Lostad T100

Rx

Indications

• Hypertension.
• Reduction in the risk of cardiovascular morbidity and mortality in hypertensive adult patients with left ventricular hypertrophy.
  Lostad T100 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.
• Renal protection in adult patients with hypertension and type 2 diabetes mellitus with proteinuria ≥ 0.5 g/day.
  Lostad T100 reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation), or death; and decreased proteinuria.
• Heart failure
  Treatment of chronic heart failure in adult patients when treatment with angiotensin-converting enzyme (ACE) inhibitors is not considered suitable due to incompatibility, especially cough, or contraindication. Patients with heart failure who have been stabilised with an ACE inhibitor should not be switched to losartan. The patients should have a left ventricular ejection fraction ≤ 40% and should be clinically stable and on an established treatment regimen for chronic heart failure.

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).

Reduction in the risk of cardiovascular morbidity and mortality in hypertensive adult patients with left ventricular hypertrophy.

• 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.

Renal protection in adult patients with hypertension and type 2 diabetes mellitus 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.
• 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 hypoglycaemic agents (e.g. sulfonylureas, glitazones and glucosidase inhibitors).

Chronic 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, 100 mg daily, up to a maximum dose of 150 mg once daily) as tolerated by the patient.

Special populations

• Use in patients with intravascular volume depletion (e.g. those treated with high-dose diuretics):  Starting dose of 25 mg once daily.
• 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.

Paediatric population

• 6 months – less than 6 years: The safety and efficacy of children aged 6 months to less than 6 years has not been established.
• 6 years to 18 years:
  For patients who can swallow tablets, the recommended dose is 25 mg once daily in patients > 20 to < 50 kg (in exceptional cases the dose can be increased to a maximum of 50 mg once daily). Dosage should be adjusted according to blood pressure response.
  In patients > 50 kg: 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.
  Losartan is not recommended for use in children under 6 years old, as limited data are available in these patient groups.
  Losartan 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.
  

Usage

Lostad T100 should be swallowed whole with a glass of water. The tablets may be administered with or without food, on a full or empty stomach. Lostad T100 may be administered with other antihypertensive agents.

• Hypersensitivity to any of the ingredients.
• 2^nd and 3^rd trimester of pregnancy.
• Severe hepatic impairment.
• The concomitant use of losartan with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²).

Common

• Dizziness.
• Vertigo.
• Hyperkalaemia.
• Hypoglycaemia.
• Asthenia, fatigue.
• Blood and lymphatic system: Anaemia.
• Orthostatic hypotension (including dose- related orthostatic effects. Especially in patients with intravascular depletion, e.g. patients with severe heart failure or under treatment with high dose diuretics).
• Renal impairment, renal failure.
• Increase in blood urea, serum creatinine, and serum potassium.

• Patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be closely monitored.
• 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 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 hyperkalaemia 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, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g., trimethoprim-containing products) 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 shown to impair renal function. Therefore, concomitant use is not recommended.
  There is no experience in patients with recent kidney transplantation.
  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.
  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.
  As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
• Lostad T100 contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Dual blockade of the renin-angiotensin-aldosterone system (RAAS):
  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). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended.
  If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
  ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
• Use in paediatric patients:
  Neonates with a history of in utero exposure to Lostad T100: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
  In pediatric patients with hypovolaemia, this should be corrected prior to administration of Lostad T100.
  In clinical studies, there were no age-related differences in the efficacy and safety profiles of losartan.
• When pregnancy is detected, Lostad T100 must be discontinued as soon as possible.
• Losartan is not recommended during breastfeeding are preferable, especially while nursing a new-born or preterm infant.
• When driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose increased.