Angizaar/Angizaar-H

Angizaar/Angizaar-H

losartan + hydrochlorothiazide

losartan

Manufacturer:

Micro Labs

Distributor:

Zizawa Healthcare
Full Prescribing Info
Contents
Losartan potassium alone, or with hydrochlorothiazide.
Description
Losartan is 2-butyl-4-chloro-1-(p-(0-1 H-tetrazol-5-ylphenyl)-benzyl) imidazole-5-methanol monopotassium salt. It has an empirical formula of C22H22ClKN6O and a molecular weight of 461.01.
Angizaar-H: Each tablet contains losartan potassium 50 mg and hydrochlorothiazide IP 12.5 mg.
Hydrochlorothiazide is 6-chloro-3, 4-dihydro-2H-1,2,4-benzo-thiadiazine-7-sulfonamide-1, 1-dioxide.
Action
Pharmacology: Angizaar: Mechanism of Action: Angiotensin II is a potent vasoconstrictor, stimulant of aldosterone secretion and an important component in the pathophysiology of hypertension. Both losartan and its principal active carboxylic acid metabolite, (10-40 times more potent by weight than losartan) block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (eg, vascular smooth muscle, adrenals). Losartan does not inhibit ACE (kininase II), the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin.
Pharmacodynamics: Losartan 100 mg inhibits the pressor effect of angiotensin II infusion by 85% at peak with 25-40% of the inhibition persisting for 24 hrs. Predictably, plasma renin activity and angiotensin II concentrations increase and aldosterone concentrations fall. Single-dose losartan has no effect on glomerular filtration rate, renal plasma flow and filtration. Multiple-dose studies have shown no effects on renal or systemic prostaglandins, lipids or plasma glucose concentrations.
The effect of losartan is evident to a substantial degree within 1 week of continued administration, but it may take 3-6 weeks for the maximal effect to occur in some patients. The effect of losartan is maintained on prolonged administration and there is no rebound effect on abrupt withdrawal. There is no change in average heart rate during treatment.
Angizaar-H: Losartan is an angiotensin II receptor antagonist with antihypertensive activity mainly due to the selective blockade of angiotensin I receptors and consequently, reduced pressor effect of angiotensin II.
Hydrochlorothiazide, a diuretic, affects electrolyte absorption at the level of distal convoluted tubule and increases the excretion of sodium and chloride in approximately equivalent amounts by its inhibitory effect on Na+Cl- symport located in the luminal membrane.
Pharmacokinetics: Losartan is well absorbed on oral administration and undergoes substantial first-pass metabolism by cytochrome P-450 enzymes to form an active carboxylic acid metabolite, E-3174. Peak concentrations of losartan and its major active carboxylic acid metabolite are achieved in 1 hr and 3-4 hrs, respectively. The systemic bioavailability of losartan is about 33%.
Food does not have any effect on the AUC of losartan or its active metabolite. Pharmacokinetics of losartan and its active metabolite are linear with doses up to 200 mg. There is no accumulation on repeated dosing. Plasma concentrations of losartan and its active metabolite are similar in the young and elderly hypertensives.
The elimination half-life of losartan is 2 hrs and that of its major active metabolite is 6-9 hrs. Both losartan and its active metabolite are highly protein bound. Losartan is excreted both in the bile and urine. Following oral administration of losartan, approximately 35% of this radioactivity is recovered in the urine and about 60% in the feces.
Renal Insufficiency: The plasma concentration of losartan is not altered in patients with creatinine clearance >30 mL/min. AUCs are 50% greater in patients with low creatinine clearance and doubled in patients on hemodialysis. Losartan or its active metabolite cannot be removed by hemodialysis.
Hepatic Insufficiency: The plasma concentrations of losartan and its active metabolite are higher and the total plasma clearance is lower in patients with hepatic insufficiency.
Angizaar-H: On oral administration, hydrochlorothiazide is fairly and rapidly absorbed from the gastrointestinal tract. Its diuretic action begins within 2 hrs, peaks in about 4 hrs and lasts about 6-12 hrs. Hydrochlorothiazide was reported to have a bioavailability of about 65-70% and plasma half-life of about 5-15 hrs. It is bound to red blood cells. Hydrochlorothiazide is mainly excreted in the urine without undergoing metabolism. At least 61% of Angizaar-H is eliminated unchanged within 24 hrs.
Indications/Uses
Treatment of hypertension; losartan may be used alone or in combination with other antihypertensives.
Treatment of heart failure.
Dosage/Direction for Use
Angizaar/Angizaar-H: Usual Starting Dose: 50 mg once daily.
