OMNISART-H

Pharmacokinetics
Losartan
Absorption: Readily absorbed from the gastrointestinal tract
Bioavailability: About 33%
Metabolism: Liver; active metabolite is carboxylic acid derivative (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

Hydrochlorothiazide
Absorption: Fairly rapidly absorbed from the gastrointestinal tract
Bioavailability: About 65 to 70%
Metabolism: Minimally metabolized
Peak Effect: Diuresis: 4-6 hours
Protein Binding: 40-68%
Elimination Half-life: 5.6-14.8 hours
Excretion: Mainly unchanged in the urine

Indications and Dosage
Hypertension: Initially 1 tablet OD every day; Max: 2 tablets OD or 1 tablet every 12 hours

Side Effects
Losartan
MILD to TRANSIENT: Dizziness, headache, dose-related orthostatic hypotension, hypotension, and impaired renal function
RARE: Rash, urticaria, pruritus, angioedema, and raised liver enzyme values
REPORTED: Hyperkalaemia, myalgia, arthralgia, respiratory tract disorders, back pain, gastrointestinal disturbances, fatigue, and neutropenia
RERELY REPORTED: Rhabdomyolysis

Hydrochlorothiazide
COMMON: Nausea, vomiting, loss of appetite, diarrhoes, constipation, muscle spasm,
dizziness, headache; signs of electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain and cramps, seizures, oliguria, hypotension, and gastrointestinal disturbances
OTHER: Anorexia, Sialadenitis, photosensitivity reactions, orthostatic hypotension, paraesthesia, impotence, and yellow vision
REPORTED: Hypersensitivity reactions include skin rashes, fever, pulmonary oedema,
pneumonitis, anaphylaxis, and toxic epidermal necrolysis. Cholestatic jaundice, pancreatitis, and blood dyscrasias including thrombocytopenia
RARE: Granulocytopenia, leucopenia, and aplastic and haemolyticanaemia

Contraindications
Hypersensitivity, pregnancy, coadministration with aliskiren in patients with diabetes, severe hepatic/ renal impairment, anuria, hypercalcaemia, and Addison’s disease

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.
• Serum potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and potassium-sparing diuretics should be avoided.
• Caution in elderly and patients with existing fluid and electrolyte disturbances.
• May cause hyperuricaemia and precipitate attacks of gout in some patients.
• May be associated with electrolyte imbalances including hypochloraemic alkalosis,
hyponatraemia, and hypokalaemia.
• Hypokalaemia intensifies the effect of digitalis on cardiac muscle and treatment with digitalis or its glycosides may have to be temporarily suspended.
• Patients with hepatic cirrhosis are particularly at risk from hypokalaemia.
• May cause hyperglycaemia and aggravate or unmask diabetes mellitus. Blood-glucose concentrations should be monitored in patients taking antidiabetics, since requirements may change.
• Can reduce urinary excretion of calcium, sometimes resulting in mild hypercalcaemia.

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.
• Interactions may occur with drugs that affect cytochrome P450 enzymes.
• Concomitant use of digoxin with hydrochlorothiazide may increase the toxicity of digoxin by hypokalaemic effect.
• May increase the risk of arrhythmias with drugs that prolong the QT interval.
• May enhance the effect of other antihypertensives, particularly the first-dose hypotension that occurs with alpha blockers or ACE inhibitors.
• Orthostatic hypotension associated with diuretics may be enhanced by alcohol, barbiturates,or opioids.
• The antihypertensive effects may be antagonised by drugs that cause fluid retention, such as corticosteroids, NSAIDs, or carbenoxolone; diuretics may enhance the nephrotoxicity of NSAIDs.
• Should not usually be used with lithium because of lithium toxicity. Other drugs for which increased toxicity has been reported when given with thiazides include allopurinol and tetracyclines.
• May alter the requirements for hypoglycaemics in diabetic patients.

Pregnancy Category: D; contraindicated in all trimesters

Presentations
OMNISART-H: 10 X 10’s

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