Adelfan-Ezidrex - description of the drug, instructions for use, reviews

Write a review

Reviews: 2

Manufacturers: Sandoz Inc. (USA)

Active ingredients

• Hydrochlorothiazide
• Reserpine

Disease class

• Essential [primary] hypertension
• Secondary hypertension

Clinical and pharmacological group

• Not indicated. See instructions

Pharmacological action

• Antihypertensive

Pharmacological group

• Sympatholytics in combinations
• Diuretics in combinations

Pharmacodynamics and pharmacokinetics

Adelfan Esidrex is a combination of 3 antihypertensive components that differ in the point of action, while mutually complementing the antihypertensive effect of each other:

• Reserpine is known as a sympatholytic , capable of leading to a fairly long-term depletion of the catecholamine at the endings of the postganglionic fibers of the sympathetic part of the central nervous system and, as a consequence, disruption of impulse transmission and a decrease in tone in the sympathetic part (without changes in activity in the parasympathetic part). Reserpine is also capable of depleting other neurotransmitters, including serotonin , dopamine , and neuropeptides in both central and peripheral neurons. As a result, there is a decrease in elevated blood pressure and heart rate , and a sedative effect is observed. The therapeutic effect develops slowly and can reach its maximum after 2–3 weeks and persist for a long time.
• Dihydralazine is an arterial vasodilator that reduces the tone of the smooth muscles of centripetal vessels (mostly arterioles, which reduces the severity of orthostatic hypotension and helps to increase cardiac output) and reduces peripheral vascular resistance mainly in the vessels of the heart, brain, internal organs, as well as skin and skeletal muscles. When the antihypertensive effect is not pronounced, the strength of blood flow in the dilated bed generally increases.
• The reflex increase in heart rate due to vasodilation and a decrease in blood pressure is neutralized by the complex influence of dihydralazine and reserpine , which suppress the sympathetic part of the nervous system.
• Hydrochlorothiazide is a thiazide diuretic that acts on the cortical segment of the loop of Henle and the distal renal tubules. Inhibition of the reabsorption of sodium and chlorine ions occurs due to antagonistic mutual influence with transport enzymes, which increases the reabsorption of calcium ions, and also leads to increased secretion and excretion of hydrogen and potassium ions. Due to diuresis caused by thiazides , blood volume, cardiac output and systemic blood pressure first decrease, and there is a possibility of activation of the renin-angiotensin-aldosterone system . Long-term therapy with hydrochlorothiazide leads to the maintenance of the hypotensive effect, probably by reducing the peripheral vascular resistance.

Pharmacokinetics of the absorption process of the active components

• reserpine is absorbed quickly after oral administration, with systemic bioavailability up to 50%;
• absorption of dihydralazine in the human body occurs quickly, entering the bloodstream in the unchanged form of dihydralazine and hydrazone metabolites (up to 10%);
• As a result of oral administration of hydrochlorothiazide, approximately 60–80% is absorbed and gives maximum concentration in the bloodstream after 1.5–3 hours.

Distribution

• the relative steady-state volume of distribution for reserpine ranges from 6.4-1.8 l/kg (average value - 9.1 l/kg), binds to albumin and blood lipoproteins by 96%;
• hydrochlorothiazide can accumulate in erythrocytes (during excretion there can be up to 3–9 times more hydrochlorothiazide in erythrocytes than in the blood), and also bind to plasma proteins by 40–70%; the indicator of the steady-state volume of distribution of the final phase of excretion is 3–6 l/kg.

Metabolism information

• Metabolism of reserpine occurs in the liver and intestines to metabolites - methyl reserpate and trimethoxybenzoic acid ;
• Dihydralazine metabolism is largely carried out along the path of oxidation (to hydrazones ), as well as acetylation;
• the level of metabolism of hydrochlorothiazide is very low - it can only be found in trace amounts in the form of 2-amino-4-chloro-M-benzene disulfonamide .

Hatch Characteristics

• Reserpine elimination has two phases: the half-life of phase I is 4.5 hours; II - 271 hours. Up to 8% of the dose taken is excreted through the kidneys mainly in the form of metabolites, 62% of the unchanged substance is excreted by the intestines;
• T1/2 for unchanged dihydralazine is 4 hours: approximately 46% of the orally administered dose is excreted in the form of metabolites by the intestines, 0.5% of the dose is unchanged substance that is excreted in the urine;
• elimination of hydrochlorothiazide is also two-phase: the half-life of the initial phase is 2 hours, the final phase is 10 hours. 50–75% of the dose taken orally is removed from the body in the urine.

