Triampur Compositum, tablets 12.5mg+25 mg 50 pcs

Pharmacotherapeutic group: diuretic combination medicine.

ATX code: C03EA01.

Pharmacological properties

Pharmacodynamics

A combination drug, contains hydrochlorthiazide and triamterene. It has diuretic and hypotensive effects.

Hydrochlorothiazide – The mechanism of action of thiazide diuretics (thiazides) is not fully understood. Thiazides block reabsorption of sodium and chlorine ions in the renal tubules. Thus they increase the excretion of sodium and chlorine and therefore the excretion of water from the body.

The diuretic effect of hydrochlorthiazide decreases the volume of circulating fluid, resulting in increased renin activity and plasma aldosterone content. This leads to increased urinary excretion of potassium ions and a decrease in blood potassium content (hypokalemia).

Hydrochlorthiazide also increases the excretion of magnesium ions and decreases the excretion of calcium ions in the urine. Thiazide diuretics decrease renal excretion of uric acid and increase its content in the blood.

Thiazide diuretics also reduce carboangiradase activity by increasing the excretion of bicarbonate ions. But this effect is usually weak and has no effect on urine pH.

In the maximum therapeutic doses, the diuretic/natriuretic effect of all thiazide diuretics is approximately the same. Natriuresis and diuresis occur within 2 hours after administration and reach their maximum after about 4 hours. Duration of diuretic action of hydrochlorothiazide is from 6 to 12 hours.

Hydrochlorothiazide has an antihypertensive effect. Normal arterial pressure is not affected by thiazide diuretics.

Triamterene is a potassium-saving diuretic that reduces the permeability of distal tubule cell membranes to sodium ions and increases their excretion with urine without increasing the excretion of potassium ions. The secretion of potassium ions in the distal tubules is reduced. In combination with hydrochlorothiazide, triamterene is able to reduce hypokalemia caused by thiazide diuretics and increase the diuretic effect of hydrochlorothiazide. Diuretic effect of triamterene after oral administration is observed in 15-20 minutes. The maximum effect is after 2-3 hours, the duration of action is 12 hours.

Pharmacokinetics

Hydrochlorothiazide

absorption and distribution.

Hydrochlorothiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. After oral administration in a dose of 100 mg, the maximum concentration of hydrochlorothiazide in blood plasma is reached after 1.5-2.5 hours. At the maximum diuretic activity (about 4 hours after intake), the plasma concentration of hydrochlorothiazide is 2 µg/ml. Binding with plasma proteins is 40%. Hydrochlorothiazide penetrates through the placental barrier and is excreted into breast milk, it does not penetrate through the blood-brain barrier.

Metabolism

Hydrochlorothiazide is not metabolized in humans.

Evolution

The primary route of excretion is through the kidneys (filtration and secretion) unchanged. Approximately 61% of the ingested dose is excreted within 24 hours. In patients with normal renal function, the elimination half-life ranges from 5.6 to 14.8 hours (6.4 hours on average).

Pharmacokinetics in special patient groups

Disordered renal function

In patients with moderate renal impairment, the half-life of hydrochlorothiazide averages 11.5 hours, and in patients with creatinine clearance less than 30 mL/min.- 20.7 hours.

Triamterene is rapidly but not completely (30-70% of the dose taken) absorbed from the gastrointestinal tract. To a moderate extent (67%) it is bound to plasma proteins. Maximum plasma concentration is reached 2-4 hours after administration. The drug is biotransformed in the liver to form both active and inactive metabolites. The normal half-life of the drug is 1.5-2 hours (with anuria – 10 hours), metabolites – up to 12 hours. The main route of excretion of triamterene is through the intestine, the secondary route is by the kidneys.

Indications

Active ingredient

How to take, the dosage

Ingestion, without chewing, with a small amount of water, after a meal. In each case, the dosage of the drug is determined by the severity of water-electrolyte metabolism disorders in the patient.

