Drug Description

Presentation

Indications

Adult Dosage

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 (in the morning).

Losartan may be administered with other antihypertensive agents, especially with diuretics (e.g. hydrochlorothiazide).

Hypertensive type II diabetic patients with proteinuria 0.5 g/day

The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response from one month onwards after initiation of therapy. Losartan may be administered with other antihypertensive agents (e.g. diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents) as well as with insulin and other commonly used hypoglycemic agents (e.g.sulfonylureas, glitazones and glucosidase inhibitors).

Heart failure

The usual initial dose of losartan in patients with heart failure is 12.5 mg once daily. The dose should generally be titrated at weekly intervals (i.e. 12.5 mg daily, 25 mg daily, 50 mg daily) to the usual maintenance dose of 50 mg once daily, as tolerated by the patient.

Reduction in the risk of stroke in hypertensive patients with left-ventricular hypertrophy documented by ECG

The usual starting dose is 50 mg of losartan once daily. A low dose of hydrochlorothiazide should be added and/ or the dose of losartan should be increased to 100 mg once daily based on blood pressure response.

Special populations

Use in patients with intravascular volume depletion:

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.

Use in patients with renal impairment and haemodialysis patients:

No initial dosage adjustment is necessary in patients with renal impairment and in haemodialysis patients.

Use in patients with hepatic impairment:

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.

Use in paediatric patients

There are limited data on the efficacy and safety of losartan in children and adolescents aged 618 years old for the treatment of hypertension. Limited pharmacokinetic data are available in hypertensive children above one month of age.

The recommended starting dose in patients >20 to <50 kg is 0.7 mg/kg once daily (up to 25 mg total, in exceptional cases where target doses above 25 mg are required, the maximal dose is 50 mg). Dosage should be adjusted according to blood pressure response.

In patients>50 kg, the usual dose is 50 mg once daily. In exceptional cases the dose can be adjusted to a maximum of 100 mg once daily. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in paediatric patients.

For patients who can swallow tablets, this dosage form is also available.

Losartan is not recommended for use in children below 6 years old due to insufficient data on safety and/or efficacy in these patient groups.

It is not recommended in children with glomerular filtration rate < 30 ml/ min / 1.73 m², as no data are available.

Losartan is also not recommended in children with hepatic impairment.

Use in elderly

Although consideration should be given to initiating therapy with 25 mg in patients over 75 years of age, dosage adjustment is not usually necessary for the elderly.

Administration of the oral suspension

Shake the closed bottle of losartan oral suspension well before use. Push the plunger of the dispenser completely down toward the tip of the dispenser. Insert the dispenser into the adapter on the medication bottle until a tight seal is made between the bottle and the adapter. With the dispenser, adapter, and bottle attached, turn the entire assembly upside down. Pull out the plunger to withdraw the medication medicinal product into the dispenser. Return the entire assembly to the upright position. Remove the dispenser and administer the medication. Replace the original cap onto the bottle.

Losartan may be administered with or without food.

Contra Indications

Special Precautions

Hypersensitivity

Angio-oedema. Patients with a history of angio-oedema (swelling of the face, lips, throat, and/ or tongue) should be closely monitored.

Hypotension and electrolyte/fluid imbalance

Symptomatic hypotension, especially after the first dose and after increasing of the dose, may occur in patients who are volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. These conditions should be corrected prior to administration of losartan, or a lower starting dose should be used. This also applies to children 6 to 18 years of age.

Electrolyte imbalances

Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. In a clinical study conducted in type 2 diabetic patients with nephropathy, the incidence of hyperkalemia was higher in the group treated with losartan as compared to the placebo group. Therefore, the plasma concentrations of potassium as well as creatinine clearance values should be closely monitored especially patients with heart failure and a creatinine clearance between 30-50 ml/min should be closely monitored.

The concomitant use of potassium sparing diuretics, potassium supplements and potassium containing salt substitutes with losartan is not recommended.

