Losartan Potassium And Hydrochlorothiazide

Fetal Toxicity

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces 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 potassium and hydrochlorothiazide as soon as possible. These adverse outcomes are usually associated with the use of these drugs in the second and third trimester 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 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 rennin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment.

If oligohydramnios is observed, discontinue losartan potassium and hydrochlorothiazide, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Closely observe infants with histories of in utero exposure to losartan potassium and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use).

There was no evidence of teratogenicity in rats or rabbits treated with a maximum losartan potassium dose of 10 mg/kg/day in combination with 2.5 mg/kg/day of hydrochlorothiazide. At these dosages, respective exposures (AUCs) of losartan, its active metabolite, and hydrochlorothiazide in rabbits were approximately 5, 1.5, and 1 times those achieved in humans with 100 mg losartan in combination with 25 mg hydrochlorothiazide. AUC values for losartan, its active metabolite and hydrochlorothiazide, extrapolated from data obtained with losartan administered to rats at a dose of 50 mg/kg/day in combination with 12.5 mg/kg/day of hydrochlorothiazide, were approximately 6, 2, and 2 times greater than those achieved in humans with 100 mg of losartan in combination with 25 mg of hydrochlorothiazide. Fetal toxicity in rats, as evidenced by a slight increase in supernumerary ribs, was observed when females were treated prior to and throughout gestation with 10 mg/kg/day losartan in combination with 2.5 mg/kg/day hydrochlorothiazide. As also observed in studies with losartan alone, adverse fetal and neonatal effects, including decreased body weight, renal toxicity, and mortality, occurred when pregnant rats were treated during late gestation and/or lactation with 50 mg/kg/day losartan in combination with 12.5 mg/kg/day hydrochlorothiazide. Respective AUCs for losartan, its active metabolite and hydrochlorothiazide at these dosages in rats were approximately 35, 10 and 10 times greater than those achieved in humans with the administration of 100 mg of losartan in combination with 25 mg hydrochlorothiazide. When hydrochlorothiazide was administered without losartan to pregnant mice and rats during their respective periods of major organogenesis, at doses up to 3000 and 1000 mg/kg/day, respectively, there was no evidence of harm to the fetus.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Hypotension – Volume-Depleted Patients

In patients who are intravascularly volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with losartan potassium and hydrochlorothiazide. This condition should be corrected prior to administration of losartan potassium and hydrochlorothiazide (see DOSAGE AND ADMINISTRATION).

Impaired Hepatic Function

Hypersensitivity Reaction

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 a history.

Systemic Lupus Erythematosus

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Lithium Interaction

Lithium generally should not be given with thiazides. Monitor serum lithium levels in patients receiving lithium and hydrochlorothiazide (see PRECAUTIONS, Drug Interactions, Hydrochlorothiazide , Lithium).

Acute Myopia and Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute 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 hydrochlorothiazide 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.