CoAprovel Drug Interactions

Based on in vitro data, no interactions with irbesartan 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 pharmacokinetic and pharmacodynamic interactions were observed when irbesartan was co-administered with warfarin (a drug metabolized by CYP2C9). Irbesartan does not affect the pharmacokinetics of digoxin or simvastatin. The pharmacokinetics of irbesartan are not affected by coadministration with nifedipine or hydrochlorothiazide.
The combination of CoAprovel 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 CoAprovel 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. Concurrent therapy with hydrochlorothiazide may reduce the frequency of this effect.
Non-steroidal anti-inflammatory agents including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors): 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.
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.
Alcohol, barbiturates or narcotics: Potentiation of thiazide diuretic-induced orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): Thiazides may elevate blood glucose levels, thus, dosage adjustments of antidiabetic agents may be necessary.
Antigout medication: Dosage adjustments of antigout medication may be needed since HCTZ may raise the blood level of uric acid.
Cardiac glycosides (eg, digoxin) and other antiarrhythmic drugs (eg, sotalol): Diuretic-induced hypokalemia may accentuate cardiac arrhythmias.
Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium or a calcium sparing drug (eg, Vitamin D therapy) is prescribed, serum calcium levels should be monitored and calcium dosage adjusted accordingly.
Cholestyramine resin and colestipol HCl: May delay or decrease absorption of HCTZ. CoAprovel should be taken at least one hour before or four hours after these mediations.
Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of irbesartan.
Diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity. Coadministration with CoAprovel should be approached with caution and the frequent monitoring of serum lithium levels is recommended.
Inhibitors of endogenous prostaglandin synthesis (ie, NSAIDs): In some patients, these agents can reduce the effects of thiazide diuretics.
Other diuretics and antihypertensive medications: The thiazide component of CoAprovel may potentiate the actions of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. HCTZ may interact with diazoxide; blood glucose, serum uric acid levels and blood pressure should be monitored.
Drugs used during surgery: The effects of nondepolarizing muscle relaxants, preanesthetics and anesthetics used in surgery (eg, tubocurarine) may be potentiated by HCTZ; dosage adjustments may be required. Preanesthetic and anesthetic agents should be given in reduced dosage, and if possible, HCTZ therapy discontinued one week prior to surgery.
Carbamazepine: Concomitant use of carbamazepine and hydrochlorothiazide has been associated with the risk of symptomatic hyponatraemia. Electrolytes should be monitored during concomitant use. If possible, another class of diuretics should be used.