Irbesartan

Usage

• Irbesartan is prescribed for the treatment of hypertension (high blood pressure) and diabetic nephropathy (kidney disease) in patients with type 2 diabetes and hypertension.
• Pharmacological classification: Angiotensin II Receptor Blocker (ARB) or Angiotensin Receptor Antagonist.
• Mechanism of action: Irbesartan works by blocking the action of angiotensin II, a hormone that causes blood vessels to constrict (narrow). By blocking angiotensin II receptors, irbesartan allows blood vessels to relax, thereby lowering blood pressure and protecting kidney function in patients with diabetic nephropathy.

Alternate Names

• International and regional variations: The generic name “irbesartan” is widely used internationally.
• Brand names: Avapro, Karvea, Aprovel (and numerous others depending on the region). It is also available in combination with hydrochlorothiazide under various brand names, such as Avalide, CoAprovel, and Karvezide.

How It Works

• Pharmacodynamics: Irbesartan blocks the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor subtype in vascular smooth muscle and other tissues. It has no agonist effect on AT1 receptors. This receptor blockade prevents vasoconstriction, aldosterone release, and norepinephrine release mediated by angiotensin II, which leads to lower blood pressure, reduction in proteinuria (in kidney disease), and decreased disease progression of nephropathy in Type 2 Diabetes Mellitus.
• Pharmacokinetics:
  • Absorption: Irbesartan is well absorbed after oral administration, with a bioavailability of approximately 60-80%. Food does not significantly affect its absorption.
  • Metabolism: Irbesartan is primarily metabolized in the liver by cytochrome P450 2C9 (CYP2C9) to an inactive metabolite.
  • Elimination: Irbesartan is eliminated by both biliary (via feces) and renal (via urine) excretion, with a half-life of 11-15 hours.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose is 150 mg once daily, which can be increased to a maximum of 300 mg once daily if needed.
• Diabetic Nephropathy: The preferred maintenance dose is 300 mg once daily.

Children:

• Not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy.

Special Cases:

• Elderly Patients: A lower starting dose (75 mg) may be considered in patients over 75 years, but dosage adjustment is not usually necessary.
• Patients with Renal Impairment: No dosage adjustment is generally necessary. A lower starting dose (75 mg) should be considered for patients undergoing hemodialysis.
• Patients with Hepatic Dysfunction: No dosage adjustment is necessary for mild to moderate hepatic impairment. No clinical experience is available for patients with severe hepatic impairment.
• Patients with Comorbid Conditions: Use with caution in volume and/or sodium depleted patients.

Clinical Use Cases

Irbesartan is typically not indicated for acute situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is in the long-term management of hypertension and diabetic nephropathy. Other drugs are preferred for short-term management of blood pressure.

Dosage Adjustments

• For volume- and/or sodium-depleted patients, correct the depletion before starting irbesartan or consider a lower starting dose (75 mg).

Side Effects

Common Side Effects:

• Dizziness, fatigue, upper respiratory tract infection.

Rare but Serious Side Effects:

• Angioedema, hypotension (especially after the first dose in volume-depleted patients), rash, hyperkalemia, renal impairment (worsening of renal function), rhabdomyolysis.

Long-Term Effects:

• Potential for worsening of renal function in patients with pre-existing renal disease. Regular monitoring of kidney function is recommended.

Adverse Drug Reactions (ADR):

• As described under “Rare but Serious Side Effects”, ADRs like angioedema, hypotension, and hyperkalemia require urgent medical attention.

Contraindications

• Hypersensitivity to irbesartan.
• Second and third trimesters of pregnancy.
• Concomitant use of aliskiren in patients with diabetes.

