ADESAN

What it is

ADESAN contains candesartan cilexetil and hydrochlorothiazide in three fixed-dose combinations: 16 mg/12.5 mg, 32 mg/12.5 mg, and 32 mg/25 mg. Candesartan cilexetil is a prodrug that is rapidly converted to the active medicine candesartan during absorption from the gastrointestinal tract, and candesartan is an angiotensin II receptor antagonist selective for AT1 receptors. 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 ADESAN must be determined by careful titration of the dose of each of the individual components. The recommended dose is one tablet once daily, taken with or without food. ADESAN 16 mg/12.5 mg may be administered in patients whose blood pressure is not optimally controlled with hydrochlorothiazide alone or with candesartan 16 mg monotherapy. ADESAN 32 mg/12.5 mg or 32 mg/25 mg may be administered in patients whose blood pressure is not optimally controlled with hydrochlorothiazide alone or candesartan 32 mg monotherapy, or at a lower dose of ADESAN. Most of the antihypertensive effect is usually attained within four weeks of initiation of treatment. Treatment should not be initiated with this fixed dose combination.

Key safety warnings

In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system, treatment with medicines that affect this system has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. 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, and dual blockade of the RAAS through the combined use of ADESAN with these medicines is therefore not recommended. An increased risk of non-melanoma skin cancer with increasing cumulative dose of hydrochlorothiazide exposure has been observed, and patients taking hydrochlorothiazide should be informed of this risk and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. 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. Treatment with a thiazide diuretic may impair glucose tolerance and dosage adjustment of antidiabetic medicines, including insulin, may be required. Thiazide diuretics increase serum uric acid concentration and may precipitate gout in susceptible patients.

Contraindications

Hypersensitivity to any component of ADESAN or to sulfonamide derived medicines. Pregnancy and lactation. Severe renal impairment (creatinine clearance < 30 mL/minute/1.73 m² body surface area). Severe hepatic impairment and/or cholestasis. Gout. The use of candesartan/HCT in combination with aliskiren-containing medicines in patients with diabetes mellitus (type I or II) or with moderate to severe renal impairment (GFR<60 ml/min/1.73m²).

PBS listing

No information regarding PBS listing is available in the provided documents.

Regulatory history

ADESAN candesartan cilexetil monotherapy formulations (4 mg, 8 mg, 16 mg and 32 mg tablets) were first listed on the ARTG on 20 February 2013, and ADESAN HCT 16 mg/12.5 mg was also first listed on 20 February 2013. ADESAN HCT 32 mg/12.5 mg and 32 mg/25 mg combinations were first listed on 9 January 2014.