Indication
Losartan, an angiotensin II receptor blocker (ARB) and hydrochlorothiazide, a diuretic indicated for:
Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions
Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy. There is evidence that this benefit does not apply to Black patients
Pharmacology
Losartan is an angiotensin II receptor antagonist. It selectively and competitively blocks the vasoconstricting and aldosterone-secreting effects of angiotensin II by selectively antagonising its binding to AT1 receptors.Hydrochlorothiazide inhibits the reabsorption of Na in the distal tubules causing increased excretion of Na and water including K and hydrogen ions.
Dosage
Hypertension:
Usual starting dose: 50/12.5 mg once daily. Titrate as needed to a maximum dose of 100/25 mg.
Hypertensive Patients with Left Ventricular Hypertrophy:
Not controlled on monotherapy: Initiate with 50/12.5 mg. Titrate as needed to a maximum of 100/25 mg.
Dosing must be individualised. The usual starting dose of Losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) and patients with a history of hepatic impairment. Losartan can be administered once or twice daily at total daily doses of 25 to 100 mg. If the antihypertensive effect measured trough using once a day dosing is inadequate, a twice a day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 to 25 mg. To minimise dose independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy
Interaction
Losartan, administered for 12 days, did not affect the pharmacokinetics or pharmacodynamics of a single dose of Warfarin. Losartan did not affect the pharmacokinetics of oral or intravenous Digoxin. Coadministration of Losartan and Cimetidine led to an increase of about 18% in AUC of Losartan but did not affect the pharmacokinetics of its active metabolite. Coadministration of Losartan and Phenobarbital led to a reduction of about 20% in the AUC of Losartan and that of its active metabolite. Hydrochlorothiazide when administered concurrently may interact with drugs like alcohol, barbiturates, or narcotics. Antidiabetic drugs (oral agents and insulin) require dosage adjustment. Lithium should not generally be given with diuretics. In some patients, the administration of NSAIDs can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.
Contradiction
This combination is contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Side Effect
Abdominal pain, Edema/swelling, Palpitation, Back pain, Dizziness, Cough, Sinusitis, Upper respiratory tract infection, rash etc.
Pregnancy
When pregnancy is detected, Losartan & Hydrochlorothiazide?ÿshould be discontinued as soon as possible. It is not known whether Losartan is excreted in human milk. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Precaution
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatraemia, hypochloraemic alkalosis, and hypokalaemia. Because Losartan decreases uric acid, Losartan in combination with Hydrochlorothiazide attenuates the diuretic-induced hyperuricaemia. In diabetic patients dosage adjustments of Insulin or oral hypoglycaemic agents may be required. Hyperglycaemia may occur with thiazide diuretics. The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient. If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy. Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesaemia. Thiazides may decrease urinary calcium excretion. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy
Overdose
Limited data are available in regard to overdosage of Losartan Potassium in humans. The most likely manifestations of overdosage would be hypotension, tachycardia, and bradycardia. If symptomatic hypotension occurs, supportive treatment should be instituted. Neither Losartan nor its active metabolite can be removed by hemodialysis. The most common signs and symptoms observed for Hydrochlorothiazide are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis.
Storage
Store in a cool dry place protected from light. Keep out of reach of children.