Other Antihypertensive Agents: The antihypertensive effect of CoAprovel may be increased with the concomitant use of other antihypertensive agents. Irbesartan and hydrochlorothiazide (at doses up to irbesartan 300 mg/hydrochlorothiazide 25 mg) have been safely administered with other antihypertensive agents including calcium-channel blockers, β-adrenergic blockers. Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with irbesartan with or without thiazide diuretics unless the volume depletion is corrected first (see Precautions).
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Furthermore, renal clearance of lithium is reduced by thiazides so the risk of lithium toxicity could be increased with CoAprovel. Therefore, the combination of lithium and CoAprovel is not recommended (see Precautions). If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Medicinal Products Affecting Potassium: The potassium-depleting effect of hydrochlorothiazide is attenuated by the potassium-sparing effect of irbesartan. However, this effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other drugs associated with potassium loss and hypokalemia (eg, other kaliuretic diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium). Conversely, based on the experience with the use of other drugs that blunt the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other drugs that may increase serum potassium levels (eg, heparin sodium) may lead to increases in serum potassium. Adequate monitoring of serum potassium in patients at risk is recommended (see Precautions).
Medicinal Products Affected by Serum Potassium Disturbances: Periodic monitoring of serum potassium is recommended when CoAprovel is administered with drugs affected by serum potassium disturbances (eg, digitalis glycosides, antiarrhythmics).
Nonsteroidal Anti-Inflammatory Drugs: When angiotensin II antagonists are administered simultaneously with nonsteroidal anti-inflammatory drugs [ie, selective cyclooxygenase (COX)-2 inhibitors, acetylsalicylic acid (>3 g/day) and nonselective NSAIDs], attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of angiotensin II and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor preexisting renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Additional Information on Irbesartan Interactions: In clinical studies, the pharmacokinetics of irbesartan is not affected by hydrochlorothiazide. Irbesartan is mainly metabolized by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was co-administered with warfarin, a drug metabolized by CYP2C9.
The effects of CYP2C9 inducers eg, rifampicin, on the pharmacokinetics of irbesartan have not been evaluated. The pharmacokinetic of digoxin was not altered by co-administration of irbesartan.
Additional Information on Hydrochlorothiazide Interactions: When administered concurrently, the following drugs may interact with thiazide diuretics:
Alcohol: Potentiation of orthostatic hypotension may occur.
Antidiabetic Drugs (oral agents and insulins): Dosage adjustment of the antidiabetic drug may be required (see Precautions).
Cholestyramine and Colestipol Resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Corticosteroids, ACTH: Electrolyte depletion, particularly hypokalemia, may be increased.
Digitalis Glycosides: Thiazide-induced hypokalemia or hypomagnesemia favor the onset of digitalis-induced cardiac arrhythmias (see Precautions).
Nonsteroidal Anti-Inflammatory Drugs: The administration of a nonsteroidal anti-inflammatory drug may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics in some patients.
Pressor Amines (eg, Noradrenaline): The effect of pressor amines may be decreased, but not sufficiently to preclude their use.
Nondepolarizing Skeletal Muscle Relaxants (eg, Tubocurarine): The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.
Antigout Medication: Dosage adjustments of antigout medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary. Co-administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Calcium Salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements or calcium-sparing drugs (eg, vitamin D therapy) must be prescribed, serum calcium levels should be monitored and calcium dosage adjusted accordingly.
Other Interactions: The hyperglycemic effect of β-blockers and diazoxide may be enhanced by thiazides. Anticholinergic agents (eg, atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach-emptying rate. Thiazides may increase the risk of adverse effects caused by amantadine. Thiazides may reduce the renal excretion of cytotoxic drugs (eg, cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.
Incompatibilities: Not applicable.