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DAPA-TABS
Anti-hypertensive, diuretic agent.
Formula:
Each tablet contains 2.5 mg indapamide hemihydrate.
Pharmacokinetics:
Indapamide is rapidly and completely absorbed after oral administration.
Peak blood levels are obtained after 1 to 2 hours. Indapamide is
concentrated in the erythrocytes and is 79% bound to plasma proteins and to
erythrocytes. It is taken up by the vascular wall in smooth vascular muscle
according to its high lipid solubility. 70% of a single oral dose is
eliminated by the kidneys and 23% by the gastrointestinal tract. Indapamide
is extensively metabolised with only 7% of the unchanged product found in
the urine during the 48 hours following administration. Elimination
half-life (13 phase) of indapamide is approximately 15 to 18 hours.
Pharmacology:
The mechanism whereby indapamide exerts its action in the control of
hypertension has not been completely elucidated; both renal and extrarenal
actions may be involved. The renal site of action is the promixal part of
the distal tubule and the ascending part of Henle's loop. Sodium and
chloride ions are excreted in approximately equivalent amounts. The
increased delivery of sodium to the distal tubular exchange site results in
increased potassium excretion.
The proposed extrarenal mechanisms of antihypertensive action of indapamide
may include a reduction in peripheral arterial resistance and normalisation
of vascular hyper-reactivity.
Whilst indapamide given at 2.5 mg daily produces minimal diuresis with serum
potassium and uric acid usually remaining within the range of normal values,
occasional patients may develop hypokalaemia or hyperuricaemia.
At the dosage recommended for hypertension indapamide does not usually
adversely influence triglycerides, LDL cholesterol or the LDL-HDL
cholesterol ratio. Indapamide does not appear to adversely affect glucose
tolerance.
Indications:
Management of essential hypertension. It may be tried as a sole therapeutic
agent in the treatment of mild to moderate hypertension. Normally indapamide
is used as the initial agent in multiple drug regimens.
Contraindications:
Anuria, progressive and severe oliguria, hepatic coma, known
hypersensitivity to indapamide or to other sulphonamide derivatives.
Warnings:
Electrolyte changes observed with indapamide become significant at doses
above 2.5 mg/day. As doses above 2.5 mg only increases the diuretic effect
and electrolyte disturbances consequent to diuresis without any further anti
hypertensive effect. The maximum recommended dose of indapamide is 2.5 mg
administered as one tablet daily.
Hypokalaemia may occur at all doses. Symptoms of hypokalaemia include
weakness, cramps, and cardiac dysrrhythmias. Hypokalaemia is a particular
hazard in digitalised patients; dangerous of fatal arrhythmias may be
precipitated.
Caution should be observed when the drug
is administered to patients with severe renal impairment since the drug is
excreted primarily by the renal route.
Hyperuricaemia may occur during administration of indapamide. Rarely, gout
has been reported. Blood uric acid levels should be monitored, particularly
in patients with a history of gout who should continue to receive
appropriate treatment.
Precautions:
Patients receiving indapamide should be carefully observed and serum
electrolytes monitored for signs and symptoms of fluid or electrolyte
imbalance; namely hyponatraemia, hypochloraemia and hypokalaemia. Blood urea
nitrogen and uric acid should also be assessed during therapy. Hypokalaemia
will be more common in association with concomitant steroid or ACTH therapy
and with inadequate electrolyte intake. The serum potassium should be
determined at regular intervals and potassium supplementation instituted
when indicated (see Warnings).
The signs of electrolyte imbalance are: dryness of the mouth, thirst,
weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscle
fatigue, hypotension, oliguria, gastrointestinal disturbances such as nausea
and vomiting, tachycardia and ECG changes.
Special caution should be used in treating patients with severe hepatic
disease to avoid metabolic alkalosis in cases of potassium depletion which
may precipitate episodes of hepatic encephalopathy.
Orthostatic hypotension may occur and may be potentiated by alcohol,
barbiturates, narcotics of concurrent therapy with other antihypertensives.
When indapamide is given with other nondiuretic antihypertensive agents, the
effects on blood pressure are additive.
Sulphonamide derivatives have been reported to exacerbate or activate
systemic lupus erythematosus. These possibilities should be kept in mind
with the use of indapamide although no case has been reported to date.
Although indapamide 2.5 mg daily can safely be administered to hypertensive
patients with impaired renal function, the treatment should be discontinued
if increasing azotaemia and oliguria occur. Studies in functionally anephric
patients for one month undergoing chronic haemodialysis have not shown
evidence of drug accumulation, despite the fact that indapamide is not
dialysable.
