KARVEZIDE

What it is

Karvezide is an oral antihypertensive agent combining a nonpeptide angiotensin II receptor (AT1 subtype) antagonist, irbesartan, and a thiazide diuretic, hydrochlorothiazide. Karvezide is available in three strengths: 150/12.5 tablets containing 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide; 300/12.5 tablets containing 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide; and 300/25 tablets containing 300 mg of irbesartan and 25 mg of hydrochlorothiazide.

Approved indications

— Treatment of hypertension.

Dosing overview

Treatment should not be initiated with this fixed dose combination, and Karvezide should not be initiated as first-line therapy. Karvezide 150/12.5 mg may be administered to patients whose blood pressure is not adequately controlled with hydrochlorothiazide or irbesartan 150 mg alone. Karvezide 300/12.5 mg may be administered to patients insufficiently controlled by irbesartan 300 mg or by Karvezide 150/12.5 mg, whilst Karvezide 300/25 mg may be administered to patients insufficiently controlled by Karvezide 300/12.5 mg. Doses higher than 300 mg irbesartan/25 mg hydrochlorothiazide once daily are not recommended. The daily dose can be administered with or without food.

Key safety warnings

An increased risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) with increasing cumulative dose of hydrochlorothiazide exposure has been observed in epidemiological studies. Patients taking hydrochlorothiazide should be informed of the risk and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions, and should be advised to minimise exposure to sunlight and ultraviolet rays. Intestinal angioedema has been reported in patients treated with Karvezide, presenting with abdominal pain, nausea, vomiting and diarrhoea, with symptoms resolving after discontinuation; if intestinal angioedema is diagnosed, Karvezide should be discontinued. Severe cases of acute respiratory distress syndrome have been reported after taking hydrochlorothiazide, with pulmonary oedema typically developing within minutes to hours after intake with symptoms of dyspnoea, fever, pulmonary deterioration and hypotension; if diagnosis of acute respiratory distress syndrome is suspected, Karvezide should be withdrawn. Sulfonamide derivative drugs can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, secondary acute angle-closure glaucoma and/or acute myopia, with symptoms including acute onset of decreased visual acuity or ocular pain typically occurring within hours to weeks of drug initiation.

Contraindications

Karvezide is contraindicated in patients who are hypersensitive to irbesartan, sulphonamide derived drugs (such as thiazides), or to any other component of the formulation. Karvezide is contraindicated in patients who are anuric. Karvezide should not be co-administered with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment. Karvezide should not be co-administered with ACE inhibitors in patients with diabetic nephropathy. Karvezide is contraindicated in pregnancy.

Regulatory history

Karvezide 150/12.5 and 300/12.5 were first listed on the Australian Register of Therapeutic Goods on 18 May 2005. Karvezide 300/25 was first listed on 18 April 2007.