Irbesartan

Pronunciation: IR-be-SAR-tan
Class: Angiotensin II receptor antagonist

Trade Names

Avapro
- Tablets, oral 75 mg
- Tablets, oral 150 mg
- Tablets, oral 300 mg

Pharmacology

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the AT ₁ angiotensin II receptor in vascular smooth muscle and the adrenal gland, producing decreased BP.

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Pharmacokinetics

Absorption

The mean absolute bioavailability is 60% to 80%. The T _max is 1.5 to 2 h.

Distribution

90% is protein bound. The mean Vd is 53 to 93 L. Weakly crosses blood-brain barrier and placenta.

Metabolism

Metabolized via glucuronide conjugation and oxidation, primarily via CYP2C9.

Elimination

Renal Cl is 3 to 3.5 mL/min. The mean half-life is 11 to 15 h. Approximately 20% is eliminated in the urine and 80% in the feces.

Peak

4 h.

Duration

24 h.

Special Populations

The pharmacokinetics were not altered in patients with renal impairment or on hemodialysis.

The pharmacokinetics were not significantly affected in patients with mild to moderate cirrhosis of the liver.

The elimination half-life was not significantly altered, but AUC and C _max values were approximately 20% to 50% greater than those of younger subjects.

There was no gender difference in half-life or accumulation, but somewhat higher plasma concentrations were observed in females (11% to 44%).

In healthy black patients, AUC values were approximately 25% greater than white patients; there were no differences in C _max values.

Indications and Usage

Treatment of hypertension; nephropathy in type 2 diabetes.

Contraindications

Hypersensitivity to any component of the product.

Dosage and Administration

PO Start with 150 mg once daily; then titrate to 300 mg once daily as necessary (max, 300 mg/day).

PO 300 mg once daily.

PO Start with 75 mg.

General Advice

• May administer with or without food.
• May administer with other antihypertensive agents.
• Volume depletion should be corrected prior to administration.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

The risk of hyperkalemia and renal dysfunction may be increased. Use with caution and closely monitor renal function and potassium levels.

The risk of hyperkalemia may be increased, particularly in diabetic patients. Coadministration is not recommended in diabetic patients. If coadministration cannot be avoided, closely monitor potassium concentrations and renal function.

Increased lithium concentrations and toxicity may occur during coadministration. Monitor lithium serum concentrations and observe the clinical response of the patient. Adjust the lithium dose as needed.

The antihypertensive effect of irbesartan may be decreased. Coadministration of NSAIDs with irbesartan in patients who are elderly or volume-depleted (including those on diuretics), or those with decreased renal function may result in deterioration of renal function.

The risk of hyperkalemia may be increased. Closely monitor serum potassium concentrations.

The risk of hyperkalemia, especially in elderly patients, may be increased. If coadministration cannot be avoided, closely monitor potassium concentrations and the clinical response.

Adverse Reactions

Cardiovascular

Orthostatic dizziness/hypotension (5%); tachycardia (at least 1%).

CNS

Dizziness (10%); fatigue (4%); anxiety/nervousness, headache (at least 1%).

GI

Diarrhea (3%); dyspepsia/heartburn (2%); abdominal pain, nausea/vomiting (at least 1%).

Genitourinary

UTI (at least 1%); impaired renal function, including renal failure (postmarketing).

Hepatic

Hepatitis, increased LFTs, jaundice (postmarketing).

Metabolic

Hyperkalemia (19%); edema (at least 1%); increased CPK and rhabdomyolysis (postmarketing).

Respiratory

Cough (3%); pharyngitis, rhinitis, sinus abnormality (at least 1%).

Miscellaneous

Chest pain, influenza, musculoskeletal pain, rash (at least 1%); angioedema (involving swelling of the face, lips, pharynx, and/or tongue), thrombocytopenia (postmarketing).

Precautions

Pregnancy

Category D . Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

Lactation

Undetermined.

Children

Irbesartan did not appear to lower BP effectively in pediatric patients 6 to 16 y of age. Not studied in patients younger than 6 y.

Renal Function

Patients with unilateral or bilateral renal artery stenosis may have increases in serum creatinine or BUN.

Hypotension in volume- or salt-depleted patients

Symptomatic hypotension may occur after irbesartan initiation in intravascularly volume- or salt-depleted patients (eg, those treated with high-dose diuretics, patients on dialysis). Correct these conditions prior to administration or use a lower starting dose.

Renal effects

Use with caution in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF); use may be associated with oliguria, progressive azotemia, acute renal failure, and/or death.

Overdosage

Symptoms

Bradycardia, hypotension, tachycardia.

Patient Information

• Advise women of childbearing age about the consequences of exposure to irbesartan during pregnancy. Ask these patients to report pregnancies to their health care provider as soon as possible.
• Advise patients to take the prescribed dose once daily without regard to meals.
• Advise patients to try to take each dose at about the same time each day.
• Inform patients that the drug controls, but does not cure, hypertension and that they should continue taking the drug as prescribed, even when BP is not elevated.
• Advise patients to monitor and record BP and pulse at home and to inform their health care provider if abnormal measurements are noted. Also advise patients to take a record of their BP and pulse to each follow-up visit.
• Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patients to lie or sit down if they experience dizziness or light-headedness when standing.
• Caution patients 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 patients the importance of other modalities on BP: weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt.
• Instruct patients to stop taking the drug and immediately report any of these symptoms to their health care provider: fainting; swelling of the face, lips, eyelids, or tongue.

Copyright © 2009 Wolters Kluwer Health.