Akripamide^® (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

AKRIKHIN JSC (Russia)

ATC Code

C03BA11 (Indapamide)

Active Substance

Indapamide

Dosage Form

Akripamide®

Film-coated tablets, 2.5 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or white with a creamy or grayish tint, round, biconvex; roughness is allowed; the cross-section is white or almost white.

Excipients: lactose (milk sugar), potato starch, povidone, sodium lauryl sulfate, talc, magnesium stearate.

Shell composition hypromellose (hydroxypropyl methylcellulose), macrogol 6000 (polyethylene glycol 6000), glycerol (glycerin), titanium dioxide, talc.

10 pcs. – blister packs (3) – cardboard packs.

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Antihypertensive drug, diuretic, possesses vasodilating activity. In terms of pharmacological properties, it is close to thiazide diuretics – it causes impaired reabsorption of sodium ions 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. Having the ability to selectively block slow calcium channels, it increases the elasticity of arterial walls and reduces total peripheral vascular resistance. It helps reduce left ventricular hypertrophy of the heart.

It does not affect the lipid content in plasma (triglycerides, HDL and LDL) or carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

It reduces the sensitivity of the vascular wall to norepinephrine and angiotensin II, stimulates the synthesis of PgE₂ and prostacyclin PgI₂, and reduces the production of free and stable oxygen radicals.

When prescribed in high doses, it does not affect the degree of blood pressure reduction, despite the increase in diuresis. After repeated administration, the therapeutic effect is noted after 1-2 weeks, reaches a maximum by 8-12 weeks, and persists for up to 8 weeks. After a single dose of the drug, the maximum effect is noted after 24 hours.

Pharmacokinetics

Absorption

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is high (93%). Food intake somewhat slows the rate but does not affect the final amount of the absorbed drug. C_max in blood is reached in 1-2 hours.

After oral administration, C_max at a dose of 5 mg is 260 ng/L. With repeated doses, fluctuations in the plasma concentration of the drug between two doses decrease. Steady-state concentration is reached after 7 days of regular use.

Distribution and Metabolism

Plasma protein binding is 70-80%. It also binds to elastin of the smooth muscles of the vascular wall. It has a large volume of distribution.

It penetrates through histohematic (including placental) barriers and is excreted in breast milk.

It is metabolized in the liver.

Does not accumulate.

Elimination

The T_1/2 of indapamide averages 14 hours. It is eliminated from the body by the kidneys (up to 70%) mainly in the form of metabolites, and through the intestines – 20-23%.

Pharmacokinetics in Special Clinical Cases

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

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

The drug is prescribed orally, preferably in the morning, regardless of meals.

The daily dose is 2.5 mg (1 tab.). If the desired therapeutic effect is not achieved after 4-8 weeks of therapy, it is not recommended to increase the drug dose (increased risk of side effects without enhancing the antihypertensive effect). In such cases, it is recommended to include another antihypertensive drug that is not a diuretic in the medication regimen. If treatment is started with two antihypertensive agents, the dose of Akripamide^® remains 2.5 mg once/day in the morning.

The tablets should be taken with a sufficient amount of liquid.

Adverse Reactions

From the cardiovascular system: orthostatic hypotension, arrhythmia, palpitations.

From the central and peripheral nervous system: headache, dizziness, nervousness, asthenia, drowsiness, vertigo, insomnia, depression, increased fatigue, malaise, tension, irritability, anxiety.

From the digestive system: constipation or diarrhea, dyspepsia (including nausea, vomiting), anorexia, dry mouth, abdominal pain, hepatic encephalopathy (against the background of hepatic insufficiency), pancreatitis.

From the urinary system: nocturia, polyuria.

From the respiratory system: rhinitis, cough, pharyngitis, sinusitis.

Allergic reactions: skin itching, maculopapular rash, urticaria, hemorrhagic vasculitis.

