Aprovel Drug Interactions

Based on in vitro data, no interactions would be expected to occur with drugs whose metabolism is dependent upon cytochrome P450 isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1 or CYP3A4. Irbesartan is primarily metabolized by CYP2C9, however, during clinical interaction studies, no significant pharmacodynamic interactions were observed when irbesartan was coadministered with warfarin (a drug metabolized by CYP2C9). Irbesartan does not affect the pharmacokinetics of digoxin or simvastatin. The pharmacokinetic parameters of irbesartan are not affected by coadministration with nifedipine or hydrochlorothiazide.
The combination of Aprovel with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or moderate to severe renal impairment (GFR <60 mL/min/1.73 m²) and is not recommended in other patients (see Contraindications and Precautions).
Angiotensin-converting enzyme inhibitors (ACEIs): The use of Aprovel in combination with an ACEI is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see Contraindications and Precautions).
Based on experience with the use of other drugs that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase kalaemia with irbesartan may lead to increases in serum potassium, sometimes severe, and requires close monitoring of serum potassium.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including irbesartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving irbesartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including irbesartan, may be attenuated by NSAIDs including selective COX-2 inhibitors.
Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of irbesartan. Monitor lithium levels in patients receiving irbesartan and lithium.
Repaglinide: irbesartan has the potential to inhibit OATP1B1. In a clinical study, it was reported that irbesartan increased the C_max and AUC of repaglinide (substrate of OATP1B1) by 1.8-fold and 1.3-fold, respectively, when administered 1 hour before repaglinide. In another study, no relevant pharmacokinetic interaction was reported, when the two drugs were co-administered. Therefore, dose adjustment of antidiabetic treatment such as repaglinide may be required (see Precautions).