Angizaar: In patients with possible depletion of intravascular volume, patients on diuretics and those with hepatic impairment, the starting dose should be 25 mg once daily. Losartan can be administered once or twice daily with total daily doses ranging from 25-100 mg. If the antihypertensive effect measured at trough using once-daily dosage is inadequate, a twice-daily dosage at the same total daily dose or an increase in dose may give a more satisfactory response. No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment. Losartan may be administered with other antihypertensive agents. Hydrochlorothiazide has been shown to have additive effects with losartan if blood pressure is not controlled with losartan alone. Losartan may be administered with or without food.
Overdosage
In case of overdosage, symptomatic therapy should be instituted.
Contraindications
Patients who are hypersensitive to any of the components of Angizaar or Angizaar-H.
Special Precautions
General: Losartan should not be used with potassium-sparing diuretics. Serum potassium should be monitored in elderly patients and in patients with renal impairment.
In patients who are volume-depleted, hypotension may occur on initiation of therapy. In such patients, the condition should be corrected and a lower starting dose of losartan is recommended. Changes in renal function have been reported in susceptible patients treated with losartan.
In patients whose renal function may be dependent on a functioning renin-angiotensin system (eg, patients with congestive heart failure), treatment with ACE inhibitors or losartan has been associated with oliguria and/or progressive azotemia and rarely, with renal failure and/or death. A lower dose is also recommended for cirrhotic patients.
In patients with unilateral or bilateral renal artery stenosis, treatment with ACE inhibitors and losartan has been associated with an increase in BUN or serum creatinine which was reversible on discontinuation.
Angizaar-H: Due to hyperglycaemic effects of thiazide diuretics, dosage adjustments for insulin or oral hypoglycaemic agents in diabetic patients are required.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Losartan was not carcinogenic when administered at maximally tolerated dosages to rats and mice for 105 and 92 weeks, respectively. Losartan potassium and its active metabolite were negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays.
Fertility and reproductive performance were not affected in the studies with rats given oral doses of losartan up to approximately 150 mg/kg/day.
Use in pregnancy: As with other drugs that act on the renin-angiotensin system, losartan should not be administered to pregnant patients and should be discontinued as soon as pregnancy is detected.
Use in lactation: Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue losartan, taking into account the importance of the drug to the mother.
Use in children: Efficacy and safety of losartan have not been investigated in patients <18 years.
Use in the elderly: Some older individuals may be more sensitive to the effects of losartan and a lower starting dose for patients >75 years is recommended.
Use In Pregnancy & Lactation
Use in pregnancy: As with other drugs that act on the renin-angiotensin system, losartan should not be administered to pregnant patients and should be discontinued as soon as pregnancy is detected.
Use in lactation: Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue losartan, taking into account the importance of the drug to the mother.
Adverse Reactions
Losartan has been evaluated for safety in >4000 patients. Treatment with losartan is usually well tolerated. The overall incidence of adverse effects was similar to placebo in clinical studies. The adverse effects reported in clinical trials include:
Angizaar: Diarrhoea, angina, arrhythmias, angioedema and photosensitivity have rarely been reported.
Angizaar-H: Diarrhoea, dyspepsia, myalgia, edema, dizziness, insomnia and headache. Anxiety, respiratory congestion, angina, arrhythmias, angioedema and photosensitivity have rarely been reported. Other effects include first dose hypotension, skin rash, oedema, transient elevation of liver enzymes, hyperkalemia and taste disturbances.
Drug Interactions
Angizaar/Angizaar-H: Co-administration with cimetidine may increase the serum concentration of losartan. Co-administration with phenobarbital may reduce the serum concentration and that of its active metabolite. There is no pharmacokinetic interaction between losartan and hydrochlorothiazide.
Laboratory Value Alterations: Minor increases in blood urea nitrogen, serum creatinine, serum bilirubin or hepatic enzymes may occur.
Angizaar-H: Reports indicate that concomitant administration of thiazide diuretics and lithium is not recommended since the association may lead to toxic blood concentrations of lithium.
Storage
Angizaar: Store below 25°C. Protect from moisture and light.
Angizaar-H: Store in a cool, dry place.
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.
C09CA01 - losartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Presentation/Packing
Angizaar: FC tab 50 mg x 3 x 10's.
Angizaar-H: FC tab 3 x 10's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in