COZAVAN

What it is

COZAVAN is a film-coated tablet containing 25 mg or 50 mg of losartan potassium as the active ingredient. Losartan potassium is the first non-peptide orally active angiotensin II receptor (type AT1) antagonist to be used for the treatment of hypertension. Losartan is an oral angiotensin II receptor (type AT1) antagonist. Angiotensin II binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone.

Approved indications

— Treatment of hypertension. — Delay of progression of renal disease in hypertensive type 2 diabetics with proteinuria, defined as urinary albumin to creatinine ratio ≥ 300 mg/g.

Dosing overview

The usual starting and maintenance dose is 50 mg once daily for most patients. The maximal antihypertensive effect is attained 3–6 weeks after initiation of therapy. If the antihypertensive effect using 50 mg once daily is inadequate, 25 mg twice daily is recommended prior to increasing the dose. For patients with intravascular volume-depletion (e.g., those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered. The total daily dose ranges from 25 mg to 100 mg.

Key safety warnings

Use of COZAVAN during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue COZAVAN as soon as possible. In patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of COZAVAN, or a lower starting dose should be used. In a clinical study conducted in type 2 diabetic patients with proteinuria, the incidence of hyperkalaemia was higher in the group treated with COZAVAN as compared to the placebo group. Concomitant use of other drugs that may increase serum potassium may lead to hyperkalaemia. Anaphylactic reactions and angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue has been reported rarely in patients treated with losartan. Intestinal angioedema has been reported in patients treated with angiotensin II receptor antagonists including few cases with losartan. As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported in susceptible individuals. In patients whose renal function may depend on the activity of the renin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Angiotensin II receptor antagonists would be expected to behave similarly.

Contraindications

COZAVAN is contraindicated in pregnant women and in patients who are hypersensitive to any component of this product. COZAVAN should not be administered with aliskiren in patients with diabetes.

PBS listing

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

Regulatory history

COZAVAN was first listed on the Australian Register of Therapeutic Goods on 28 June 2010, with two registered variants: losartan potassium 25 mg film-coated tablet (ARTG 156235) and losartan potassium 50 mg film-coated tablet (ARTG 156234).