Hypotension: Volume-Depleted Patients: CoAprovel has been rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may be expected to occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhea or vomiting. Such conditions should be corrected before initiating therapy with CoAprovel.
Renal Artery Stenosis: Renovascular Hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. While this is not documented with CoAprovel, a similar effect should be anticipated.
Renal Impairment and Kidney Transplantation: When CoAprovel is used in patients with impaired renal function, a periodic monitoring of potassium, creatinine and uric acid serum levels is recommended. There is no experience regarding the administration of CoAprovel in patients with a recent kidney transplantation. CoAprovel should not be used in patients with severe renal impairment (creatinine clearance <30 mL/min) (see Contraindications). Thiazide diuretic-associated azotemia may occur in patients with impaired renal function. No dosage adjustment is necessary in patients with renal impairment whose creatinine clearance is ≥30 mL/min. However, in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min but <60 mL/min), this fixed dose combination should be administered with caution.
Hepatic Impairment: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. There is no clinical experience with CoAprovel in patients with hepatic impairment.
Aortic and Mitral Valve Stenosis, Obstructive Hypertrophic Cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Primary Aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of CoAprovel is not recommended.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Latent diabetes mellitus may become manifest during thiazide therapy.
Increase in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however at the 12.5 mg dose contained in CoAprovel, minimal or no effects were reported.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Electrolyte Imbalance: As for any patient receiving diuretic therapy, periodic determination of serum electrolyte should be performed at appropriate intervals.
Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypokalemia, hyponatremia, and hypochloremic alkalosis). Warning signs of fluid electrolyte imbalance are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances eg, nausea and vomiting.
Although hypokalemia may develop with the use of thiazide diuretics, concurrent therapy with irbesartan may reduce diuretic-induced hypokalemia. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH. Conversely, due to the irbesartan component of CoAprovel hyperkalemia might occur, especially in the presence of renal impairment and/or heart failure, and diabetes mellitus. Adequate monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics, potassium supplements or potassium-containing salts substitutes should be co-administered cautiously with CoAprovel (see Interactions).
There is no evidence that irbersartan would reduce or prevent diuretic-induced hyponatremia.
Chloride deficit is generally mild and usually does not require treatment.
Thiazides may decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesemia.
Lithium: The combination of lithium and CoAprovel is not recommended (see Interactions).
Anti-Doping Test: Hydrochlorothiazide contained in CoAprovel could produce a positive analytic result in an anti-doping test.
General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists that affect this system has been associated with acute hypotension, azotemia, oliguria, or rarely acute renal failure. As with any antihypertensive agent, excessive blood pressure decrease in patients with ischemic cardiopathy or ischemic cardiovascular disease could result in a myocardial infarction or stroke.
Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such history.
Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Lactose: CoAprovel contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take CoAprovel.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects on the ability to drive and use machines have been performed. Based on its pharmacodynamic properties, CoAprovel is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that occasionally, dizziness or weariness may occur during treatment of hypertension.
Use in children: Safety and efficacy of CoAprovel have not been established in children (<18 years).