Akripamide^® retard (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 (Rec.INN registered by WHO)

Dosage Form

Akripamide® retard

Extended-release tablets, film-coated, 1.5 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Extended-release tablets, film-coated white or white with a creamy or grayish tint, round, biconvex.

Excipients: ludipress LCE (lactose monohydrate 94.7-98.3%, povidone – 3-4%) – 94.4 mg, hypromellose – 42 mg, colloidal silicon dioxide – 700 mcg, magnesium stearate – 1.4 mg.

Shell composition hypromellose – 4.83 mg, macrogol 6000 – 140 mcg, glycerol – 280 mcg, titanium dioxide – 910 mcg, talc – 490 mcg, lactose monohydrate – 350 mcg.

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

Clinical-Pharmacological Group

Diuretic. Antihypertensive drug

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

An antihypertensive drug, a diuretic, with vasodilating activity.

In its pharmacological properties, it is close to thiazide diuretics. It impairs the 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 contributes to the reduction of left ventricular hypertrophy of the heart.

It does not affect lipid and carbohydrate metabolism (including in patients with diabetes mellitus), and does not impair the sensitivity of peripheral tissues to the action of insulin.

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

The hypotensive effect develops by the end of the first week and is maintained for 24 hours against the background of a single dose.

Pharmacokinetics

Absorption

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is high – 93%. Food intake somewhat slows down the rate of absorption but does not affect the amount of the absorbed substance. After oral administration, C_max in blood plasma is reached after 12 hours. With repeated doses, fluctuations in the concentration of the drug in the blood plasma in the interval between two doses are reduced.

Distribution

Steady state is established after 7 days of regular intake. Binding to plasma proteins is 79%. It also binds to elastin of the vascular wall smooth muscles.

It has a large V_d, penetrates through histohematic barriers (including the placental barrier), and is excreted in breast milk. It does not accumulate.

Metabolism and excretion

It is metabolized in the liver.

T_1/2 – 18 hours. 60-80% is excreted by the kidneys in the form of metabolites, about 5% unchanged, and 20% through the intestines.

Pharmacokinetics in special clinical cases

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

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

Take one 1.5 mg extended-release tablet orally once daily.

Administer the dose preferably in the morning to minimize nocturia.

Swallow the tablet whole; do not chew or crush it.

Take with a sufficient amount of liquid.

Initiate therapy with this single daily dose; do not exceed the 1.5 mg dose.

Perform the first measurement of blood potassium within the initial week of treatment.

Regularly monitor serum electrolytes, particularly potassium, sodium, and magnesium.

Monitor renal function and fluid balance, especially at the start of treatment in at-risk patients.

In patients with diabetes, monitor blood glucose levels, particularly if hypokalemia is present.

For patients with arterial hypertension and hyponatremia, discontinue diuretics three days prior to initiating an ACE inhibitor.

Adverse Reactions

From the digestive system: nausea, anorexia, dry mouth, gastralgia, vomiting, diarrhea, constipation, abdominal pain, possible development of hepatic encephalopathy; rarely – pancreatitis.

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

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

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

From the urinary system: frequent infections, nocturia, polyuria.

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

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

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

Other: exacerbation of systemic lupus erythematosus.

Contraindications

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

With caution should be prescribed for impaired liver and/or kidney function, water-electrolyte imbalance, hyperparathyroidism, patients with an increased QT interval on ECG or receiving combination therapy, 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 (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency (including with encephalopathy). With caution should be prescribed for impaired liver function.

Use in Renal Impairment

With caution should be prescribed for impaired kidney function. Contraindicated in severe renal failure (anuria stage).

Pediatric Use

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

Special Precautions

It should be taken into account that in patients taking cardiac glycosides, laxatives, against the background of hyperaldosteronism, as well as in elderly patients, regular monitoring of potassium ion and creatinine levels is indicated.

While taking Akripamide retard, the concentration of potassium, sodium, and magnesium ions in the blood plasma (electrolyte disturbances may develop), pH, the concentration of glucose, 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, as there is a risk of developing metabolic alkalosis, which enhances the manifestations of hepatic encephalopathy), coronary artery disease, heart failure, as well as in 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 measurement of blood potassium concentration should be performed within the first week of treatment.

Hypercalcemia while taking Akripamide retard may be a consequence of previously undiagnosed hyperparathyroidism.

In patients with diabetes mellitus, blood glucose levels should be monitored, 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 carefully monitor kidney function at the beginning of treatment.

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 later), or they should be prescribed ACE inhibitors at low initial doses.

When using indapamide, positive results during doping control are possible.

Effect on the ability to drive vehicles and operate machinery

In some cases, individual reactions associated with changes in blood pressure are possible, especially at the beginning of treatment and when adding another antihypertensive agent. As a result, the ability to drive a car and operate machinery requiring increased attention may be reduced.

Overdose

Symptoms nausea, vomiting, weakness, impaired gastrointestinal function, water-electrolyte imbalances, in some cases – excessive decrease in blood pressure, respiratory depression. In patients with liver cirrhosis, the development of hepatic coma is possible.

Treatment gastric lavage, correction of water-electrolyte balance, symptomatic therapy. There is no specific antidote.

Drug Interactions

With the simultaneous use of Akripamide retard with saluretics, cardiac glycosides, gluco- and mineralocorticoids, tetracosactide, amphotericin B (for intravenous administration), and laxatives, the risk of hypokalemia increases.

With the simultaneous use of Akripamide retard with cardiac glycosides, the likelihood of digitalis intoxication increases.

With the simultaneous use of Akripamide retard with calcium preparations, the likelihood of hypercalcemia increases.

With the simultaneous use of Akripamide retard with metformin, lactic acidosis may be exacerbated.

Akripamide^® retard increases the concentration of lithium in the blood plasma (due to reduced urinary excretion), which increases the risk of developing its nephrotoxic effect.

With simultaneous use with Akripamide retard of astemizole, erythromycin (for intravenous administration), pentamidine, sultopride, terfenadine, vincamine, class IA antiarrhythmic agents (quinidine, disopyramide) and class III (amiodarone, bretylium, sotalol), the development of torsades de pointes arrhythmia is possible.

With the simultaneous use of Akripamide retard with NSAIDs, corticosteroids, tetracosactide, and sympathomimetics, the hypotensive effect is reduced.

With the simultaneous use of Akripamide retard with baclofen, the hypotensive effect is enhanced.

The combination of Akripamide retard 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.

With the simultaneous use of Akripamide retard, ACE inhibitors increase the risk of arterial hypotension and/or acute renal failure (especially with existing renal artery stenosis).

With the simultaneous use of Akripamide retard with high doses of iodine-containing contrast agents, dehydration of the body and an increased risk of impaired renal function may develop. Before using iodine-containing contrast agents, patients need to restore fluid loss.

Imipramine-type (tricyclic) antidepressants and antipsychotics enhance the hypotensive effect of Akripamide retard and increase the risk of orthostatic hypotension.

With the simultaneous use of Akripamide retard with cyclosporine, the risk of hypercreatininemia increases.

Akripamide^® retard 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 the volume of circulating blood and an increase in their production by the liver (dose adjustment may be required).

Akripamide^® retard 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 not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 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.