losartan + hydrochlorothiazide




Pharma Dynamic
Full Prescribing Info
Losartan potassium, hydrochlorothiazide.
Each film-coated tablet contains: Losartan Potassium 50 mg, Hydrochlorothiazide 12.5 mg.
Chemical Name: Losartan Potassium: 2-Butyl-4-chloro-1-[p-o-1H-tetrazol-5-ylphenyl]benzyl]imidazole-5-methanol potassium.
Hydrochlorothiazide: 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulphonamide 1,1-dioxide.
Molecular Weight: Losartan Potassium: 461.0; Hydrochlorothiazide: 297.7.
Empirical Formula: Losartan Potassium: C22H22ClKN6O; Hydrochlorothiazide: C7H8ClN3O4S2.
Pharmacology: Pharmacodynamics/Pharmacokinetics: Losartan Potassium: It is an angiotensin II receptor antagonist with antihypertensive activity due mainly to selective blockade of AT1 receptors and the consequent reduced pressure effect of angiotensin II.
Losartan potassium is readily absorbed from the gastrointestinal tract following oral administration, with an oral bioavailability of about 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than losartan, and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of losartan, and E-3174 occur at 1 hour and 3 to 4 hours, respectively after an oral dose. Both losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the feces via bile, as unchanged drug and metabolites. Following oral dosing about 35% of the dose is excreted in the urine and about 60% in the feces. The terminal elimination half-lives of losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours respectively.
Hydrochlorothiazide: It is a diuretic antihypertensive. It is fairly rapidly absorbed from the gastrointestinal tract. It is reported to have a bioavailability of about 65% to 70%. It has been estimated to have a plasma half-life of between 5 and 15 hours and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine. Hydrochlorothiazide crosses the placenta barrier and is distributed into breast milk.
Losartan Potassium is used in the management of hypertension and may have a role in patients who develop cough with Angiotensin Converting Enzyme inhibitors and to reduce the risk of stroke in patients with left ventricular hypertrophy, and in the treatment of diabetic nephropathy.
Hydrochlorothiazide is used in the treatment of edema associated with heart failure and with renal hepatic disorders. It is used in hypertension, either alone or together with other antihypertensives such as Angiotensin Converting Enzyme inhibitors and beta blockers.
Hydrochlorothiazide is also indicated in the treatment of edema accompanying premenstrual syndrome, prevention of water retention associated with corticosteroids and estrogens, treatment of diabetes insipidus, and prevention of renal calculus formation in patients with hypercalciuria.
Dosage/Direction for Use
Usual dose: Losartan Potassium 50 mg / Hydrochlorothiazide 12.50 mg once daily. The dose may be increased, if necessary, to 100 mg / 25 mg daily as single dose or in two divided doses. An initial dose of 25 mg once daily may be used in the elderly over 75 years, and for patients with moderate to severe renal impairment (creatinine clearance less than 20 mL per minute), or intravascular fluid depletion. Or as prescribed by a physician.
Losartan Potassium: Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg respectively, about 44 and 170 times the maximum recommended human dose on an mg/m2 basis.
Limited data are available in regard to overdosage in humans. The most likely manifestation of overdose would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan potassium nor its active metabolite can be removed by hemodialysis.
Hydrochlorothiazide: The oral Lethal Dose50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats. The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed has not been established.
It must not be given to pregnant women because it crosses the placenta and is distributed in breast milk. Hydrochlorothiazide is not effective in patients with creatine clearance of less than 30 mL per minute and thus should not be given to patients with severe renal impairment or anuria. It is also contraindicated with Addison's disease.
Thiazide can reduce urinary excretion of calcium, sometimes resulting in mild hypercalcemia and is therefore contraindicated to patients with pre-existing hypercalcemia.
Special Precautions
It should be used with caution in patients with renal artery stenosis / renal impairment since it can further reduce renal function. Patients should be carefully observed for signs of fluid and electrolyte imbalance, especially in the presence of vomiting or during parenteral fluid therapy.
Use In Pregnancy & Lactation
It is contraindicated in pregnancy since it has been associated with fetal toxicity in animal studies and other drugs such as Angiotensin Converting Enzyme inhibitors that act on the renin-angiotensin system have been associated with fetal toxicity in humans.
Adverse Reactions
Losartan Potassium: Adverse effects include dizziness and dose related orthostatic hypotension. Hypotension may occur particularly in patients with volume depletion (for example those who have received high-dose diuretics). Losartan potassium may cause hyperkalemia in patients with renal disease. Other adverse effects that have been reported with angiotensin II receptor antagonist include respiratory-tract disorder, back pain, gastrointestinal disturbances, fatigue, and neutropenia.
Hydrochlorothiazide: Thiazide diuretics may cause a number of metabolic disturbances especially at high doses. They may provoke hyperglycemia and glycosuria in diabetic and other susceptible patients. They may cause hyperuricemia and precipitate attacks of gout in some patients. Administration of hydrochlorothiazide may be associated with electrolyte imbalances including hypochloremic alkalosis, hyponatremia, and hypokalemia. Hypokalemia intensifies the effect of digitalis on cardiac muscle and administration of digitalis or its glycosides may be temporarily suspended. Patients with cirrhosis of the liver are particularly at risk from hypokalaemia.
Drug Interactions
Losartan Potassium: In clinical trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital (phenobarbitone), (see Hydrochlorothiazide; Alcohol, barbiturates, or narcotics as follows) ketoconazole and erythromycin. Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences have not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of other drugs which retain potassium or may increase potassium levels (e.g. Potassium sparing diuretics, potassium supplements, or salt substitutes containing potassium) may lead to increases in serum potassium.
Hydrochlorothiazide: When given concurrently, the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs: There may be an additive effect.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Corticosteroids, Adrenocorticotrophic hormone: There may be intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g. adrenaline): Possible decreased response to pressor amines, but not sufficient to preclude their use.
Store at temperatures not exceeding 30°C.
ATC Classification
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.
FC tab 50 mg/12.5 mg (white to off-white, round, biconvex, plain on both sides) x 50's.
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