Arindap^® (Tablets) Instructions for Use

Marketing Authorization Holder

Polpharma Pharmaceutical Works, Sa (Poland)

Manufactured By

Medana Pharma, SA (Poland)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide (Rec.INN registered by WHO)

Dosage Form

Arindap®

Film-coated tablets, 2.5 mg: 20, 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex; on the cross-section – white or almost white.

Excipients: microcrystalline cellulose, crospovidone, magnesium stearate.

Shell composition hypromellose, stearic acid, microcrystalline cellulose, titanium dioxide.

10 pcs. – blisters (2) – carton packs.
10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (6) – carton packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Antihypertensive drug. In its pharmacological properties, it is close to thiazide diuretics (the mechanism of action is associated with impaired sodium reabsorption in the cortical segment of the loop of Henle). It increases the excretion of sodium and chloride ions in the urine, and to a lesser extent – potassium and magnesium ions.

By having the ability to selectively block slow calcium channels, it increases the elasticity of arterial walls and reduces total peripheral vascular resistance. It helps to reduce left ventricular hypertrophy of the heart. It does not affect the lipid content in blood plasma (triglycerides, LDL, HDL) and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

It reduces the sensitivity of the vascular wall to norepinephrine (noradrenaline) and angiotensin II, stimulates the synthesis of prostaglandin E₂, and reduces the production of free and stable oxygen radicals.

The antihypertensive effect persists for 24 hours when the drug is taken once a day, the optimal therapeutic effect develops by the end of the first week of administration.

Pharmacokinetics

Absorption

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Taking with food somewhat slows down the rate of absorption but does not affect its extent. C_max is reached 1-2 hours after oral administration.

Distribution

With repeated doses, fluctuations in the plasma concentration of the drug in the interval between taking two doses decrease. Steady state is established after 7 days of regular use. Binding to plasma proteins is 79%. It also binds to elastin of the smooth muscles of the vascular wall. Does not accumulate. Has a high V_d, penetrates histohematic barriers (including the placental barrier), and is excreted in breast milk.

Metabolism and excretion

Metabolized in the liver. T_1/2 is 18 hours. Excreted by the kidneys mainly in the form of metabolites 60-80% (about 5% is excreted unchanged), through the intestines – 20%.

Pharmacokinetics in special clinical cases

In patients with renal failure, the pharmacokinetics do not change.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

The tablets are taken orally, without chewing. The recommended dose of the drug is 2.5 mg (1 tab.) once a day (in the morning).

If after 4-8 weeks of treatment the desired therapeutic effect is not achieved, it is not recommended to increase the dose of the drug (increased risk of side effects without enhancing the antihypertensive effect). Instead, it is recommended to include another antihypertensive drug (not a diuretic) in the drug treatment regimen.

In cases where treatment must be started with two drugs, the dose of Arindap^® remains 2.5 mg (once a day, in the morning).

Adverse Reactions

From the digestive system nausea/anorexia, dry mouth, gastralgia, vomiting, diarrhea, constipation, pancreatitis are possible.

From the central nervous system asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression; rarely – increased fatigue, general weakness, malaise, muscle spasm, tension, irritability, anxiety.

From the organ of vision conjunctivitis, visual impairment.

From the respiratory system cough, pharyngitis, sinusitis, rhinorrhea; rarely – rhinitis.

From the cardiovascular system orthostatic hypotension, ECG changes (hypokalemia), arrhythmia, palpitations.

From the urinary system frequent infections, nocturia, polyuria.

Allergic reactions rash, urticaria, itching, hemorrhagic vasculitis.

From laboratory parameters hyperuricemia, hypokalemia, hypochloremia, hyponatremia, hypercalciuria, increased blood urea nitrogen, hypercreatininemia, glucosuria.

Other flu-like syndrome, chest pain, back pain, infections, decreased potency, decreased libido, sweating, weight loss, tingling in the extremities, exacerbation of systemic lupus erythematosus.

Contraindications

• Anuria;
• Hypokalemia;
• Severe hepatic insufficiency (including with encephalopathy);
• Renal failure;
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety have not been established);
• Concomitant use of drugs that prolong the QT interval;
• Hypersensitivity to the drug and other sulfonamide derivatives.

Use with caution in decompensated diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

The drug is contraindicated in severe hepatic insufficiency (including with encephalopathy).

