PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Olmesartan Medoxomil and Hydrochlorothiazide Tablets 20 mg/12.5 mg- NDC 70756-812-30 -30s Bottle Label


Olmesartan Medoxomil and Hydrochlorothiazide Tablets 40 mg/12.5 mg- NDC 70756-813-90 -90s Bottle Label


Olmesartan Medoxomil and Hydrochlorothiazide Tablets 40 mg/25 mg- NDC 70756-814-12 -1000s Bottle Label


8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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 olmesartan medoxomil and hydrochlorothiazide tablets 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 intraamniotic environment. If oligohydramnios is observed, discontinue olmesartan medoxomil and hydrochlorothiazide tablets, 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 olmesartan medoxomil and hydrochlorothiazide tablets for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations ( 8.4)].

8.3 Nursing Mothers

It is not known whether olmesartan is excreted in human milk, but olmesartan is secreted at low concentration 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 olmesartan medoxomil and hydrochlorothiazide tablets, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Neonates with a history of in utero exposure to olmesartan medoxomil and hydrochlorothiazide tablets:

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.

Safety and effectiveness of olmesartan medoxomil and hydrochlorothiazide tablets in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of olmesartan medoxomil and hydrochlorothiazide tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.

Olmesartan and hydrochlorothiazide are substantially excreted by the kidney, and the risk of toxic reactions to olmesartan medoxomil and hydrochlorothiazide tablets may be greater in patients with impaired renal function.

8.6 Renal Impairment

Safety and effectiveness of olmesartan medoxomil and hydrochlorothiazide tablets in patients with severe renal impairment (CrCl ≤ 30 mL/min) have not been established. No dose adjustment is required in patients with mild (CrCl 60-90 mL/min) or moderate (CrCl 30-60) renal impairment.

8.7 Hepatic Impairment

Olmesartan medoxomil
No dose adjustment is necessary for patients with mild-to-severe liver disease.

Hydrochlorothiazide
Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

11 DESCRIPTION

Olmesartan medoxomil and hydrochlorothiazide tablets is a combination of an angiotensin II receptor antagonist (AT 1subtype), olmesartan medoxomil, and a thiazide diuretic, hydrochlorothiazide (HCTZ).
Olmesartan medoxomil is 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[ p­ ( o-1 H-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate.
Its empirical formula is C 29H 30N 6O 6and its structural formula is:


Olmesartan medoxomil is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.59. It is practically insoluble in water and sparingly soluble in methanol.

Hydrochlorothiazide is 6-chloro-3,4-dihydro-2 H-1,2,4-benzo- thiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C 7H 8ClN 3O 4S 2and its structural formula is:


Hydrochlorothiazide is a white, or practically white, practically odorless, crystalline powder with a molecular weight of 297.74. Hydrochlorothiazide is slightly soluble in water but freely soluble in sodium hydroxide solution.

Olmesartan medoxomil and hydrochlorothiazide tablets are available for oral administration in tablets containing 20 mg or 40 mg of olmesartan medoxomil combined with 12.5 mg of hydrochlorothiazide, or 40 mg of olmesartan medoxomil combined with 25 mg of hydrochlorothiazide. Inactive ingredients include: hydroxy propyl cellulose, hypromellose, iron oxide red, iron oxide yellow, lactose monohydrate, low substituted hydroxy propyl cellulose, magnesium stearate, microcrystalline cellulose, talc and titanium dioxide.

16 HOW SUPPLIED/STORAGE AND HANDLING

Olmesartan medoxomil and hydrochlorothiazide tablets are supplied as follows:

Tablets are packaged as follows:

Storage
Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Keep this and all medicines out of the reach of children.