Drug Interactions

• Aliskiren: Co-administration is contraindicated in patients with diabetes or renal impairment. Increased risk of hypotension, hyperkalemia, and renal impairment.
• Potassium supplements and potassium-sparing diuretics: Increased risk of hyperkalemia.
• NSAIDs: May reduce the antihypertensive effect of irbesartan and increase the risk of renal impairment.
• Lithium: Irbesartan may increase lithium levels.
• Other antihypertensive drugs: Additive antihypertensive effect. Monitor blood pressure.
• CYP2C9 inhibitors: These may increase irbesartan levels.
• CYP2C9 inducers: These may decrease irbesartan levels.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D (second and third trimesters); C (first trimester).
• Irbesartan can cause fetal harm and is contraindicated during the second and third trimesters. Its use in the first trimester should be avoided if possible.
• Breastfeeding: It is not known whether irbesartan is excreted in human milk. Use with caution in breastfeeding mothers.

Drug Profile Summary

• Mechanism of Action: Blocks angiotensin II AT1 receptors, leading to vasodilation and reduced blood pressure.
• Side Effects: Dizziness, fatigue, upper respiratory tract infection (common). Angioedema, hypotension, hyperkalemia, renal impairment (rare but serious).
• Contraindications: Hypersensitivity, pregnancy (second and third trimesters), concomitant use of aliskiren in patients with diabetes.
• Drug Interactions: Aliskiren, potassium supplements, NSAIDs, lithium, other antihypertensives, CYP2C9 inhibitors/inducers.
• Pregnancy & Breastfeeding: Contraindicated in the second and third trimesters of pregnancy. Use with caution during breastfeeding.
• Dosage: Hypertension: 150-300 mg once daily; Diabetic nephropathy: 300 mg once daily.
• Monitoring Parameters: Blood pressure, serum creatinine, serum potassium.

Popular Combinations

• Irbesartan + Hydrochlorothiazide: This combination enhances the antihypertensive effect by combining the mechanisms of an ARB and a diuretic. Various fixed-dose combinations are available (e.g., 150mg/12.5mg, 300mg/12.5mg, 300mg/25mg).

Precautions

• General Precautions: Monitor renal function, potassium levels, and blood pressure regularly. Assess for volume depletion before initiating therapy.
• Pregnant Women: Contraindicated during the second and third trimesters. Avoid use in the first trimester.
• Breastfeeding Mothers: Use with caution.
• Children & Elderly: Not recommended for children under 18. Consider lower starting dose for elderly patients.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Irbesartan?

A: The recommended starting dose for hypertension is 150 mg once daily, which can be increased to 300 mg once daily if needed. For diabetic nephropathy, the preferred maintenance dose is 300 mg once daily.

Q2: Can Irbesartan be used in patients with renal impairment?

A: Yes, usually no dosage adjustment is necessary in patients with renal impairment, including those on hemodialysis. However, a lower starting dose (75 mg) should be considered for patients undergoing hemodialysis.

Q3: What are the common side effects of Irbesartan?

A: Common side effects include dizziness, fatigue, and upper respiratory tract infections.

Q4: Is Irbesartan safe to use during pregnancy?

A: No, Irbesartan is contraindicated during the second and third trimesters of pregnancy as it can cause fetal harm. Its use should also be avoided during the first trimester.

Q5: What medications interact with Irbesartan?

A: Irbesartan can interact with medications such as aliskiren, potassium supplements, NSAIDs, lithium, and other antihypertensive drugs. It can also interact with CYP2C9 inhibitors and inducers.

Q6: Can Irbesartan be used with other antihypertensive medications?

A: Yes, Irbesartan can be used in combination with other antihypertensive agents, such as thiazide diuretics, beta-blockers, and calcium channel blockers, if blood pressure is not adequately controlled with irbesartan alone.

Q7: How long does it take for Irbesartan to take effect?

A: The maximum blood pressure-lowering effect of Irbesartan is usually achieved within 4-6 weeks of starting treatment.

Q8: How should Irbesartan be taken?

A: Irbesartan should be taken orally once a day, with or without food.

Q9: What should I do if I miss a dose of Irbesartan?

A: If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and take your next dose at the regular time. Do not double the dose to catch up.

Q10: Should Irbesartan be discontinued before surgery?

A: Although not always mandatory, it is advisable to consult with the anesthesiologist regarding perioperative management of irbesartan, especially if the patient is volume depleted. Some guidelines suggest omitting the dose on the day of surgery.