Instructions Ipamid film-coated tablets 2.5 mg blister No. 30
Composition
active ingredient: 1 tablet contains indapamide 2.5 mg;
excipients: lactose monohydrate, microcrystalline cellulose, hypromellose (hydroxypropylmethylcellulose), copovidone; colloidal anhydrous silicon dioxide, magnesium stearate;
shell: Opadry II Yellow film coating mixture: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol (macrogol); triacetin; quinoline yellow (E 104); titanium dioxide (E 171); indigo carmine (E 132); sunset yellow FCF (E 110).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a yellow film coating.
Pharmacotherapeutic group
Non-thiazide diuretics with moderate activity. Sulfonamides, simple. ATX 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 kidneys. 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:
- a decrease in the contractile ability 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 lipid metabolism: triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; does not affect carbohydrate metabolism, even in patients with arterial hypertension and diabetes mellitus.
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 (Tmax) after taking a dose of 2.5 mg is reached in approximately 1-2 hours.
Distribution
Binding to blood plasma proteins is above 75%.
The half-life is 14 to 24 hours (average 18 hours).
With regular administration of the drug, the steady-state plasma concentration (plateau) increases 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 indapamide, other sulfonamides or to any of the excipients;
- severe renal failure;
- hepatic encephalopathy or severe liver dysfunction;
- hypokalemia.
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 medications:
- phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine);
- benzamides (amisulpride, sulpiride, sultopride, tiapride);
- butyrophenones (droperidol, haloperidol);
· other medicines: bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, intravenous vincamine.
Before prescribing such a combination, the level of potassium in the blood plasma should be checked and, if necessary, corrected. The clinical condition of the patients, blood plasma electrolytes and ECG should be monitored. 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):
· may reduce the antihypertensive effect of indapamide;
· in patients with dehydration, the risk of acute renal failure increases (due to reduced glomerular filtration). Before starting treatment, it is necessary to restore water balance and check kidney function.
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 angiotensin-converting enzyme (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 levels should be monitored and, if necessary, corrected, special attention should be paid to concomitant 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.
Combinations that require attention
Potassium-sparing diuretics (amiloride, spironolactone, triamterene). If the appointment of such a combination is advisable, the possibility of hypokalemia (especially in patients with diabetes mellitus or renal failure) or hyperkalemia cannot be ruled out. Monitoring of potassium levels in the blood plasma, ECG monitoring and, if necessary, adjustment of therapy should be carried out.
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 fluid and sodium depletion.
Corticosteroids, tetracosactide (systemic action). Reduction of the antihypertensive effect of indapamide due to fluid and sodium retention under the influence of corticosteroids.
Application features
Patients with hepatic impairment
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, the diuretic 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 medicine contains lactose, therefore it should not be prescribed to patients with hereditary galactose intolerance, glucose-galactose malabsorption syndrome, Lapp lactase deficiency.
Fluid and electrolyte balance
It is necessary to monitor the level of sodium in the blood plasma before starting treatment and then regularly during treatment. Any diuretic can cause hyponatremia, which sometimes has serious consequences. A decrease in the level of sodium in the blood plasma may initially be asymptomatic, therefore monitoring of sodium levels is necessary, which should be carried out regularly, especially in elderly patients and in patients with cirrhosis of the liver.
Potassium
A decrease in plasma potassium with hypokalemia is the main risk with thiazide and thiazide-like diuretics. The development of hypokalemia (< 3.4 mmol/l) should be prevented in high-risk patients, such as: elderly patients; malnourished patients and/or patients receiving multiple medications; 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 predispose to serious 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.
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 due to previously undiagnosed hyperparathyroidism. In such cases, treatment should be discontinued and parathyroid function should be checked.
Blood glucose
In patients with diabetes, it is important to control blood glucose levels, 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 levels should be adjusted for age, weight and sex. Hypovolemia, associated with fluid 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.
Use during pregnancy or breastfeeding
Pregnancy
Diuretics should be avoided in pregnant women and should never be used to treat physiological edema in pregnant women. Diuretics may cause fetoplacental ischemia with a risk of fetal growth retardation.
Breast-feeding
The use of the drug is not recommended during breastfeeding due to the availability of data on the penetration of indapamide into breast milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
Ipamide 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
For oral use: 1 tablet per day, preferably in the morning. The tablet should be swallowed whole, without chewing, with water.
The use of higher doses of the drug does not lead to an increase in the antihypertensive effect, but the diuretic effect increases.
Kidney failure
(See sections “Special instructions for use” and “Contraindications”)
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.
Old age
(See section "Features of use")
In elderly patients, the level of creatinine in the blood plasma should correspond to age, body weight and gender. Ipamide can be prescribed to elderly patients if renal function is not impaired or if the impairment is minor.
Patients with hepatic impairment
(See sections “Special instructions for use” and “Contraindications”)
In case of severe liver dysfunction, treatment with the drug is contraindicated.
Children
Ipamide is not recommended for use in children due to insufficient data on the safety and efficacy of the drug in this group of patients.
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, followed by restoration of water and electrolyte balance in a hospital setting.
Adverse reactions
Most adverse effects, both clinical and laboratory, are dose-dependent.
From the blood and lymphatic system: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Nervous system: dizziness (vertigo), fatigue, headache, paresthesia; fainting.
From the cardiovascular system:
Arrhythmia, hypotension; torsades de pointes, which may be fatal (see sections 4.4 and 4.5).
Gastrointestinal: vomiting; nausea, constipation, dry mouth; pancreatitis.
Renal and urinary disorders: renal failure.
From the hepatobiliary system:
Liver dysfunction; hepatic encephalopathy may occur in case of liver failure (see sections "Special instructions for use", "Contraindications"), hepatitis.
Skin and subcutaneous tissue disorders:
Hypersensitivity reactions, mainly of the skin, in patients with a predisposition to allergic and asthmatic reactions: maculopapular rashes; purpura; angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; possible exacerbation of existing acute systemic lupus erythematosus; cases of photosensitivity reactions have been reported (see section "Special warnings and precautions for use").
Research: QT prolongation
On the electrocardiogram (see sections "Peculiarities of use", "Interaction with other medicinal products and other types of interactions"); increased levels of uric acid and glucose in blood plasma during treatment with diuretics, the rationality of their administration should be carefully weighed before prescribing to patients with gout or diabetes mellitus; increased levels of liver enzymes.
From the side of metabolism and metabolism:
Hypercalcemia; decreased potassium levels with the development of hypokalemia, particularly severe, in high-risk patients (see section "Special warnings and precautions for use"); hyponatremia with hypovolemia may lead to dehydration and orthostatic hypotension; concomitant loss of chloride ions may cause secondary compensatory metabolic alkalosis (frequency and severity of this phenomenon are low).
Expiration date
4 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
