Indap tablets 2.5 mg No. 30

Instructions for Indap tablets 2.5 mg No. 30

Composition

active ingredient: indapamide;

1 tablet contains 1.25 mg or 2.5 mg of indapamide;

excipients:

Indap®, tablets 1.25 mg: lactose monohydrate, microcrystalline cellulose, talc, magnesium stearate, colloidal anhydrous silica, red iron oxide (E 172);

Indap®, 2.5 mg tablets: lactose monohydrate, microcrystalline cellulose, talc, magnesium stearate, colloidal anhydrous silica, TopMill ORANGE 231.05.C (yellow iron oxide (E 172), red iron oxide (E 172), lactose monohydrate).

Dosage form

Pills.

Main physicochemical properties: 1.25 mg tablets: pink round flat tablets with a diameter of approximately 7 mm, barely noticeable marbling is allowed;

2.5 mg tablets: light orange round tablets with a diameter of approximately 8 mm with a cross-shaped score for separation on one side, barely noticeable marbling is allowed.

Pharmacotherapeutic group

Non-thiazide diuretics with moderate diuretic activity. Sulfonamides, simple. ATC code C03B A11.

Pharmacological properties

Pharmacodynamics

Indapamide is a sulfonamide diuretic that is pharmacologically related to thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment of the kidney. This increases the urinary excretion of sodium and chloride and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing diuresis.

The antihypertensive effect of indapamide is manifested at doses at which the diuretic effect is insignificant. Moreover, its antihypertensive effect is maintained even in patients with arterial hypertension who are on hemodialysis.

Indapamide acts at the vascular level by:

decreased contractility of vascular smooth muscles, which is associated with changes in transmembrane ion exchange (mainly calcium);

stimulation of the synthesis of prostaglandin PGE2 and prostacyclin PGI2 (vasodilator and platelet aggregation inhibitor).

Indapamide reduces left ventricular hypertrophy.

Moreover, as studies of various durations (short, medium and long) involving patients with arterial hypertension have shown, indapamide:

does not affect the metabolism of lipids: triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol;

does not affect carbohydrate metabolism, even in patients with hypertension and diabetes.

When the recommended dose is exceeded, the therapeutic effect of thiazides and thiazide-like diuretics does not increase, while the number of undesirable effects increases. If the treatment is not effective enough, increasing the dose is not recommended.

Pharmacokinetics

Absorption

The bioavailability of indapamide is high – 93%.

The maximum plasma concentration (Cmax) after taking a dose of 2.5 mg is reached in approximately 1-2 hours.

Distribution

Binding to plasma proteins is above 75%.

The half-life is 14-24 hours (average – 18 hours).

With regular administration of the drug, a stable plasma concentration level (plateau) is achieved compared to the concentration of indapamide after a single dose. This plasma concentration level remains stable for a long time without cumulation.

Breeding

Renal clearance accounts for 60-80% of total clearance.

Indapamide is excreted mainly in the form of metabolites, the proportion of the drug excreted by the kidneys in unchanged form is 5%.

Patients with renal insufficiency

In patients with renal insufficiency, pharmacokinetic parameters do not change.

Indication

Essential hypertension.

Contraindication

Hypersensitivity to sulfonamides or to any auxiliary component of the drug;

severe renal failure (creatinine clearance below 30 ml/min);

hepatic encephalopathy or severe liver disease;

hypokalemia;

pregnancy and breastfeeding.

Interaction with other medicinal products and other types of interactions

Not recommended combinations

Lithium: Increased plasma lithium levels and symptoms of overdose may occur, as with a salt-free diet (reduced urinary lithium excretion). If a diuretic is necessary, careful monitoring of plasma lithium levels and adjustment of the lithium dose are necessary.

Combinations requiring caution

Drugs that can cause paroxysmal torsades de pointes:

class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);

class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);

some antipsychotic drugs:

o phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine);

o benzamides (amisulpride, sulpiride, sultopride, tiapride);

o butyrophenones (droperidol, haloperidol);

other medications: bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, intravenous vincamine.

Before prescribing such a combination, potassium levels should be checked and corrected if necessary. Patients should be monitored for clinical status, plasma electrolytes, and ECG. In the presence of hypokalemia, it is recommended to prescribe drugs that do not cause torsades de pointes.

Nonsteroidal anti-inflammatory drugs (for systemic use), including selective cyclooxygenase 2 inhibitors, high doses of salicylates (≥ 3 g/day):

o may reduce the antihypertensive effect of indapamide;

o Dehydrated patients are at increased risk of acute renal failure (due to decreased glomerular filtration). Before starting treatment, it is necessary to restore water balance and check kidney function.

Angiotensin-converting enzyme (ACE) inhibitors: Sudden onset of hypotension and/or acute renal failure may occur in patients with low sodium levels (especially in patients with renal artery stenosis).

