Olmesartan Medoxomil

Pronunciation: (OL-me-SAR-tan meh-DOX-oh-mil)
Class: Angiotensin II receptor antagonist

Trade Names

Benicar
- Tablets 5 mg
- Tablets 20 mg
- Tablets 40 mg

Pharmacology

Blocks vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT ₁ receptor in vascular smooth muscle.

Pharmacokinetics

Absorption

Rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the GI tract. Steady state is 3 to 5 days. Bioavailability is approximately 26%. T _max is 1 to 2 h.

Distribution

Vd is 17 L. 99% is protein bound.

Elimination

Approximately 35% to 50% is eliminated through urine, the remainder is eliminated in feces via bile.

Total plasma Cl is 1.3 L/h. Renal Cl is 0.6 L/h. Half-life is approximately 13 h.

Special Populations

Renal Function Impairment

AUC is approximately tripled when CrCl is less than 20 mL/min.

Hepatic Function Impairment

In patients with moderate hepatic impairment, AUC increased by approximately 60%; C _max was also increased.

Elderly

AUC increased by 33%, and there is a 30% reduction in renal clearance.

Children

Cl was similar to adults when adjusted by body weight.

Gender

AUC and C _max increased 10% to 15% in women.

Race

Antihypertensive effect was smaller in black patients.

Indications and Usage

Treatment of hypertension.

Unlabeled Uses

Prevention of migraine.

Contraindications

None well documented.

Dosage and Administration

Adults

PO Start with 20 mg once daily; after 2 wk, dosage may be increased to 40 mg/day if further reduction in BP is needed.

Children (6 to 16 yr of age)

PO Start with 10 mg once daily for patients who weigh 20 to less than 35 kg, or 20 mg for patients who weigh 35 kg or more. After 2 wk, dosage may be increased to a max of 20 mg/day for patients who weigh 20 to less than 35 kg, or 40 mg/day for patients who weigh 35 kg or more.

General Advice

• If BP is not controlled by olmesartan alone, a diuretic or other antihypertensive agent may be added.
• For patients with depletion of intravascular volume, consider using a lower starting dose.
• May be administered with or without food.
• For children who cannot swallow tablets, the same dose can be given using an extemporaneous suspension.

Storage/Stability

Store at 68° to 77°F.

Drug Interactions

ACE inhibitors (eg, captopril)

Coadministration of olmesartan and ACE inhibitors may be associated with an increased risk of renal dysfunction. Use with caution. Closely monitor renal function.

Potassium-sparing diuretics (eg, spironolactone)

The risk of hyperkalemia may be increased when potassium-sparing diuretics are coadministered with olmesartan. Closely monitor serum potassium concentrations and renal function in patients receiving olmesartan with potassium-sparing diuretics. Adjust therapy as needed.

Adverse Reactions

CNS

Dizziness (3%); vertigo (more than 1%); headache (1% or more); asthenia (postmarketing).

Dermatologic

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

GI

Diarrhea (1% or more); abdominal pain, dyspepsia, gastroenteritis, nausea (more than 1%); vomiting (postmarketing).

Genitourinary

Hematuria (1% or more); acute renal failure (postmarketing).

Metabolic

Hypercholesterolemia, hyperlipemia, hyperuricemia (more than 1%); hyperglycemia, hypertriglyceridemia (1% or more); hyperkalemia (postmarketing).

Musculoskeletal

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

Respiratory

Bronchitis, pharyngitis, rhinitis, sinusitis (1% or more); cough (1%).

Miscellaneous

Chest pain, facial edema, peripheral edema, tachycardia (more than 1%); CPK increase, influenza-like symptoms (1% or more); angioedema, increased blood creatinine levels (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 even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.

Pregnancy

Category C (first trimester); Category D (second and third trimester). Can cause injury or death to the fetus if used during second or third trimester.

Lactation

Undetermined.

Children

No dosing information is available in children 6 yr of age and younger.

Hypotension in volume- or salt-depleted patients

Symptomatic hypotension may be anticipated after initiation of treatment.

Renal effects

In patients whose renal function may depend on activity of the renin-angiotensin–aldosterone enzyme system (eg, patients with severe CHF), treatment may be associated with oliguria and/or progressive azotemia, rarely resulting in acute renal failure and/or death.

Overdosage

Symptoms

Bradycardia, hypotension, tachycardia.

Patient Information

• Advise patient to take once daily as prescribed, without regard to meals, but to take with food if GI upset occurs.
• Inform patient that the drug controls, but not does cure, hypertension, and to continue taking the drug as prescribed, even when BP is not elevated.
• Instruct patient to continue taking other BP medications as prescribed by health care provider.
• Instruct patient to sit or lie down if experiencing dizziness or light-headedness when standing.
• Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, resulting in light-headedness or fainting.
• Emphasize to hypertensive patient the importance of the following other modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
• Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: fainting; swelling of the face, lips, eyelids, or tongue.
• Advise women of childbearing age about the consequences of second and third trimester exposure to drugs that act on the renin-angiotensin system and instruct them to report pregnancies to their health care provider.

Copyright © 2009 Wolters Kluwer Health.