The likelihood of interaction of aliskiren with other drugs is low. Was not clinically identified significant interaction of aliskiren with asenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide 5-mononitrate, irbesartan, digoxin, ramipril and hydrochlorothiazide, hypoglycemic agents for ingestion and insulin.
When using aliskiren with one of the following drugs, a change in CmOh or AUC aliskiren: valsartan (a decrease of 28%), metformin (a decrease of 28%), amlodipine (an increase of 29%), cimetidine (an increase of 19%). Wherein aliskiren has no significant effect on the pharmacokinetics of atorvastatin, valsartan, metformin, amlodipine, and when administered simultaneously, no change in the doses of the above drugs is required.
Interaction at the level of cytochrome P450.
Aliskiren does not inhibit cytochrome P450 isoenzymes (CYP1A2, 2С8, 2С9, 2С19, 2D6, 2E1 and CYP3A) and does not induce isoenzyme CYP3A4. Because the aliskiren is slightly metabolized by cytochrome P450 isoenzymes, the clinically significant effect of Racileus on the bioavailability of drugs that are inducers or inhibitors of cytochrome P450 or metabolized with his participation is unlikely.
Interaction at the level of P-glycoprotein, encoded by the genesMDR1. Since it has been established in in vitro studies that the P-glycoprotein (membrane transporter of molecules) plays an important role in regulating the absorption and distribution of aliskiren, it is possible to alter the pharmacokinetics of the latter when used simultaneously with drugs inhibiting P-glycoprotein (depending on the degree of inhibition).
Substrates and weak P-glycoprotein inhibitors
There is no clinically significant interaction of aliskiren with weakly active P-glycoprotein inhibitors, such as atenolol, digoxin, amlodipine and cimetidine. With simultaneous use with atorvastatin (at a dose of 80 mg), an increase in AUC and C is observed in the equilibrium statemOh aliskiren (at a dose of 300 mg) by 50%.
Moderate P-glycoprotein inhibitors
With the simultaneous administration of a moderate inhibitor of P-glycoprotein ketoconazole (200 mg) and aliskiren (300 mg), an increase in the maximum plasma concentration of the latter and AUC by 80% (AUC and CmOh). AT experimental studies, the simultaneous administration of aliskiren with ketoconazole led to an increase in the absorption of aliskiren in the gastrointestinal tract and a decrease in its excretion through the intestine with bile.With a single application of verapamil (at a dose of 240 mg), together with aliskirenom (at a dose of 300 mg), there was an increase AUC and CmOh aliskiren in 2 times.
Changes in the plasma concentration of aliskiren with simultaneous use with ketoconazole or verapamil are expected in the range of concentrations determined with an increase in the aliskiren dose by a factor of 2. In controlled clinical trials, the safety of the drug at a dose of 600 mg was demonstrated, that is, with an increase in the maximum recommended therapeutic dose by a factor of 2. Therefore, when aliskiren is used together with ketoconazole or verapamil, dose adjustment of aliskiren is not required.
Powerful P-glycoprotein inhibitors
When used with such a highly active inhibitor P-glycoprotein, as ciclosporin (in doses of 200 and 600 mg), in healthy volunteers there was an increase in CmOh and AUC aliskiren (at a dose of 75 mg) in 2.5 and 5 times, respectively. At healthy volunteers at application of aliskiren (in a dose of 150 mg) together with itraconazole (at a dose of 100 mg) there was an increase in AUC and CmOh aliskiren at 6.5 and 5.8 times, respectively.
In this regard, it is not recommended to apply aliskiren simultaneously with powerful inhibitors of P-glycoprotein.
Double blockade of RAAS
Simultaneous use of aliskiren with other drugs that affect RAAS, including those with ACE inhibitors and APA II, leads to an increased incidence of severe lowering of blood pressure, hyperkalemia, renal dysfunction (including acute renal failure). It is necessary to monitor blood pressure indicators, kidney function, as well as the content of plasma electrolytes when using Racilez with other drugs that affect RAAS.
Furosemide
With the simultaneous use of aliskiren (300 mg / day) with furosemide (20 mg / day) in healthy volunteers, a decrease in AUC and CmOh furosemide by 28% and 49%, respectively. In patients with heart failure, the simultaneous use of aliskiren (300 mg / day) with furosemide (60 mg / day) resulted in a decrease in AUC and CmOh furosemide by 17% and 27%, respectively, and by a decrease in furosemide excretion by the kidneys by 29% within 24 hours after administration. In addition, the excretion of sodium by the kidneys and the volume of urine were reduced during the first 4 hours after admission by 31% and 24%, respectively, compared with the use of furosemide in monotherapy.Given the possible decrease in the systemic bioavailability of furosemide, and to prevent possible fluid retention when using aliskiren in conjunction with furosemide, it is necessary to adjust the dose of furosemide at the beginning and during treatment, depending on the clinical effect.
Potassium and potassium-sparing diuretics
Given the experience of using other drugs that affect RAAS, caution should be exercised aliskiren together with potassium salts, potassium-sparing diuretics, potassium-containing substitutes for edible salt, or any other drugs capable of increasing the potassium content in the blood serum.
Non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2 (COX-2)
In elderly patients, patients with reduced circulating blood volume (BCC) (including patients on diuretic therapy), patients with impaired renal function, concurrent use of NSAIDs with drugs that affect RAAS can lead to impaired renal function, including acute renal failure, in most cases reversible.The antihypertensive effect of drugs that affect RAAS can decrease with the use of NSAIDs.
Grapefruit juice
It is not recommended to apply aliskiren simultaneously with grapefruit juice, the effectiveness of aliskiren can be reduced.