Hepatic 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 with losartan in patients with severe hepatic impairment. Therefore losartan must not be administered in patients with severe hepatic impairment.

Losartan is not recommended in children with hepatic impairment.

Renal impairment

As a consequence of inhibiting the renin-angiotensin system, changes in renal function including renal failure have been reported (in particular, in patients whose renal function is dependent on the renin angiotensin aldosterone system such as those with severe cardiac insufficiency or pre-existing renal dysfunction). As with other medicinal products that affect the renin-angiotensin-aldosterone system, increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Use in paediatric patients with renal impairment

Losartan is not recommended in children with glomerular filtration rate < 30 ml/ min/1.73 m² as no data are available.

Renal function should be regularly monitored during treatment with losartan as it may deteriorate. This applies particularly when losartan is given in the presence of other conditions (fever, dehydration) likely to impair renal function.

Concomitant use of losartan and ACE-inhibitors has been shown to impair renal function. Therefore, concomitant use is not recommended.

Renal transplantation

There is no experience in patients with recent kidney transplantation.

Primary hyperaldosteronism

Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of losartan is not recommended.

Coronary heart disease and cerebrovascular disease

As with any antihypertensive agents, excessive blood pressure decrease in patients with ischaemic cardiovascular and cerebrovascular disease could result in a myocardial infarction or stroke.

Heart failure

In patients with heart failure, with or without renal impairment, there is, as with other medicinal products acting on the renin-angiotensin system, a risk of severe arterial hypotension, and (often acute) renal impairment.

There is no sufficient therapeutic experience with losartan in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA class IV) as well as in patients with heart failure and symptomatic life-threatening cardiac arrhythmias. Therefore, losartan should be used with caution in these patient groups. The combination of losartan with a beta-blocker should be used with caution.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

Pregnancy

Losartan should not be initiated during pregnancy. Unless continued losartan therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with losartan should be stopped immediately, and, if appropriate, alternative therapy should be started.

Other warnings and precautions:

As observed for angiotensin converting enzyme inhibitors, losartan and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.

Excipients: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sorbitol/Fructose intolerance

The solvent contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Methylhydroxybenzoate and propylhydroxybenzoate

May cause allergic reactions (possibly delayed).

Interactions

Adverse Reactions

Losartan has been evaluated in clinical studies as follows:

• In controlled clinical trials in approximately 3300 adult patients 18 years of age and older for essential hypertension

• In a controlled clinical trial in 9193 hypertensive patients 55 to 80 years of age with left ventricular hypertrophy

• In a controlled clinical trial in approximately 3900 patients 20 years of age and older with chronic heart failure

• In a controlled clinical trial in 1513 type 2 diabetic patients 31 years of age and older with proteinuria

• In a controlled clinical trial in 177 hypertensive paediatric patients 6 to 16 years of age

In these clinical trials, the most common adverse event was dizziness.

The frequency of adverse reactions listed below is defined using the following convention:

very common ( 1/10); common ( 1/100, to < 1/10); uncommon ( 1/1,000, to < 1/100); rare ( /10,000, to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

Hypertension

In controlled clinical trials of approximately 3300 adult patients 18 years of age and older for essential hypertension with losartan the following adverse reactions were reported.

Nervous system disorders:

common: dizziness, vertigo

uncommon: somnolence, headache, sleep disorders

Cardiac disorder:

uncommon: palpitations, angina pectoris

Vascular disorders:

uncommon: symptomatic hypotension (especially in patients with intravascular volume depletion, e.g. patients with severe heart failure or under treatment with high-dose diuretics), dose-related orthostatic effects, rash.

Gastro-intestinal disorders:

uncommon: abdominal pain, obstipation

General disorders and administration site conditions:

uncommon: asthenia, fatigue, oedema

Investigations:

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan tablets. Elevations of ALT occurred rarely and usually resolved upon discontinuation of therapy. Hyperkalaemia (serum potassium>5.5 mmol/l) occurred in 1.5 % of patients in hypertension clinical trials.

