Benicar Hct Information
Benicar hct (Olmesartan) Description
Benicar hct (Olmesartan) (olmesartan medoxomil-hydrochlorothiazide) is a combination of an angiotensin II receptor antagonist (AT subtype), olmesartan medoxomil, and a thiazide diuretic, hydrochlorothiazide (HCTZ).
Olmesartan medoxomil, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract.
Olmesartan medoxomil is 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[-(-1-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate.
Its empirical formula is CHNO and its structural formula is:
Olmesartan medoxomil is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.6. It is practically insoluble in water and sparingly soluble in methanol.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2-1,2,4-benzo-thiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is CHClNOS and its structural formula is:
Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.7. Hydrochlorothiazide is slightly soluble in water but freely soluble in sodium hydroxide solution.
Benicar hct (Olmesartan) is 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: hydroxypropylcellulose, hypromellose, lactose, low-substituted hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, red iron oxide, talc, titanium dioxide and yellow iron oxide.
Benicar hct (Olmesartan) Clinical Pharmacology
Pediatric:
Geriatric:
Gender:
max
Renal Insufficiency:
Hepatic Insufficiency:
Benicar hct (Olmesartan) Indications And Usage
Benicar hct (Olmesartan) is indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy (see ).
Benicar hct (Olmesartan) Contraindications
Benicar hct (Olmesartan) is contraindicated in patients who are hypersensitive to any component of this product.
Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Benicar hct (Olmesartan) Warnings
Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature of patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, Benicar hct (Olmesartan) should be discontinued as soon as possible.
The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development. Prematurity, intrauterine growth retardation and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.
These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of Benicar hct (Olmesartan) as soon as possible.
Rarely (probably less often than once in every thousand pregnancies), no alternative to a drug acting on the renin-angiotensin system will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses and serial ultrasound examinations should be performed to assess the intra-amniotic environment.
If oligohydramnios is observed, Benicar hct (Olmesartan) should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a nonstress test (NST) or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of 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 means of reversing hypotension and/or substituting for disordered renal function.
There is no clinical experience with the use of Benicar hct (Olmesartan) 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/m basis) or pregnant rats at oral doses up to 1625 mg/kg/day (280 times the MRHD on a mg/m 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/m basis, the MRHD of Benicar hct (Olmesartan) (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.
Benicar hct (Olmesartan) Precautions
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with olmesartan medoxomil. In patients whose renal function may depend upon the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with olmesartan medoxomil. (See, )
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.
Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Pregnancy:
All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea or vomiting can lead to an excessive fall in blood pressure, with the same consequences of light-headedness and possible syncope.
Pregnancy Categories C (first trimester) and D (second and third trimesters)
(See )
It is not known whether olmesartan is excreted in human milk, but olmesartan is secreted at low concentration in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
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 the drug, taking into account the importance of the drug to the mother.
Clinical studies of Benicar hct (Olmesartan) 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 this drug may be greater in patients with impaired renal function.
Benicar hct (Olmesartan) Adverse Reactions
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of olmesartan medoxomil-hydrochlorothiazide.
Creatinine, Blood Urea Nitrogen:
Hemoglobin and Hematocrit:
Post-Marketing Experience
Benicar hct (Olmesartan) Dosage And Administration
The usual recommended starting dose of BENICAR (olmesartan medoxomil) is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose may be increased to 40 mg. Doses above 40 mg do not appear to have greater effect. Twice-daily dosing offers no advantage over the same total dose given once daily. No initial dosage adjustment is recommended for elderly patients, for patients with moderate to marked renal impairment (creatinine clearance
Hydrochlorothiazide is effective in doses between 12.5 mg and 50 mg once daily.
The side effects (see ) of BENICAR are generally rare and independent of dose; those of hydrochlorothiazide are most typically dose-dependent (primarily hypokalemia). Some dose-independent phenomena (e.g., pancreatitis) do occur with hydrochlorothiazide. Therapy with any combination of olmesartan medoxomil and hydrochlorothiazide will be associated with both sets of dose-independent side effects.
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
Benicar hct (Olmesartan) How Supplied
Benicar hct (Olmesartan) is supplied as 20 mg/12.5 mg: reddish-yellow, circular, film-coated tablets, approximately 8.5 mm in diameter, with "Sankyo" debossed on one side and “C22” on the other side. Each tablet contains 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide.
40 mg/12.5 mg: reddish-yellow, oval, film-coated tablets, approximately 15 x 7 mm, with "Sankyo" debossed on one side and “C23” on the other side. Each tablet contains 40 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide.
40 mg/25 mg: pink, oval, film-coated tablets, approximately 15 x 7 mm, with "Sankyo" debossed on one side and "C25" on the other side. Each tablet contains 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide.
Tablets are supplied as follows:
