NEW ZEALAND DATA SHEET - Medsafe

1 NEW ZEALAND data SHEET 1 PRODUCT NAME COZAAR mg tablet COZAAR 25 mg tablet COZAAR 50 mg tablet COZAAR 100 mg tablet 2 QUALITATIVE AND QUANTITATIVE COMPOSITION COZAAR mg tablet: Each tablet contains mg of losartan potassium . COZAAR 25 mg tablet: Each tablet contains 25 mg of losartan potassium . COZAAR 50 mg tablet: Each tablet contains 50 mg of losartan potassium . COZAAR 100 mg tablet: Each tablet contains 100 mg of losartan potassium . List of excipients with known effect: lactose (as monohydrate). For the full list of excipients, see Section losartan potassium is a white to off-white free-flowing crystalline powder with a molecular weight of It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone.

2 Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan . 3 PHARMACEUTICAL FORM COZAAR mg tablet: An oval blue tablet marked 11 on one side and plain on the other, containing mg of losartan potassium . Dimensions are mm x mm. COZAAR 25 mg tablet: An oval white tablet marked 951 on one side and plain on the other, containing 25 mg of losartan potassium . Dimensions are mm x mm. COZAAR 50 mg tablet: An oval white scored tablet marked 952 on one side and plain on the other, containing 50 mg of losartan potassium . Dimensions are mm x mm. S-WPC-MK0954-T-032018 Page 1 of 14 NEW ZEALAND data SHEET COZAAR 100 mg tablet: A teardrop shaped white tablet marked 960 on one side and plain on the other, containing 100 mg of losartan potassium .

3 Dimensions are mm x mm. 4 CLINICAL PARTICULARS THERAPEUTIC INDICATIONS Hypertension COZAAR is indicated for the treatment of hypertension. Reduction in the Risk of Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy COZAAR is indicated to reduce the risk of cardiovascular morbidity and mortality as measured by the combined incidence of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy (see Section , Race). Heart Failure COZAAR is indicated for the treatment of heart failure in patients who cannot tolerate an ACE inhibitor. Switching patients with heart failure who are stable on an ACE inhibitor to COZAAR is not recommended. Renal Protection in Type 2 Diabetic Patients with Proteinuria COZAAR is indicated to delay the progression of renal disease as measured by a reduction in the combined incidence of doubling of serum creatinine, end stage renal disease (need for dialysis or renal transplantation) or death; and to reduce proteinuria.

4 DOSE AND METHOD OF ADMINISTRATION COZAAR may be administered with or without food. COZAAR may be administered with other antihypertensive agents. Hypertension 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. Some patients may receive an additional benefit by increasing the dose to 100 mg once daily. For patients with intravascular volume-depletion ( , those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered (see Section ). No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis. A lower dose should be considered for patients with a history of hepatic impairment (see Section ).

5 Reduction in the Risk of Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy The usual starting dose is 50 mg of COZAAR once daily. A low dose of hydrochlorothiazide should be added and/or the dose of COZAAR should be increased to 100 mg once daily based on blood pressure response. S-WPC-MK0954-T-032018 Page 2 of 14 NEW ZEALAND data SHEET Heart Failure The initial dose of COZAAR in patients with heart failure is mg once daily. The dose should generally be titrated at weekly intervals ( , mg daily, 25 mg daily, 50 mg daily, 100 mg daily, up to a maximum dose of 150 mg once daily), as tolerated by the patient. COZAAR is usually given in combination with diuretics and digitalis. Renal Protection in Type 2 Diabetic Patients with Proteinuria The usual starting dose is 50 mg once daily.

6 The dose may be increased to 100 mg once daily based on blood pressure response. COZAAR may be administered with other antihypertensive agents ( , diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents) as well as with insulin and other commonly used hypoglycaemic agents ( , sulfonylureas, glitazones and glucosidase inhibitors). CONTRAINDICATIONS COZAAR is contraindicated in patients who are hypersensitive to any component of this product. COZAAR is contraindicated during the 2nd and 3rd trimester of pregnancy (see Section ). COZAAR is contraindicated in patients with severe hepatic impairment. COZAAR should not be administered with aliskiren in patients with diabetes (see Section ). SPECIAL WARNINGS AND PRECAUTIONS FOR USE Foetal Toxicity Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces foetal renal function and increases foetal and neonatal morbidity and death.

7 Resulting oligohydramnios can be associated with foetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue COZAAR as soon as possible. See Section , Pregnancy. Hypersensitivity Angioedema (See Section ). Hypotension and Electrolyte/Fluid Imbalance In patients who are intravascularly volume-depleted ( , those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of COZAAR, or a lower starting dose should be used (see Section ). In type 2 diabetic patients with nephropathy treated with an angiotensin II antagonist, serum potassium levels should be monitored. Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed.

8 In a clinical study conducted in type 2 diabetic patients with proteinuria, the incidence of hyperkalaemia was higher in the group treated with COZAAR as compared to the placebo group; however, few patients discontinued therapy due to hyperkalaemia (see Section , Laboratory Test Findings). S-WPC-MK0954-T-032018 Page 3 of 14 NEW ZEALAND data SHEET Concomitant use of other medicines that may increase serum potassium may lead to hyperkalaemia (see Section ). Dual blockade of the renin-angiotensin-aldosterone system Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin receptor blockers, ACE inhibitors or aliskiren is associated with increased risks of hypotension, syncope, hyperkalaemia, and changes in renal function (including acute renal failure) compared to monotherapy.

9 Closely monitor blood pressure, renal function and electrolytes in patients on COZAAR and other agents that affect the RAAS. Do not co-administer aliskiren with COZAAR in patients with diabetes. Avoid use of aliskiren with COZAAR in patients with renal impairment (GFR <60 ml/min). Liver Function Impairment Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a lower dose should be considered for patients with a history of hepatic impairment. There is no therapeutic experience in patients with severe hepatic impairment. Therefore, losartan is contraindicated in patients with severe hepatic impairment (see Section and ). Renal Function Impairment As a consequence of inhibiting the renin-angiotensin system, changes in renal function including renal failure have been reported in susceptible individuals; these changes in renal function may be reversible upon discontinuation of therapy.

10 Other medicines that affect the renin-angiotensin system may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects have been reported with COZAAR; these changes in renal function may be reversible upon discontinuation of therapy. Paediatric Use Antihypertensive effects of COZAAR have been established in hypertensive paediatric patients aged >1 month to 16 years. Use of COZAAR in these age groups is supported by evidence from adequate and well-controlled studies of COZAAR in paediatric and adult patients as well as by literature in paediatric patients. The pharmacokinetics of losartan have been investigated in 50 hypertensive paediatric patients >1 month to <16 years of age following once daily oral administration of approximately to mg/kg of losartan (mean doses).