Enagexal Compositum

Enagexal compositum is a complex drug from the ACE inhibitor category.

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Indications Enagexala compositum

It is used for therapy of different types of hypertension with varying degrees of severity.

Release form

The drug is released in tablets, which are packed in 10 pieces in blister strips. The pack contains 3 such strips.

Pharmacodynamics

A combination antihypertensive drug that contains enalapril, an ACE inhibitor, and hydrochlorothiazide, a thiazide-type diuretic.

Enalapril inhibits the formation of angiotensin 2 and eliminates its vasoconstrictor effect. In addition, it reduces the overall resistance of peripheral vessels, reduces the severity of afterload, blood pressure, and pressure in the right atrium and pulmonary circulation. At the same time, enalapril reduces the vascular resistance of the kidneys, as a result of which renal blood circulation improves.

Hydrochlorothiazide has a natriuretic and diuretic effect, and also enhances the antihypertensive properties of enalapril.

A decrease in blood pressure values is observed approximately 1 hour after taking the drug, and this effect lasts for about 24 hours (on average).

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Pharmacokinetics

Enalapril.

After taking the tablet, about 50-70% of the enalapril maleate substance is absorbed.

Serum Cmax values are noted after 1 hour. After absorption, the substance is hydrolyzed, transforming into enalaprilat, which is an even more powerful ACE inhibitor than enalapril. Peak values of enalaprilat in blood plasma are noted after 3-4 hours from the moment of drug administration.

Approximately 50-60% of enalaprilat undergoes protein synthesis within plasma.

About 94% of the enalapril maleate dose is excreted in the urine and feces as enalapril with enalaprilat. The main component of the urine is the substance enalaprilat, which makes up approximately 94% of the dose. The half-life of the drug is 35 hours.

Excretion decreases in people with weakened renal function - in accordance with the degree of insufficiency. Dialysis of the enalaprilat component occurs at a rate of 62 ml/hour.

Hydrochlorothiazide.

The absorption rate of hydrochlorothiazide is 65-75%. In patients with congestive heart failure, absorption of the substance is reduced. Peak plasma levels of hydrochlorothiazide are in the range of 70-490 ng/ml, and it takes 1.5-4 hours to achieve them after oral administration of 12.5 mg, and 25 hours after oral administration of 25 mg of the substance.

Protein synthesis of the element within the plasma is approximately 40-68%.

Excretion of hydrochlorothiazide is almost complete – >95% is excreted unchanged through the kidneys. Half-life is within 6-15 hours.

Hydrochlorothiazide crosses the placenta but does not cross the blood-brain barrier. In renal failure, the excretion rate may be reduced and the half-life may be prolonged.

Dosing and administration

The medication is taken orally, selecting a dosage regimen individually for each patient, taking into account his condition and the degree of hypertension. Therapy begins with the use of small doses of the medication, gradually increasing them.

Prescription of the fixed combination of Enahexal Compositum is allowed only in cases where previous adjustments of the dose (titration) or individual combinations (enalapril or hydrochlorothiazide) have not yielded results. People with appropriate clinical indications should consider the possibility of a direct transition from monotherapy to the use of a fixed combination of drugs.

Schemes for using the drug dosage 10/25.

The size of the initial daily dose for people who are prescribed complex treatment: taking 1 tablet in the form of 10/25 mg, once a day.

The average daily dosage is 1-2 of these tablets, taken once or twice a day.

In maintenance treatment, the medication is also used for once-daily use.

A maximum of 40 mg of enalapril and 0.1 g of hydrochlorothiazide, which is 4 tablets of the therapeutic substance, is allowed per day. This portion should be consumed in 1 or 2 doses.

Methods of administration of the medicine dose 20/12.5.

Initially, individuals who have been prescribed combination therapy should take 0.5 tablets of the medication at a dosage of 20/12.5 mg per day.

The average daily serving size is a single dose of 1 tablet of 20/12.5 mg.

For maintenance treatment, take 0.5 tablets of 20/12.5 mg once a day.

You can take a maximum of 2 tablets of 20/12.5 mg Enahexal Compositum per day – either as a single dose or divided into 2 doses.

The medication is taken regardless of food intake, washing down the tablet with plenty of plain water.

Use Enagexala compositum during pregnancy

Enahexal compositum should not be used during pregnancy or lactation.

Contraindications

Among the contraindications:

• the presence of strong sensitivity to enalapril or other ACE inhibitors;
• presence of Quincke's edema in the anamnesis;
• severe renal impairment (creatinine clearance level below 30 ml/minute) or dialysis sessions;
• clinically significant deviations in electrolyte levels (development of hypercalcemia or hypokalemia and hyponatremia);
• arterial stenosis in the renal area (bilateral or 1-sided (if the patient has only 1 kidney));
• patients who have recently received a kidney transplant;
• mitral or aortic stenosis of hemodynamic significance;
• obstructive cardiomyopathy of the hypertrophic type;
• severe liver dysfunction (comatose state or hepatic coma);
• diabetes mellitus or gout in a severe stage.

