Losartan oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of losartan potassium.
Drugs List
Therapeutic Indications
Uses
Adjunct for chronic heart failure in adult patients
Renal dx in hypertensive pts with type 2 diabetes & proteinuria > 0.5 g/day
Stroke-risk reduction in hypertensive pts with left ventricular hypertrophy
Treatment of essential hypertension
Treatment of hypertension.
Treatment of renal disease in adult patients with type 2 diabetes with proteinuria greater than or equal to 0.5 g/day and hypertension, as part of an antihypertensive treatment.
Treatment of adult patients who cannot receive ACE inhibitor treatment for chronic heart failure. The patient should be stabilised on treatment for chronic heart failure and have a left ventricular ejection fraction less than or equal to 40%. Patients who are stabilised on an ACE inhibitor should not be switched to losartan.
Hypertensive patients with left ventricular hypertrophy documented by ECG: reduced risk of stroke.
Dosage
Adults
Hypertension:
The starting and maintenance dose is 50 mg once daily for most patients. The maximal antihypertensive effect is attained 3 to 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).
For patients with intravascular volume depletion (e.g. those treated with high-dose diuretics), a starting dose of 25 mg once daily is recommended.
Hypertensive type 2 diabetic patients with proteinuria greater than or equal to 0.5 g/day:
The starting dose is 50 mg once daily for most patients. The dose may be increased to 100 mg once daily according to blood pressure response after one month.
For patients with intravascular volume depletion (e.g. those treated with high-dose diuretics), a starting dose of 25 mg once daily is recommended.
Cardiac failure:
The starting dose is 12.5 mg once daily for most patients. In general the dose should be titrated at weekly intervals (e.g. 12.5 mg daily, 25 mg daily, 50 mg daily, 100 mg daily, up to a maximum of 150 mg once daily) as tolerated by the patient.
Stroke reduction in hypertensive left ventricular hypertrophy patients:
Initial starting dose 50 mg once daily. A low dose of hydrochlorothiazide may be added to the therapy and/or increase the dose of losartan up to 100 mg once daily according to blood pressure.
For patients with intravascular volume depletion (e.g. those treated with high-dose diuretics), a starting dose of 25 mg once daily is recommended.
Elderly
Patients up to 75 years:
(See Dosage; Adult)
Patients over 75 years:
A lower starting dose of 25 mg once daily should be considered.
Children
Losartan is only licensed for hypertension in children.
There are limited data on the efficacy and safety of losartan in patients aged 6 to 18 years. There are limited pharmacokinetic data in patients above one month and under 6 years.
Treatment should take place under specialist supervision. Correct any intravascular volume depletion prior to administration of losartan.
Children aged 6 to 18 years
The recommended starting dose in patients weighing between 20 kg to 50 kg:
Tablets: 25 mg once daily
Oral suspension: 700 microgram/kg once daily up to 25 mg daily in total.
In exceptional cases where target doses above 25 mg are required, the maximum dose is 50 mg once daily. Dosage should be adjusted according to blood pressure response.
Bodyweight greater than or equal to 50 kg - usually 50 mg once daily adjusted according to response. 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.
Patients with Renal Impairment
The Renal Drug Handbook states:
Glomerular Filtration Rate (GFR)
GFR 20 to 50 ml/minute - dose as in normal renal function.
GFR 10 to 20 ml/minute - Initial dose 25 mg and titrate according to response.
GFR less than 10 ml/minute - Initial dose 25 mg and titrate according to response.
Patients with Hepatic Impairment
Significantly high plasma concentrations of losartan have been observed in patients with cirrhosis.
Adults with mild to moderate hepatic impairment
In adults with a history of hepatic impairment a lower dose should be considered.
Additional Dosage Information
Losartan may be administered with other antihypertensive agents (especially with diuretics e.g. hydrochlorothiazide), insulin and other commonly used hypoglycaemic agents.
