Losartan potassium, hydrochlorothiazide.
Each film-coated tablet contains losartan potassium 50 mg and hydrochlorothiazide 12.5 mg.
Losartan potassium is 2-Butyl-4-chloro-1-[p-o-1H-tetrazol-5-yl-phenyl)benzyl]imidazole-5-methanol potassium. Its empirical formula is C22H22ClKN6O and molecular weight is 461.
Hydrochlorothiazide is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2 and molecular weight is 297.7.
Pharmacology: Pharmacodynamics: Losartan Potassium: It is an angiotensin II receptor blocker with antihypertensive activity due mainly to selective blockage of AT1 receptors and the consequent reduced pressure effect of angiotensin II.
Hydrochlorothiazide: It is a diuretic antihypertensive.
Pharmacokinetics: Losartan Potassium: It is readily absorbed from the gastrointestinal tract (GIT) 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 isoenzyme CYP2C9 and CYP3A4. Peak plasma concentrations of losartan and E-3174 occur about 1 hr and 3-4 hrs, 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 t½ of losartan and E-3174 are about 1.5-2.5 hrs and 3-9 hrs, respectively.
Hydrochlorothiazide: It is fairly rapidly absorbed from the GIT. It is reported to have a bioavailability of about 65-70%. It has been estimated to have a plasma t½ of between about 5-15 hrs and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine. Hydrochlorothiazide crosses the placental barrier and is distributed into breast milk.
Losartan Potassium: Management of hypertension and may have a role in patients who develop cough with angiotensin-converting enzyme (ACE) inhibitors.
Hydrochlorothiazide: Treatment of edema associated with heart failure and renal or hepatic disorder. It is also used in hypertension, either alone or together with other antihypertensives such as ACE inhibitors and β-blockers. Also, for treatment of edema accompanying premenstrual syndrome, prevention of water retention associated with corticosteroid and estrogens, treatment of diabetes insipidus and prevention of renal calculus formation in patients with hypercalciuria.
Usual Dose: 1 tablet once daily. If necessary may be increased to 2 tablets as a single dose or in 2 divided doses. Or, as prescribed by a physician.
Elderly >75 years and Patients with Moderate to Severe Renal Impairment (creatinine clearance <20 mL/min) or Intravascular Fluid Depletion: Initial Dose: 25 mg once daily.
Losartan Potassium: Significantly, 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 a mg/m2 basis.
Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage 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 metabolites can be removed by hemodialysis.
Hydrochlorothiazide: The oral lethal dose50 (LD50) of hydrochlorothiazide is >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 by hemodialysis has not been established.
Hydrochlorothiazide is not effective in patients with CrCl <30 mL/min and thus, should not be given to patients with severe renal impairment or anuria. It is also contraindicated in patients with Addison's disease. Thiazide can reduce urinary excretion of calcium, sometimes resulting in mild hypercalcemia and is therefore contraindicated to patients with preexisting hypercalcemia.
Used with caution in patients with renal artery stenosis/renal impairment since Neosartan Plus 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.
Neosartan Plus is contraindicated to pregnant and lactating women since it has been associated with fetal toxicity in animal studies, crosses the placenta and is distributed in breast milk. Other drugs eg, ACE inhibitors that act on the renin-angiotensin system have been associated with fetal toxicity in humans.
Adverse effects include dizziness and dose-related orthostatic hypotension. Hypotension may occur particularly in patients with volume depletion (eg, those who 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.
Thiazide diuretics may cause a number of metabolic disturbances especially at high doses. It may provoke hyperglycemia and glycosuria in diabetic and other susceptible patients. It 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 glycoside may be temporarily suspended. Patients with cirrhosis of the liver are particularly at risk from hypokalemia.
Losartan Potassium: In clinical trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital (phenobarbitone), 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 (eg, 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 exchanged resins.
Corticosteroids, Adrenocorticotropic Hormone (ACTH): There may be intensified electrolyte depletion, particularly hypokalemia.
Pressor Amines (eg, Adrenaline): Possible decreased response to pressor amines, but not sufficient to preclude their use.
Store at temperatures not exceeding 30°C.
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 (white to off-white, round, biconvex, plain on both sides) 30's.