Cilzec/Cilzec Plus Special Precautions

Serum Electrolytes: Telmisartan and Hydrochlorothiazide: No discontinuations due to hypokalemia were reported during treatment with the telmisartan/hydrochlorothiazide combination. The absence of significant changes in serum potassium levels may be due to the opposing mechanisms of action of telmisartan and hydrochlorothiazide on potassium excretion on the kidney.
Hydrochlorothiazide: Periodic determinations 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: Hyponatremia, hypochloremic alkalosis and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient experiences excessive vomiting or receives 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 eg, nausea and vomiting.
In actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required.
Hyperglycemia may occur with thiazide diuretics. Thus, latent diabetes mellitus may manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides may decrease urinary calcium excretion. 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 tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Impaired Hepatic Function: Telmisartan: As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Cilzec/Cilzec Plus should therefore be used with caution in these patients.
Impaired Renal Function: Telmisartan: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists 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 telmisartan.
There has been no long-term use of telmisartan in patients with unilateral or bilateral renal artery stenosis but an effect similar to that seen with ACE inhibitors should be anticipated.
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.
Dual Blockade of the Renin-Angiotensin-Aldosterone System: Telmisartan: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (eg, by adding an ACE inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.
Effects on the Ability to Drive or Operate Machinery: No studies on the effect on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery, it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Telmisartan and Hydrochlorothiazide: No carcinogenicity, mutagenicity or fertility studies have been conducted with the combination of telmisartan and hydrochlorothiazide.
Telmisartan: There was no evidence of carcinogenicity when telmisartan was administered in the diet of mice and rats for up to 2 years.
Genotoxicity assays did not reveal any telmisartan-related effects at either the gene or chromosomal level.
No drug-related effects on the reproductive performance of male and female rats were noted at 100 mg/kg/day (the highest dose administered), about 13 times, on a mg/m² basis, the MRHD of telmisartan.
Hydrochlorothiazide: Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day).
Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.
Use in pregnancy: Female patients of childbearing age should be told about the consequences of 2nd and 3rd trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the 1st trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Use in lactation: It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: Safety and effectiveness in pediatric patients have not been established.
Use in the elderly: No overall differences in effectiveness and safety of telmisartan/hydrochlorothiazide were observed in geriatric patients compared to younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.