Losartan

Registered South African indications:

• Hypertension
• Renal protection in type 2 diabetic patients with hypertension and proteinuria

Should a woman become pregnant while receiving losartan, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Lactation
• Severe renal function impairment (CrCl<30l/min)
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Porphyria
• A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Aortic stenosis, left ventricular outflow track obstruction
• Coadministration with fluoroquinolones in patients with moderate to severe renal impairment (CrCl≤30ml/min) and in elderly patients
• Coadministration with potassium sparing diuretics such as spironolactone, triamterene, amiloride
• Coadministration with lithium may lead to toxic blood concentrations of lithium
• Coadministration with renin inhibitors, such as aliskiren-containing products

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• 2nd and 3rd trimester of pregnancy
• Severe hepatic impairment
• Coadministration of losartan with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73 m²)

• First trimester of pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Mild to moderate renal impairment (South African recommendations)
• Renal impairment (Recommendations in other jurisdictions)
• Hepatic impairment (South African recommendations)
• Mild to moderate hepatic impairment (Recommendations in other jurisdictions)
• Elderly (Recommendations in other jurisdictions)
• History of angioedema
• Hypotension in volume-depleted patients
• Renal artery stenosis
• Primary aldosteronism 
• Heart failure
• Aortic or mitral stenosis
• Obstructive hypertrophic cardiomyopathy
• Ethnic differences
• Dual blockade of the renin-angiotensin-aldosterone system
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Ischaemic cardiovascular disease
• Cerebrovascular disease
• Hyperkalaemia
• Kidney transplantation

Forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

Hypertension

• Oral (fct, tab): Initial and maintenance: 50mg, once daily; Maximum antihypertensive effect achieved in 3-6 weeks after initiation; May increase to 100mg, once daily based on response

Renal protection in type 2 diabetic patients with hypertension and proteinuria

• Oral (fct, tab): Initial: 50mg, once daily; May increase to 100mg, once daily based on blood pressure response

---

Losartan can 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)

---

Losartan may be administered with or without food

---

Missed dose: Advise patients who forget to take losartan to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy and lactation has not been established
• When pregnancy is planned or confirmed, losartan should be discontinued. Medicines affecting the renin-angiotensin system, such as losartan, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women
• Women of childbearing age should ensure effective contraception

Recommendations in other jurisdictions

• First trimester: Caution; not recommended
• Second and third trimester: Contraindicated
• 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
• Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE-inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Blockers (ARBs), similar risks may exist for this class of medicinal products
• Exposure to ARB therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia)
• Should exposure to losartan have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended
• Infants whose mothers have taken losartan should be closely observed for hypotension

Breastfeeding

South African recommendations

• Contraindicated
• It is not known whether losartan is excreted in human milk. Safety of breastfeeding in mothers taking losartan has not been established. However, significant levels of losartan and the active metabolite were shown to be present in rat milk

Recommendations in other jurisdictions

• Caution; not recommended
• Because no information is available regarding the use of losartan during breastfeeding, losartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  No initial dosage adjustment is necessary for patients with renal impairment, including patients on dialysis
• Severe (CrCl<30ml/min): Contraindicated
• Coadministration with fluoroquinolones in moderate to severe renal impairment: Contraindicated
• Bilateral renal artery stenosis and renal artery stenosis in patients with a single kidney: Contraindicated

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  No initial dosage adjustment is necessary for patients with renal impairment, including patients on dialysis
• GFR<60ml/min/1.73m² and coadministration of aliskiren-containing agents: Contraindicated

South African recommendations

• Caution; dose adjustment recommended
  A dose of 25mg should be considered for patients with a history of hepatic impairment

Recommendations in other jurisdictions

• Mild to moderate: Caution; dose adjustment recommended
  A lower dose should be considered for patients with a history of hepatic impairment
• Severe: Contraindicated

South African recommendations

• No dose adjustment recommended
• Coadministration with fluoroquinolones in elderly patients: Contraindicated

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Although consideration should be given to initiating therapy with 25mg in patients over 75 years of age, dosage adjustment is not usually necessary for the elderly

Central Nervous System Disorders

• Depression
• Dizziness
• Somnolence
• Headache
• Sleep disorders
• Paraesthesia
• Migraine
• Insomnia
• Dysgeusia
• Fatigue

