CoAprovel Warnings

Hypotension - Volume-Depleted Patients: CoAprovel has been rarely associated with hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may be expected to occur in patients who develop sodium or volume-depletion. Volume and/or sodium-depletion should be corrected before initiating therapy with CoAprovel. Thiazides may potentiate the action of other antihypertensive drugs (see Interactions).
Fetal/Neonatal Morbidity and Mortality: Although there is no experience with CoAprovel in pregnant women, in utero exposure to ACE inhibitors given to pregnant women during the second and third trimesters has been reported to cause injury and death to the developing fetus. Thus, as for any drug that also acts directly on the renin-angiotensin-aldosterone system, CoAprovel should not be used during pregnancy. If pregnancy is detected during therapy, CoAprovel should be discontinued as soon as possible.
Thiazides cross the placental barrier and appear in cord blood. The routine use of diuretics in otherwise healthy pregnant women is not recommended and exposes mother and fetus to unnecessary hazard, including fetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions which have occurred in the adult.
Impaired Hepatic and Renal Function: CoAprovel is not recommended for patients with severe renal impairment (creatinine clearance ≤30 mL/min) (see Contraindications). Hydrochlorothiazide-associated precipitation of azotemia may occur in patients with impaired renal function. CoAprovel should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations in fluid and electrolyte balance may precipitate hepatic coma.
Electrolyte and Metabolic Imbalances: Thiazides, including HCTZ, can cause fluid or electrolyte imbalance (hypokalemia, hyponatremia and hypochloremic alkalosis). Although hypokalemia may develop when thiazide diuretics are used alone, especially with higher doses, concurrent therapy with irbesartan reduces the frequency of diuretic-induced hypokalemia. Chloride deficit is generally mild and usually does not require treatment. Calcium excretion is decreased by thiazides which may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia suggests the possibility of 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.
Hyperuricemia may occur, and an acute attack of gout may be precipitated in certain patients receiving thiazide therapy. Insulin requirements in diabetic patients may be increased and latent diabetes mellitus may become manifest during thiazide administration. Irbesartan may induce hypoglycaemia, particularly in diabetic patients. In patients treated with insulin or antidiabetics an appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required when indicated. Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however, minimal or no effects were reported at the 12.5 mg hydrochlorothiazide dose contained in COAPROVEL. Monitoring of laboratory parameters may be necessary in patients at risk for electrolyte and metabolic disturbances.
Systemic Lupus Erythematosus: Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Choroidal effusion, Secondary Acute Angle-Closure Glaucoma and/or Acute Myopia: Hydrochlorothiazide is a sulfonamide. Sulfonamide, or sulfonamide derivative, drugs can cause an idiosyncratic reaction, which may result in choroidal effusion with visual field defect, secondary acute angle-closure glaucoma and/or acute myopia.
Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours 4 to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue drug intake as rapidly as possible.
Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of HCTZ may also need to be reconsidered in patients who have experienced previous NMSC.
Acute Respiratory Toxicity: Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS) have been reported after taking Hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after Hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of ARDS is suspected, Irbesartan / Hydrochlorothiazide (CoAprovel) should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following Hydrochlorothiazide intake.