Ipamide

Ipamide contains the substance indapamide, which is a sulfonamide diuretic with pharmacological affinity for thiazide diuretic drugs.

Indapamide slows down the processes of Na reabsorption within the cortical renal segment. As a result, urinary excretion of Cl and Na increases, as well as (to a lesser extent) Mg and K, which increases diuresis. The hypotensive effect of indapamide develops at dosages that have a weak diuretic effect. In addition, the hypotensive effect of the drug persists in people with elevated blood pressure who are on hemodialysis. [1]

Indications Ipamide

It is used in case of primary hypertension .

Release form

The release of the drug substance is realized in tablets - 10 pieces inside the cell package; inside the box - 3 such packages.

Pharmacodynamics

Indapamide acts on blood vessels in the following ways: [2]

• reduces the contractile activity of vascular smooth muscles, changing the transmembrane metabolism of ions (mostly Ca);
• stimulates the binding of PGE2 elements, as well as PGI2 prostacyclin (dilates blood vessels and slows down platelet aggregation).
• Indapamide weakens left ventricular hypertrophy. In addition, clinical tests conducted at different times (short-term, medium and long-term) with the participation of people with elevated blood pressure showed the following result:
• the drug does not change lipid metabolism: LDL cholesterol and HDL cholesterol, as well as triglycerides;
• does not affect carbohydrate metabolism, even in diabetics and people with increased blood pressure.

Exceeding the standard dose does not lead to an increase in the medicinal effect of thiazide diuretics and thiazides, while the severity of negative symptoms increases. If the effectiveness of therapy is weak, the dosage should not be increased. [3]

Pharmacokinetics

Suction.

Indapamide has a high bioavailability rate of 93%. Tmax values within plasma when using a 2.5 mg portion are noted approximately after 1-2 hours.

Distribution processes.

The level of synthesis with plasma protein is over 75%. The half-life is in the range of 14-24 hours (average value is 18 hours).

With constant use of the drug, its stable plasma index increases in comparison with the values of the substance when taking a single serving. Such indicators continue to remain stable for a long time, without leading to accumulation.

Excretion.

The intrarenal clearance values are within 60-80% of the systemic level.

The excretion of indapamide is mainly realized in the form of metabolic elements; only 5% of Ipamide is excreted unchanged (via the kidneys).

Dosing and administration

The medication should be taken inside - 1 tablet per day (recommended in the morning). It is necessary to swallow the pill whole without chewing; drink with plain water.

• Application for children

Ipamide is prohibited from use in pediatrics due to the small amount of information regarding drug efficacy and its safety for children.

Use Ipamide during pregnancy

Diuretics are not prescribed during pregnancy; it is also forbidden to use them for physiological edema of pregnant women. With the introduction of diuretic substances, fetoplacental ischemia may develop, which can lead to fetal growth retardation.

When breastfeeding, the medication is not used, because there is information regarding the excretion of indapamide in mother's milk.

Contraindications

Among the contraindications:

• severe intolerance to indapamide, other sulfonamides or other auxiliary components;
• failure of kidney function in a severe stage;
• severe hepatic dysfunction or encephalopathy affecting the liver;
• hypokalemia.

Side effects Ipamide

Most of the negative signs (clinical and test-related) develop depending on the serving size. The main side symptoms:

• lesions of the blood system and lymph: leuko- or thrombocytopenia, anemia, which has a hemolytic or aplastic form, and agranulocytosis;
• disorders of the NS function: fatigue, fainting, vertigo, paresthesias and headaches;
• problems with the activity of the cardiovascular system: a decrease in the level of blood pressure or arrhythmia, and in addition, a paroxysmal tachycardia of the ventricles of the "pirouette" type, which can cause death;
• disorders associated with the work of the gastrointestinal tract: nausea, xerostomia, vomiting, pancreatitis and constipation;
• signs from the urinary tract and kidneys: failure of the kidneys;
• disorders affecting the hepatobiliary system: hepatic dysfunction, hepatitis or encephalopathy, which can develop in case of liver failure;
• lesions of subcutaneous tissues and epidermis: manifestations of intolerance (mainly in the area of the epidermis) in people with a tendency to develop asthma and allergies: maculopapular rashes, Quincke's edema or urticaria, purpura, SS and TEN. An exacerbation of existing SLE may occur. There is also information about the development of photosensitivity;
• laboratory test data: prolongation of the QT interval on the ECG. There is an increase in the values of uric acid and sugar inside the plasma when using diuretics, which is why the situation must be carefully assessed before using them in diabetics and people with gout. The index of liver enzymes may increase;
• problems associated with metabolic processes: the development of hypercalcemia. A decrease in potassium values with the onset of hypokalemia (may be severe) in people at risk. The development of hyponatremia with -volemia, which can cause orthostatic collapse and dehydration. The loss of Cl ions observed against the background can provoke a secondary form of alkalosis, which has a metabolic compensatory character (the intensity and frequency of the development of such a disorder are very low).

Overdose

Signs of poisoning are mainly in the form of disorders of EBV indicators (hypokalemia or -natremia). In addition, there may be vomiting, vertigo, drowsiness, decreased blood pressure, nausea, seizures, confusion and polyuria or oliguria, reaching anuria (associated with hypovolemia).

First, the drug should be excreted from the body as quickly as possible through gastric lavage or intake of activated carbon; then the EBV level is restored (in the hospital).

Interactions with other drugs

Prohibited combinations.

Lithium.

