Adult: Available preparations:
Losartan 50 and hydrochlorothiazide 12.5 mg tab
Losartan 100 and hydrochlorothiazide 12.5 mg tab
Losartan 100 and hydrochlorothiazide 25 mg tab
In patients with inadequately controlled blood pressure on either losartan or hydrochlorothiazide monotherapy: Initially, 50 mg/12.5 mg once daily; titrate after 3 weeks as needed based on blood pressure response. Max: 100 mg/25 mg once daily.
Oral Hypertension with left ventricular hypertrophy
Adult: Available preparations:
Losartan 50 and hydrochlorothiazide 12.5 mg tab
Losartan 100 and hydrochlorothiazide 12.5 mg tab
Losartan 100 and hydrochlorothiazide 25 mg tab
To reduce the risk of stroke, in patients whose blood pressure is not adequately controlled on 50 mg losartan: Initially, 50 mg/12.5 mg; may be increased to 100 mg/12.5 mg, then 100 mg/25 mg if necessary.
Renal Impairment
CrCl (mL/min)
Dosage
≤30
Not recommended.
Hepatic Impairment
Not recommended.
Administration
May be taken with or without food.
Contraindications
Hypersensitivity to losartan, hydrochlorothiazide or sulfonamide-derived drugs. Anuria, intravascular volume depletion. Pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min).
Special Precautions
Patient with significant aortic/mitral stenosis, prediabetes or diabetes mellitus, history of gout, SLE, moderate or high cholesterol concentrations, unstented unilateral/bilateral renal artery stenosis, or those undergoing surgery. Black patients. Hepatic and severe renal impairment. Lactation.
Adverse Reactions
Significant: Hypersensitivity reactions, electrolyte disturbance (e.g. hyperkalaemia, hypokalaemia, hypochloraemic alkalosis, hyponatraemia, hypomagnesaemia), symptomatic hypotension, acute transient myopia, acute angle-closure glaucoma, exacerbation of SLE, photosensitivity, renal function deterioration. Rarely, angioedema. Blood and lymphatic system disorders: Anaemia, agranulocytosis, leucopenia. Cardiac disorders: Tachycardia, palpitations, chest pain. Eye disorders: Transient blurred vision, xanthopsia. Gastrointestinal disorders: Abdominal pain, nausea, vomiting, dyspepsia, gastric irritation, cramping, pancreatitis, sialoadenitis, dysgeusia. General disorders and administration site conditions: Malaise, weakness. Hepatobiliary disorders: Jaundice. Investigations: Liver function abnormalities. Metabolism and nutrition disorders: Anorexia, hyperglycaemia, hyperuricaemia. Musculoskeletal and connective tissue disorders: Back pain, leg pain, myalgia, muscle cramps or spasms. Nervous system disorders: Dizziness, headache, paraesthesia, migraine. Psychiatric disorders: Restlessness, insomnia. Renal and urinary disorders: Glycosuria, renal dysfunction, interstitial nephritis. Reproductive system and breast disorders: Impotence, erectile dysfunction. Respiratory, thoracic and mediastinal disorders: Nasal congestion, cough, upper respiratory infection, sinusitis, sinus disorder. Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, purpura. Vascular disorders: Orthostatic effects (dose-related), necrotising angiitis (vasculitis, cutaneous vasculitis).
Monitor blood pressure, serum electrolytes and renal function at baseline and periodically. Observe for clinical signs of fluid or electrolyte imbalance.
Drug Interactions
May increase serum K with K-sparing diuretics (e.g. spironolactone, triamterene, amiloride), K supplements, K-containing salt substitutes. May increase serum lithium concentration and toxicity.
Losartan: Increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects with NSAIDs (including cyclooxygenase-2 inhibitors). May lead to a further decrease of blood pressure with TCA, antipyschotics. Dual blockade of the renin-angiotensin system with ACE inhibitors or aliskiren leads to increased risks of hypotension, syncope, hyperkalaemia and changes in renal function.
Hydrochlorothiazide: May aggravate hypotension with barbiturates, narcotics or antidepressants. May reduce or delay absorption with colestyramine and colestipol resins. May enhance hypokalaemic effect with corticosteroids and adrenocorticotropic hormone (ACTH). Reduced diuretic, natriuretic and antihypertensive effects with NSAIDs. May impair glucose tolerance. Potentially Fatal: Coadministration of aliskiren in diabetic patients may increase the risk of hyperkalaemia, renal impairment and hypotension.
Food Interaction
Alcohol may aggravate the hypotensive effect of hydrochlorothiazide.
Lab Interference
Hydrochlorothiazide may interfere with parathyroid function tests.
Action
Description: Losartan is a selective and competitive angiotensin II receptor (type AT1) antagonist antihypertensive. It acts by blocking the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.
Hydrochlorothiazide, a thiazide diuretic, inhibits Na reabsorption in the distal tubules resulting in increased excretion of Na, water, K and hydrogen ions. Onset: Losartan: Approx 6 hours.
Hydrochlorothiazide: Diuresis: Within 2 hours. Duration: Hydrochlorothiazide: Diuresis: 6-12 hours. Pharmacokinetics: Absorption: Losartan: Well-absorbed from the gastrointestinal tract. Bioavailability: Approx 33%. Time to peak plasma concentration: 1 hour.
Hydrochlorothiazide: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 65-70%. Time to peak plasma concentration: Approx 1-5 hours. Distribution: Losartan: Volume of distribution: Approx 34 L. Plasma protein binding: >98%, mainly to albumin.
Hydrochlorothiazide: Crosses the placenta; enters breast milk. Plasma protein binding: Approx 40-68%. Metabolism: Losartan: Metabolised mainly by CYP2C9 and CYP3A4 and converted to an active carboxylic acid metabolite. Undergoes substantial first-pass metabolism. Excretion: Losartan: Mainly via faeces (Approx 60%); urine (approx 35%). Elimination half-life: Approx 2 hours.
Hydrochlorothiazide: Via urine (mainly as unchanged drug). Elimination half-life: Approx 6-15 hours.
Chemical Structure
Losartan Source: National Center for Biotechnology Information. PubChem Database. Losartan, CID=3961, https://pubchem.ncbi.nlm.nih.gov/compound/Losartan (accessed on Jan. 22, 2020)
Hydrochlorothiazide Source: National Center for Biotechnology Information. PubChem Database. Hydrochlorothiazide, CID=3639, https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide (accessed on Jan. 20, 2020)
C09DA01 - losartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.
References
Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/07/2021.Anon. Losartan and Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/07/2021.Anon. Losartan Potassium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/07/2021.Anon. Losartan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/07/2021.Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2021.Buckingham R (ed). Losartan Potassium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2021.Hyzaar Tablet, Film Coated (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/07/2021.Hyzaar/Fortzaar 50 mg/12.5 mg, 100 mg/12.5 mg, 100 mg/25 mg (Merck Sharp & Dohme Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/07/2021.Losartan Potassium and Hydrochlorothiazide Tablet, Film Coated (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/07/2021.Losartan Potassium/Hydrochlorothiazide 100 mg/12.5 mg Film-Coated Tablets (Aurobindo Pharma Malta Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/07/2021.Losartan Potassium/Hydrochlorothiazide 50 mg/12.5 mg Tablets (Nucleus ehf). MHRA. https://products.mhra.gov.uk. Accessed 07/07/2021.Teva Pharma New Zealand Limited. Arrow-Losartan Potassium & Hydrochlorothiazide, Film-Coated Tablets 50 mg/12.5 mg data sheet 24 April 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 06/07/2021.
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