Composition, form of production and packaging
Capsules 1 caps.
indapamide 2.5 mg
10 pieces. - packings of cellular contour (1) - packs cardboard.
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (4) - packs cardboard.
10 pieces. - packings cellular planimetric (5) - packs cardboard.
10 pieces. - packings cellular planimetric (10) - packs cardboard.
100 pieces. - polymer containers (1) - packs of cardboard.
50 pcs. - polymer containers (1) - packs of cardboard.
40 pcs. - polymer containers (1) - packs of cardboard.
30 pcs. - polymer containers (1) - packs of cardboard.
20 pcs. - polymer containers (1) - packs of cardboard.
10 pieces. - polymer containers (1) - packs of cardboard.
30 pcs. - packings cellular planimetric (5) - packs cardboard.
30 pcs. - packings cellular planimetric (4) - packs cardboard.
30 pcs. - packings cellular planimetric (3) - packs cardboard.
30 pcs. - packings cellular planimetric (2) - packs cardboard.
30 pcs. - packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
A hypotensive agent, a thiazide-like diuretic with a moderate in strength and long duration of action, a benzamide derivative. Has moderate saluretic and diuretic effects, which are associated with blockade of reabsorption of sodium, chlorine, hydrogen ions, and to a lesser extent potassium ions in the proximal tubules and cortical segment of the nephron distal tubule. The vasodilator effects and the reduction of the overall peripheral vascular resistance are based on the following mechanisms: a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandins with vasodilating activity; oppression of calcium current in the smooth-muscle walls of blood vessels.
Reduces the tone of the smooth muscles of the arteries, reduces the overall peripheral resistance of the vessels. Helps reduce hypertrophy of the left ventricle of the heart. In therapeutic doses does not affect lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).
Antihypertensive effect develops at the end of the first / beginning of the second week with a constant intake of the drug and persists for 24 hours against a background of a single dose.
PHARMACOKINETICS
After oral administration, it is quickly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Eating somewhat slows the rate of absorption, but does not affect the completeness of absorption. C max in blood plasma - 12 hours after ingestion. With repeated administration of fluctuations in the concentration of indapamide in blood plasma in the interval between doses of two doses decrease. The equilibrium concentration is established after 7 days of regular intake. T 1/2 - 18 h, communication with blood plasma proteins - 79%. It also binds to the elastin of the smooth muscles of the vascular wall. Has a high V d , passes through the histohematological barriers (including placental), penetrates into breast milk. Metabolised in the liver. The kidneys excrete 60-80% in the form of metabolites (in unchanged form, about 5% is excreted), through the intestine - 20%. In patients with renal insufficiency, pharmacokinetics does not change. Do not cumulate.
INDICATIONS
Arterial hypertension.
DOSING MODE
Capsules are taken orally, without chewing. Daily dose - 1 capsule of the drug Tenzar 1 times a day (in the morning), with plenty of liquid.
When treating patients with hypertension, the dose of the drug should not exceed 2.5 mg (increased risk of side effects without increasing antihypertensive effect).
Elderly patients. In elderly patients, plasma concentrations of creatinine should be monitored, taking into account age, body weight and sex.
The drug Tensar at a dose of 2.5 mg / day (1 capsule) can be administered to elderly patients with normal or slightly impaired renal function.
SIDE EFFECT
Most adverse reactions (laboratory and clinical indicators) are dose-dependent.
The incidence of adverse reactions that may be caused by thiazide-like diuretics, including indapamide, is given in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); frequency (frequency can not be calculated from available data).
From the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
From the side of the central nervous system: rarely - dizziness, fatigue, headache, paresthesia.
From the cardiovascular system: very rarely - arrhythmia, lowering blood pressure.
From the side of the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis.
From the side of the urinary system: very rarely - kidney failure.
From the liver and biliary tract: very rarely - a violation of the liver; unspecified frequency - the possibility of developing hepatic encephalopathy in the case of liver failure.
On the part of the skin : reactions of increased sensitivity, 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;unspecified frequency - possibly worsening in the presence of an acute form of disseminated lupus erythematosus.
Cases of photosensitivity reactions are described.
Laboratory indicators: very rarely - hypercalcemia; Unspecified frequency - decrease in potassium content and development of hypokalemia, especially significant for patients at risk; hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous loss of chloride ions can lead to compensatory metabolic alkalosis, however, the frequency of development of alkalosis and its severity is negligible; increase in the concentration of uric acid and glucose in the blood plasma. Thiazide and thiazide-like diuretics should be used with caution in patients with gout and diabetes.