Changes in pharmacokinetics in certain groups of patients

• for elderly patients, as well as patients with functional renal impairment: it is recommended to reduce the average therapeutic dose due to a significant decrease in the clearance of hydrochlorothiazide and an increase in its concentration in the blood;
• impaired renal and liver function can lead to the accumulation of dihydralazine ;
• in case of renal failure, the process of excretion of reserpine , which is compensated by increased excretion through the intestines. However, in order to avoid the accumulation of reserpine, a single dose is adjusted or the time between doses is increased, monitoring the dynamics of blood pressure and tolerability.

Contraindications

• presence of depression , incl. in the anamnesis;
• epilepsy;
• Parkinson's disease;
• ulcerative colitis , exacerbation of gastric and duodenal ulcers ;
• electroconvulsive therapy;
• pheochromocytoma;
• therapy with MAO inhibitors and 14 days after cessation (due to the likelihood of hyperactivity , hypertensive crisis );
• idiopathic systemic lupus erythematosus;
• a combination of severe tachycardia and heart failure with high cardiac output, as well as thyrotoxicosis ;
• aortic or mitral stenosis , constrictive pericarditis and other forms of heart failure associated with mechanical obstructions;
• arising against the background of pulmonary hypertension (the so-called “pulmonary” heart );
• liver failure;
• anuria or renal failure , where creatinine is less than 30 ml per 1 minute;
• refractory hypokalemia , hypercalcemia , hyponatremia ;
• clinical manifestations of hyperuricemia ;
• pregnant and breastfeeding patients;
• children under 18 years of age;
• hypersensitivity to reserpine , its related substances, hydrochlorothiazide and dihydralazine , other ulphonamide derivatives and hydrazinophthalazines , as well as to any auxiliary component;

Prescription and use with caution

• if necessary, avoid a sharp decrease in blood pressure due to the risk of decreased blood flow;
• after myocardial infarction until complete stabilization;
• cerebral/coronary atherosclerosis ;
• erosive gastritis;
• cholelithiasis;
• sinus bradycardia , various conduction disorders;
• suspicion of ischemic heart disease ;
• previous treatment with ACE , especially in combination with potassium-sparing diuretics and potassium-containing drugs ;
• diabetes;
• gout.

Side effects

In general, the components in Adelfan Esidrex tablets are contained in smaller quantities than those used individually for arterial hypertension , but there is a possibility of adverse events occurring under the influence of each of the active components of the drug.

• Therapy with Adelfan Esidrex can lead to the following digestive system symptoms: diarrhea, dry mouth, increased secretion of gastric juice, increased salivation, nausea and vomiting, increased appetite, pancreatitis , ulcer formation, gastrointestinal bleeding.
• Liver disorders: Less than 1% of subjects experienced jaundice , liver dysfunction, or hepatitis .
• CVS: developing sinus bradycardia , tachycardia , angina , heart failure, swelling, arrhythmias , chest pain, orthostatic hypotension , fainting, hot flashes , cerebral circulatory disorders.
• Respiratory organs: swelling of the nasal mucosa or lungs, shortness of breath, nosebleeds, pneumonitis .
• Central nervous system: depression , dizziness, headache, irritability, increased anxiety, nightmares, fatigue, agitation, anorexia , extrapyramidal disorders (for example: parkinsonism ), peripheral neuritis , paresthesia , impaired attention and orientation, possible stupor , as well as cerebral edema .
• Sense organs: blurred vision, lacrimation, conjunctival hyperemia; hearing impairment.
• Genitourinary system: disturbances of potency and the ejaculation process, development of dysuria , glomerulonephritis .
• Endocrine system and metabolism: weight gain, increased secretion of prolactin , swelling or spontaneous leakage of milk from the mammary glands, gynecomastia .
• Disturbances of water-electrolyte balance: hyperuricemia , hypokalemia , hyponatremia , hypomagnesemia , hypercalcemia , increased concentration of lipids in the blood, glycosuria , hypochloremic alkalosis .
• Epidermis: urticaria , eczema , itching, skin rash, photosensitivity , necrotizing vasculitis , Lyell's syndrome , lupus-like syndrome .
• Other reactions: arthralgia , decreased libido, fever , anemia , thrombocytopenia , leukopenia , agranulocytosis , purpura , hypersensitivity reactions.

special instructions

Due to the risk of suicidal behavior, if symptoms of depression occur, the drug should be discontinued. A depressive state provoked by reserpine (at high doses of Adelfan-Ezidrex) can continue for a long period after discontinuation of the drug.

The presence of dihydralazine can cause water and sodium retention in the body, and cause edema and decreased diuresis.

