Ipamide

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

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

Indications Ipamide

It is used in case of primary hypertension.

Release form

The medicinal substance is released in tablets - 10 pieces in a blister pack; there are 3 such packs in a box.

Pharmacodynamics

Indapamide affects blood vessels in the following ways: [ 2 ]

• reduces the contractile activity of vascular smooth muscles by altering transmembrane ion metabolism (mostly Ca);
• stimulates the binding of PGE2 elements, as well as prostacyclin PGI2 (expands blood vessels and slows down platelet aggregation).
• Indapamide reduces left ventricular hypertrophy. In addition, clinical trials (short-term, medium-term, and long-term) conducted at different times in people with elevated blood pressure showed the following result:
• the drug does not change lipid metabolism: LDL-C and HDL-C, as well as triglycerides;
• does not affect carbohydrate metabolism, even in diabetics and people with high 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%. The Tmax values in plasma when using a 2.5 mg dose are observed after approximately 1-2 hours.

Distribution processes.

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

With continuous use of the drug, its stable plasma level increases compared to the substance values when taking a single dose. Such levels remain stable for a long time, without causing accumulation.

Excretion.

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

Indapamide is excreted mainly in the form of metabolic components; only 5% of Indapamide is excreted unchanged (via the kidneys).

Dosing and administration

The medication should be taken orally - 1 tablet per day (recommended in the morning). The tablet should be swallowed whole, without chewing; washed down with plain water.

• Application for children

Ipamid is prohibited for use in pediatrics due to the lack of information regarding its medicinal efficacy and safety for children.

Use Ipamide during pregnancy

Diuretics are not prescribed during pregnancy; their use is also prohibited in case of physiological edema of pregnant women. When diuretics are administered, fetoplacental ischemia may develop, which can lead to fetal growth retardation.

The medication is not used during breastfeeding, because there is information regarding the excretion of indapamide in breast milk.

Contraindications

Among the contraindications:

• severe intolerance to indapamide, other sulfonamides or other excipients;
• severe renal failure;
• severe liver dysfunction or liver-damaging encephalopathy;
• hypokalemia.

Side effects Ipamide

The majority of adverse symptoms (clinical and related to test data) develop depending on the portion size. The main side effects are:

• lesions of the blood system and lymph: leukopenia or thrombocytopenia, anemia of hemolytic or aplastic form, and agranulocytosis;
• disorders of the nervous system function: fatigue, fainting, vertigo, paresthesia and headaches;
• problems with the functioning of the cardiovascular system: decreased blood pressure or arrhythmia, as well as paroxysmal ventricular tachycardia of the "pirouette" type, which can cause death;
• disorders associated with the gastrointestinal tract: nausea, xerostomia, vomiting, pancreatitis and constipation;
• signs from the urinary tract and kidneys: renal failure;
• disorders affecting the hepatobiliary system: liver dysfunction, hepatitis or encephalopathy, which can develop in case of liver failure;
• lesions of subcutaneous tissues and epidermis: manifestations of intolerance (mainly in the epidermis) in people with a tendency to develop asthma and allergies: maculopapular rashes, Quincke's edema or urticaria, purpura, SJS and TEN. Exacerbation of existing SLE may be observed. There is also information about the development of photosensitivity;
• laboratory test data: prolongation of the QT interval on the ECG. Increased uric acid and sugar levels in plasma are observed when using diuretics, which is why the situation should be carefully assessed before using them in diabetics and people with gout. Liver enzyme levels may increase;
• problems associated with metabolic processes: development of hypercalcemia. A decrease in potassium values with the appearance of hypokalemia (may be severe) in individuals at risk. Development of hyponatremia with -volemia, which can cause orthostatic collapse and dehydration. The loss of Cl ions observed against this background can provoke a secondary form of alkalosis, which has a metabolic compensatory nature (the intensity and frequency of development of such a disorder are very low).