Side effects Enagexala compositum

The use of the drug may lead to the development of some side effects:

• systemic symptoms: dizziness, feeling of weakness, and pain in the abdomen or chest;
• disorders associated with the functioning of the cardiovascular system: tachycardia, orthostatic collapse or palpitations;
• digestive disorders: bloating, dry mouth, pancreatitis, constipation, cholestatic jaundice or vomiting;
• lesions affecting the nervous system: feeling of drowsiness or nervousness, agitation, insomnia and paresthesia;
• symptoms related to the epidermis: erythema multiforme, pruritus, as well as Stevens-Johnson syndrome and exfoliative dermatitis, including hair loss and TEN;
• problems with kidney function: renal failure or tubulointerstitial nephritis;
• signs of allergy: urticaria, Quincke's edema, anaphylactoid reactions, as well as RDS;
• disorders of hematopoietic function: agranulocytosis, thrombocyto- or leukopenia, and also aplastic or hemolytic anemia;
• visual impairment: xanthopsia or transient visual blurring;
• Other symptoms include back pain, muscle weakness or cramps, dyspnea, tinnitus, arthralgia, profuse sweating and decreased libido.

Long-term use of drugs can lead to the development of hyponatremia or -kalemia.

Overdose

Depending on the severity of the poisoning, the following symptoms may appear: salt imbalance, paresis, decreased blood pressure, decreased consciousness (up to a comatose state), arrhythmia, cardiovascular shock, and in addition, convulsions, bradycardia, paralytic ileus, Quincke's edema and renal failure.

In case of intoxication, it is necessary to carry out procedures that help remove the drug from the body (gastric lavage and the use of activated charcoal for half an hour from the moment of taking the drug), and in addition to this, monitor the work of vital systems in the hospital.

In severe cases of poisoning, hospital procedures are performed to stabilize blood pressure values: intravenous injection of NaCl solution with plasma substitutes; as well as hemodialysis sessions and angiotensin 2 injections, if necessary.

If Quincke's edema or other anaphylactic symptoms develop, desensitizing treatment is prescribed, during which antihistamines (such as loratadine with suprastin) and GCS (including dexamethasone with prednisolone) are used, and in addition, measures are taken to ensure the patency of the respiratory tract.

Along with this, it is necessary to regularly monitor the values of acid-base, water and salt balances, as well as glucose and compounds excreted in the urine. If hypokalemia occurs, potassium reserves must be replenished.

Interactions with other drugs

Combination with antihypertensive drugs (including other diuretic drugs and drugs that block the activity of β-receptors), vasodilators, nitrates, phenothiazines, as well as barbiturates, tricyclics and alcoholic beverages causes potentiation of the hypotensive properties of the drug.

Anti-inflammatory and analgesic drugs (including indomethacin and aspirin) may reduce the antihypertensive effect of Enahexal Compositum. In people with hypovolemia, this combination may lead to acute renal failure.

The use of large doses of salicylates together with the drug leads to a potentiation of their toxic properties in relation to the central nervous system (this is influenced by the activity of hydrochlorothiazide).

Diuretics, potassium and potassium-sparing agents (for example, amiloride with spinorolactone and triamterene), as well as other medications that increase potassium levels (including heparin) lead to a strong increase in potassium levels under the influence of enalapril.

Combination of the drug with diuretics (such as furosemide), carbenoxolone, GCS, as well as salicylates, ACTH, amphotericin B and penicillin G, or abuse of laxative drugs leads to an increase in magnesium or potassium deficiency under the influence of hydrochlorothiazide.

Combination with lithium causes an increase in serum lithium levels (this indicator must be constantly monitored), as a result of which its neurotoxic and cardiotoxic effects may be potentiated.

Digitalis glycoside substances may increase the severity of the effects and side effects of digitalis in people with hypomagnesemia or -kalemia.

Catecholamines (such as epinephrine) reduce the therapeutic effect of hydrochlorothiazide.

Narcotics, sleeping pills and anesthetics significantly increase blood pressure values (therefore, before administering anesthesia, you must inform the anesthesiologist about the treatment using Enahexal Compositum).

Immunosuppressants, procainamide, as well as allopurinol with systemic GCS and drugs that suppress bone marrow activity, reduce the number of leukocytes in the blood and cause leukopenia.

The use of cytostatics (including cyclophosphamide and methotrexate with fluorouracil) leads to potentiation of the toxic effect on the bone marrow (especially granulocytopenia) – occurs due to the action of hydrochlorothiazide.

Combination with orally administered hypoglycemic drugs (including biguanides or sulfonylurea), as well as insulin, leads to a weakening of the hypoglycemic effect.

Taking it together with colestipol or cholestyramine reduces the extent of absorption of hydrochlorothiazide.

Curare-like muscle relaxants, as well as non-polarizing agents that block neuromuscular transmission, increase the duration and potentiate the muscle relaxing effect of hydrochlorothiazide (the anesthesiologist should be notified in advance of the use of the drug).

The combination with methyldopa sometimes causes hemolysis due to the formation of antibodies against the substance hydrochlorothiazide.

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Storage conditions

Enagexal Compositum should be stored in a dark and dry place, inaccessible to small children. Temperature values should not exceed 25°C.

Shelf life

Enagexal Compositum is allowed to be used within 36 months from the date of manufacture of the medicinal product.

Application for children

It is prohibited to prescribe the drug in pediatrics.

Analogues

The analogs of the drug are Berlipril plus, Enap H, Enalozid 25, Enafril with Enzix, as well as Enap HL, Enapril H, Enap 20 HL with Enzix Duo and Ena Sandoz with Enzix Duo Forte.