WARNINGS

Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin 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 BENICAR HCT as soon as possible.

These adverse outcomes are usually associated with 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 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 BENICAR HCT , unless it is considered lifesaving 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 BENICAR HCT for hypotension, oliguria, and hyperkalemia(see PRECAUTIONS , Pediatric Use).

There is no clinical experience with the use of BENICAR HCT® in pregnant women.

No teratogenic effects were observed when 1.6:1 combinations of olmesartan medoxomil and hydrochlorothiazide were administered to pregnant mice at oral doses up to 1625 mg/kg/day (122 times the maximum recommended human dose [MRHD] on a mg/m2 basis) or pregnant rats at oral doses up to 1625 mg/kg/day (280 times the MRHD on a mg/m2 basis).

In rats, however, fetal body weights at 1625 mg/kg/day (a toxic, sometimes lethal dose in the dams) were significantly lower than control.

The no observed effect dose for developmental toxicity in rats, 162.5 mg/kg/day, is about 28 times, on a mg/m2 basis, the MRHD of BENICAR HCT® (40 mg olmesartan medoxomil /25 mg hydrochlorothiazide/day).

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 in Volume- or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with BENICAR HCT ® , as with any angiotensin receptor blocker.

Treatment should start under close medical supervision.

If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline (See DOSAGE AND ADMINISTRATION ).

When electrolyte and fluid imbalances have been corrected, therapy usually can be continued without difficulty.

A transient hypotensive response is not a contraindication to further treatment.

Sprue-like Enteropathy Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation.

Intestinal biopsies of patients often demonstrated villous atrophy.

If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies.

Consider discontinuation of BENICAR HCT ® where no other etiology is identified.

Hydrochlorothiazide Hepatic Impairment Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

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.

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.