Adults

In Oedema syndrome: The usual starting and maintenance dose is 1 tablet 1 time per day after meals, then it is possible to increase the dose to the maximum daily dose (4 tablets per day): 2 tablets after breakfast and 2 tablets after lunch.

If edema is compensated, maintenance therapy of 1-2 tablets every 1-2 days is started.

In arterial hypertension: the initial dose of 1 tablet per day (morning, after breakfast), then, if necessary, the dose is gradually increased to 2 tablets per day.

Application in special groups of patients

Interaction

Hydrochlorothiazide + triamterene

. Potassium preparations and/or potassium-saving diuretics (spironolactone, amiloride) should not be used concomitantly with Triampur Compositum® due to the risk of potentially serious hyperkalemia.

Tripur Compositum® has hypotensive effects. If the drug is administered against the background of continuing existing antihypertensive therapy, it is reasonable to reduce the dose of Tryampur Compositum® by half. Conversely, if a patient is already taking Triampur Compositum®, it is reasonable to halve the dose of a new antihypertensive drug (e.g. a beta-blocker) added to Tryampur Compositum®.

Disopyramide combined with Triampur Compositum® increases the adverse effects of hyperkalemia and may cause moderate to life-threatening hyperkalemia.

In diabetic patients, the need for insulin may change.

The use of ACE inhibitors may result in increased serum potassium levels. Caution should be exercised when this type of drug is used concomitantly with Triampur Compositum®.

Lithium preparations should generally not be combined with diuretics because diuretics decrease renal excretion of lithium and therefore increase the risk of lithium intoxication.

In recent years, interactions between diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported in the literature, which can lead to acute decreased renal function. This interaction has also been described for triamterene and indomethacin. Therefore, caution is recommended in patients receiving these drugs concomitantly.

When Triampur Compositum® is coadministered with agents that may cause hypokalemia, such as corticosteroids, corticotropin, amphotericin B or carbenoxolone, caution should be exercised. Myocardial effects of cardiac glycosides and nondepolarizing neuromuscular blockers may be enhanced in patients with hypokalemia; previously tolerated doses of foxglove drugs may cause intoxication symptoms.

Concomitant use with chlorpropamide may increase the risk of severe hyponatremia.

Hydrochlorothiazide

.Unrecommended drug combinations

Lithium preparations

p> Concomitant use of hydrochlorothiazide and lithium preparations decreases renal clearance of lithium, which may increase plasma lithium concentrations and toxicity. If concomitant use of

Hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, plasma lithium concentration should be monitored regularly, and the dose of the drug should be adjusted accordingly.

Drug combinations that require special attention

The followingDrugs that can cause polymorphic pirouette-type ventricular tachycardia

Hydrochlorothiazide should be used with special caution concomitantly with drugs such as:

– neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, thiapride), butyrophenones (droperidol, haloperidol); pimozide, sertindol;

– antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);

– antibacterials: Fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin); macrolides (erythromycin when given intravenously, azithromycin, clarithromycin, roxithromycin, spiramycin), co-trimoxazole;

– antifungal agents: azoles (voriconazole, itraconazole, ketoconazole, fluconazole);

– antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);

– antiprotozoal agents (pentamidine in parenteral administration);

– antianginal agents (ranolazine, bepridil);

– antitumor agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);

– antiemetics (domperidone, ondansetron);

– drugs that affect gastrointestinal motility (cisapride);

–

Anionic exchange resins (colestyramine and colestipol)

The anionic exchange resins decrease absorption of hydrochlorothiazide. Single doses of colestyramine and colestipol reduce absorption of hydrochlorothiazide in the

gastrointestinal tract by 85% and 43%, respectively.

Triamterene

.Non-steroidal anti-inflammatory drugs (NSAIDs)

Concomitant use with NSAIDs may reduce antihypertensive effects, progression of renal failure.

Drugs that increase blood potassium

There is a risk of hyperkalemia with spironolactone, potassium salts, ACE inhibitors.

