Losartan potassium, hydrochlorothiazide.
Each film-coated tablet contains 50 mg of Losartan Potassium and 12.5 mg of Hydrochlorothiazide.
Each film-coated tablet contains 100 mg of Losartan Potassium and 12.5 mg of Hydrochlorothiazide.
Each film-coated tablet contains 100 mg of Losartan Potassium and 25 mg of Hydrochlorothiazide.
Pharmacology: Losartan and Hydrochlorothiazide is a combination of an angiotensin II receptor (type AT1) antagonist and a diuretic.
Losartan Potassium is an angiotensin II receptor (type AT1) antagonist. Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE; kininase II)] is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. Its effects are vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal re-absorption of sodium. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues (e.g. vascular smooth muscle, adrenal gland). There is also an AT2 receptor in many tissues but it is not known to be associated with cardiovascular homeostasis. Both Losartan and its principal active metabolite have much greater affinity (about 1,000 fold) for the AT1 than for the AT2 receptor and do not exhibit any agonist activity.
In vitro binding studies indicate that Losartan is a reversible, competitive inhibitor of the AT1 receptor. The active metabolite is 10 to 40 times more potent by weight than Losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor.
Losartan do not inhibit ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin) nor do they bind to or block other hormone receptor or ion channels known to be important in cardiovascular regulation. It inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. Removal of the negative feedback of angiotensin II causes 2- to 3-fold rise in plasma renin activity and a consequent rise in angiotensin II plasma concentration in hypertensive patients. The resulting increased plasma renin activity and angiotensin II circulating levels are insufficient to alter the effects of Losartan and its principal active metabolite on blood pressure. There was a small uricosuric effects with Losartan leading to a minimal decrease in serum uric acid (mean decrease less than 0.4 mg/dL) during chronic oral administration.
Hydrochlorothiazide is a moderately potent diuretic and exerts its diuretic effect by reducing the reabsorption of electrolytes from the renal tubules, thereby increasing the excretion of sodium and chloride ions, and consequently of water. It acts mainly at the beginning of the distal tubules. The excretion of other electrolytes, notably potassium and magnesium, is also increased. The excretion of calcium is reduced. It also reduces carbonic-anhydrase activity so that bicarbonate excretion is increased, but this effect is generally small compared with the effect of chloride excretion and does not appreciably alter the pH of the urine. It may also reduce the glomerular filtration rate.
Hydrochlorothiazide's hypotensive effect is probably partly due to a reduction in peripheral resistance; it also enhances the effects of other antihypertensives. Paradoxically, hydrochlorothiazide has an antidiuretic effect in patients with diabetes insipidus.
Pharmacokinetics: 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, which has a greater pharmacological activity than Losartan Potassium, and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of Losartan Potassium and its active metabolite occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both Losartan Potassium and its active metabolite are more than 98% bound to plasma proteins. Losartan Potassium 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 Potassium and its metabolite are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
Hydrochlorothiazide is fairly absorbed from the gastrointestinal tract. It is reported to have a bioavailability of about 65 to 70%. It acts within 2 hours of oral administration and reaches peak effect in about 4 hours, within 6 to 12 hours duration. It has been estimated to have plasma half-life of between about 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 placental barrier and is distributed into breast milk.
Treatment of hypertension, where combination therapy is appropriate.
Losartan Potassium and Hydrochlorothiazide (Arbloc Plus) may be administered with or without food. It may also be administered with other antihypertensive agents.
The usual initial and maintenance dose of losartan potassium and hydrochlorothiazide (Arbloc Plus) is 1 tablet of losartan potassium 50 mg and hydrochlorothiazide 12.5 mg (Arbloc Plus) once daily. Losartan potassium + Hydrochlorothiazide (Arbloc Plus) 100 mg/12.5 mg and 100 mg/25 mg is available for patients titrated to 100 mg of Losartan who require additional blood pressure control.
For patients who do not respond adequately to losartan potassium 50 mg and hydrochlorothiazide 12.5 mg (Arbloc Plus) the dosage may be increased to 2 tablets of losartan potassium 50 mg and hydrochlorothiazide 12.5 mg (Arbloc Plus) once daily and if needed, the dose should then be increased to 100 mg/25 mg once daily. In general, the antihypertensive effect is attained within 3 weeks after initiation of therapy.
Losartan Potassium: 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: Hypokalaemia may be avoided or treated by concurrent use of potassium or a potassium-sparing diuretic and can be reduced by moderate sodium restriction; dilutional hyponatraemia is best treated with water restriction rather than salt therapy; in massive overdosage, treatment should be symptomatic and directed at fluid and electrolyte replacement.
Losartan Potassium and Hydrochlorothiazide: Patients with hypersensitivity reactions to any component of this product.
Hydrochlorothiazide: Anuria; renal decompensation; Addison's disease.
Losartan Potassium and Hydrochlorothiazide: Renal and hepatic impairment; Pregnancy and breastfeeding.
