Zylovaa-H Tablet 50/12.5mg:
Each film-coated tablet contains 50mg Losartan Potassium and 12.5mg
Zylovaa-H Tablet 100/25mg:
Each film-coated tablet contains 100mg Losartan Potassium and 25mg
The components of losartan-hydrochlorothiazide have been shown to have an
additive effect on
blood-pressure reduction, reducing blood pressure to a greater degree than
alone. This effect is thought to be a result of the complimentary actions of
Further, as a result of its diuretic effect, hydrochlorothiazide increases
increases aldosterone secretion, decreases serum potassium, and increases
the levels of angiotensin
II. Administration of losartan blocks all the physiologically relevant
actions of angiotensin II and
through inhibition of aldosterone could tend to attenuate the potassium loss
associated with the
Losartan has been shown to have a mild and transient uricosuric effect.
been shown to cause modest increases in uric acid; the combination of losartan and
hydrochlorothiazide tends to attenuate the diuretic-induced hyperuricaemia.
Following oral administration, losartan is well absorbed and undergoes
forming an active carboxylic acid metabolite and other inactive metabolites.
bioavailability of losartan tablets is approximately 33%. Mean peak
concentrations of losartan and
its active metabolite are reached in 1 hour and in 3-4 hours, respectively.
There was no clinically
significant effect on the plasma concentration profile of losartan when the
drug was administered
with a standardised meal.
Both losartan and its active metabolite are ≥99% bound to plasma proteins,
primarily albumin. The
volume of distribution of losartan is 34 litres. Studies in rats indicate
that losartan crosses the
blood-brain barrier poorly, if at all.
Hydrochlorothiazide crosses the placental but not the blood-brain barrier
and is excreted in breast
About 14% of an intravenously or orally-administered dose of losartan is
converted to its active
metabolite. In addition to the active metabolite, inactive metabolites are
formed, including two
major metabolites formed by hydroxylation of the butyl side chain and a
minor metabolite, an N-2
Plasma clearance of losartan and its active metabolite is about 600 ml/min
and 50 ml/min,
respectively. Renal clearance of losartan and its active metabolite is about
74 ml/min and 26
ml/min, respectively. When losartan is administered orally, about 4% of the
dose is excreted
unchanged in the urine, and about 6% of the dose is excreted in the urine as
active metabolite. The
pharmacokinetics of losartan and its active metabolite are linear with oral losartan potassium doses
up to 200 mg.
Following oral administration, plasma concentrations of losartan and its
active metabolite decline
polyexponentially with a terminal half-life of about 2 hours and 6-9 hours,
once-daily dosing with 100 mg, neither losartan nor its active metabolite
Both biliary and urinary excretions contribute to the elimination of
losartan and its metabolites.
Hydrochlorothiazide is not metabolised but is eliminated rapidly by the
kidney. When plasma levels
have been followed for at least 24 hours, the plasma half-life has been
observed to vary between 5.6
and 14.8 hours. At least 61% of the oral dose is eliminated unchanged
within 24 hours.
Characteristics in patients
The plasma concentrations of losartan and its active metabolite and the
hydrochlorothiazide in elderly hypertensives are not significantly different
from those in young
Following oral administration in patients with mild to moderate alcoholic
cirrhosis of the liver, plasma concentrations of losartan and its active
metabolite were, respectively, 5-fold and 1.7-fold greater than those seen
in young male volunteers. Plasma concentrations of losartan are not altered
in patients with creatinine clearance above 10 ml/min.
Neither losartan nor the active metabolite can be removed by haemodialysis.
Zylovaa-H is indicated for the treatment of hypertension, for patients in
whom combination therapy is appropriate.
In hypertensive patients with left ventricular hypertrophy, a reduced risk
of stroke was demonstrated with losartan administered usually in combination
DOSAGE AND ADMINISTRATION
To be administered orally.
Fixed dose combination is not indicated for initial therapy.
Zylovaa-H may be administered with or without food.
Zylovaa-H may be administered with other antihypertensive agents.