There may be an increase in plasma levels of lithium and the development of signs of poisoning similar to a salt-free diet (a decrease in lithium excretion in the urine). If you need to use a diuretic, you need to carefully monitor the plasma values of lithium and adjust its dosage.

Combinations to be used with care.

Medicines that can provoke a paroxysmal ventricular tachycardia ("pirouette"):

• antiarrhythmic substances from subgroup Ia (disopyramide with hydroquinidine and quinidine);
• antiarrhythmic drugs from subcategory 3 (sotalol and ibutilide with amiodarone and dofetilide);
• certain antipsychotics: phenothiazines (among them cyamemazine, thioridazine, chlorpromazine with trifluoperazine and levomepromazine), benzamides (this includes sulpiride, tiapride with sultopride and amisulpride) and butyrophenones (haloperidol with droperidol);
• other drugs: cisapride, pentamidine and bepridil with mizolastine, moxifloxacin and difemanil with sparfloxacin, halofantrine and intravenous vincamine with erythromycin.

The use of indapamide in combination with the above-described substances increases the likelihood of ventricular arrhythmias, including torsades de pointes (hypokalemia is a risk factor).

Before using this combination, it is necessary to determine the plasma potassium values and, if necessary, correct them. It is also necessary to monitor the patient's clinical condition, ECG readings and plasma electrolyte levels. If hypokalemia develops, medications should be used that do not lead to the appearance of torsades de pointes.

Systemic drugs NSAIDs, including selective inhibitors of the COX-2 element, as well as salicylates used in large portions (≥3 g per day):

• are able to weaken the hypotensive activity of indapamide;
• people with dehydration are more likely to develop ARF (due to weakened glomerular filtration). Before starting therapy, it is necessary to check the renal function and restore the indicators of the water balance.

Substances of ACE inhibitors.

Individuals with low Na values (especially with stenosis affecting the renal arteries) may suddenly develop ARF or decrease blood pressure.

With elevated blood pressure - if the preliminary administration of a diuretic has led to a decrease in Na values, it is necessary to cancel its use 3 days before starting therapy with an ACE inhibitor. Later, if necessary, the intake of a diuretic is resumed or the administration of an ACE inhibitor begins with a small initial portion, followed by its increase.

In the case of CHF, the use of ACE inhibitors begins with the lowest dosage and, sometimes, after reducing the portion of the previously prescribed potassium-excreting diuretic.

It is required to monitor renal activity (plasma creatinine level) during the first weeks of therapy with an ACE inhibitor.

Medicines that can provoke hypokalemia (including systemic mineralocorticoids and corticosteroids, intravenous amphotericin B, laxatives that stimulate peristalsis, and tetracosactide).

The above substances increase the likelihood of hypokalemia (development of an additive effect). It is necessary to monitor the plasma levels of potassium and, if necessary, correct them. These processes should be monitored very carefully when using a combination with SG. Requires the use of laxatives that do not stimulate peristalsis.

SG medicines.

With hypokalemia, the cardiotoxic properties of SG are enhanced. It is necessary to monitor the plasma potassium level and ECG readings, and, if necessary, adjust the therapy.

Baclofen potentiates the hypotensive activity of Ipamide. At the initial stage of treatment, it is necessary to restore the EBV values, as well as monitor the patient's renal function.

Combinations that need to be treated with increased attention.

Potassium-sparing diuretics (this includes spironolactone with amiloride and triamterene).

If you need to use this combination, there is a risk of developing hypokalemia (especially in people with impaired renal function and diabetics) or hyperkalemia. It is required to monitor plasma potassium values with ECG readings and, if necessary, adjust treatment accordingly.

Metformin.

The likelihood of developing acidosis of the lactic acid type increases - with the appearance of failure of renal activity due to the use of diuretics (especially loop). It is forbidden to use metformin with plasma creatinine levels of more than 15 mg / l (for a man) and 12 mg / l (for a woman).

Iodine contrast agents.

With dehydration associated with the use of diuretics, the likelihood of ARF increases (especially if large doses of iodine-contrast elements are used). Before the introduction of such drugs, it is necessary to restore the water balance indicators.

Antipsychotics and antidepressants of the imipramine-like type.

In connection with the additive effect, there is a potentiation of the hypotensive activity of Ipamide and the likelihood of orthostatic collapse.

Calcium salts.

Due to the weakening of renal elimination of Ca, hypercalcemia may develop.

Tacrolimus with cyclosporine.

There is a likelihood of an increase in plasma creatinine values without affecting circulating cyclosporine values (also when there is no decrease in Na and fluid values).

Tetracosactide with corticosteroids (systemic effects).

Under the influence of corticosteroids, sodium and fluid retention occurs, which leads to a weakening of the hypotensive effect of indapamide.

Storage conditions

Ipamide must be kept out of the reach of small children. Temperature values - no more than 25 ° С.

Shelf life

Ipamide can be used within a 4-year term from the date of sale of the therapeutic product.

Analogs

Analogues of drugs are the medicines Indyur, Indapamid with Akuter, Xipogama and Arifon with Ipress Long, Indaten and Indap with Indopres, and in addition Indapen, Softenzif, Lorvas with Indaten, Hemopamid and Ravel.

Reviews

Ipamide receives good reviews from patients, which note its effectiveness in reducing swelling. In addition, they also isolate the fact that the drug does not excrete potassium, which makes it possible to abandon the additional use of potassium substances. Good marks are also left about the effect of the drug in the case of a combination with other drugs, which allows, with a joint effect, to stabilize the pressure for the whole day.