Combizar Special Precautions

Fetal Toxicity: When pregnancy is detected, discontinue losartan potassium as soon as possible. Drugs that act directly on the renin-angiotensin-aldosterone system can cause injury and death to the developing fetus.
Losartan potassium: Fetal toxicity: The use of drugs that act on the renin-angiotensin-aldosterone system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue losartan as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimesters of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin-aldosterone system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin-aldosterone system for a particular patient, the mother should be informed of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue losartan, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. However, physicians and patients should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to losartan for hypotension, oliguria and hyperkalemia.
Infants with history of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
Hypersensitivity: Angioedema (swelling of the face, lips, pharynx, and/or tongue) has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Patients with history of angioedema should be closely monitored (see Adverse Reactions).
Hypotension and Electrolyte/Fluid Imbalance: Symptomatic hypotension may be observed in patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics). These conditions should be corrected before starting losartan therapy, or a lower starting dose should be used.
Monitor serum potassium levels in type 2 diabetic patients with nephropathy treated with an angiotensin II antagonist. Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed.
The concomitant use of potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes with losartan is not recommended.
Renal Impairment: Due to inhibition of the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been seen in susceptible patients (e.g., patients whose renal function is dependent on the renin-angiotensin-aldosterone system such as those with severe cardiac insufficiency, pre-existing renal dysfunction or volume depletion) treated with losartan. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function.
As with other drugs affecting the renin-angiotensin-aldosterone system, increases in blood urea nitrogen (BUN) and serum creatinine have been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects have been observed with losartan; these effects may be reversible upon discontinuation of therapy in some patients.
There is no experience with losartan in patients with recent kidney transplantation.
Hepatic Impairment: In patients with a history of hepatic impairment, a lower dose of losartan should be given since significantly increased plasma concentrations of the drug in cirrhotic patients has been observed in pharmacokinetic studies. There is no therapeutic experience with losartan in patients with severe hepatic impairment; thus, losartan should not be administered in patients with severe hepatic impairment.
Primary hyperaldosteronism: Patients with primary hyperaldosteronism will not generally respond to antihypertensive drugs acting through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of losartan is not recommended.
Coronary Heart Disease and Cerebrovascular Disease: As with any antihypertensive agent, excessive hypotension in patients with ischemic cardiovascular and cerebrovascular disease could result in a myocardial infarction or stroke.
Heart Failure: There is a risk of severe arterial hypotension and (often acute) renal impairment in patients with heart failure with or without renal impairment.
Aortic and Mitral Valve Stenosis, Obstructive Hypertrophic Cardiomyopathy: Special caution is indicated in patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Race: In the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study, the benefits of losartan on cardiovascular morbidity and mortality compared with atenolol do not apply to Black patients with hypertension and left ventricular hypertrophy although both treatment regimens effectively reduced blood pressure in Black patients. In the overall LIFE study population, treatment with losartan resulted in a 13% risk reduction compared with atenolol for patients reaching the primary composite endpoint of the combined incidence of cardiovascular death, stroke, and myocardial infarction. Losartan reduced the risk of cardiovascular morbidity and mortality compared with atenolol in non-Black, hypertensive patients with left ventricular hypertrophy as measured by the primary endpoint of the combined incidence of cardiovascular death, stroke, and myocardial infarction. However, Black patients treated with atenolol were at lower risk of experiencing the primary composite endpoint compared with Black patients treated with losartan.
Hydrochlorothiazide: Fluid/Electrolyte Imbalance: Serum electrolytes should be monitored regularly. Patients should be observed for clinical signs of fluid or electrolyte imbalance (e.g., volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia). Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances including nausea and vomiting.
Hypokalemia may develop, particularly with brisk diuresis, when liver cirrhosis is present, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia 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 situations (e.g., liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilutional hyponatremia may be seen in edematous patients in hot weather. Appropriate treatment is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. Appropriate replacement therapy is the treatment of choice in actual salt depletion.
Renal Impairment: Use with caution in patients with renal disease resulting in severe renal impairment because HCTZ decreases glomerular filtration rate and may precipitate azotemia.
Hepatic Impairment: Use with caution in patients with hepatic disease or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Hypersensitivity: Hypersensitivity reactions to HCTZ may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. As a sulfonamide derivative, HCTZ can cause skin rashes and blood dyscrasias.
Systemic Lupus Erythematosus: Exacerbation or activation of systemic lupus erythematosus has been associated with the use of thiazide diuretics.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Discontinue thiazides before taking parathyroid function test.
Thiazide diuretic therapy may increase cholesterol and triglyceride levels.
Thiazides have been reported to increase the urinary excretion of magnesium. This may result in hypomagnesemia.
Hyperuricemia may occur or acute gout may be precipitated in certain patients taking thiazide therapy.
Acute Myopia and Secondary Angle-closure Glaucoma: HCTZ, a sulfonamide, can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours 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.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed with losartan + HCTZ. However, dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, particularly during initiation of treatment or when the dose is increased. Patients should exercise caution when driving vehicles or operating machinery.
Use in Children: The safety and efficacy of losartan + HCTZ in pediatric patients have not been established.
Use in Elderly: In clinical studies, there were no clinically significant differences in the efficacy and safety profiles of losartan + HCTZ in older (≥65 years) and younger (<65 years) patients.