Olmesartan and hydrochlorothiazide: uses, appearance and warnings

Olmesartan medoxomil and hydrochlorothiazide tablets is indicated for the treatment of hypertension, to lower blood pressure [see Dosage and Administration ( 2 )]. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with olmesartan medoxomil and hydrochlorothiazide tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Olmesartan medoxomil and hydrochlorothiazide tablets may be used alone or in combination with other antihypertensive drugs. Limitations of Use Olmesartan medoxomil and hydrochlorothiazide tablets is not indicated for the initial therapy of hypertension. • Olmesartan medoxomil and hydrochlorothiazide tablets is a combination of olmesartan, an angiotensin II receptor blocker and hydrochlorothiazide, a thiazide diuretic indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1 ) Limitations of Use Olmesartan medoxomil and hydrochlorothiazide tablets is not indicated for initial therapy. ( 1 )

Olmesartan modoxomil and hydrochlorothiazide tablets are supplied as: 20 mg/12.5 mg: light orange, round, film coated tablets debossed with ‘SG’ on one side and ‘342’ on other side. Each tablet contains 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide. 40 mg/12.5 mg: light orange, oval, film coated tablets debossed with ‘SG’ on one side and ‘343’ on other side. Each tablet contains 40 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide. 40 mg/25 mg: brownish red, oval, film coated tablets debossed with ‘SG’ on one side and ‘344’ on other side. Each tablet contains 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide. Tablets: (olmesartan medoxomil and hydrochlorothiazide) 20/12.5 mg; 40/12.5 mg; 40/25 mg ( 3 )

Olmesartan medoxomil and hydrochlorothiazide tablets are supplied as follows: 20 mg/12.5 mg - light orange, round, film coated tablets debossed with ‘SG’ on one side and ‘342’ on other side. Each tablet contains 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide. 40 mg/12.5 mg - light orange, oval, film coated tablets debossed with ‘SG’ on one side and ‘343’ on other side. Each tablet contains 40 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide. 40 mg/25 mg - brownish red, oval, film coated tablets debossed with ‘SG’ on one side and ‘344’ on other side. Each tablet contains 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide. Tablets are supplied as follows: 20 mg/12.5 mg Bottle of 90 tablets: NDC 84677-056-90 Bottle of 1000 tablets: NDC 84677-056-10 40 mg/12.5 mg Bottle of 90 tablets: NDC 84677-057-90 Bottle of 1000 tablets: NDC 84677-057-10 40 mg/25 mg Bottle of 90 tablets: NDC 84677-058-90 Bottle of 1000 tablets: NDC 84677-058-10 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Olmesartan medoxomil and hydrochlorothiazide tablets is contraindicated: • In patients with hypersensitivity to any component of olmesartan medoxomil and hydrochlorothiazide tablets [see Adverse Reactions ( 6.1 , 6.2 )] • In patients with anuria [see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )] • For co-administration with aliskiren in patients with diabetes [see Drug Interactions ( 7.4 )] • Hypersensitivity to any component of olmesartan medoxomil and hydrochlorothiazide tablets ( 4 ) • Anuria ( 4 ) • Do not co-administer aliskiren with olmesartan medoxomil and hydrochlorothiazide tablets in patients with diabetes.( 4 )

• Hypotension: Correct volume-depletion prior to administration. ( 5.2 ) • Monitor renal function and potassium in susceptible patients ( 5.3 ) • Observe for signs of fluid or electrolyte imbalance. ( 5.5 ) • Acute angle-closure glaucoma ( 5.6 ) • Sprue-like enteropathy has been reported. Consider discontinuation of olmesartan medoxomil and hydrochlorothiazide tablets in cases where no other etiology is found ( 5.8 ) 5.1 Fetal Toxicity Olmesartan medoxomil and hydrochlorothiazide tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system (RAS) 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 [see Use in Specific Populations ( 8.1 )]. Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice and thrombocytopenia [see Use in Specific Populations ( 8.1 )]. 5.2 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 olmesartan medoxomil and hydrochlorothiazide tablets. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. When electrolyte and fluid imbalances have been corrected, olmesartan medoxomil and hydrochlorothiazide tablets usually can be continued without difficulty. A transient hypotensive response is not a contraindication to further treatment. 5.3 Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system ( e.g. , patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on olmesartan medoxomil and hydrochlorothiazide tablets. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on olmesartan medoxomil and hydrochlorothiazide tablets [see Drug Interactions ( 7 )]. 5.4 Hypersensitivity Reactions 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. 5.5 Electrolyte and Metabolic Imbalances Olmesartan medoxomil and hydrochlorothiazide tablets contains hydrochlorothiazide which can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Olmesartan medoxomil and hydrochlorothiazide tablets also contains olmesartan, a drug that inhibits the RAS. Drugs that inhibit the RAS can cause hyperkalemia. Monitor serum electrolytes periodically. Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hyperuricemia may occur or frank gout may be precipitated in patients receiving thiazide therapy. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels. 5.6 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. 5.7 Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. 5.8 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 olmesartan medoxomil and hydrochlorothiazide tablets in cases where no other etiology is identified.

The following adverse reactions with olmesartan medoxomil and hydrochlorothiazide tablets are described elsewhere: • Hypotension in Volume-or Salt-Depleted Patients [see Warnings and Precautions ( 5.2 )] • Impaired Renal Function [see Warnings and Precautions ( 5.3 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] • Electrolyte and Metabolic Imbalances [see Warnings and Precautions ( 5.5 )] • Acute Myopia and Secondary Angle-Closure Glaucoma [see Warnings and Precautions ( 5.6 )] • Systemic Lupus Erythematosus [see Warnings and Precautions ( 5.7 )] • Sprue-Like Enteropathy [see Warnings and Precautions ( 5.8 )] Most common adverse reactions (incidence ≥2%) are nausea, hyperuricemia, dizziness, and upper respiratory infection ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ScieGen Pharmaceuticals, Inc. …

• Agents increasing potassium levels may lead to increase in serum potassium ( 7.1 ). • Lithium: Risk of lithium toxicity ( 7.2 ) • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic and antihypertensive effects; increased risk of renal toxicity ( 7.3 ) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.4 ) • Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose ( 7.5 ) • Antidiabetic drugs: Dosage adjustment may be required ( 7.6 ) • Cholestyramine and colestipol: Reduced absorption of thiazides ( 7.6 ) 7.1 Agents Increasing Serum Potassium Coadministration of olmesartan medoxomil and hydrochlorothiazide with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. …