Arterial hypertension. If previous use of a diuretic has caused a decrease in sodium levels, it is necessary to stop taking the diuretic 3 days before starting treatment with an ACE inhibitor and then, if necessary, resume diuretic therapy or start taking the ACE inhibitor at a low initial dose with subsequent gradual increase.

In congestive heart failure, the use of an ACE inhibitor should be initiated at the lowest dose and, possibly, after reducing the dose of the previously prescribed potassium-sparing diuretic.

In any case, renal function (plasma creatinine) should be monitored during the first weeks of treatment with an ACE inhibitor.

Drugs that can cause hypokalemia: gluco- and mineralocorticoids (for systemic use), amphotericin B (intravenous), tetracosactide, laxatives that stimulate peristalsis - increase the risk of hypokalemia (additive effect). Plasma potassium should be monitored and corrected if necessary, special attention should be paid to simultaneous therapy with cardiac glycosides. It is recommended to prescribe laxatives that do not stimulate peristalsis.

Cardiac glycosides. The presence of hypokalemia contributes to the cardiotoxicity of cardiac glycosides. Plasma potassium should be monitored, ECG should be monitored and treatment adjusted if necessary.

Baclofen enhances the antihypertensive effect of the drug. At the beginning of therapy, it is necessary to restore the patient's water and electrolyte balance and monitor kidney function.

Digitalis preparations:

Hypokalemia and/or hypomagnesemia contribute to the toxicity of digitalis. Monitoring of plasma potassium, magnesium and ECG is recommended and, if necessary, treatment adjustment.

Combinations that require attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene). If such a combination is considered appropriate, the possibility of hypokalemia (especially in patients with diabetes mellitus or renal failure) or hyperkalemia cannot be ruled out. Plasma potassium levels should be monitored, ECG should be monitored and therapy adjusted if necessary.

Metformin: The risk of lactic acidosis increases in patients with functional renal failure due to diuretics, especially loop diuretics. Metformin should not be prescribed if the plasma creatinine level exceeds 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.

Iodine contrast media. In case of dehydration caused by diuretics, the risk of developing acute renal failure increases, especially when using large doses of iodinated contrast media. It is necessary to restore the water balance before administering iodinated contrast media.

Imipramine-like antidepressants, neuroleptics. Increased antihypertensive effect and risk of orthostatic hypotension due to additive effect.

Calcium salts. Hypercalcemia may occur due to decreased renal calcium elimination.

Cyclosporine, tacrolimus: Risk of increased plasma creatinine without effect on circulating cyclosporine levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (systemic action). Decreased antihypertensive effect of indapamide due to water and sodium retention under the influence of corticosteroids.

Application features

Patients with liver dysfunction

In patients with impaired liver function, the use of thiazide-like diuretics may cause hepatic encephalopathy, especially if electrolyte imbalance is present. In such cases, diuretics should be discontinued immediately.

Photosensitivity

Photosensitivity reactions have been reported in patients receiving thiazide and thiazide-like diuretics (see section 4.8). If such reactions occur, diuretic treatment should be discontinued. If diuretics are re-administered, the affected areas should be protected from sunlight or artificial ultraviolet light sources.

Excipients

The drug contains lactose, so it should not be prescribed to patients with congenital galactose intolerance, glucose-galactose malabsorption syndrome, Lapp lactase deficiency.

Water and electrolyte balance

It is necessary to monitor the level of sodium in the blood plasma before starting treatment and then regularly during treatment. A decrease in the level of sodium in the blood plasma may be asymptomatic at first, therefore regular monitoring is necessary. Monitoring of sodium levels should be carried out more often in elderly patients and in patients with cirrhosis of the liver. Any diuretic can cause hyponatremia, which sometimes has serious consequences. Hyponatremia with hypovolemia can lead to dehydration and orthostatic hypotension; the concomitant loss of chloride ions can cause secondary compensatory metabolic alkalosis (the frequency and severity of this phenomenon are low).

Plasma potassium

The development of hypokalemia (< 3.4 mmol/l) should be avoided in certain high-risk patient groups, such as the elderly, malnourished and/or heavily medicated patients, patients with cirrhosis of the liver accompanied by edema and ascites, patients with ischemic heart disease and patients with heart failure. In such cases, hypokalemia increases the cardiotoxicity of cardiac glycosides and the risk of arrhythmias.

Patients with congenital or iatrogenic QT prolongation are also at risk. Hypokalemia, like bradycardia, can lead to the development of severe cardiac arrhythmias, including torsades de pointes, which can be fatal.

In all of the above cases, more frequent monitoring of blood potassium levels is necessary. The first analysis should be performed within the first week of treatment. If hypokalemia is detected, it should be corrected.

Hypokalemia, identified in association with low serum magnesium concentrations, may be poorly treatable unless serum magnesium levels are corrected.

Magnesium in blood plasma:

Thiazides and related diuretics, including indapamide, have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia (see sections 4.5 and 4.8).