Amantadine

Concomitant use with amantadine shows increased concentration of amantadine, there is a risk of toxic effects.

Trimethoprim

Possible risk of severe hyponatremia with trimethoprim.

Special Instructions

Since Triampur Compositum is a combination of two diuretics, the possibility of electrolyte imbalances – especially in patients on a low-salt diet and in patients with conditions affecting electrolyte balance such as heart failure, renal disease and liver disease (cirrhosis) – should be considered during long-term treatment with high doses of its constituents.

Water-electrolyte balance disorders and metabolic disorders (hyperkalemia, hyponatremia, metabolic acidosis and other electrolyte and fluid imbalances)

Periodic monitoring of serum electrolytes is not required. During long-term treatment with Triampur Compositum® potassium concentrations should be determined before the start of therapy and 3 to 4 weeks after the end of therapy. If potassium balance is not impaired, further potassium measurements should be done every 4-6 months.

In case of signs of hyperkalemia, Triampur Compositum® ® should be stopped. In elderly patients and patients receiving simultaneous digitalis, glucocorticosteroid drugs, laxatives, or intravenous infusions, close monitoring of fluid and electrolyte balance is necessary.

Renal failure

Tiazide diuretics should be used with caution in patients with impaired renal function. The dosage should be reduced in patients with renal insufficiency (CK>30 ml/min). Thiazide diuretics are ineffective in progressive renal impairment (CK<30 ml/min) and may worsen impaired renal function or may cause azotemia. Periodic monitoring of serum urea clearance and creatinine is necessary in patients with impaired renal function.

Help failure

.Triamterene + hydrochlorothiazide, like other thiazide diuretics, should be used with caution in patients with severe liver dysfunction or advanced liver disease because even small changes in water-electrolyte balance may cause hepatic coma.

Hydrochlorothiazide

Kidney function disorders .

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. Cumulation of hydrochlorothiazide is possible in renal failure.

In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal function impairment progresses and/or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Hepatic disorders

The use of thiazide diuretics in patients with hepatic dysfunction may result in hepatic encephalopathy. In patients with severe hepatic insufficiency or hepatic encephalopathy the use of thiazides is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease hydrochlorothiazide should be used with caution, since even a slight change of electrolyte-water balance and ammonium accumulation in blood serum may cause hepatic coma. In case of symptoms of encephalopathy, the use of diuretics should be stopped immediately.

water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) may cause decreased circulating fluid volume (hypovolemia) and water-electrolyte imbalances (including hypovolemia).hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of electrolyte-water balance disorders are dry mouth, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease of blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with prolonged course of treatment), clinical symptoms of water-electrolyte imbalances should be identified and blood electrolyte levels should be monitored regularly.

Natrium

All diuretics may cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant decrease in plasma levels of chlorine ions may lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine plasma sodium ion content prior to treatment start and monitor this index regularly against the background of hydrochlorothiazide administration.

Kalium

.When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in plasma potassium content and development of hypokalemia (potassium concentration less than 3.4 mmol/l). Hypokalemia increases the risk of cardiac rhythm disorders (including severe arrhythmias) and enhances the toxic effects of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic pirouette-type ventricular tachycardia, which can be fatal.

Hypokalemia poses the greatest danger to the following groups of patients: 1) the elderly, 2) patients receiving concurrent therapy with antiarrhythmic and nonantiarrhythmic drugs that may cause pirouette-type polymorphic ventricular tachycardia or prolong QT interval duration on ECG, 3) patients with impaired liver function, coronary heart disease, and chronic heart failure. In addition, patients with prolonged QT interval are at high risk. It does not matter if this increase is caused by congenital causes or by medications.

