the application of aliskiren with atorvastatin or ketoconazole aliskiren dose adjustment is required. When applied to such highly active inhibitor of Pgp-like cyclosporin (200 and 600 mg) in healthy subjects was an increase in C max and AUC of aliskiren (75 mg) in 2.5 and 5 times, respectively. In this connection it is recommended not to use Rasilez concurrently with cyclosporine.
With simultaneous use of aliskiren with furosemide marked reductionbuy primobolan depot furosemide at 28% and 49%, respectively. To prevent a possible delay in the appointment liquid aliskiren together with furosemide in the beginning and in the treatment necessary to adjust the dose of furosemide depending on clinical effect.