Blopress Plus Special Precautions

General: Candesartan cilexetil - hydrochlorothiazide: In clinical trials of various doses of candesartan cilexetil and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalaemia (serum 3.5 meq/L) was 2.5% versus 2.1% for placebo; the incidence of hyperkalaemia (serum potassium >5.7 meq/L) was 0.4% versus 1% for placebo. No patient receiving Blopress plus 16-12.5 mg was discontinued due to increases or decreases in serum potassium. Overall, the combination of candesartan cilexetil and hydrochlorothiazide had no clinically significant effect on serum potassium.
Hydrochlorothiazide: Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance; namely, hyponatraemia, hypochloremic alkalosis, and hypokalaemia.
Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalaemia. Hypokalaemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilution hyponatraemia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salts, except in rare instances when the hyponatraemia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricaemia may occur or acute gout may be precipitated in certain patients receiving thiazide therapy.
In diabetic patients, dosage adjustment of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus, latent diabetes mellitus may be manifested during thiazide therapy.
The antihypertensive effect of the drug may be enhanced in the post-sympathectomy patient.
If progressive renal impairment becomes evident, consider with holding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium, this may result in hypomagnesemia.
Thiazides have been shown to decrease the urinary calcium excretion or may impair glucose tolerance. Thiazides may cause 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 test for parathyroid function.
Increase in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Impaired renal function: Candesartan cilexetil: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with candesartan cilexetil. In patients whose renal function may depend upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonist has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with candesartan cilexetil. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of candesartan cilexetil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected. Renal function may worsen in patients with renal artery stenosis. When candesartan cilexetil/hydrochlorothiazide is used in patients with impaired renal function, a periodic monitoring of serum potassium, creatinine and uric acid levels is recommended.
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 exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of hydrochlorothiazide could act as a possible mechanism for NMSC.
Patients taking candesartan cilexetil/hydrochlorothiazide 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 candesartan cilexetil/hydrochlorothiazide may also need to be reconsidered in patients who have experienced previous NMSC.
Hydrochlorothiazide: Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Anaesthesia and surgery: Hypotension may occur during anaesthesia and surgery in patients treated with angiotensin II antagonists due to blockade of the renin-angiotensin system. Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors.
Aortic and mitral valve stenosis (obstructive hypertrophic cardiomyopathy): As with other vasodilators, special caution is indicated in patients suffering from haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.
Effects on ability to drive and use machines: The effect of candesartan cilexetil/hydrochlorothiazide on the ability to drive and use machines has not been studied, but based on its pharmacodynamic properties candesartan cilexetil/hydrochlorothizide 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 the treatment of hypertension.