Patients with impaired liver function must ensure systematic monitoring of water and electrolyte balance, since even minor disturbances can lead to hepatic coma, especially with cirrhosis of the liver.

The likelihood of developing lupus-like syndrome is directly dependent on the dose and period of use of the drug, therefore, for long-term maintenance therapy, the minimum effective dose is required. A symptom of mild forms of the syndrome is arthralgia, which may be accompanied by skin rashes and fever. After discontinuation of the drug, the patient's condition returns to normal on its own. Severe cases are characterized by signs of the clinical picture of systemic lupus erythematosus.

Treatment with dihydralazine should be accompanied by regular (every 6 months) determination of antinuclear factor in the blood plasma, and if detected, titers should be recorded and their dynamics monitored. In the event of the development of clinical manifestations of lupus-like syndrome, immediate discontinuation of Adelfan-Ezidrex is required.

Due to the presence of reserpine, the drug should be discontinued at least 7 days before electroconvulsive therapy.

When performing a planned surgical operation, it is necessary to warn the anesthesiologist about taking the drug, since the preliminary withdrawal of the combined drug itself does not guarantee hemodynamic stability during the operation; a pronounced decrease in blood pressure is possible.

Hydrochlorothiazide causes the development of hypokalemia, especially in patients with rapidly developing diuresis, liver cirrhosis, deficiency of potassium intake from food, simultaneous therapy with glucocorticosteroids, adrenocorticotropic hormone or beta-adrenergic receptor stimulants. Hypokalemia may potentiate the cardiac response to digitalis drug toxicity and increase myocardial sensitivity. For timely detection of electrolyte imbalances, taking the drug should be accompanied by regular monitoring of the content of electrolytes in the blood plasma. If you experience nausea, thirst, dry mouth, weakness, anxiety, drowsiness, muscle weakness, muscle pain and cramps, decreased blood pressure, tachycardia, oliguria (nonspecific symptoms of electrolyte imbalance), you should consult a doctor.

With the use of thiazide diuretics, hypercalcemia and hypophosphatemia may develop.

The use of thiazide diuretics can lead to hypomagnesemia, since they increase the excretion of magnesium in the urine.

At high doses of hydrochlorothiazide, the patient may develop a decrease in glucose tolerance, which causes a risk of increased plasma concentrations of triglycerides, cholesterol, and uric acid.

Reserpine affects laboratory parameters in urine of 17-hydroxycorticosteroids and 17-ketosteroids using the colorimetric method, underestimating their results.

Adelfan-Ezidrex affects the speed of psychomotor reactions, especially at the beginning of use. Patients operating vehicles and machinery should be warned to exercise caution.

Instructions for Adelfan Esidrex (method of administration and dosage)

Take the tablets orally during meals with plenty of clean water. The dosage should be selected individually.

Standard dosage

• initial minimum dose, which gradually increases after 2-3 weeks: 1-3 tablets. (must take into account the patient's response to therapy);
• frequency of administration - up to 2-3 times a day;
• maximum daily dose - no more than 3 tablets.

Attention!

When it is not possible to achieve adequate control over blood pressure, the treatment regimen is reviewed and, possibly, even switching to a drug from another pharmacological group, for example, β-blockers , CCBs , ACE inhibitors .

Instructions for use in patients with impaired liver or kidney function, for elderly patients: single doses of the drug, as well as the interval between doses, should be set with caution, taking into account the level of expected required clinical reaction, response and tolerability of treatment.

Price and where to buy

Many patients ask the question: “Why was such a high-quality medicine Adelfan removed from mass production?” But the whole point is that this drug was included in the category of outdated medicines.

Today, you can purchase the improved and effective drug Adelfan-Ezidrex in specialized pharmacies.

The price of Adelfan blood pressure pills varies depending on the region of residence. On average, a package of 30 tablets costs 170 rubles, but a package of 250 tablets will cost 1,200 rubles. The drug is commercially available; you can buy Adelfan-Ezidrex blood pressure tablets without a doctor's prescription.

Overdose

Supposed symptoms

Headache, drowsiness, dizziness, confusion, extrapyramidal disorders, coma , convulsions, muscle weakness, paresthesia , persistent miosis , water-electrolyte imbalance, tachycardia , marked decrease in blood pressure, myocardial ischemia with angina pectoris and arrhythmia , respiratory depression, oliguria , collapse . From the digestive system: dyspeptic symptoms (nausea, vomiting, diarrhea).