Hypertensive patients with left-ventricular hypertrophy

In a controlled clinical trial in 9193 hypertensive patients 55 to 80 years of age with left-ventricular hypertrophy the following adverse events were reported:

Nervous system disorders:

common: dizziness

Ear and labyrinth disorders:

common: vertigo

General disorders and administration site conditions:

common: asthenia/fatigue

Chronic heart failure

In a controlled clinical trial in approximately 3900 patients 20 years of age and older with cardiac insufficiency the following adverse events were reported:

Nervous system disorders:

uncommon: dizziness, headache

rare: paraesthesia

Cardiac disorders:

rare: syncope, atrial fibrillation, cerebrovascular accident

Vascular disorders:

uncommon: hypotension, including orthostatic hypotension

Respiratory, thoracic and mediastinal disorders:

uncommon: dyspnoea

Gastrointestinal disorders:

uncommon: diarrhoea, nausea, vomiting

Skin and subcutaneous tissue disorders:

uncommon: urticaria, pruritus, rash

General disorders and administration site conditions:

uncommon: asthenia/fatigue

Investigations:

uncommon: increase in blood urea, serum creatinine and serum potassium has been reported.

Hypertension and type 2 diabetes with renal disease

In a controlled clinical trial in 1513 type 2 diabetic patients, 31 years of age and older with proteinuria, the most common drug-related adverse reactions which were reported for losartan are as follows:

Nervous system disorders:

common: dizziness

Vascular disorders:

common: hypotension

General disorders and administration site conditions:

common: asthenia/fatigue

Investigations:

common: hypoglycaemia, hyperkalaemia

The following adverse reactions occurred more often in patients receiving losartan than placebo:

Blood and lymphatic system disorders:

not known: anaemia

Cardiac disorders:

not known: syncope, palpitations

Vascular disorders:

not known: orthostatic hypotension

Gastrointestinal disorders:

not known: diarrhoea

Musculoskeletal and connective tissue disorders:

not known: back pain

Renal and urinary disorders:

not known: urinary tract infections

General disorders and administration site conditions:

not known: flu-like symptoms

Investigations:

In a clinical study conducted in type 2 diabetic patients with nephropathy, 9.9 % of patients treated with losartan tablets developed hyperkalaemia >5.5 mEq/l and 3.4 % of patients treated with placebo.

Post-marketing experience

The following adverse reactions have been reported in post-marketing experience:

Blood and lymphatic system disorders:

not known: anaemia, thrombocytopenia

Ear and labyrinth disorders:

not known: tinnitus

Immune system disorders:

rare: hypersensitivity: anaphylactic reactions, angio-oedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue; in some of these patients angio-oedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors; vasculitis, including Henoch-Schönlein purpura.

Nervous system disorders:

not known: migraine

Respiratory, thoracic and mediastinal disorders:

not known: cough

Gastro-intestinal disorders:

not known: diarrhoea, pancreatitis

General disorders and administration site conditions:

not known: malaise

Hepatobiliary disorders:

rare: hepatitis

not known: liver function abnormalities

Skin and subcutaneous tissue disorders:

not known: urticaria, pruritus, rash, photosensitivity

Musculoskeletal and connective tissue disorders:

not known: myalgia, arthralgia, rhabdomyolysis

Reproductive system and breast disorders:

not known: erectile dysfunction/impotence

Renal and urinary disorders:

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported in patients at risk; these changes in renal function may be reversible upon discontinuation of therapy.

Psychiatric disorders:

not known: depression

Investigations:

not known: hyponatraemia

Paediatric population

The adverse reaction profile for paediatric patients appears to be similar to that seen in adult patients. Data in the paediatric population are limited.

Manufacturer

Drug Availability

Updated