Olmesartan Medoxomil / Hydrochlorothiazide

Pronunciation: OL-me-SAR-tan me-DOX-oh-mil/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Benicar HCT
- Tablets, oral olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral olmesartan medoxomil 40 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg

Pharmacology

Olmesartan

Blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT ₁ receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension.

Contraindications

Anuria; hypersensitivity to sulfonamide derivatives or any component of the product.

Dosage and Administration

Adults

PO 1 tablet once daily. Olmesartan is effective in the dosage range of 20 to 40 mg daily and hydrochlorothiazide is effective in dosages of 12.5 to 50 mg daily. Depending on the BP response, the dose may be titrated at intervals of 2 to 4 wk.

General Advice

• Individualize dosage.
• May be given with other antihypertensive agents.
• May be given with or without food.
• This fixed-dose combination is not indicated for initial therapy; it may be substituted for its individual components.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

No drug interaction studies have been conducted between olmesartan/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the olmesartan/hydrochlorothiazide combination.

ACE inhibitors (eg, captopril, ramipril)

Concurrent use may be associated with an increased risk of renal dysfunction and hyperkalemia. Consider monotherapy.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur. Monitor BP.

Aliskiren

Renal excretion of potassium may be decreased, resulting in hyperkalemia, particularly in diabetic patients. Use alternatives to aliskiren in patients with diabetes or moderate to severe renal impairment. If coadministration is undertaken, closely monitor serum potassium concentrations and renal function.

Antihypertensives (eg, propranolol)

Additive or potentiation of hypotension effects may occur.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by at least 4 h. Adjust hydrochlorothiazide dose as needed.

Corticosteroids, corticotropin

Coadministration may cause intensified electrolyte depletion, particularly hypokalemia.

Cyclooxygenase 2 inhibitors (eg, celecoxib); NSAIDs (eg, ibuprofen, indomethacin, ketorolac [nasal])

The diuretic, natriuretic, and antihypertensive effects of olmesartan and the antihypertensive effects of telmisartan may be reduced. In addition, concomitant use may further deteriorate renal function, especially in volume-depleted patients, patients with renal impairment, or in elderly patients. The risk of hyperkalemia may also be increased. Monitor BP, renal function, and serum potassium. If an interaction is suspected, it may be necessary to discontinue the NSAID.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid. Adjust dosage as needed.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium, and monitor patients for signs of digoxin toxicity.

Dofetilide

Plasma concentrations of dofetilide may be increased; prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Insulin

Insulin requirements may increase or decrease, or remain unchanged. Monitor blood glucose and adjust the insulin dose as needed.

Lithium

Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Avoid coadministration. If coadministration cannot be avoided, closely monitor serum lithium levels and adjust the dose of lithium as needed.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. In contrast, loop diuretics and hydrochlorothiazide have synergistic effects that may result in profound diuresis and electrolyte abnormalities. Monitor fluid status and electrolytes.

Nondepolarizing muscle relaxants (eg, pancuronium)

A possible increase in responsiveness to the muscle relaxant due to diuretic-induced hypokalemia may occur. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Potassium preparations, potassium-sparing diuretics (eg, amiloride, spironolactone), potassium supplements, salt substitutes containing potassium

Serum potassium concentrations may be increased. Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Sulfonylureas (eg, glyburide)

Hydrochlorothiazide may increase fasting blood glucose and decrease the hypoglycemic action of sulfonylureas. Closely monitor blood glucose and adjust therapy as needed.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Trimethoprim

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur, especially in elderly patients. Closely monitor serum potassium. Adjust therapy as needed.

Laboratory Test Interactions

Hydrochlorothiazide may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Interrupt therapy for a few days before carrying out tests of parathyroid function.

Adverse Reactions

CNS

Dizziness (9%); headache (more than 2%); vertigo (more than 1%); asthenia (postmarketing).

Dermatologic

Rash (more than 1%); alopecia, pruritus, urticaria (postmarketing).

GI

Nausea (3%); abdominal pain, diarrhea, dyspepsia, gastroenteritis (more than 1%); vomiting (postmarketing).

Genitourinary

UTI (more than 2%); hematuria (more than 1%); acute renal failure, increased blood creatinine levels (postmarketing).

Hepatic

Increased AST, ALT, and GGT (more than 1%).

Lab Tests

Increased BUN and serum creatinine (1%).

Metabolic-Nutritional

Hyperuricemia (4%); hyperkalemia (2%); hyperglycemia, hyperlipidemia, increased CPK (more than 1%).

Musculoskeletal

Arthralgia, arthritis, back pain, myalgia (more than 1%); rhabdomyolysis (postmarketing).

Respiratory

Upper respiratory tract infection (7%); coughing (more than 1%).

Miscellaneous

Chest pain, peripheral edema (more than 1%); anaphylactic reactions, angioedema (postmarketing).

Precautions

Warnings When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue olmesartan/hydrochlorothiazide as soon as possible.

Monitor Ensure that volume and/or salt depletion have been corrected before initiating therapy. Perform periodic determinations of serum electrolytes and renal function. Observe all patients for clinical signs of fluid or electrolyte imbalance. Monitor BP and pulse on a regular basis. Monitor blood glucose in patients with diabetes when drug is started or dose is changed.

Pregnancy

Category C (first trimester); Category D (second and third trimesters). Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death, when administered to pregnant women during the second and third trimesters. Oligohydramnios has also been reported, and 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. Pregnant women whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed.

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.

Lactation

It is not known whether olmesartan is excreted in human milk; thiazides appear in human milk. A decision should be made whether to discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother.

Children

Safety and efficacy not established.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

May occur in patients with or without a history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur.

Renal Function

Not recommended in patients with severe renal impairment. Use with caution in renal disease. Thiazides may precipitate azotemia in these patients.

Hepatic Function

Use with caution in patients with impaired hepatic function or progressive liver disease.

Diabetes

Hyperglycemia may occur; latent diabetes mellitus may become manifest.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, hypophosphatemia, and hypomagnesemia may occur.

Hyperuricemia

Hyperuricemia may occur or frank gout may be precipitated.

Hypotension

Symptomatic hypotension may occur after initiation of therapy in patients who are intravascularly volume depleted (eg, those treated with diuretics). Use with caution in these patients. Correct these conditions prior to administration or start treatment under close medical supervision.

Lipid disorders

Increases in cholesterol and triglyceride levels may occur.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms typically occur within hours to weeks of initiation of therapy.

Postsympathectomy

The antihypertensive effects may be enhanced in these patients.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors has been associated with oliguria and and/or progressive azotemia, and, rarely, acute renal failure and/or death. In addition, increased BUN and serum creatinine may occur.

Systemic lupus erythematosus

Activation or exacerbation may occur.

Overdosage

Symptoms

Bradycardia, dehydration, electrolyte depletion (ie, hypochloremia, hypokalemia, hyponatremia), hypotension, tachycardia.

Patient Information

• Inform female patients of childbearing age about the consequences of second and third trimester exposure to drugs that act on the renin-angiotensin system and that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Patients should be asked to report pregnancies to their health care provider as soon as possible.
• Caution patients that light-headedness can occur, especially during the first few days of therapy, and that it should be reported to the prescribing health care provider. Inform patients that if syncope occurs, olmesartan/hydrochlorothiazide should be discontinued until the health care provider has been consulted.
• Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, with the same consequences of light-headedness and possible syncope.

Copyright © 2009 Wolters Kluwer Health.