ATACAND

What it is

ATACAND PLUS is a combination of candesartan cilexetil and hydrochlorothiazide tablets. The medicine is available in three strengths: ATACAND PLUS 16/12.5 containing 16 mg candesartan cilexetil and 12.5 mg hydrochlorothiazide; ATACAND PLUS 32/12.5 containing 32 mg candesartan cilexetil and 12.5 mg hydrochlorothiazide; and ATACAND PLUS 32/25 containing 32 mg candesartan cilexetil and 25 mg hydrochlorothiazide. Candesartan is an angiotensin II receptor antagonist, selective for AT1 receptors, with tight binding to and slow dissociation from the receptor. Hydrochlorothiazide inhibits the active reabsorption of sodium, mainly in the distal kidney tubules, and promotes the excretion of sodium, chloride and water.

Approved indications

— Treatment of hypertension .

Dosing overview

The dose of ATACAND PLUS must be determined by careful titration of the dose of each of the individual components. The recommended dose of ATACAND PLUS is 1 tablet once daily. Most of the antihypertensive effect is usually attained within 4 weeks of initiation of treatment. ATACAND PLUS 16/12.5 may be administered in patients whose blood pressure is not optimally controlled with hydrochlorothiazide alone or ATACAND 16 mg monotherapy, while ATACAND PLUS 32/12.5 or 32/25 may be administered in patients whose blood pressure is not optimally controlled with hydrochlorothiazide alone or ATACAND 32 mg monotherapy, or at a lower dose of ATACAND PLUS. ATACAND PLUS should not be used to initiate treatment.

Key safety warnings

In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with drugs that affect this system has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic heart disease or atherosclerotic cerebrovascular disease could result in a myocardial infarction or stroke. There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure), and dual blockade of the renin-angiotensin-aldosterone system through the combined use of ATACAND PLUS with these agents is therefore not recommended. 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 of non-melanoma skin cancer and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions, and possible preventive measures such as limited exposure to sunlight and UV rays and adequate protection should be advised. Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome, have been reported after taking hydrochlorothiazide, with pulmonary oedema typically developing within minutes to hours after hydrochlorothiazide intake and symptoms including dyspnoea, fever, pulmonary deterioration and hypotension. Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma, with symptoms including acute onset of decreased visual acuity or ocular pain typically occurring from hours to weeks of drug initiation, and untreated acute angle-closure glaucoma can lead to permanent vision loss.

Contraindications

ATACAND PLUS is contraindicated in patients with hypersensitivity to any component or to sulfonamide derived drugs. It is contraindicated in pregnancy and lactation. ATACAND PLUS is contraindicated in severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m² body surface area). It is contraindicated in severe hepatic impairment and/or cholestasis. ATACAND PLUS is contraindicated in gout. The use of ATACAND PLUS in combination with aliskiren-containing medicines in patients with diabetes mellitus (type I or II) or with moderate to severe renal impairment (GFR less than 60 mL/min/1.73 m²) is contraindicated.

Regulatory history

ATACAND PLUS 16/12.5 was first listed on the Australian Register of Therapeutic Goods on 7 November 2000. ATACAND PLUS 32/12.5 and 32/25 were first listed on 23 September 2009.