Losartan + Hydrochlorothiazide


Concise Prescribing Info
Indications/Uses
HTN.
Dosage/Direction for Use
Adult : PO Per tab contains losartan 50 mg and hydrochlorothiazide 12.5 mg: 1 tab once daily. Up to 2 tab once daily 2-4 wk later if needed. Max: 2 tab/day.
Dosage Details
Oral
Hypertension
Adult: Per tablet contains losartan 50 mg and hydrochlorothiazide 12.5 mg. For patients who are not adequately controlled on losartan or hydrochlorothiazide monotherapy: 1 tab once daily. May increase to 2 tabs once daily 2-4 wk later if needed. Max: 2 tabs/day.
Renal Impairment
Dialysis patients: Avoid.
CrClDosage
<20Avoid.
Administration
May be taken with or without food.
Contraindications
Pregnancy, lactation; intravascular volume depletion.
Special Precautions
Existing electrolyte disturbances; hepatic cirrhosis; severe hepatic failure; oedema; elderly (>75 yr); renal impairment; hepatic impairment; diabetes, gout, hyperlipidaemia; hyperuricaemia; ECG: LVH and/or ventricular ectopics extrasystoles); volume depleted patients; patients on diuretics and salt restriction; renal artery stenosis; aortic and mitral stenosis. Monitor potassium concentration. Discontinue before performing tests for parathyroid function.
Adverse Reactions
Volume depletion and electrolyte imbalance (especially hyperkalaemia); dry mouth, thirst; lethargy, drowsiness; muscle pain and cramps; rashes, photosensitivity, thrombocytopenia, jaundice, pancreatitis; fatigue, weakness; may precipitate an attack of gout; impotence; hyperglycaemia; anorexia, nausea, vomiting, constipation, diarrhoea; sialdenitis; raised urinary calcium concentration; headache, dizziness; back pain, myalgia; first-dose hypotension; angiodema; neutropenia; GI disturbances; transient elevation of liver enzymes; taste disturbances, cough; exacerbation or activation of systemic lupus erythematous; palpitations; xanthopsia; leucopenia, agranulocytosis, aplastic anaemia; necrotising angiitis; glucosuria; renal dysfunction, interstitial nephritis, renal failure; migraine; hyponatraemia; UTI; chest pain; gastritis, wt gain, dyspepsia, abdominal pain; bronchitis, upper respiratory infection, nasal congestion, sinusitis; rise in cholesterol and/or triglycerides.
Potentially Fatal: Hypersensitivity reactions; hemolytic anaemia; toxic epidermal necrolysis.
Overdosage
Symptoms: hypotension and tachycardia. Treatment: supportive and symptom specific. Not removed via haemodialysis.
Drug Interactions
Hydrochlorothiazide increases plasma concentration fluconazole. Increased hypotensive effect with: ACE inhibitors, alcohol, adrenergic neurone blockers, aldesleukin, α-blockers, alprostadil, general anaesthetics, antipsychotics, anxiolytics and hypnotics, baclofen, β-blockers, calcium-channel blockers, clonidine, diazoxide, epoetin, hydralazine, levodopa, MAOIs, methyldopa, minoxidil, monoxidine, nitrates, NSAIDs, oestrogens, sodium nitroprusside, tizanidine, phenothiazines. Increased risk of renal impairment with aspirin (in doses >300 mg daily), NSAIDs. Hypotensive effect antagonised by aspirin, corticosteroids, indomethacin, ketorolac. Increased risk of hyperkalaemia with potassium-sparing and aldosterone antagonists, drospirenone (monitor serum potassium during 1st cycle), epoetin, heparin, ketorolac, potassium salts. Increased risk of hypersensitivity with allopurinol (especially in renal impairment). May antagonise hypoglycaemic effects of antidiabetics. Increased risk of hypercalcaemia with calcium salts and vitamin D. Increased risk of hyponatraemia with chlorpropamide. Increased risk of hypermagnesaemia with ciclosporin. Absorption may be reduced by colestipol and colestyramine (take at least 2 hr apart).
Potentially Fatal: Increased risk of nephrotoxicity and ototoxicity with platinum compounds, aminoglycosides. Hypokalaemia caused by diuretics may cause cardiac toxicity with amiodarone (interaction may occur for several weeks or months due to long half life of amiodarone). Increased risk of nephrotoxicity and hyperkalaemia with ciclosporin. Reduced excretion of lithium (risk of lithium toxicity with diuretics).
Food Interaction
Avoid dong quai (if using for hypertension as it has estrogenic activity; ephedra, ginseng, yohimbe (may worsen hypertension), garlic (may have additive effects), St John's wort (may decrease levels).
Action
Description: Hydrochlorothiazide increases renal excretion of sodium and chloride and reduces cardiac load. Losartan is an angiotensin II receptor (type AT1) antagonist antihypertensive which acts by blocking the actions of angiotensin II of renin-angiotensin-aldosterone system. The drug and its active metabolite selectively block the vasoconstrictor and aldosterone secreting effects of angiotensin II. The two drugs exert additive effects in hypertension.
Onset: Hydrochlorothiazide: diuresis: approx 2 hr; losartan: 6 hr.
Duration: Hydrochlorothiazide: 6-12 hr.
Pharmacokinetics:
Absorption: Hydrochlorothiazide: oral absorption: Approx 50-80%; time to peak: 1-2.5 hr; peak effect: 4-6 hr; bioavailability: 50-80%. Losartan: time to peak: 1 hr; losartan's active metabolite (E-3174): time to peak 3-4 hr (AUC is 4 times greater than that of losartan); bioavailability: 25-33%.
Distribution: Hydrochlorothiazide: 3.6-7.8 L/kg; protein binding: 68%. Losartan: volume of distribution: 34 L; plasma protein binding: high. Losartan's active metabolite (E-3174): volume of distribution:12 L.
Metabolism: Hydrochlorothiazide: Not metabolised. Losartan: Hepatic (14%) via CYP2CP and CYP3A4 to active metabolite, E-3174 (40 more times potent than losartan), extensive 1st-pass effect.
Excretion: Hydrochlorothiazide: half life elimination: 5.6-14.8 hr; excretion: via urine (as unchanged drug). Losartan: excretion via urine (4% as unchanged drug and 6% as active metabolite); plasma clearance: 600 ml/minute (active metabolite: 50 ml/min).
Storage
Protect from light and store at 15-30 °C.
Disclaimer: This information is independently developed by MIMS based on Losartan + Hydrochlorothiazide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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