losartan/hydrochlorothiazide (Rx)

>10%

Losartan

• Fatigue (14%)
• Hypoglycemia (14%)
• Chest pain (12%)
• Cough, incidence higher in previous cough related to ACE therapy (3-11%)

1-10%

Losartan

• Diarrhea (2-10%)
• URI (8%)
• Hypotension (7%)
• Dizziness (4%)
• Nausea (2%)

Hydrochlorothiazide

• Hypotension
• Anorexia
• Epigastric distress
• Hypokalemia
• Phototoxicity
• Thrombocytopenia

Postmarketing Reports

Hydrochlorothiazide

• Non-melanoma skin cancer

Contraindications

Hypersensitivity to losartan, hydrochlorothiazides, or sulfonamides

Anuria

Coadministration with aliskiren in patients with diabetes

Cautions

In patients with activated renin-angiotensin system, such as volume-or salt-depleted patients (eg, those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment; correct volume or salt depletion prior to administration; do not use drug combination as initial therapy in patients with intravascular volume depletion

Stroke risk reduction may be less effective in African-Americans

Intravascular volume or salt depletion should be corrected prior to use

Monitor serum lithium levels in patients receiving lithium and hydrochlorothiazide

Inform female patients of childbearing age about consequences of exposure to losartan during pregnancy and importance of informing their physician about a pregnancy while on therapy; discontinue if pregnancy detected

Monitor for signs of fluid or electrolyte imbalance, including hyponatremia, hypomagnesemia, hypochloremic alkalosis, and hypokalemia

Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides

If oliguria or hypotension occurs in neonate with history of in utero exposure, direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function

Acute transient myopia and acute angle-closure glaucoma have been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)

Coadministration with corticosteroids, ACTH, or glycyrrhizin (found in liquorice) may intensify electrolyte depletion, particularly hypokalemia

Monitor renal function and potassium in susceptible patients

Exacerbation of systemic lupus erythematosus reported

Dual blockade of the renin-angiotensin-aldosterone system (ie, ARB plus an ACE inhibitor) in patients with established atherosclerotic disease, heart failure, or with diabetes with end organ damage is associated with a higher frequency of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) as compared with use of a single renin-angiotensin-aldosterone system agent; closely monitor blood pressure, renal function and electrolytes in patients on losartan and other agents that affect the renin-angiotensin system (RAS)

Hyperuricemia may occur or frank gout may be precipitated in patients receiving thiazide therapy; because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates diuretic-induced hyperuricemia

Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium; monitor calcium levels

Concomitant use of other drugs that may increase serum potassium may lead to hyperkalemia

Photosensitivity reported; instruct patients to protect skin from sun and undergo regular skin cancer screening

Pregnancy

Therapy can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting renin-angiotensin system from other antihypertensive agents; when pregnancy is detected, discontinue therapy as soon as possible

Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section, post-partum hemorrhage)

Hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

Fetal/neonatal adverse reactions

• Losartan

  • Use of drugs that act on the renin-angiotensin system in second and third trimesters of pregnancy can result in oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death
  • In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin- 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 therapy, unless it is considered lifesaving for the mother
  • Fetal testing may be appropriate, based on week of gestation
  • Patients and physicians should be aware, however, that oligohydramnios may not appear until after fetus has sustained irreversible injury; closely observe neonates with histories of in utero exposure to drug combination for hypotension, oliguria, and hyperkalemia
  • In neonates with a history of in utero exposure to drug combination, if oliguria or hypotension occurs, support blood pressure and renal perfusion
  • Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function

• Hydrochlorothiazide

  • Thiazides can cross placenta, and concentrations reached in umbilical vein approach those in maternal plasma
  • Like other diuretics, the drug can cause placental hypoperfusion; it accumulates in amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma
  • Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia
  • Since they do not alter the course of preeclampsia, these drugs should not be used to treat hypertension in pregnant women
  • The use of hydrochlorothiazide for other indications in pregnancy should be avoided

Lactation

Not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were shown to be present in rat milk; thiazides appear in human milk; because of potential for adverse effects on nursing infant, a decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.