Use in Renal Impairment

Contraindicated in renal failure.

Pediatric Use

The efficacy and safety of the drug in children and adolescents under 18 years of age have not been established.

Special Precautions

When prescribing the drug to patients taking cardiac glycosides, laxatives, against the background of hyperaldosteronism, as well as to elderly patients, regular monitoring of potassium ion levels and creatinine levels is indicated.

While taking Arindap^®, the concentration of potassium, sodium, magnesium ions in blood plasma (electrolyte disturbances may develop), pH, glucose concentration, uric acid and residual nitrogen should be systematically monitored.

The most thorough monitoring is indicated for patients with liver cirrhosis (especially with edema or ascites due to the risk of developing metabolic alkalosis, which enhances the manifestations of hepatic encephalopathy), as well as for coronary artery disease, heart failure and elderly patients.

The high-risk group also includes patients with an increased QT interval on the ECG (congenital or developed against the background of any pathological process). The first determination of the concentration of potassium ions in the blood should be carried out within the first week of using the drug.

Hypercalcemia while taking Arindap^® may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes mellitus, it is extremely important to control blood glucose levels, especially in the presence of hypokalemia.

Significant dehydration can lead to the development of acute renal failure (decreased glomerular filtration). Patients need to compensate for water loss and at the beginning of treatment carefully monitor kidney function.

Arindap^® may give a positive result during doping control.

Patients with arterial hypertension and hyponatremia (due to diuretic use) must stop taking diuretics 3 days before starting ACE inhibitors (if necessary, diuretics can be resumed a little later), or ACE inhibitors are prescribed in low initial doses.

When prescribing indapamide, it should be borne in mind that sulfonamide derivatives can exacerbate the course of systemic lupus erythematosus.

Use in pediatrics

The efficacy and safety of the drug in children have not been established.

Overdose

Symptoms nausea, vomiting, weakness, impaired gastrointestinal function, water-electrolyte balance disorders, in some cases – excessive decrease in blood pressure, respiratory depression. In patients with liver cirrhosis, hepatic coma may develop.

Treatment gastric lavage, correction of water-electrolyte balance; if necessary, symptomatic therapy is carried out. There is no specific antidote.

Drug Interactions

When used concomitantly with indapamide, saluretics, cardiac glycosides, gluco- and mineralocorticoids, tetracosactide, amphotericin B (for intravenous administration), and laxatives increase the risk of hypokalemia.

When taken simultaneously with cardiac glycosides, the likelihood of digitalis intoxication increases; with calcium preparations – hypercalcemia; with metformin – aggravation of lactic acidosis is possible.

When used concomitantly with indapamide, the concentration of lithium ions in plasma increases (due to decreased urinary excretion); lithium has a nephrotoxic effect.

When used concomitantly with indapamide, it should be taken into account that astemizole, intravenous erythromycin, pentamidine, sultopride, terfenadine, vincamine, class Ia antiarrhythmic drugs (quinidine, disopyramide) and class III antiarrhythmic drugs (amiodarone, bretylium, sotalol) can lead to the development of torsades de pointes arrhythmia.

When used concomitantly, NSAIDs, corticosteroids, tetracosactide, and sympathomimetics reduce the hypotensive effect of indapamide, while baclofen enhances it.

The combination with potassium-sparing diuretics may be effective in some categories of patients, but the possibility of developing hypo- or hyperkalemia is not completely excluded, especially in patients with diabetes mellitus and renal failure.

When used concomitantly with indapamide, ACE inhibitors increase the risk of arterial hypotension and/or acute renal failure (especially with existing renal artery stenosis).

Indapamide increases the risk of impaired renal function when using high doses of iodine-containing contrast agents (due to dehydration of the body). Before using iodine-containing contrast agents, patients must restore fluid loss.

Imipramine-type (tricyclic) antidepressants and antipsychotic agents enhance the hypotensive effect and increase the risk of orthostatic hypotension.

When used concomitantly, cyclosporine increases the risk of hypercreatininemia.

Indapamide reduces the effect of indirect anticoagulants (coumarin or indandione derivatives) due to an increase in the concentration of coagulation factors as a result of a decrease in circulating blood volume and an increase in their production by the liver (dose adjustment may be required).

Indapamide enhances the neuromuscular blockade developing under the action of non-depolarizing muscle relaxants.

Storage Conditions

List B. The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature below 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.