Indapamid-Teva - instructions for use, dose, side effects, contraindications

active substance: indapamide anhydrous (in the form of indapamide hemihydrate) 2.44 mg (2.50 mg); Excipients: lactose monohydrate 60.06 mg, corn starch 60.00 mg, sodium carboxymethyl starch 6.25 mg, magnesium stearate 2.50 mg;

gelatin capsule: gelatin 37,070 mg, titanium dioxide 0,517 mg, iron oxide dye red 0.280 mg, iron oxide dye yellow 0.088 mg, ferric oxide black oxide 0.046 mg.

Description:

Hard opaque gelatin capsules No. 4, containing a white powder or almost white; the capsule body is pink, the lid is brown.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide - refers to derivatives of sulfonamide and by its pharmacological properties is close to thiazide diuretics. Has moderate saluretic and diuretic effects, which are due to inhibition of the reabsorption of sodium, chlorine and, to a lesser extent, potassium and magnesium ions in the proximal tubules of the kidneys and in the cortical segment of the distal tubule of the nephron.

Indapamide reduces the tone of the smooth muscles of the arteries and has a vasodilating effect, reduces the overall peripheral resistance of the vessels. These effects are mediated by a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandin E2, which has vasodilator activity; suppression of calcium current in smooth muscle cells of blood vessels.

Indapamide reduces the hypertrophy of the left ventricle of the heart.

Has antihypertensive effect in doses that do not have a pronounced diuretic effect.

Thiazide and thiazide-like diuretics after exceeding a certain dose are characterized by the formation of a plateau of therapeutic effect, while the severity of unwanted effects continues to increase.Therefore, do not increase the dose, if a therapeutic effect has not been achieved with the recommended dose.

Pharmacokinetics:

Suction. After oral administration indapamide quickly and completely absorbed in the gastrointestinal tract (GIT). Eating somewhat slows the rate of absorption of indapamide, but does not affect the amount of absorbed substance. After taking a single dose, the maximum concentration of indapamide in the blood plasma is reached after 0.5-2 h.

Distribution and Metabolism. Indapamide on 76-79% binds to blood plasma proteins and due to the presence of high affinity for elastin concentrates in the smooth muscles of the vascular walls. It also combines with the carbonic anhydrase of erythrocytes, without inhibiting the activity of this enzyme. Metabolised in the liver. Equilibrium concentration is achieved after 7 days of regular intake. Multiple use is not accompanied by cumulation of indapamide. Has a large volume of distribution, penetrates through the histohematological barriers (including placental), is excreted in breast milk.

Excretion. Indapamide is excreted primarily by the kidneys (60-70% of the dose taken) and through the intestine (16-20%) in the form of inactive metabolites, in unchanged form about 7% is released.

The half-life of indapamide from plasma is 14-18 hours. In renal failure, the pharmacokinetic properties of indapamide do not change.

Indications:Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of sulfonamide or any of the components of the drug, severe renal failure (creatinine clearance (CC) less than 30 ml / min / 1.73 m²), anuria, hepatic encephalopathy or severe liver dysfunction, hypokalemia, pregnancy, breastfeeding, age under 18 (insufficient safety and efficacy data), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

Diabetes mellitus, hyperuricemia (especially accompanied by gout and urate nephrolithiasis), hyponatremia and other disorders of water-electrolyte balance, moderate hepatic and / or renal insufficiency, ascites, ischemic heart disease (CHD), chronic heart failure (CHF), simultaneous use of drugs, extending the interval QT, hyperparathyroidism, in weakened patients, patients with an increased interval QT on ECG or patients receiving combined therapy with other antiarrhythmics, elderly.

Pregnancy and lactation:

The use of Indapamid-Teva during pregnancy is not recommended. The use of the drug may cause fetoplacental ischemia with the risk of slowing the development of the fetus.

It is not recommended to use the drug during breast-feeding, because indapamide excreted in breast milk. If treatment with Indapamid-Teva is necessary during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 capsule per day, in the morning.

Capsule must be swallowed whole, with enough liquid. Capsules can not be broken or chewed.

In severe renal failure (QC less than 30 ml / min), taking Indapamid-Teva is contraindicated (see the section "Contraindications"),

In the treatment of elderly patients the threshold value of the concentration of creatinine in the blood plasma varies depending on age, body weight and gender.For older patients, Indapamid-Teva can be used only with normal kidney function or with minor renal impairment.

In severe violations of liver function taking Indapamid-Teva is contraindicated (see the section "Contraindications"),

Side effects:

The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely (including individual reports) - less than 0.01%; the frequency is unknown (the frequency can not be calculated from the available data).

