Rosart Losartan Potassium Tablets

ROSART
(Losartan Potassium Tablets)

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory.

 

ROSART TABLETS 25 mg

Each film coated tablet contains:

Losartan Potassium 25 mg

ROSART TABLETS 50 mg

Each film-coated tablet contains:

Losartan Potassium 50mg

 

DESCRIPTION

(Losartan) is an angiotensin II receptor antagonist. It is chemically designed as 2-butyl-40chloro-1- (p-(0-1 H1-tetrazol-5-ylphenyl)-benzyl) imidazole-5-methanol monopotassium salt. Its empirical formula is C22H22CIKN6O and its molecular weight is 461.01.

 

PHARMACOLOGY1

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 (e.g. 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 hours. Predictably, plasma renin activity and Angiotensin II concentrations increase and aldosterone concentration falls. Single dose losartan has no effect on glomerular filtration rate, renal plasma flow and filtration fraction. Multiple dose studies have shown no effects on renal or systemic prostaglandis, 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 them is no rebound effect on abrupt withdrawal. There is no change in average heart rate during treatment.

Pharmacokinetics

Losartan is well absorbed on oral administration and undergoes substantial first pass metabolism. Peak concentrations of losartan and its major active carboxlic acid metabolite are achieved in 1 hour and 3-4 hours respectively. The systemic bioavailability of losartan is about 33%. Food does not have any effect on AUC of losartan or its active metabolite. Pharmscokinetics 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 young and elderly hypertensives.

The elimination half life of losartan is 2 hours and that of its major active metabolite is 6-9 hours. Both losartan and its active metabolite are highly protein bound. Losartan is excreted both in the bile and the urine. Following oral administration of losartan, approximately 35% of the radioactivity is recovered in the urine and about 60% in the faeces.

 

RENAL INSUFFICIENCY

Plasma concentration of losartan is not altered in patients with creatinine clearance above 30 ml/min.

AUCs are 50% greater in patients with low creatinine clearance and doubled in patients on haemodialysis. Losartan or its active metabolite cannot be removed by haemodialysis. A lower starting dose is recommended for patients with moderate to severe renal insufficiency.

Hepatic Insufficiency

The plasma concentrations of losartan and its active metabolite are higher and total plasma clearance is lower in patients with hepatic insufficiency. A lower starting dose of ROSART is recommended in patients with hepatic insufficiency.

 

INDICATIONS1,2

Rosart is indicated for the treatment of hypertension; it may be used alone or in combination with other antihypertensive agents. Rosart is also indicated in the treatment of heart failure.

 

DOSAGE AND ADMINISTRATION

The usual starting dose of Rosart is 50 mg once daily. 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. Rosart can be administered once or twice daily with total daily doses ranging from 25 mg to 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 mild renal impairment (creatinine clearance 20-50 ml/mm). For patients with moderate to severe renal impairment (creatinine clearance < 20 ml/mm) or on dialysis, a lower starting dose of 25 mg once daily is recommended. ROSART 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. ROSART may be administered with or without food.

 

PRECAUTIONS1,2

General

ROSART should not be used with potassium sparing diuretics. Serum potassium should be monitored in elderly patients and patients with renal impairment.

Warnings

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 ROSART 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 (such as 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 does is also recommended for cirrhotic patients or those with moderate to severe renal failure. (Please see ‘DOSAGE AND ADMINISTRATION’).

In patients with unilateral or bilateral renal artery stenosis, treatment with ACE inhibitors or losartan has been associated with increase in blood urea nitrogen or serum creatinine which was reversible on discontinuation.

 

Contraindication

ROSART is contraindicated in patients who are hypersensitive to any component of this product.

 

Carcinogenecity/mutagenicity

Losartan potassium 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.

 

Pregnancy/fertility

Fertility and reproductive performance were not affected in studies with rats given oral doses of losartan potassium up to approximately 150 mg/kg/day. However, as with other drugs that act on the rennin angiotensin system ROSART should not be administered to pregnant patients or should be discontinued as soon as pregnancy is detected.

 

Nursing mothers

Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue ROSART, taking into account the importance of the drug to the mother.

 

Pediatrics

Efficacy and safety of losartan have not been investigated in patients <18 years of age.

 

Geriatrics

Some older individuals may be more sensitive to the effects of losartan and a lower starting dose is recommended. A lower starting dose is recommended for patients over 75 years of age.

 

Drug Interactions

Coadministration with cimetidine may increase the serum concentration of ROSART. Co-administration with phenobarbital may reduce the serum concentration of ROSART and that of its active metabolite. There is no pharmacokinetic interaction between ROSART and hydrochlorothiazide.

 

Laboratory value alterations

Minor increases in blood urea nitrogen, serum creatinine, serum bilirubin or hepatic enzymes may occur.

 

Adverse Effects

Losartan has been evaluated for safety in more than 4000 patients. Treatment with ROSART 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 diarrhoea, dyspepsia, myalgia, edema, dizziness, insomnia and headache. Anxiety, respiratory congestion, angina , arrhythmias, angioedema and photosensitivity have been rarely reported.

 

OVERDOSE

In case of overdosage symptomatic therapy should be instituted.

 

STORAGE

Store below 25°C, protected from light and moisture.

Keep all medicines out of the reach of children.

 

SUPPLY

ROSART TABLETS 25 mg: Blister strip of 10’s and Carton of 5 x 10’s

ROSART TABLETS 50 mg: Blister strip of 10’s and Carton of 5 x 10’s

 

REFERENCES

1. Physicians’ Drug Reference. 1998. Pp 1623.

2. ABPI Datasheet Compendium. 1998-99. pp 726.

Information compiled in Nov’ 98

 

Manufactured in India by

Sun Pharmaceutical Ind. Ltd.

PLOT NO. B-2, MADKAI INDUSTRIAL

ESTATE, PONDA, GOA – 403 404