Apo-Indapamide

Apo-Indapamide

indapamide

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Indapamide.
Description
Each tablet contains 2.5 mg indapamide.
Action
Pharmacology: Indapamide is a diuretic antihypertensive agent. The mechanism whereby indapamide exerts its action in the control of hypertension is not completely elucidated: both renal and extrarenal actions may be involved. The renal site of action is the proximal 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 and hypokalemia.
Indapamide is rapidly and completely absorbed after prat 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. Seventy percent of a single oral dose is eliminated by the kidneys and 23 percent by the gastrointestinal tract. Indapamide is metabolised to a marked degree, the unchanged product representing approximately 5 percent of the total dose found in the urine during the 48 hours following administration. Elimination of indapamide from the plasma is biphasic with half-lives of 14 and 25 hours respectively.
Indications/Uses
APO-INDAPAMIDE (indapamide) is indicated in the management of essential hypertension. It may be tried as a sole therapeutic agent in the treatment of mild to moderate hypertension. Normally APO-INDAPAMIDE, as other diuretics, is used as the initial agent in multiple drug regimens.
Dosage/Direction for Use
One 2.5 mg tablet per day taken in the morning as a single dose. If the response is not satisfactory after 4 to 8 weeks, increase in dosage is not recommended (see WARNINGS). Instead a non-diuretic antihypertensive agent should be added to the drug regimen. Alternatively, if in the opinion of the physician, an important diuretic effect is desirable for the patient's control, a different diuretic which allows for dose titration could be tried instead of indapamide.
In cases where two drugs are considered necessary to initiate treatment, the dose of APO-INDAPAMIDE (indapamide) remains 2.5 mg per day, taken in the morning as a single dose.
Overdosage
Symptoms: There have been no reports of overdosage. Based on the pharmacological activities of APO-INDAPAMIDE (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 dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.
Contraindications
Anuria, progressive and severe oliguria, hepatic coma. Known hypersensitivity to indapamide or to other sulphonamide derivatives.
Warnings
Electrolyte changes observed with indapamide become severe at doses above 2.5 mg per day. Therefore the maximum daily dose should not exceed this dose.
Hypokalemia may occur at all doses with consequent weakness, cramps, and cardiac dysrhythmias. Hypokalemia is a particular hazard in digitalized patients; dangerous or fatal arrhythmias may be precipitated.
Patients with renal insufficiency receiving APO-INDAPAMIDE (indapamide) should be carefully monitored. If increasing azotemia and oliguria occur during treatment, the diuretic should be discontinued.
Hyperuricemia may occur during administration of APO-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.
Special Precautions
Patients receiving APO-INDAPAMIDE (indapamide) should be carefully observed and serum electrolytes monitored for signs and symptoms of fluid or electrolyte imbalance; namely hyponatremia, hypochloremia and hypokalemia. Blood urea nitrogen, uric acid, and glucose levels should also be assessed during therapy. Hypokalemia, an ever present hazard with most diuretics 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 since diuretics may induce 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 or concurrent therapy with other antihypertensives.
When indapamide is given with other non-diuretic 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.
Severe dermatological adverse reactions, some accompanied by systemic manifestations, have been rarely reported with the use of indapamide. In the majority of cases, the condition subsided within 14 days following discontinuation of indapamide therapy. (See ADVERSE REACTIONS).
Caution should be observed when administering the drug to patients with severely impaired renal function, since the drug is excreted primarily by the renal route.
Although indapamide exerts minimal effect on glucose metabolism, insulin requirements may be affected in diabetics and hyperglycemia and glycosuria may occur in patients with latent diabetes.
Use in Children: The safety and effectiveness of indapamide have not been established in children.
Use In Pregnancy & Lactation
Use in Pregnancy: Since indapamide has not been studied in human pregnancy, the drug should not be given to pregnant women. The use in patients of child-bearing potential requires that the anticipated benefit be weighed against possible hazards.
Use in Nursing Mothers: It is not known whether indapamide is excreted in breast milk. APO-INDAPAMIDE should not be administered to nursing mothers. If use of the drug is deemed essential, the patient should stop nursing.
Adverse Reactions
The most severe and common adverse effect is electrolyte imbalance. Electrolyte changes reported include: Hypokalemia - 14.2% (requiring K+ supplementation 6%; with clinical symptoms 1.2%); Hypochloremia - 9.4%; Hyponatremia - 3.1%.
The other changes observed in laboratory parameters are minor and infrequent: elevation in blood uric acid (8.6%), blood glucose (6.0%), BUN (5.7%), and blood creatinine (3.6%).
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, diarrhea, constipation.
MUSCULOSKELETAL (1.4%): Incidence 1-3%: Muscle cramps.
Incidence <1%: Joint pain, back pain, weakness of legs.
CARDIOVASCULAR (1.0%): Incidence <1%: Orthostatic hypotension, tachycardia, ECG changes (non-specific ST-T change, U waves, left ventricular strain).
UROGENITAL (0.5%): Incidence <1%: Impotence, modification of libido, polyuria.
DERMATOLOGICAL (0.5%): Incidence <1%; Rash, pruritus.
Since the drug has been marketed, the following dermatological adverse effects have been rarely reported: Stevens-Johnson's syndrome, bullous eruption, photosensitivity with bullae, erythroderma, purpura. Relationship with the administration of indapamide has not been proven in all cases.
ENDOCRINE (0.2%): Incidence <1%; Gout.
OTHER (0.5%): Incidence <1%: Tinnitus, malaise/fainting, sweat.
Drug Interactions
Concurrent use of indapamide with amiodarone may lead to an increased risk of arrhythmias associated with hypokalemia. The effects of Anticoagulants, coumarin- or indandione-derivatives may be decreased when used concurrently with indapamide, resulting in a reduction of plasma volume leading to a concentration of procoagulant factors in the blood. In addition, diuretic-induced improvement of hepatic congestion may lead to improved hepatic function resulting in increased procoagulant factor synthesis. Dosage adjustments may be necessary. Concurrent use of Digitalis glycosides with indapamide may enhance the possibility of digitalis toxicity associated with hypokalemia. Antihypertensive and/or diuretic effects may be increased when Hypotension-producing medications are used concurrently with indapamide. Although some antihypertensive and/or diuretic combinations are used frequently for therapeutic advantage. Dosage adjustment may be necessary during concurrent use. Concurrent use of Lithium is not recommended as it may provoke lithium toxicity because of reduced renal clearance. Lithium also has nephrotoxic effects. Indapamide may induce hypokaiemia, which may enhance the blockade of nondepotarizing neuromuscular blocking agents. Careful postoperative monitoring of the patient may be necessary following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade. The antihypertensive effects of indapamide may be reduced when it is used concurrently with sympathomimetics. The patient should be carefully monitored to confirm that the desired effect is being obtained. Indapamide may decrease arterial responsiveness to norepinephrine, but does not usually significantly interfere with its clinical effects. 
Storage
Store at room temperature (15 - 30°C) in tightly-closed containers.
MIMS Class
ATC Classification
C03BA11 - indapamide ; Belongs to the class of low-ceiling sulfonamide diuretics.
Presentation/Packing
Tab 2.5 mg (pink, round, biconvex, film-coated,  engraved "2.5" on one side and plain on the other) x 100's.
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