Lortell 25, 50, 100 mg TABLETS

LORTELL is indicated for:

• The treatment of hypertension
• Renal protection in type 2 diabetic patients with hypertension and proteinuria

Posology

Hypertension

The usual starting and maintenance dose is 50 mg once daily for most patients. The maximum antihypertensive effect is achieved 3-6 weeks after initiation of therapy. The dose may be increased to 100 mg once daily.

Renal protection in type 2 diabetic patients with hypertension and proteinuria

The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response.

Special populations

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 (see section 4.4).

Renal impairment

No initial dosage adjustment is necessary for patients with renal impairment, including patients on dialysis.

Hepatic impairment

A lower dose should be considered for patients with a history of hepatic impairment (see section 4.4).

Elderly population

No initial dosage adjustment is necessary for the elderly patients.

Paediatric population

The safety and efficacy of LORTELL in children have not yet been established.

Method of administration

LORTELL is indicated for oral administration. LORTELL may be administered with or without food. LORTELL may be administered with other antihypertensive medicines of a different class.

• Hypersensitivity to the losartan potassium or to any of the excipients listed in section 6.1
• In patients with a history of angio-oedema related to ACE-inhibitors or angiotensin receptor antagonists such as LORTELL
• Hypertrophic obstructive cardiomyopathy
• LORTELL is not recommended for patients with severe renal impairment or for patients with hepatic impairment
• Aortic stenosis, left ventricular outflow track obstruction
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene and amiloride
• Pregnancy and lactation (see section 4.6)
• Concomitant use of fluoroquinolones in patients with moderate to severe renal impairment.

Pregnancy

Women of childbearing age should ensure adequate contraception (see sections 4.3 and 4.6).

Renal function impairment

LORTELL should be used with caution in patients with bilateral renal artery stenosis or stenosis of an artery to a single kidney, aortic valve stenosis or hypertrophic obstructive cardiomyopathy. When impaired renal function is present, changes in renal function as a consequence of inhibiting the renin-angiotensin system including renal failure have been reported in susceptible individuals. These changes in renal function may be reversible upon discontinuation of LORTELL therapy, in some patients. In patients whose renal function may depend on the activity of the renin-angiotensin-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 (less frequently) with acute renal failure and/or death. Similar outcomes are likely with LORTELL therapy.

Medicines affecting 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. These changes in renal function may be reversible upon discontinuation of LORTELL therapy.

Symptomatic hypotension

Symptomatic hypotension may occur after initiation of LORTELL.

Hepatic impairment

Reduced doses must be considered in patients with hepatic impairment. Based on reported pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a dose of 25 mg should be considered for patients with a history of hepatic impairment (see section 4.2).

Volume-depletion

Patients with volume-depletion (e.g. those treated with high-dose diuretics) may experience hypotension, which may be minimised by initiating treatment with a low dose of LORTELL. Halving of the dose should also be considered for patients with a history of hepatic impairment (see section 4.2).

Electrolyte imbalance

Since hyperkalaemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment and the concomitant use of potassium-sparing diuretics should generally be avoided (see section 4.5).

Fluoroquinolones

Concomitant use of fluoroquinolones with ACE inhibitors, such as LORTELL, may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients (see section 4.3 and 4.5). Renal function should be assessed before initiating treatment and monitored during treatment with LORTELL.

Combinations containing any of the following medications, depending on the amount present, may also interact with LORTELL:

• Non-steroidal anti-inflammatory drugs (NSAIDs) - NSAIDs may antagonise the antihypertensive effect of LORTELL.
• Sympathomimetic medicines - Concurrent use with sympathomimetics may reduce the antihypertensive effects of LORTELL.
• Potassium - Potassium-sparing diuretics, potassium containing medication or potassium supplements used concurrently with LORTELL may result in hyperkalaemia since reduction of aldosterone production induced by LORTELL may lead to elevation of serum potassium.
• Fluoroquinolones - Concomitant use of fluoroquinolones and ACE inhibitors, such as LORTELL, may precipitate acute kidney injury (see sections 4.3 and 4.4).
• Lithium - As with other medicines which affect the elimination of sodium, lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with angiotensin II receptor antagonists.

Women of childbearing potential / Contraception in males and females

Women of childbearing age should ensure adequate contraception.

Pregnancy

LORTELL is contraindicated for use during pregnancy (see section 4.3). When pregnancy is detected, LORTELL should be discontinued as soon as possible. Not to be used in pregnancy as teratogenicity has been shown in experimental animals (see section 4.3).

Breastfeeding

Safety has not been established.

Fertility

There are no fertility data.

Dizziness or hypotension may occur when taking LORTELL, in particular during initiation of treatment or when the dose is increased. Patients should see how LORTELL affects them before driving or operating machinery.

b) Tabulated list of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with losartan.

System Organ Class

Frequency

Frequent

Less Frequent

Not known

Infections and infestations

Upper respiratory infection

Blood and lymphatic system disorders

Thrombocytopenia

Symptomatic anaemia, decreased haemoglobin concentrations, neutropenia, anaemia

Immune system disorders

Angioedema (involving swelling of the face, lips, and/or tongue) has been reported in patients treated with LORTELL.

Psychiatric disorders

Insomnia

Nervous system disorders

Headache, dizziness, vertigo

Migraine

Cardiac disorders

Palpitations, tachycardia

Hypotension, chest pain

Vascular disorders

Orthostatic hypotension

Oedema /swelling, vasculitis, including Henoch-Schu00f6nlein purpura

Respiratory, thoracic and mediastinal disorders

Cough, nasal congestion, pharyngitis, sinus disorder

Gastrointestinal disorders

Diarrhoea, dyspepsia, nausea, abdominal pain

taste disturbances, complete taste loss, vomiting

Hepatobiliary disorders

Severe acute hepatotoxicity, cholestasis, acute pancreatitis, hepatitis

Skin and subcutaneous tissue disorders

Urticaria, rash

Atypical cutaneous lymphoid infiltrates, pruritus, erythroderma, photosensitivity

Musculoskeletal and connective tissue disorders

Back pain, muscle cramps, leg pain, myalgia

Arthralgia

Renal and urinary disorders

Impaired renal function

Reproductive system and breast disorders

Erectile dysfunction/ impotence

General disorders and administration site conditions

Asthenia/fatigue

Malaise

Investigations

Hyperkalaemia, elevations of ALT

Liver function abnormalities

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

The symptoms of an overdosage of LORTELL would be hypotension and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither LORTELL nor the active metabolite can be removed by haemodialysis.