Treatment of Hypertension
The usual starting and maintenance dose is 1 tablet Zylovaa-H 50/12.5mg (losartan
potassium 50mg/ hydrochlorothiazide 12.5mg) once daily for most patients.
For patients who do not respond adequately, the dosage may be increased to 2
tablets Zylovaa-H 50/12.5mg (losartan potassium 50mg/ hydrochlorothiazide
12.5mg) or 1 tablet Zylovaa-H 100/25mg (losartan potassium 100mg/
hydrochlorothiazide 25mg) once daily. The maximum dose is 2 tablets Zylovaa-H
50/12.5mg (Iosartan potassium 50mg/ hydrochlorothiazide 12.5mg) or 1 tablet
Zylovaa-H 100/25mg (losartan potassium 100mg/ hydrochlorothiazide 25mg). In
general, the antihypertensive effect is attained within three weeks after
initiation of therapy.
Zylovaa-H should not be initiated in patients who are intravascularly
volume-depleted (e.g. those treated with high-dose diuretics).
Zylovaa-H is not recommended for patients with severe renal impairment (creatinine
clearance ≤30ml/min) or for patients with hepatic impairment.
No initial dosage adjustment of Zylovaa-H is necessary for elderly patients.
Zylovaa-H Tablet 100/25mg should not be used as initial therapy in elderly
Reduction in the risk of stroke in hypertensive patients with left
The usual starting dose is 50mg of losartan once daily. If goal blood
pressure is not reached with losartan 50mg, therapy should be titrated using
a combination of losartan and a low dose of hydrochlorothiazide (12.5mg)
and, if needed the dose should then be increased to losartan 100mg and
hydrochlorothiazide 12.5mg once daily. If necessary, the dose should be
increased to losartan 100mg and hydrochlorothiazide 25mg daily. Zylovaa-H
Tablet 50/12.5mg and 100/25mg are suitable alternative formulations in
patients who would otherwise be treated concomitantly with losartan plus
Zylovaa-H is contraindicated in:
• Patients who are hypersensitive to any component of this product.
• Patients with anuria.
• Patients who are hypersensitive to other sulfonamide-derived drugs
WARNINGS AND PRECAUTIONS
Hypersensitivity: Angioedema (See Side Effects)
Hepatic and renal impairment: Losartan-hydrochlorothiazide is not
recommended for patients with hepatic impairment or severe renal impairment
(creatinine clearance ≤30ml/min). (See Dosage and Administration)
Renal function impairment
As a consequence of inhibiting the renin-angiotensin-aldosterone system,
changes in renal function including renal failure have been reported in
susceptible individuals; as with other drugs that affect the
renin-angiotensin-aldosterone system, increases in blood urea and serum
creatinine have also been reported in patients with bilateral renal artery
stenosis or stenosis of the artery to a solitary kidney. These changes in
renal function may be reversible upon discontinuation of therapy.
Hypotension and electrolyte/fluid imbalance: Symptomatic hypotension
may occur in some patients. Patients should be observed for clinical signs
of fluid or electrolyte imbalance, e.g. volume depletion, hyponatremia,
hypochloremic alkalosis, hypomagnesemia or hypokalemia which may occur
during intercurrent diarrhea or vomiting. Periodic determination of serum
electrolytes should be performed at appropriate intervals in such patients.
Metabolic and endocrine effects: Thiazide therapy may impair
glucose tolerance. Dosage adjustment of antidiabetic agents, including
insulin, may be required. (See Drug Interactions). Thiazides may decrease
urinary calcium excretion and may cause intermittent and slight elevation of
serum calcium. Marked hypercalcaemia may be evidence of hidden
hyperparathyroidism. Thiazides should be discontinued before carrying out
tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with
thiazide diuretic therapy.
Thiazide therapy may precipitate hyperuricaemia and/or gout in certain
patients. Because losartan decreases uric acid, losartan in combination with
hydrochlorothiazide attenuates the diuretic-induced hyperuricaemia.
Other: In patients receiving thiazides, hypersensitivity reactions
may occur with or without a history of allergy or bronchial asthma.
Exacerbation or activation of systemic lupus erythematosus has been reported
with the use of thiazides.