Method of treatment

• in conscious patients, induce vomiting, perform gastric lavage , and prescribe activated carbon ;
• with a pronounced decrease in blood pressure, the patient must take a position where the legs are elevated, as well as use plasma substitutes and correct electrolyte disturbances;
• if necessary, it is possible to use vasoactive agents ;
• for diarrhea, therapy with anticholinergic drugs ;
• seizures are controlled with anticonvulsants , for example, slow intravenous administration of Diazepam ;
• with severe respiratory depression - mechanical ventilation ;
• Due to the prolonged action of reserpine, the patient should be monitored for at least 72 hours.

Interaction

• The hypotensive effect is enhanced in combination with other antihypertensive drugs , for example, with guanethidine , α-Methyldopa , β-blockers , vasodilators , CCBs , ACE inhibitors .
• the reserpine included in the composition, the depressant effect on the central nervous system of ethanol , general anesthesia , barbiturates, certain antihistamines , tricyclic antidepressants (which in turn can weaken the hypotensive effect of reserpine ) is enhanced and enhances the hypotensive effect of dihydralazine .
• Reserpine reduces the effects of Levodopa .
• Simultaneous therapy with reserpine and antiarrhythmic drugs or digitalis increases the likelihood of acquiring sinus bradycardia .
• With reserpine, it is possible to potentiate the effects of epinephrine ( adrenaline ), other sympathomimetic substances , which may also be contained in antitussives , nasal drops, eye drops.
• Hydrochlorothiazide with lithium preparations causes an increase in the concentration of lithium in the bloodstream. If therapy with Lithium drugs leads to polyuria , then hydrochlorothiazide may have a paradoxical antidiuretic effect .
• Hydrochlorothiazide can enhance the effect of non-depolarizing muscle relaxants .
• NSAIDs (including Indomethacin ) can weaken the diuretic and natriuretic , as well as the antihypertensive effect of hydrochlorothiazide .
• Thiazide diuretics , incl. hydrochlorothiazide , may increase the risk of hypersensitivity reactions to Allopurinol , adverse reactions of Amantadine , enhance the hyperglycemic effect of Diazoxide , significantly reduce the excretion of cytotoxic drugs by the kidneys (for example, Cyclophosphamide , Methotrexate ), enhance their myelosuppressive effect.
• With anticholinergic drugs ( Atropine , Biperiden ), due to a decrease in peristalsis and rate of emptying, the bioavailability of hydrochlorothiazide .
• Therapy with hydrochlorothiazide with vitamin D and calcium supplements leads to an increase in the level of calcium in the bloodstream.
• Hydrochlorothiazide with Cyclosporine increases the likelihood of developing gout and hyperuricemia , and with Methyldopa - hemolytic anemia .

During pregnancy and lactation

Pregnancy is included in the list of contraindications for several reasons:

• when using reserpine before childbirth, the newborn may experience severe drowsiness, swelling of the nasal mucosa and anorexia;
• Thiazide diuretics (hydrochlorothiazide) of thrombocytopenia in the fetus and unborn newborn child .

In addition, all three active components are capable of passing into breast milk, which can lead to the adverse reactions described above, and hydrochlorothiazide can suppress lactation.

Video on the topic

About the main and auxiliary groups of antihypertensive drugs for high blood pressure in the video:

In conclusion, we can summarize that Adelfan is considered a complex drug, the positive properties of which are due to the presence of active components. Thanks to this, cerebral and renal blood flow improves, and the overall vascular tone is normalized.

Despite the fact that the drug itself has many contraindications and side reactions, the correct dosage and compliance with all doctor’s recommendations will certainly give a positive effect without harm to other organs and systems of the body.

Analogs

Level 4 ATC code matches:
Brinerdine

Trirezide K

Normatens

Adelfan

There is no complete coincidence in the composition of the active substances, but there are analogues according to the ATC code, where the active substance is the same - reserpine and the drugs are supplemented with the active dihydroergocristine and clopamide :

• Kristepin (producer Czech Republic);
• Normatens (manufacturer: Poland/Germany).

Release form and composition

Dosage form - tablets: from almost white to white, without a shell, round in shape, flat with beveled edges, marked “CIBA” on one side and a dividing line between the letters “A” and “F” on the other (10 pcs. . in a blister, in a cardboard pack of 1, 2, 3, 5 or 25 blisters).

Contents of active ingredients of Adelfan-Ezidrex in 1 tablet:

• Dihydralazine sulfate hydrated – 10.25 mg (anhydrous – 10 mg);
• Reserpine – 0.1025 mg;
• Hydrochlorothiazide – 10 mg.

Auxiliary components: corn starch, mannitol (mannitol), magnesium stearate (magnesium stearate), disodium edetate, talc (magnesium hydroxysilicate).