Most adverse reactions (laboratory and clinical indicators) are dose-dependent.

On the part of the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system: infrequently - lethargy, feelings of anxiety, increased motor activity; rarely - dizziness, headache, paresthesia, increased fatigue; unknown frequency - fainting.

From the cardiovascular system: very rarely - a marked decrease in blood pressure, orthostatic hypotension; very rarely - arrhythmia; unknown frequency - arrhythmia of the "pirouette" type (possibly fatal) (see "Interactions with other medicinal products" and "Special instructions"), increase QT interval on the ECG (see section "Special instructions").

From the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis.

From the liver and bile ducts: very rarely - a violation of liver function; unknown frequency - the possibility of developing hepatic encephalopathy in case of liver failure (see the sections "Contraindications", "Special instructions"); hepatitis.

From the immune system: reactions of hypersensitivity, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions: often - maculopapular rash; infrequently - hemorrhagic vasculitis; very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; an unknown frequency in patients with acute form of systemic lupus erythematosus, possibly worsening of the course of the disease.

Cases of photosensitivity reactions are described (see section "Special instructions" and "Interaction with other medicinal products").

From the side of the kidneys and urinary tract: very rarely - kidney failure.

Laboratory indicators: very rarely - hypercalcemia; unknown frequency - increasing concentration of uric acid and glucose in the blood (thiazide and thiazide diuretics should be used with caution in patients with gout and diabetes), elevated "liver" enzymes, and reduction in the potassium content of hypokalemia development especially significant for patients at risk (see. section "Special instructions"), hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous hypochloraemia can lead to metabolic alkalosis of compensatory nature (the probability and severity of this effect is low).

Overdose:

Symptoms: marked reduction of blood pressure, fluid and electrolyte disturbances (hyponatraemia, hypokalaemia), nausea, vomiting, cramps, dizziness, drowsiness, lethargy, confusion, respiratory depression,polyuria or oliguria up to anuria (due to hypovolemia). Patients with cirrhosis may develop hepatic coma.

Treatment: symptomatic (gastric lavage and / or the appointment of activated charcoal, restoration of water-electrolyte balance). There is no specific antidote.

Interaction:

Not recommended combinations

With simultaneous application from lithium preparations it is possible to increase the concentration of lithium in blood plasma due to the decrease in excretion of it from the body by the kidneys, accompanied by the appearance of signs of an overdose (nephrotoxic effect), as well as when observing a salt-free diet (decrease in excretion of lithium ions by the kidneys).

Combinations that require special attention

Drugs that can cause arrhythmia, by the type of "pirouette":

antiarrhythmics IA class (quinidine, hydroquinidine, disopyramide), antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide, brethil tosylate), sotalol, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other (bepridil, cisapride, difemanyl, erythromycin (intravenous (iv)), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, wincamine (w / w), astemizole. Simultaneous use with any of these drugs, especially against hypokalemia, increases the risk of ventricular arrhythmias as pirouettes. Before starting the combination therapy with the drug Indapamid-Teva and the above drugs should monitor the content of potassium in the blood plasma and, if necessary, adjust it. It is recommended: monitoring the clinical condition of the patient, as well as the content of plasma electrolytes and ECG. Patients with hypokalemia should use drugs that do not trigger the development of piruet-type arrhythmias.

With the simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) (for systemic use), including selective inhibitors cyclooxygenase-2 (COX-2), high doses of salicylic acid (3 g / day or more) possibly: a reduction in the antihypertensive effect of indapamide, the development of acute renal failure in dehydrated patients (due to a decrease in glomerular filtration rate).At the beginning of Indapamide-Teva therapy, it is necessary to restore the water-electrolyte balance and control the kidney function.

Angiotensin converting enzyme (ACE) inhibitors in patients with hyponatremia (especially in patients with renal artery stenosis) increase the risk of arterial hypotension and / or acute renal failure.

Patients with hypertension and possibly with hyponatraemia, due to the intake of diuretics, should:

- stop taking the drug 3 days before the start of therapy with ACE inhibitors and switch to potassium-sparing diuretics;

- or initiate therapy with ACE inhibitors from low doses, followed by a gradual increase in dose if necessary.

In the first week of therapy with ACE inhibitors, it is recommended to monitor the concentration of plasma creatinine.

Other drugs that can cause hypokalemia:

- amphotericin B (IV);

- gluco- and mineralocorticosteroids (for systemic use) (see also the information in the section "Combinations of drugs requiring attention");

- tetrakozaktid (see also the information in the section "Combinations of drugs requiring attention");

- laxatives, stimulating intestinal motility.

With the simultaneous administration of the above drugs with indapamide, the risk of developing hypokalemia (additive effect) increases.