CONTRAINDICATIONS
Hypersensitivity to indapamide and other components of the drug, as well as to other derivatives of sulfonamide, severe renal failure (creatinine clearance less than 30 ml / min), hypokalemia, hepatic encephalopathy or severe liver dysfunction, pregnancy, lactation, age under 18 years (efficacy and security is not established);simultaneous reception of drugs that extend the QT interval.
With caution: for violations of the liver and / or kidney function, violations of water-electrolyte balance, hyperparathyroidism, in weakened patients or in patients receiving co-therapy with other antiarrhythmics, while taking medications that extend the QT interval, diabetes, hyperuricemia (especially, accompanied by gout and urate nephrolithiasis).
PREGNANCY AND LACTATION
During pregnancy, do not prescribe diuretic drugs. Do not use these drugs to treat physiological swelling in pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development (hypotrophy).
Tenzar is not recommended during pregnancy. Indapamide is excreted in breast milk. Given the possibility of the emergence of adverse events in infants, breastfeeding during treatment with the drug Tenzar is not recommended.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated: severe renal failure (creatinine clearance less than 30 ml / min).
With caution: for violations of kidney function.
Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentrations in adults below 25 mg / L or 220 Ојmol / L in adults).
It should be borne in mind that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the kidney function is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated: hepatic encephalopathy or severe impairment of liver function.
With caution: for violations of the liver. With the appointment of thiazide and thiazide-like diuretics in patients with impaired liver function, it is possible to develop hepatic encephalopathy, especially in the case of violations of the water-electrolyte balance. In this case, the taking of diuretics should be stopped immediately.
APPLICATION FOR CHILDREN
Contraindicated at the age of 18 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, plasma concentrations of creatinine should be monitored, taking into account age, body weight and sex.
The drug Tenzar can be prescribed for elderly patients with normal or slightly impaired renal function (according to the dosing regimen).
SPECIAL INSTRUCTIONS
Dysfunction of the liver
With the appointment of thiazide and thiazide-like diuretics in patients with impaired liver function, it is possible to develop hepatic encephalopathy, especially in the case of violations of the water-electrolyte balance. In this case, the taking of diuretics should be stopped immediately.
Photosensitivity
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.
Water-electrolyte balance :
- Content of sodium ions in blood plasma:
Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to regularly monitor the content of sodium ions, since initially a decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms. The most thorough control of sodium ions is indicated for patients with cirrhosis of the liver and elderly people.
- Content of potassium ions in blood plasma:
With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and development of hypokalemia. It is necessary to avoid the risk of developing hypokalemia (<3.4 mmol / l), in patients: elderly patients who are weakened or are receiving concomitant medication with other antiarrhythmic drugs and drugs that may increase the QT interval, patients with cirrhosis, peripheral edema or ascites, ischemic disease heart, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.
In addition, patients with an increased QT interval are at increased risk, but it does not matter whether this increase is due to congenital causes or effects of drugs.
Hypokalemia, as well as bradycardia, is a condition conducive to the development of severe arrhythmias and, especially, pirouette-type arrhythmias, which can lead to death. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma. The first measurement of the potassium content in the blood should be carried out within the first week after the start of treatment. When hypokalemia occurs, appropriate treatment should be prescribed.
- Calcium in the blood plasma:
It should be borne in mind that thiazide and thiazide-like diuretics can reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in calcium 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 the parathyroid glands.
- Concentration of glucose in blood plasma:
It is necessary to monitor the concentration of glucose in the blood in patients with diabetes mellitus, especially in the presence of gmkokalemii.
- Uric acid:
In patients with gout, the frequency of seizures may increase or the course of gout may worsen.
- Diuretic drugs and kidney function:
Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentrations in adults below 25 mg / L or 220 Ојmol / L in adults). In elderly patients, the normal concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.
It should be borne in mind that at the beginning of treatment, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the kidney function is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.
Application in athletes. The active substance, which is part of the drug Tenzar, can give a positive result in the conduct of doping control in athletes.
Impact on the ability to drive vehicles and other mechanisms. During the period of treatment, care must be taken when driving vehicles and occupations of other potentially hazardous waters of activity that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Indapamide even in very high doses (up to 40 mg, i.e. 27 times more than the therapeutic dose) does not have a toxic effect.