From the hematopoietic system: thrombocytopenia, leukopenia, agranulocytosis, bone marrow aplasia, hemolytic anemia.

Laboratory parameters: hypercalcemia, hyperuricemia, hypochloremia, hypokalemia, hyponatremia, hyperglycemia, increased blood urea nitrogen, hypercreatininemia, glucosuria.

Other: muscle spasm, exacerbation of systemic lupus erythematosus.

Contraindications

• Anuria;
• Severe hepatic insufficiency (including with encephalopathy);
• Severe renal failure;
• Hypokalemia;
• Concomitant use of drugs that prolong the QT interval;
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years (efficacy and safety not established);
• Lactose intolerance, galactosemia, glucose/galactose malabsorption syndrome;
• Hypersensitivity to the components of the drug;
• Hypersensitivity to other sulfonamide derivatives.

With caution the drug should be used for disorders of water-electrolyte balance, mild and moderate hepatic and/or renal insufficiency, prolongation of the QT interval, hyperuricemia (especially with gout or urate nephrourolithiasis), hyperparathyroidism.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency (including with encephalopathy).

Use in Renal Impairment

Contraindicated in severe renal failure.

Pediatric Use

Contraindication: age under 18 years (efficacy and safety not established).

Geriatric Use

The most thorough monitoring is indicated in elderly individuals.

Special Precautions

Patients receiving cardiac glycosides, laxative medications, against the background of hyperaldosteronism, as well as elderly patients, require careful monitoring of potassium ion and creatinine levels.

During treatment with Akripamide^®, the plasma concentrations of potassium, sodium, and magnesium ions (possible development of electrolyte disturbances), pH, glucose concentration, uric acid, and residual nitrogen should be systematically monitored. The most thorough monitoring is indicated in patients with liver cirrhosis (especially with edema or ascites – high risk of developing metabolic alkalosis, which enhances the manifestations of hepatic encephalopathy), coronary artery disease, chronic heart failure, as well as in elderly individuals. 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 blood potassium ion concentration should be performed within the first week of treatment.

Hypercalcemia during treatment with Akripamide^® may be a consequence of previously undiagnosed hyperparathyroidism.

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

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

During treatment with Akripamide^®, positive results are possible when conducting doping control.

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

Overdose

Symptoms: nausea, vomiting, weakness, arterial hypotension, dizziness, drowsiness, confusion, respiratory depression, impaired gastrointestinal function; in patients with impaired liver function, hepatic coma may develop.

Treatment: gastric lavage and/or administration of activated charcoal, correction of water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Drug Interactions

Akripamide^® increases the plasma concentration of lithium ions (reduced urinary excretion), lithium has a nephrotoxic effect.

Increases the risk of impaired renal function when using high doses of iodine-containing contrast agents (dehydration of the body). Before using iodine-containing contrast agents, it is necessary to restore fluid loss in the body.

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 increased production by the liver (dose adjustment may be required).

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

Loop and thiazide diuretics, cardiac glycosides, corticosteroids and mineralocorticoids, tetracosactide, amphotericin B (with intravenous administration), laxative medications increase the risk of hypokalemia. When used concomitantly with cardiac glycosides, the likelihood of digitalis intoxication increases; with calcium ion preparations – hypercalcemia; with metformin, lactic acidosis may worsen.

Astemizole, erythromycin (with intravenous administration), pentamidine, sultopride, terfenadine, vincamine, class I A antiarrhythmic drugs (quinidine, disopyramide) and class III antiarrhythmic drugs (amiodarone, bretylium tosilate, sotalol) can lead to the development of torsades de pointes arrhythmia due to synergy regarding QT interval prolongation.

NSAIDs, corticosteroids, tetracosactide, adrenergic stimulants reduce, and baclofen enhances the hypotensive effect of indapamide.

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.

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

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

Cyclosporine increases the risk of hypercreatininemia.

Storage Conditions

The drug should be stored in a dry, light-protected place, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 4 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.