Irbesartan

Products

Irbesartan is commercially available in the form of film-coated tablets as a monopreparation (Aprovel, generic) and as a fixed combination with hydrochlorothiazide (Co-Aprovel). It has been approved in many countries since 1997. Generics entered the market in many countries in August 2012. Generic versions of the combination preprinted with hydrochlorothiazide went on sale in 2013 and 2014.

Structure and properties

Irbesartan (C₂₅H₂₈N₆O, M_r = 428.5 g/mol) is a nonpeptidic inhibitor and not a prodrug such as losartan or candesartancilexetil. It is a tetrazole, biphenyl and diazaspiro compound. It exists as a white crystalline powder that is virtually insoluble in water.

Effects

Irbesartan (ATC C09CA04) has antihypertensive and renoprotective effects by selectively abolishing the physiologic effects of angiotensin II at the AT1 receptor. Angiotensin II is a peptide hormone directly involved in the development of hypertension. It has a potent vasoconstrictor effect and increases aldosterone release, which in turn causes increased water and sodium retention. Adverse effects of irbesartan include potassium retention, which is a risk factor for the development of hyperkalemia.

Indications

For the treatment of hypertension (essential hypertension) and for the treatment of renal disease in patients with hypertension and type 2 diabetes mellitus (diabetic nephropathy).

Dosage

According to the drug label. Irbesartan can be administered once daily due to its long half-life of 11-15 hours. The usual dose is 150-300 mg and intake is independent of meals. Irbesartan can be combined with thiazides (hydrochlorothiazide), calcium channel blockers, and beta blockers.

Contraindications

Hypersensitivity
Patients with hereditary angioedema, a history of angioedema caused by medication
Severely impaired liver function
Pregnancy, especially in the 2nd and 3rd trimesters.
Combination with aliskiren in patients with diabetes mellitus or impaired renal function.

For complete precautions, see the drug label.

Interactions

Irbesartan retains potassium in the body. The risk for hyperkalemia may be increased by concomitant use of potassium-sparing diuretics, potassium salts, and sea salt, among others (see Hyperkalemia). Irbesartan is metabolized primarily by CYP2C9 and -conjugated at tetrazole to irbesartan glucuronide. Relevant interactions were not observed in interaction studies, but cannot be completely excluded. For example, when combined with fluconazole, a CYP2C9 inhibitor, a significant increase in bioavailability was observed. However, this was not considered clinically relevant. Combination with lithium and NSAIDs is not advised.

Adverse effects

Possible adverse effects include headache, dizziness, lightheadedness, fatigue, indigestion, low blood pressure, rapid heartbeat, chest pain, cough, and sexual dysfunction. In rare cases, hypersensitivity reactions with urticaria and angioedema, hyperkalemia, liver and kidney disorders have been reported.