If necessary, monitor and adjust the potassium content in the blood plasma.

Simultaneous therapy from baclofen enhances the antihypertensive effect of indapamide.

Cardiac glycosides: hypokalemia increases the toxic effect of cardiac glycosides (glycoside intoxication). With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium ions in the blood plasma, the ECG parameters, and, if necessary, adjust the therapy.

Combinations of drugs requiring attention

Simultaneous application from potassium-sparing diuretics (amiloride, spironolactone, triamterene) is suitable in some patients, but the possibility of hypokalemia is not ruled out. Against the background of diabetes or kidney failure may develop hyperkalemia. It is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG, and, if necessary, adjust the therapy.

Metformin increases the risk of developing lactic acidosis, t. It is possible to develop renal failure with diuretics, especially "loop". Metformin should not be taken at a plasma creatinine concentration of more than 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

The simultaneous use of large doses iodine-containing contrast agents against the background of hypovolemia and the use of diuretics increases the risk of acute renal failure. It is recommended to restore the electrolyte balance of blood before applying the drugs.

Tricyclic antidepressants (imipramine-like) and antipsychotics increase the antihypertensive effect and the risk of developing orthostatic hypotension (additive effect).

Preparations containing calcium salt, increase the risk of hypercalcemia due to a decrease in the excretion of calcium by the kidneys.

Cyclosporin, tacrolimus - The risk of increasing the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine.

Glucorticosteroid preparations, tetracosactide (with systemic application) reduce the antihypertensive effect (sodium and liquid retention).

Special instructions:

In patients with impaired liver function, therapy with Indapamid-Teva can lead to the development of hepatic encephalopathy, especially with concomitant disturbances in the water-electrolyte balance. In this case, the diuretic should be discontinued immediately.

Thiazide diuretics, as well as their analogues, are effective only with normal kidney function or with minor disturbances.

The content of sodium in the blood plasma must be determined before the initiation of therapy with the drug Indapamid-Teva, which may be accompanied by the development of hyponatremia, sometimes with very serious consequences. Reduction of the content of sodium in blood plasma can initially be asymptomatic, therefore regular monitoring is necessary. When treating elderly patients and patients with liver cirrhosis, the sodium content in the blood should be determined more often.

Therapy with Indapamid-Teva is characterized by a high risk of decreasing potassium levels in the blood with the development of hypokalemia. In the treatment of patients at risk (elderly patients, weakened patients, patients receiving concomitant medication, patients with cirrhosis with peripheral edema and ascites, patients with IHD, patients with CHF), it is necessary to prevent hypokalemia.In such patients, hypokalemia increases the toxic effect of cardiac glycosides, and also increases the risk of heart rhythm disturbances. Thus, hypokalemia, as well as bradycardia, acts as a factor predisposing to the development of serious cardiac rhythm disturbances, in particular, pirouette-type arrhythmias, which can lead to death.

When treating patients at risk, regular monitoring of the potassium content in the blood plasma is necessary. The initial measurement of the plasma content of potassium should be performed within the first week after initiation of therapy with the drug Indapamid-Teva, the detection of hypokalemia requires appropriate correction.

In addition, the high-risk group includes patients with an increased interval QT, it does not matter whether this increase is due to innate causes or effects of drugs.

In the treatment of patients with diabetes, especially in the presence of hypokalemia, it is necessary to monitor the concentration of glucose in the blood.

In the treatment of patients with hyperuricemia, the likelihood of exacerbation of gout increases.Hypovolemia secondary to such effects as a diuretic, such as loss of water and sodium, at the beginning of treatment leads to a decrease in the glomerular filtration rate. As a result, the concentration of urea and creatinine in the blood plasma increases.

In patients with normal renal function, such transient functional renal failure passes without consequences.

For athletes, the fact that the active substance of Indapamid-Teva can cause a positive test result for doping is of particular importance. Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported. In the case of the development of reactions photosensitivity against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays. Thiazide and thiazide-like diuretics can reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

It is necessary to cancel the reception of diuretic drugs before the study of the function of parathyroid glands.

Effect on the ability to drive transp. cf. and fur:

Care should be taken when driving vehicles and working with machinery.

Form release / dosage:

Capsules, 2.5 mg.

Packaging:

10 capsules in a PVC / aluminum foil blister.

For 3, 5 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002538

Date of registration:21.07.2014

Expiration Date:21.07.2019

Date of cancellation:2019-07-21

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

MERCKLE, GmbH Germany

Representation: & nbspTeva Teva Israel

Information update date: & nbsp02.11.2017

Illustrated instructions

Instructions

Indapamid-Teva (Indapamide-Teva)