AVAPRO

What it is

AVAPRO is an oral antihypertensive agent combining a nonpeptide angiotensin II receptor (AT1 subtype) antagonist, irbesartan, and a thiazide diuretic, hydrochlorothiazide. The tablets contain 150 mg or 300 mg irbesartan and 12.5 mg or 25 mg hydrochlorothiazide as the active ingredients.

Approved indications

— Treatment of hypertension.

Dosing overview

AVAPRO should not be initiated as first-line therapy. Irbesartan 150 mg/hydrochlorothiazide 12.5 mg may be administered to patients whose blood pressure is not adequately controlled with hydrochlorothiazide or irbesartan 150 mg alone. Irbesartan 300 mg/hydrochlorothiazide 12.5 mg may be administered to patients insufficiently controlled by irbesartan 300 mg or by irbesartan 150 mg/hydrochlorothiazide 12.5 mg. Irbesartan 300 mg/hydrochlorothiazide 25 mg may be administered to patients insufficiently controlled by irbesartan 300 mg/hydrochlorothiazide 12.5 mg. Doses higher than irbesartan 300 mg/hydrochlorothiazide 25 mg 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. Photosensitizing actions of hydrochlorothiazide could act as a possible mechanism for non-melanoma skin cancer. 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. Possible preventive measures such as limited exposure to sunlight and ultraviolet rays and, in case of exposure, adequate protection should be advised to patients. Intestinal angioedema has been reported in patients treated with angiotensin II receptor antagonists, including AVAPRO. These patients presented with abdominal pain, nausea, vomiting and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, AVAPRO should be discontinued and appropriate monitoring should be initiated until complete resolution of symptoms has occurred. Severe cases of acute respiratory toxicity, including acute respiratory distress syndrome, have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of acute respiratory distress syndrome is suspected, AVAPRO tablets should be withdrawn and appropriate treatment should be given. Hydrochlorothiazide must not be administered to patients who previously experienced acute respiratory distress syndrome following intake of hydrochlorothiazide or another thiazide diuretic. Hydrochlorothiazide is a sulfonamide. Sulfonamide or sulfonamide derivative drugs can cause an idiosyncratic reaction, which may result in choroidal effusion with visual field defect, secondary acute angle-closure glaucoma and/or acute myopia. Isolated cases of acute angle-closure glaucoma without definite causal association have been reported with hydrochlorothiazide. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss.

Contraindications

Patients who are hypersensitive to irbesartan, sulfonamide-derived drugs (for example thiazides) or to any other ingredient listed in the product information are contraindicated. In general, hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma. Patients who are anuric should not receive AVAPRO. Do not co-administer AVAPRO with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment. Do not co-administer AVAPRO with ACE inhibitors in patients with diabetic nephropathy. AVAPRO is contraindicated in pregnancy.

PBS listing

AVAPRO tablets 150 mg and 300 mg are listed on the PBS with two items each, with both restricted and unrestricted restriction types, at ex-manufacturer prices of A$6.28 and A$7.25 respectively.

Regulatory history

AVAPRO irbesartan 150 mg and 300 mg tablets were first listed on the ARTG on 18 May 2005. AVAPRO HCT 150/12.5 and 300/12.5 combinations were first listed on 18 May 2005. AVAPRO HCT 300/25 was first listed on 18 April 2007.