Symptoms: signs of acute drug poisoning are primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). From clinical symptoms of overdose, nausea, vomiting, lowering of blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may occur.
Treatment: emergency measures are reduced to the removal of the drug from the body: gastric lavage and / or the appointment of activated charcoal, followed by the restoration of the water-electrolyte balance.
DRUG INTERACTION
Unwanted combination of drugs
Lithium preparations:
With simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.
A combination of drugs that requires special attention
Preparations that can cause arrhythmia of the "pirouette" type:
- antiarrhythmic drugs of the IA class (quinidine, hydroquinidine, disopyramide);
- antiarrhythmic drugs of the III class (amiodarone, sotalol, dofetilide, ibutilide);
- Some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiaprid), butyrophenones (droperidol, haloperidol);
- Other: bepridil, cisapride, difemanyl, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, aststmizol, vincamine (iv).
Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (risk factor - hypokalemia).
It is necessary to determine the content of potassium in the blood plasma and, if necessary, adjust it before the start of combined therapy with indalamide and the above drugs. It is necessary to monitor the clinical condition of the patient, control of plasma electrolytes, ECG parameters.
Patients with hypokalemia should use drugs that do not cause arrhythmia such as "pirouette".
Non-steroidal anti-inflammatory drugs (for systemic administration), including selective inhibitors of COX-2, high doses of salicylates (? 3 g / day):
It is possible to reduce the antihypertensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration rate).
Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.
Angiotensin-converting enzyme (ACE) inhibitors:
The administration of ACE inhibitors to patients with a reduced concentration of sodium ions in the blood (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure.
Patients with hypertension and possibly reduced, due to the use of diuretics, the content of sodium ions in blood plasma should:
- 3 days before the start of treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, the reception of diuretics can be resumed;
- or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose if necessary.
In chronic heart failure, treatment with ACE inhibitors should begin with low doses with the possible preliminary reduction of doses of diuretics.
In all cases, during the first week of ACE inhibitors in patients need to monitor renal function (creatinine concentration in blood plasma).
Other medications that can cause hypokalaemia: amphotericin B (w / w), gluco- and mineralokortikosteroidy (with systemic administration), tetrakozaktid, laxative, stimulating bowel motility:
Increased risk of hypokalaemia (additive effect). Requires regular monitoring of potassium in the blood plasma, if necessary - its correction. Particular attention should be given to patients while receiving cardiac glycosides. It is recommended to use laxatives, do not stimulate bowel motility.
baclofen:
There is a growing anti-hypertensive effect. Patients need to compensate for fluid loss and the beginning of treatment carefully monitor renal function.
Cardiac glycosides:
Hypokalaemia enhances the toxic effects of cardiac glycosides. With simultaneous use of indapamide and cardiac glycosides should control the content of potassium in the blood plasma, ECG, and, if necessary, adjust therapy.
The combination of drugs requiring attention
Potassium-sparing diuretics (amiloride, spironolactone, triamterene):
Combination therapy with indapamide and potassium-sparing diuretics suitable for some patients, but it does not exclude the possibility of hypokalemia (especially in patients with diabetes and patients with renal insufficiency) or hyperkalemia.
It is necessary to control the content of potassium in the blood plasma, ECG, and if necessary, adjust therapy.
Metformin:
A functional renal failure that can occur in the background of diuretics, particularly "loop", while the appointment of metformin increases the risk of lactic acidosis.
Metformin should not be used if the creatinine concentration exceeds 15 mg / L (135 pmol / l) in men and 12 mg / L (110 pmol / l) in women.
Iodinated contrast media:
Dehydration in patients receiving diuretics increases the risk of acute renal failure, especially when high doses of iodinated contrast agents.
Before using iodinated contrast agents to patients is necessary to compensate the loss of fluid.
Tricyclic antidepressants, antipsychotic drugs (neuroleptics):
Drugs of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).
Calcium salts:
When concomitant administration may develop hypercalcemia due to decreased excretion of calcium by the kidneys.
Cyclosporin, tacrolimus:
Possible to increase the concentration of creatinine in the blood plasma concentration of unchanged circulating cyclosporine, even with normal fluid and sodium ions.
Corticosteroids, tetracosactide (at system assignment):
Reduction of antihypertensive action (fluid retention and sodium ions by the action of corticosteroids).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store in a dry, dark place at a temperature not higher than 25 В° C. Keep out of the reach of children.
Shelf life . 3 years. Do not use after the expiration date.
