Irbesartan / Hydrochlorothiazide

Pronunciation: IR-be-SAR-tan/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Avalide
- Tablets, oral irbesartan 150 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral irbesartan 300 mg/hydrochlorothiazide 12.5 mg

Pharmacology

Irbesartan

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

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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 Irbesartan 150 mg/hydrochlorothiazide 12.5 mg once daily initially. Increase after 1 to 2 wk of therapy based on individual response (max, irbesartan 300 mg/hydrochlorothiazide 25 mg once daily). In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, the recommended doses, in order of increasing mean effect are irbesartan 150 mg/hydrochlorothiazide 12.5 mg, 300 mg/12.5 mg, and 300 mg/25 mg.

Renal Function Impairment (CrCl less than 30 mL/min)

Use is not recommended.

General Advice

  • May be administered with other antihypertensive agents.
  • Administer with or without food.
  • Not recommended as initial therapy in patients with intravascular volume depletion.
  • Max antihypertensive effects are attained within 2 to 4 wk after a change in dose.
  • May be substituted for the titrated components.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

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

ACE inhibitors (eg, captopril)

The risk of hyperkalemia and renal dysfunction may be increased. Consider monotherapy. If coadministration cannot be avoided, closely monitor serum potassium and renal function.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur. Monitor BP.

Aliskiren

The risk of hyperkalemia is increased with coadministration. Coadministration is contraindicated in diabetic patients because of an increased risk of renal impairment, hypotension, and hypokalemia. Avoid coadministration in patients with moderate to severe renal impairment (glomerular filtration rate less than 60 mL/min).

Antihypertensive agents (eg, propranolol)

Additive or potentiation of hypotension effects. Closely monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. Coadminister with caution.

Carbamazepine

Coadministration of carbamazepine and hydrochlorothiazide has been associated with symptomatic hyponatremia. Monitor electrolytes.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate irbesartan/hydrochlorothiazide by at least 1 h before or 4 h after these medications.

Corticosteroids, corticotropin

Electrolyte depletion may be intensified, particularly hypokalemia. Closely monitor serum potassium.

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin)

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide may be reduced. Monitor BP and the diuretic response. In patients who are elderly or volume-depleted, or in those with compromised renal functions, coadministration of NSAIDs and cyclooxygenase 2 inhibitors with irbesartan may result in deterioration of renal function, including possible acute renal failure.

Diazoxide

The pharmacologic effects of diazoxide and irbesartan/hydrochlorothiazide may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid, and make dosage adjustments as needed.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium; supplement low levels. Prevent further losses with dietary management.

Dofetilide

Dofetilide plasma concentrations may be increased. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Hypoglycemic agents, oral (eg, sulfonylureas)

Hydrochlorothiazide may increase fasting blood glucose. The effect of oral hypoglycemic agents and insulin may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.

Insulin

Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion. The effect of insulin may be decreased. 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.

Loop diuretics (eg, furosemide)

May cause diuresis and serious electrolyte abnormalities. Monitor for dehydration and electrolyte abnormalities during combined therapy.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increased responsiveness to the muscle relaxant because of diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Potassium preparations (eg, potassium-sparing diuretics [eg, spironolactone], potassium supplements, potassium salt substitutes)

May increase serum potassium levels. Closely monitor serum potassium concentrations, and adjust treatment as needed.

Pressor amines (eg, norepinephrine)

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

Tretinoin

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

Trimethoprim

Reduction of aldosterone activity may decrease potassium excretion as an additive effect with trimethoprim. Hyperkalemia, possibly with cardiac arrhythmias or cardiac arrest, may occur. Closely monitor serum potassium.

Adverse Reactions

Cardiovascular

Hypotension, tachycardia (1%).

CNS

Dizziness (8%); fatigue, headache (6%); orthostatic dizziness (1%).

GI

Nausea, vomiting (3%); abdominal pain, dyspepsia/heartburn (2%).

Hepatic

Hepatitis, jaundice (postmarketing).

Hypersensitivity

Allergy (1%); angioedema involving swelling of the face, lips, pharynx, and/or tongue, urticaria (postmarketing).

Lab Tests

Hypokalemia (8%); increased BUN (2%); hyperkalemia, increased serum creatinine (1%); elevations of liver enzymes and/or bilirubin; fluid and/or electrolyte imbalance (eg, hyponatremia, hypercalcemia, hyperuricemia, hypomagnesemia); increased CPK (postmarketing).

Musculoskeletal

Musculoskeletal pain (6%); rhabdomyolysis (postmarketing).

Miscellaneous

Edema, influenza (3%); abnormal urination, chest pain (2%); impaired renal function, including renal failure (postmarketing).

Precautions

Warnings

When pregnancy is detected, discontinue use as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Monitor

Observe patients for clinical signs of fluid or electrolyte imbalance. Perform periodic determinations of serum electrolytes to detect possible electrolyte imbalance. Correct volume depletion prior to administration.


Pregnancy

Category D . Use of drugs that act directly on the renin-angiotensin system 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.

Thiazides cross the placenta, and the use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and other adverse reactions that have occurred in adults.

Lactation

It is not known whether irbesartan is excreted in human milk; thiazides appear in human milk. Discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother.

Children

Safety and efficacy not established.

Hypersensitivity

May occur in patients with or without a history of allergy or bronchial asthma.

Renal Function

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported; expect a similar effect with irbesartan. In addition, hydrochlorothiazide may precipitate azotemia, and cumulative effects of the drug may develop in patients with impaired renal function. Not recommended in patients with severe renal disease.

Hepatic Function

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

Diabetes

May require adjustments of insulin or oral hypoglycemic agents. Hyperglycemia may occur with thiazide diuretics; latent diabetes mellitus may manifest during thiazide therapy.

Fluid/Electrolyte imbalance

Hypercalcemia, hypokalemia, hypomagnesemia, and/or hyponatremia may occur.

Hyperuricemia

Hyperuricemia or frank gout may be precipitated.

Hypotension

Symptomatic hypotension may occur after initiation of treatment in patients with volume or salt depletion (eg, patients treated vigorously with diuretics, patients on dialysis). Correct volume depletion prior to initiation of therapy.

Lipid disturbances

Increases in cholesterol and triglyceride levels may occur.

Ophthalmic effects

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

Postsympathectomy

Antihypertensive effects of the drugs may be enhanced.

Renal effects

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

Systemic lupus erythematosus

Activation or exacerbation may occur.

Overdosage

Symptoms

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

Patient Information

  • Inform women of childbearing age about the consequences of exposure to irbesartan/hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Women who become pregnant during therapy should notify their health care provider as soon as possible.
  • Inform patients that they may feel light-headed, especially during the first few days of use. Advise patients to inform their health care provider if they feel light-headed or faint. If fainting occurs, advise the patient to stop therapy and contact their prescribing health care provider.
  • 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.
  • Instruct diabetic patients to monitor blood glucose more frequently when drug is started or dose is changed, and to inform their health care provider of significant changes in readings.
  • Caution patients to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths), and to use sunscreen and wear protective clothing when exposed to UV light to avoid a photosensitivity reaction.
  • Caution patients to not take any prescription or OTC medications, salt substitutes, or dietary supplements unless advised to do so by a health care provider.

Copyright © 2009 Wolters Kluwer Health.

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