Use in Pregnancy: Risk Category: C
Indapamide, being a loop
diuretic, enters the fetal circulation and may cause electrolyte
disturbances.
Neonatal thrombocytopenia has been reported
with thiazides and related diuretics. Loop diuretics like frusemide and
bumetanide are probably also associated with the risk. During the latter
part of pregnancy products of this type should only be given on sound
indications, and then in the lowest effective dose.
There is no information on the use of indapamide in pregnancy. Whilst animal
studies have not suggested any teratogenic effect, indapamide is not
recommended for administration to pregnant women unless the expected benefit
outweighs the potential risk.
Use in Lactation:
It is not known whether indapamide is excreted in breast milk. It is
therefore not recommended that the drug be given to lactating women as the
possible effect on the newborn is unknown.
Use in Children:
Safety and effectiveness have not been established.
Laboratory
Abnormalities:
The following values represent the maximum variations from pre-treatment
values in occasional patients at some stage during but not necessarily
throughout treatment. Blood uric acid up 8.6%,
blood glucose up 6%, BUN up 5.7%, blood creatinine up 3.6%.
Interactions:
No interactions have been reported between indapamide and oral hypoglycaemic
agents, anticoagulants, uricosurics and anti-inflammatory agents.
It is recommended that the drug not be used in combination with a diuretic
agent since the combination may produce hypokalaemia and hyperuricaemia.
It is recommended not to be used in
combination with antiarrhythmics such as quinidine derivatives, cardiac
glycosides, corticoids or laxatives, in case of hypokalaemia.
Adverse Reactions:
The most severe and common adverse effect is the electrolyte imbalance.
Electrolyte changes reported include: hypokalaemia 14.2% (requiring K+
supplementation 6%, with clinical symptoms 1.2%); hypochloraemia 9.4%;
hyponatraemia 3.1%.
Central nervous system (8.1 %), Incidence >1 % <3%:
asthenia, headache, dizziness, vertigo. Incidence <1% drowsiness,
sleepiness, insomnia, weakness, lethargy, visual disturbance.
Gastrointestinal (2.6%). Incidence <1%:
nausea/anorexia, dryness of mouth, gastralgia, vomiting, diarrhoea, constipation.
Musculoskeletal (1.4%). Incidence >1 % <3%:
muscle cramps. Incidence <1%: joint pain, back pain, weakness of legs.
Cardiovascular (1 %). Incidence <1 %:
orthostatic
hypotension, tachycardia, ECG changes (nonspecific ST-T changes, U waves,
left ventricular strain).
Urogenital (0.5%). Incidence <1%:
impotence,
modification of libido, polyuria.
Dermatological (0.5%). Incidence <1%:
rash,
pruritus.
Endocrine (0.2%). Incidence <1%:
gout.
Other (0.5%). Incidence <1%:
tinnitus, malaise/ fainting, sweating.
Dosage and Administration:
Adults. 1 tablet (2.5 mg indapamide) daily to be taken in the
morning. The action of indapamide is progressive and whilst the optimum
reduction in blood pressure is usually seen after 4 weeks, some further
small but useful reduction in blood pressure may be observed over the
following 4 to 6 weeks. A larger dose than 2.5 mg daily is not recommended
as there is little additional antihypertensive effect, whilst the diuretic
effect becomes more prominent.
A single daily tablet of indapamide may effectively be combined with another
antihypertensive agent such as beta-blockers, methyldopa, clonidine,
prazosin and other adrenergic blocking agents.
Indapamide has slight but significant carry-over hypotensive effect lasting
up to 1 or 2 weeks after the cessation of therapy.
Overdosage:
Symptoms. There have been no reports of overdosage. Based on the
pharmacological activities of indapamide, overdosage may lead to excessive
diuresis with electrolyte depletion. In cirrhotic patients, overdosage might
precipitate hepatic coma.
Treatment. There is no specific antidote. Treatment is symptomatic
and supportive. Discontinue drug. Induce emesis or perform gastric lavage.
Correct dehydrate, electrolyte imbalance, hepatic coma and hypotension by
established procedures.
Presentation:
2.5 mg tablet: pink film coated, marked "IE"
2.5
on one side, "G" on the reverse.
Pack Sizes:
Blister Packs of 90's.
Storage Conditions:
Store at room temperature. Protect from moisture, freezing and excessive
heat. Below 30°C.
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