Cardiovascular Disorders

• Palpitations
• Angina pectoris
• Syncope
• Atrial fibrillation
• Cerebrovascular accident
• Orthostatic hypotension

Respiratory Disorders

• Dyspnoea
• Cough

Gastrointestinal Disorders

• Abdominal pain
• Obstipation
• Diarrhoea
• Nausea and vomiting
• Dyspepsia

Hepatobiliary Disorders

• Pancreatitis
• Hepatitis
• Liver function abnormalities

Genitourinary Disorders

• Renal impairment 
• Renal failure
• Erectile dysfunction 
• Impotence

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hypoglycaemia

Muscoloskeletal Disorders

• Myalgia
• Arthralgia
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Pruritus
• Rash
• Photosensitivity

Immune, Blood and Lymphatic System Disorders 

• Anaemia
• Thrombocytopenia
• Hypersensitivity reactions
• Anaphylactic reactions
• Angioedema
• Vasculitis

Sensory Disorders  

• Visual disturbance
• Tinnitus

Others

• Asthenia 
• Oedema

• Angiotensin-converting enzyme inhibitors
• Antihypertensive agents 
• CYP2C9 inhibitors
• CYP2C9 inducers
• Potassium supplements
• Potassium sparing diuretics
• Spironolactone
• Triamterene
• Amiloride
• Lithium
• Non-steroidal anti-inflammatory agents
• Tricyclic antidepressants
• Antipsychotics
• Baclofen
• Amifostine
• Heparin
• Angiotensin II receptor blockers
• Renin inhibitors
• Aliskiren
• Potassium containing salt substitutes

None routine. Specific cases may require

• Hepatic function
• Serum potassium
• Renal function

Losartan selectively binds to the angiotensin II AT1 receptors found in the vascular smooth muscle, adrenal gland, kidneys and the heart; this inhibits vasoconstriction and aldosterone secretion which results in a decrease in vascular resistance and blood pressure.

Tablet 50mg

• Annin (Aurobindo)
• Austell Losartan (Austell)
• Cipla-Losartan (Cipla)
• Ciplazar (Cipla)
• Cozaar 50 (Organon) originator
• Hytenza fct (Abex)
• Lepitrin (Adcock)
• Los-Arb (Sandoz)
• Losartan Biotech 50 (Biotech Labs)
• Losartan Macleods (Macleods)
• Losartan Unicorn (Ranbaxy)
• Losartan Winthrop (Zentiva)
• Lozaan (Akacia)
• Normoten (Trinity)
• Rasol (Novagen)
• Renicard (Unichem)
• Spec Losartan (Specpharm)
• Zaario (Unicorn)
• Zartan (Pharma Dynamics)

Tablet 100mg

• Annin (Aurobindo)
• Austell Losartan (Austell)
• Cipla-Losartan (Cipla)
• Ciplazar (Cipla)
• Cozaar 100 (Organon) originator
• Hytenza fct (Abex)
• Losartan Macleods (Macleods)
• Losartan Unicorn (Ranbaxy)
• Lozaan (Akacia)
• Normoten (Trinity)
• Rasol (Novagen)
• Spec Losartan (Specpharm)
• Zaario (Unicorn)
• Zartan (Pharma Dynamics)

COMBINATION PREPARATIONS

Losartan/ Hydrochlorothiazide

Tablet 50mg/12.5mg 

• Austell Losartan Co (Austell)
• Cozaar Comp (MSD) originator
• Hytenza Co fct (Abex)
• Lohype Plus (Ranbaxy)
• Losaar Plus (Accord)
• Losacar Co (Zydus)
• Losartan Co Unicorn (Ranbaxy)
• Lozaan Co (Thebe)
• Netrasol Co (Specpharm)
• Sartoc-Co (Pharmacare)
• Zartan Co (Pharma Dynamics)

Tablet 100mg/25mg

• Fortzaar (MSD) originator
• Hytenza Co fct (Abex)
• Lohype Plus (Ranbaxy)
• Losaar Plus (Accord)
• Losartan Co Unicorn (Ranbaxy)
• Lozaan Co (Thebe)
• Netrasol Co (Specpharm)
• Sartoc-Co (Pharmacare)
• Zartan Co (Pharma Dynamics)

Amlodipine/ Losartan

Tablet 5mg/50mg

• Amzaar (MSD) originator

Tablet 5mg/1000mg

• Amzaar (MSD) originator