Plasma calcium

Thiazide and thiazide-like diuretics may reduce urinary calcium excretion and lead to a slight and transient increase in plasma calcium levels. Marked hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. In such cases, treatment should be discontinued and parathyroid function should be monitored.

Blood glucose

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

Uric acid

Patients with elevated uric acid levels may have a tendency to have an increased number of gout attacks.

Kidney function and diuretics

Thiazide and thiazide-like diuretics are most effective when renal function is not impaired or only mildly impaired (plasma creatinine <25 mg/l, i.e. 220 mmol/l in adults). In elderly patients, plasma creatinine should be at a level appropriate for age, weight and sex. Hypovolemia, associated with water and sodium loss due to diuretics, causes a decrease in glomerular filtration rate at the beginning of treatment. This may lead to an increase in blood urea and creatinine. Such transient functional renal failure is of no consequence in individuals with normal renal function, but may worsen existing renal failure.

In athletes, indapamide may cause a positive reaction during doping control.

Choroidal effusion, acute myopia, and secondary angle-closure glaucoma.

Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug.

Untreated acute angle-closure glaucoma can lead to permanent vision loss. The main treatment is to stop the medication as soon as possible. If the intraocular pressure remains uncontrolled, urgent medical or surgical treatments may be necessary. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of indapamide in pregnant women are lacking or limited (less than 300 cases). Diuretics should be avoided in pregnant women and should never be used to treat physiological edema in pregnant women. Prolonged use of a thiazide diuretic during the third trimester of pregnancy may result in a decrease in the circulating blood volume of the pregnant woman and in uteroplacental blood flow, which may cause fetoplacental ischemia and fetal growth retardation. Animal studies do not indicate direct or indirect toxic effects on reproduction. The use of indapamide during pregnancy is contraindicated.

There are insufficient data on the excretion of indapamide/metabolites into breast milk. Hypersensitivity to sulfonamide derivatives and hypokalemia may develop. A risk to the newborn/infants cannot be excluded. Indapamide belongs to the thiazide-like diuretics, the use of which during breastfeeding has been associated with a decrease or even suppression of lactation. Indapamide is contraindicated during breastfeeding.

Fertility

Reproductive toxicity studies have shown no effect on male or female fertility in animals. No effect on human fertility is expected.

Ability to influence reaction speed when driving vehicles or other mechanisms

Indap® does not affect alertness, but in the event of adverse reactions (see section "Adverse reactions"), including symptoms associated with a decrease in blood pressure, especially at the beginning of treatment or when used in combination with another antihypertensive agent, the ability to drive a car or operate other mechanisms may be impaired.

Method of administration and doses

Method of application

For oral use.

Dosage

1 tablet of 2.5 mg per day, preferably in the morning. The tablet should be swallowed whole, without chewing, with water.

The maximum daily dose is 2.5 mg. The use of higher doses of the drug does not lead to an increase in the antihypertensive effect, but the diuretic effect increases.

Special patient groups

Renal failure (see sections "Contraindications" and "Special warnings and precautions for use").

The drug is contraindicated in patients with severe renal insufficiency (creatinine clearance <30 ml/min). Thiazide and thiazide-like diuretics are most effective if renal function is not impaired or if the impairment is minor.

Elderly (see section "Special instructions")

In elderly patients, the level of creatinine in the blood plasma should correspond to age, body weight and sex. Elderly patients can be prescribed Indap® if renal function is not impaired or if the impairment is minor.

Hepatic failure (see sections "Contraindications" and "Special precautions for use")

In case of severe liver dysfunction, treatment with the drug is contraindicated.

Children

Indap® is not recommended for use in children due to insufficient data on safety and efficacy in this patient group.

Overdose

Symptoms

Symptoms of overdose are primarily manifestations of water and electrolyte disturbances (hyponatremia, hypokalemia). Clinically, nausea, vomiting, hypotension, convulsions, drowsiness, dizziness (vertigo), confusion, polyuria or oliguria up to anuria (caused by hypovolemia) are possible.

Treatment

First aid measures include rapid removal of the drug by gastric lavage and/or administration of activated charcoal with subsequent restoration of water and electrolyte balance in a hospital setting.

Side effects

The most frequently reported adverse reactions were: hypokalemia, hypersensitivity reactions, mainly dermatological, in patients predisposed to allergic and asthmatic reactions, and maculopapular rashes.

During treatment with indapamide, the following adverse reactions were observed with the following frequencies: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10000, <1/1000), very rare (≥ 1/100000, <1/10000), frequency unknown (cannot be estimated from the available information).

Expiration date

4 years.

Storage conditions

Keep out of the reach of children. No special storage conditions required.

Packaging

1.25 mg tablets: 10 tablets in a blister, 3 or 6 blisters in a cardboard box.

2.5 mg tablets: 10 tablets in a blister, 3 or 6 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

PRO.MED.CS Praha a.s. / PRO.MED.CS Prahа as

Address

Telcska 377/1, Michle, Prague 4, 140 00, Czech Republic.