Losartan Potassium: Patients with renal artery stenosis; may experience hypotension in patients with volume depletion (e.g. patients who have received high-dose diuretic therapy) which may be minimized by initiating treatment with a low dose of Losartan Potassium; serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and the concomitant use of potassium-sparing diuretics should generally be avoided since hyperkalemia may occur.
Hydrochlorothiazide: Patients who are at risk from changes in fluid and electrolyte balance, such as the elderly; patients with hepatic cirrhosis are also more likely to develop hypokalaemia; hyperglycaemia and may exacerbate diabetes mellitus; may precipitate attacks of gout; systemic lupus erythematosus; may increase risk of developing gall stones.
Use in Pregnancy: Losartan Potassium: When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, Losartan Potassium should be discontinued as soon as possible.
Hydrochlorothiazide: Crosses the placenta and has reports of neonatal jaundice, thrombocytopenia, and electrolyte imbalances after maternal use. Reductions in maternal blood volume could also adversely affect placental perfusion.
Use in Lactation:Losartan Potassium is not known whether it is excreted in human milk. Hydrochlorothiazide may appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Large doses may suppress lactation.
Losartan Potassium and Hydrochlorothiazide:
Orthostatic hypotension; pancreatitis; gastrointestinal disturbances.
Hyperkalaemia; symptomatic anemia occurred in patient with 6 weeks after commencing therapy with Losartan Potassium, decreased hemoglobin concentrations has been reported in patients with severe renal impairment undergoing hemodialysis; atypical cutaneous lymphoid infiltrates, taste disturbances in some cases progressing to complete taste loss, it will return to normal after discontinuing therapy; raised liver enzyme values have occurred rarely in patients taking Losartan Potassium, severe acute reversible hepatotoxicity occurred in a patient who had been taking Losartan in a dose of 150 mg daily for 6 weeks; other adverse effects have been reported with angiotensin II antagonist include respiratory-tract disorders, back pain, fatigue and neutropenia.
Metabolic disturbances; hyperglycaemia and glycosuria; hyperuricemia and gout; electrolyte imbalances including hypochloraemic alkalosis, hyponatraemia and hypokalaemia; blood dyscrasias including thrombocytopenia and more rarely, granulocytopenia, leucopenia, aplastic and hemolytic anemia; other adverse effects include anorexia, gastric irritation, nausea, vomiting, constipation, diarrhea, sialadenitis, headache, dizziness, paraesthesia, impotence, yellow vision; hypersensitivity reactions include photosensitivity reactions, skin rashes, fever, pulmonary edema, anaphylaxis, and toxic epidermal necrolysis.
Losartan Potassium: Other drugs that block angiotensin II: Concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increase serum potassium.
Other antihypertensive agents: The antihypertensive effect of Losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin.
Hydrochlorothiazide: Digitalis glycoside: May enhance the toxicity of diuretic-induced hypokalaemia.
Drugs that prolong the QT interval, such as astemizole, terfenadine, halofantrine, pimozide, and sotalol: May increase the risk of arrhythmias.
Neuromuscular blockers such as atracurium: May enhance the neuromuscular blocking action probably by hypokalaemic effect.
Corticosteroids, corticotropin, beta2 agonists such as salbutamol, carbenoxolone, amphotericin B, or reboxetine: May enhance the potassium depleting effect of diuretics and hypertensive effects of diuretics may be antagonized by drugs that cause fluid retention, such as corticosteroids or carbenoxolone.
ACE inhibitors: Diuretics may enhance the effect of other antihypertensives, particularly the first dose hypotension that occurs with alpha blockers.
Alcohol, barbiturates, opioids: Orthostatic hypotension associated with diuretics may be enhanced.
NSAIDs: Cause fluid retention and may antagonize the diuretic actions of thiazides. Diuretics may enhance the nephrotoxicity of NSAIDs.
Noradrenaline: Thiazides have been reported to diminish the response to pressor amines, but the clinical significance of this effect is uncertain.
Lithium: the association may lead to toxic blood concentrations.
Antibacterials: Severe hyponatraemia has been reported in patients taking hydrochlorothiazide.
Antiepileptics: Symptomatic hyponatraemia has been reported if associated with hydrochlorothiazide and carbamazepine.
Bile-acid binding resins: Gastrointestinal absorption of hydrochlorothiazide has been reported to be reduced by colestipol and colestyramine. Colestyramine had the greatest effect on hydrochlorothiazide, decreasing absorption by 85% compared with a decrease of 43% with colestipol. Thiazides should be given ≥2 hours before the resin.
Dopaminergics: Increased amantadine toxicity associated with hydrochlorothiazide and triamterene.
Other drugs including allopurinol and tetracyclines: Increased toxicity has been reported when given with thiazides.
Thiazides: May alter the requirements for hypoglycaemics in diabetic patients.
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.
50 mg/12.5 mg FC tab 30's. 100 mg/12.5 mg FC tab 30's. 100 mg/25 mg FC tab 30's.