Contraindications
Children under 6 years
Breastfeeding
Galactosaemia
Hepatic impairment in children under 18 years
Pregnancy
Renal impairment in children under 18 years where eGFR <30ml/min/1.73m sq
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney
Precautions and Warnings
Patients over 75 years
Aortic stenosis
Bilateral renal artery stenosis
Cerebrovascular disorder
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment
Hereditary fructose intolerance
History of angioedema
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Ischaemic heart disease
Lactose intolerance
Mitral stenosis
New York Heart Association class IV failure
Peripheral vascular disease
Renal impairment - glomerular filtration rate below 20ml/minute
Renovascular disorder
Severe generalised atherosclerosis
Unilateral stenosis of solitary functioning kidney
Patients with primary aldosteronism may not benefit from this treatment
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient that first dose hypotension may occur
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Not all available brands are licensed for all indications
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Evaluate renal function before and during treatment
Monitor serum electrolytes before and during treatment
Monitor serum potassium regularly
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Advise patient to seek advice at first indications of pregnancy
Consider reducing initial dose in the elderly
Not licensed for all indications in all age groups
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment
In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/ or progressive azotaemia and in rare cases with acute renal failure and/ or death. As losartan is an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.
Pregnancy and Lactation
Pregnancy
Losartan is contraindicated in pregnancy.
Animal studies have been conducted in rats, the effects reported included: reduced body weight, delayed physical and behavioural development, mortality and renal toxicity. Losartan and its active metabolite cross the rat placenta in significant amounts only during late gestation. In fertility and reproduction performance studies, a significant decrease in foetal implants in rats was noted at a maternally toxic oral dose, approximately 24 times the maximum recommended human dose (MRHD) (Briggs, 2011).
It is not known whether losartan crosses the human placenta, however, the molecular weight is low enough that passage to the infant should be expected. Whilst there is no controlled epidemiological data on the risk of angiotensin II receptor antagonists during pregnancy in humans, the risk may be similar to those seen for ACE inhibitors (including teratogenicity and severe foetal and neonatal toxicity). Angiotensin II is essential for normal kidney development. Foetal toxic effects include: anuria, oligohydramnios, foetal renal failure, decrease calcification of the skull, foetal hypocalvaria, intrauterine growth retardation (IUGR), prematurity and patent ductus arteriosus. Oligohydramnios associated with anuria may produce foetal limb contractures, craniofacial deformations and pulmonary hypoplasia. Exposure to angiotensin II receptor antagonists in the second and third trimester is known to induce neonatal toxicity (renal failure and hyperkalaemia). Severe anuria and hypotension that are resistant to treatment may occur in the newborn (Briggs, 2011). The MHRA states that the use of angiotensin II receptor antagonists in late pregnancy has been associated with adverse effects on the kidney and other congenital anomalies, therefore angiotensin II receptor antagonists should not be used at any stage during of pregnancy unless absolutely necessary and only then after the potential risks and benefits have been discussed with the patient.
If first trimester exposure occurs, a detailed ultrasound examination is recommended. Manufacturers recommend that should exposure from the second trimester have occurred, ultrasound checks of the renal function and skull is recommended. Schaefer (2007) states that overall exposure during pregnancy is not an indication for invasive diagnostic procedure or termination of pregnancy. Long-term exposure during pregnancy should lead to foetal monitoring for oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans. Briggs (2011) recommends newborn renal function and blood pressure should be closely monitored.
If pregnancy occurs during treatment, losartan must be discontinued immediately and an alternative antihypertensive with greater experience in pregnancy should be considered. Guidelines advise that women who are taking angiotensin II receptor blockers in pregnancy, or are planning pregnancy, are told that there is an increased risk of congenital abnormalities if these drugs are taken and other antihypertensive treatments should be discussed and offered.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Losartan is contraindicated in breastfeeding.
Losartan is excreted into the milk of lactating rats. It is unknown if it is excreted in human milk, however, the molecular weight of losartan is low enough that excretion in breast milk should be expected. Hale (2010) comments that although it penetrates the CNS significantly, its high protein binding would probably reduce its ability to enter milk. The effects on the newborn are unknown.
