Brand Name: OMNISART-AM
Generic Name: Losartan 50 mg + Amlodipine 5 mg
Preparation: Tablet
Pharmacological Category: Antihypertensive
Mechanism of Action (MOA)
Losartan competitively inhibits binding of angiotensin II to AT1 in vascular smooth muscle and adrenal glands, and results in inhibition of vasoconstriction and aldosterone secretion. Hence, Losartan reduces blood pressure by decreasing peripheral resistance and increasing sodium and water excretion while decreasing potassium excretion.
Amlodipine inhibits transmembrane influx of extracellular calcium ions across membranes of myocardial cells and vascular smooth muscle cells without changing serum calcium concentrations. This inhibits cardiac and vascular smooth muscle contraction thereby dilating main coronary and systemic arteries.
Pharmacokinetics
Losartan
Absorption: Readily absorbed from the gastrointestinal tract
Bioavailability: About 33%
Metabolism: Liver; active metabolite is carboxylic acid derivvative (E-3174)
Peak Plasma Concentration: Losartan: about 1 hour; E-3174: 3 to 4 hours
Protein Binding: More than 98% (both Losartan and E-3174)
Elimination Half-life: About 1.5 to 2.5 hours, E-3174: about 3 to 9 hours
Excretion: Urine and faeces
Amlodipine
Absorption: Well absorbed after oral doses
Peack plasma concentration: 6 to 12 hours
Bioavailability: 60 to 65%
Protein Binding: About 98%
Elimination Half-life: 7 to 8 days
Metabolism: Extensively in liver
Excretion: Mostly urine
Indications and Dosage
• Hypertension: 1 to 2 tablets daily
Side effects
COMMON: Ankle oedema, flushing, headache, rash, and fatigue
MILD to TRANSIENT: Dizziness, headache, and dose-related orthostatic hypotension
MAY OCCUR: Impaired renal function and rarely rash, urticaria, pruritus, angioedema, and raised liver enzyme values
REPORTED: Hyperkalaemia, myalgia, arthralgia, respiratory tract disorders, back pain, gastrointestinal disturbances, fatigue, and neutropenia
RARELY REPORTED: Rhabdomyolysis
Contraindications:
Hypersensitivity, pregnancy, coadministration with aliskiren in patients with diabetes, severe hepatic impairment, cardiogenic shock, myocardial infarction in previous 2 to 4 weeks, and acute unstable angina
Warnings/ Precautions
• Lower doses should be considered in patients with mild or moderate hepatic impairment.
• Caution in patients with renal artery stenosis, volume depletion (e.g. those having high-dose diuretic therapy), and who are at risk of hypotension, poor cardiac reserve, and heart failure.
• Serum potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and potassiumsparing diuretics should be avoided.
• May increase the risk of developing heart failure in patients with severe aortic stenosis.
• Sudden withdrawal might be associated with an exacerbation of angina.
• Should be stopped in patients having ischaemic pain after use.
Drug Interactions
• The antihypertensive effects may be potentiated by drugs or other agents that lower blood pressure.
• An additive hyperkalaemic effect is possible with potassium supplements, potassium-sparing diuretics, or other drugs that can cause hyperkalaemia.
• NSAIDS should be used with caution, particularly in those who are inadequately hydrated as the risk of renal impairment may be increased; use of NSAID may also attenuate hypotensive effect of losartan.
• Use with ACE inhibitor may increase the risk of hyperkalaemia, hypotension, and syncope, particularly in patients with atherosclerotic disease or heart failure, or in diabetics who have
end-organ damage.
• May modify insulin and glucose responses.
• Interactions may occur with drugs like quinidine, carbamazepine, phenytoin, rifampicin,
Pregnancy Category: D; contraindicacted in all trimesters
Presentation
OMNISART-AM: A box of 10 blisters, each blister of 15 tablets