Overdose

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

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

Interactions with other drugs

Prohibited combinations.

Lithium.

An increase in plasma lithium levels and the development of toxicity symptoms similar to those seen on a salt-free diet (decreased urinary lithium excretion) may occur. If a diuretic is needed, plasma lithium levels should be closely monitored and the dosage adjusted.

Combinations to use with caution.

Medicines that can provoke paroxysmal ventricular tachycardia (pirouette):

• antiarrhythmic agents from subgroup Ia (disopyramide with hydroquinidine and quinidine);
• antiarrhythmic drugs from subcategory 3 (sotalol and ibutilide with amiodarone and dofetilide);
• individual antipsychotics: phenothiazines (including cyamemazine, thioridazine, chlorpromazine with trifluoperazine and levomepromazine), benzamides (including sulpiride, tiapride with sultopride and amisulpride) and butyrophenones (haloperidol with droperidol);
• other drugs: cisapride, pentamidine and bepridil with mizolastine, moxifloxacin and diphemanil 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, plasma potassium levels should be determined and adjusted if necessary. The patient's clinical condition, ECG readings, and plasma electrolyte levels should also be monitored. If hypokalemia develops, medications that do not cause torsades de pointes should be used.

Systemic NSAIDs, including selective COX-2 inhibitors, as well as salicylates used in large doses (≥3 g per day):

• are capable of weakening the hypotensive activity of indapamide;
• In people with dehydration, the likelihood of developing acute renal failure increases (due to weakening of glomerular filtration). Before starting therapy, it is necessary to check renal function and restore water balance indicators.

ACE inhibitor substances.

In individuals with low Na values (especially with stenosis affecting the renal arteries), acute renal failure may suddenly develop or blood pressure may decrease.

In case of elevated blood pressure - if the preliminary administration of a diuretic has led to a decrease in Na values, its use should be discontinued 3 days before the start of therapy with an ACE inhibitor. Later, if necessary, the diuretic is resumed or the administration of an ACE inhibitor is started with a small initial dose and then increased.

In case of CHF, the use of ACE inhibitors is started with the lowest dosage and, sometimes, after reducing the dose of the previously prescribed potassium-wasting diuretic.

It is necessary to monitor renal function (plasma creatinine level) during the first weeks of therapy with ACE inhibitors.

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

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

SG medicines.

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

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

Combinations that require special attention.

Potassium-sparing diuretics (these include spironolactone with amiloride and triamterene).

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

Metformin.

The risk of developing lactic acidosis increases when renal failure occurs due to the use of diuretics (especially loop diuretics). It is prohibited to use metformin when plasma creatinine levels are more than 15 mg/l (for men) and 12 mg/l (for women).

Iodine contrast agents.

Dehydration associated with the use of diuretics increases the likelihood of acute renal failure (especially if large doses of iodine contrast agents are used). Before administering such drugs, it is necessary to restore the water balance.

Neuroleptics and antidepressants of the imipramine-like type.

Due to the additive effect, there is a potentiation of the hypotensive activity of Ipamid 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 potential for increased plasma creatinine values without affecting circulating cyclosporine levels (also when there is no decrease in Na and fluid levels).

Tetracosactide with corticosteroids (systemic effects).

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

Storage conditions

Ipamid should be stored in a place closed to small children. Temperature values are no more than 25°C.

Shelf life

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

Analogues

Analogues of the drug are the medications Indiur, Indapamide with Akuter, Xipogama and Arifon with Ipress long, Indatens and Indap with Indopress, as well as Indapen, Softenzif, Lorvas with Indatens, Hemopamide and Ravel.

Reviews

Ipamid receives good reviews from patients, which note its effectiveness in reducing swelling. In addition, it is also noted that the drug does not excrete potassium, which allows you to refuse additional use of potassium substances. Good assessments are also left about the effect of the drug in combination with other drugs, which allows, with a joint effect, to stabilize blood pressure for the entire day.