Schaefer (2007) suggests that accidental administration of a single dose does not require weaning, however, therapy should be changed to an antihypertensive which has been better studied in breastfeeding. The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Alternative antihypertensive treatments with more established safety profiles during breastfeeding are preferable, especially whilst nursing a newborn or preterm baby.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal pain
Airway obstruction
Anaemia
Anaphylactic reaction
Angina pectoris
Angioedema
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Blood urea increased
Cerebrovascular accident
Cough
Depression
Diarrhoea
Dizziness
Dyspnoea
Erectile dysfunction
Fatigue
Headache
Henoch-Schonlein purpura
Hepatitis
Hyperkalaemia
Hypersensitivity reactions
Hypoglycaemia
Hyponatraemia
Hypotension
Impotence
Increase in ALT level
Influenza-like symptoms
Liver function disturbances
Malaise
Migraine
Myalgia
Nausea
Obstipation
Oedema
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Pharyngeal oedema
Photosensitivity
Pruritus
Rash
Renal failure
Renal impairment
Respiratory disorders
Rhabdomyolysis
Serum creatinine increased
Sleep disturbances
Somnolence
Swelling of lips and face
Syncope
Thrombocytopenia
Tinnitus
Tongue swelling
Urinary tract infections
Urticaria
Vasculitis
Vertigo
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2013
Reference Sources
British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.
BNF for Children (2012-2013) Pharmaceutical Press, London.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Summary of Product Characteristics: Cozaar 12.5mg, 50mg and 100mg Film-Coated Tablets. Organon Pharma (UK) Ltd. Revised December 2022.
Summary of Product Characteristics: Cozaar 2.5mg/ml powder and solvent for oral suspension. Merck, Sharp and Dohme Ltd. Revised December 2012.
Summary of Product Characteristics: Losartan potassium 25mg film-coated tablets. Accord healthcare limited. Revised March 2012.
Summary of Product Characteristics: Losartan potassium 50mg film-coated tablets. Accord healthcare limited. Revised March 2012.
Summary of Product Characteristics: Losartan potassium 100mg film-coated tablets. Accord healthcare limited. Revised March 2012.
Summary of Product Characteristics: Losartan potassium 25mg film-coated tablets. Actavis UK limited. Revised December 2012.
Summary of Product Characteristics: Losartan potassium 50mg film-coated tablets. Actavis UK limited. Revised December 2012.
Summary of Product Characteristics: Losartan potassium 100mg film-coated tablets. Actavis UK limited. Revised December 2012.
Summary of Product Characteristics: Losartan potassium 25mg film-coated tablets. Kent pharmaceuticals Ltd. Revised February 2010.
Summary of Product Characteristics: Losartan potassium 50mg film-coated tablets. Kent pharmaceuticals Ltd. Revised May 2010.
Summary of Product Characteristics: Losartan potassium 100mg film-coated tablets. Kent pharmaceuticals Ltd. Revised February 2010.
Summary of Product Characteristics: Losartan potassium 25mg film-coated tablets. Sandoz Limited. Revised February 2013.
Summary of Product Characteristics: Losartan potassium 50mg film-coated tablets. Sandoz Limited. Revised February 2013.
Summary of Product Characteristics: Losartan potassium 100mg film-coated tablets. Sandoz Limited. Revised February 2013.
Summary of Product Characteristics: Losartan potassium 25, 50 and 100mg tablets. Pfizer Limited. Revised February 2012.
Summary of Product Characteristics: Losartan potassium 25mg film-coated tablets. Zentiva. Revised June 2011.
Summary of Product Characteristics: Losartan potassium 50mg film-coated tablets. Zentiva. Revised June 2011.
Summary of Product Characteristics: Losartan potassium 100mg film-coated tablets. Zentiva. Revised June 2011.
MHRA Drug Safety Update: Breastfeeding with ACE inhibitors and angiotensin II receptor antagonists. Dated: May 2009
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: July 4, 2013.
National Institute for Health and Clinical excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107
Last accessed: July 4, 2013.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Losartan. Last revised: September 29, 2009.
Last accessed: July 4, 2013.
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