In all of the above cases the risk of hypokalemia should be avoided and plasma potassium levels should be monitored regularly. The first measurement of blood potassium ions should be done during the first week of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia may be corrected by the use of potassium-containing drugs or by the intake of foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Tiazide diuretics may decrease renal excretion of calcium ions, resulting in a slight and temporary increase in plasma calcium. In some patients with long-term use of thiazide diuretics pathological changes of parathyroid glands with hypercalcemia and hyperphosphatemia have been observed, but without typical complications of hyperparathyroidism (nephrolithiasis, decrease of bone mineral density, ulcer disease).

Synopsis

Contraindications

– hypersensitivity to hydrochlorothiazide, other sulfonamide derivatives, triamterene or any of the excipients;
– severe renal insufficiency (creatinine clearance (CK) less than 30 ml/min) or progressive renal failure;

Side effects

The side effects of Triampur Compositum® are generally dose-dependent, most of them are moderate to mild and disappear with dose reduction or withdrawal of the drug.

The undesirable reactions when using the drug are categorized into systemic organ classes with the frequency of occurrence according to the following scale: very common (≥1/10), common (≥1/100, ˂ 1/10), infrequent (≥1/1000, ˂ 1/100), rare (≥1/10000, ˂ 1/1000), very rare (˂ 1/10000), frequency unknown (cannot be estimated from available data) and are presented in the table.

Table 1. Side effects (or Adverse reactions)

System-organ

class

Unwanted

reaction

Frequency of occurrence

Hydrochlorothiazide +Triamterene

Hydrochlorothiazide

thiazide

Triamterene

Novoplasms, benign, malignant and unspecified (including cysts and polyps)1)

Overdose

Hydrochlorothiazide

Symptoms: Severe decrease in blood pressure, polyuria, nausea, vomiting, weakness, confusion, fever, flushed facial skin, increased neuromuscular excitability, heart rhythm disturbances, ECG changes, convulsions leading to coma. Most of these symptoms are caused by hyperkalemia, electrolyte imbalance, dehydration, and changes in acid-base balance.

Treatment: symptomatic, there is no specific antidote. Immediate gastric lavage and administration of activated charcoal to reduce absorption is indicated. In arterial hypotension, circulating blood volume (CBC) should be normalized, and vasopressor drugs should be administered. Monitoring and correction of water-electrolyte and metabolic balance is recommended. It has not been established to what extent hydrochlorothiazide can be removed from the body by hemodialysis.

Triamterene

No information available

Pregnancy use

Triampur Compositum® is contraindicated in pregnancy and during breastfeeding.

Hydrochlorothiazide

Pregnancy

. There is limited experience with hydrochlorothiazide during pregnancy (especially in the first trimester). Preclinical data regarding safety are insufficient.

Hydrochlorothiazide penetrates the placental barrier and is detected in umbilical cord blood. Given the mechanism of pharmacological action of hydrochlorothiazide, its use in the second and third trimesters of pregnancy may disrupt the feto-placental perfusion and lead to the development in the fetus and the newborn of such complications as jaundice, disorders of water-electrolyte balance and thrombocytopenia. Cases of thrombocytopenia have been described in newborns whose mothers received thiazide diuretics.

The use of hydrochlorothiazide in the first trimester of pregnancy is contraindicated. In the second and third trimesters of pregnancy, hydrochlorothiazide may be used only if absolutely necessary, when the benefit to the mother exceeds the potential risk to the fetus and/or child.

Hydrochlorothiazide should not be used to treat gestosis in the second half of pregnancy (edema, arterial hypertension or preeclampsia) because it increases the risk of decreased circulating blood volume and placental hypoperfusion, but has no beneficial effect on the course of these pregnancy complications. Diuretics do not prevent the development of gestosis.

Breastfeeding period

Hydrochlorothiazide penetrates the mother’s milk, therefore its use during breastfeeding is contraindicated. If use of hydrochlorothiazide during lactation is absolutely necessary, breastfeeding should be stopped.

Triamterene

Triamterene penetrates the placenta and is excreted with breast milk. Because triamterene inhibits folic acid metabolism, adverse effects cannot be excluded.