Instructions for use ADELPHANE-ESIDREX® (ADELPHANE-ESIDREX)

Most of you, pharmacy visitors, contact a specialist with a specific request. You are looking for medications prescribed by a doctor or self-medication. There are usually several options for the same drug to choose from. Among them may be original drugs

- they went through a full cycle of research and were registered first, and
generics
are copies of the original drug, registered after it.

When choosing between analogue drugs, pay attention to the equivalence of the active ingredients, dosages, release forms, the name of the manufacturer and whether the product is a medicine or dietary supplement.

Brief instructions for choosing analogue drugs:

• Analogs must have equivalent active ingredients. To find a drug, use the service for selecting analogues by INN.
• The dosage of the analogue should be either the same or less. If the dosage is less, the medication regimen changes.
• The packaging of analogues may differ. Before purchasing, calculate how much of the drug is needed for the course of treatment.
• Analogs must have the same dosage form and route of administration. That is, you should not buy tablets instead of suppositories.
• Keep in mind that not all generic drugs are equally similar to the original drug.
• Do not replace the medicine with a dietary supplement.

Read more below.

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.

Active substance

Each medicine has several names:

• trade
• international nonproprietary (INN) or grouping, or chemical

Trade name

unique for each manufacturer. It is necessary to distinguish drugs from different manufacturers.

Example of trade names of drugs containing the active substance ibuprofen:

• Dolgit
• Nurofen
• Ibuprofen-Akrikhin
• Faspik
• Mig and others

INN

is the name of the active substance.

An example of an active substance and a preparation containing it:

• ibuprofen (Nurofen, Mig)
• doxycycline (Unidox Solutab, Doxylan)
• acetylsalicylic acid (Aspirin, Upsarin UPSA)

Group name

assigned to a medicinal product if it does not have an INN or several of them.

Examples of group names:

• chondroitin sulfate
• tolperisone + lidocaine
• cod liver oil

Chemical name

- the name of the active substance, reflecting its composition and chemical structure.

The doctor must write a prescription in Latin using the INN. If there is no INN, the prescription is written by generic or chemical name. The drug is prescribed by its trade name if it does not have an INN, generic or chemical name.

The pharmacy employee offers you medications with the active ingredient that the doctor indicated in the prescription. Drugs with the same active ingredient can be produced by different factories. In this case, they will have different trade names.

Analogs must have equivalent active ingredients. To find a drug, use the service for selecting analogues by INN.

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.

Dosage

In the prescription, in addition to the name, the doctor indicates the required dose of the drug. Drugs with the same INN are available in different dosages. The dosage depends on the underlying and concomitant diseases, age, body weight of the patient and other factors.

For example: medications with the active ingredient amoxicillin can be produced in dosages of 125 mg, 250 mg, 500 mg and 1000 mg.

The effect of treatment also depends on the correct dosage. The dosages of analogue drugs should be the same.

If the pharmacy does not have the required dosage, you can recalculate it. By law, this is allowed if the pharmacy has drugs with a lower dosage than prescribed in the prescription. At the same time, the reception regimen will change.

Indications for use

Ritalin is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy, and primary hypersomnia. Methylphenidate should be prescribed for ADHD as part of complex therapy.

Lack of attention, hyperactivity and impulsivity are the three main signs of ADHD. This diagnosis is labor-intensive, complex and requires appropriate clinical experience. It involves an in-depth examination of the patient's medical history.

Symptoms must persist for more than 6 months and be observed for up to 7 years. The main diagnostic difficulty is based on the fact that symptoms are nonspecific and can have a variety of causes.

According to studies, the prevalence of ADHD is about 5% and narcolepsy is about 1%. ADHD is more common among younger men and those of low socioeconomic status. Symptoms of the disease are more common in adolescence and adulthood. Approximately 40-86% of men experience persistent symptoms of ADHD.

Available research suggests that methylphenidate can be meaningfully used for attention deficit hyperactivity disorder in children and adolescents, typically as part of multimodal therapy. A prerequisite is an adequate diagnosis of ADHD, narcolepsy or hypersomnia.

Release form

When choosing analogues, you need to take into account the amount of the drug per course of treatment. Preparations with the same active ingredient in equal dosages can be produced in different packaging. The doctor writes a prescription, indicating how much medication the patient will need for the entire course of treatment.

For example: paracetamol is available in the form of tablets of 10 pieces, 20 pieces, and the drug Panadol with the same active ingredient is available in 12 tablets.

The doctor also indicates the dosage form of the drug

: tablets, capsules, oral solution, ointment, suppositories (suppositories). Analogs must have the same dosage form and route of administration.

This means that you should not replace tablets with suppositories without consulting your doctor. The method of administration of the drug determines the therapeutic effect, the speed of its onset, as well as the likelihood of developing adverse side reactions. The doctor selects the dosage form taking into account the patient’s characteristics.

For example: the doctor prescribed the drug in the form of rectal suppositories, and you decided to use tablets. Such a replacement may change the speed of onset of the therapeutic effect, since the drug from suppositories reaches the bloodstream faster than from a tablet.

Use as a drug

Being essentially a psychostimulant, methylphenidate is used among drug addicts to obtain euphoric sensations. To do this, the dosage of the drug is exceeded 2-3 times. In some ways, its effects are comparable to those of cocaine or methamphetamine, but are more reminiscent of Prozac or Zoloft. As the dosage increases, the likelihood of not only psychological but also physical addiction increases. Regular abuse is fraught with psychosis, insomnia and disruption of the functioning of all internal organs.

Medicine or dietary supplement

Prescribed medications cannot be replaced with dietary supplements. Dietary supplements do not have a therapeutic effect, but are indicated for use as an additional source of any substances for consumption along with food.

Dietary supplements should not be used as primary treatment. They may contain the same ingredients as medications. However, medicines and dietary supplements undergo different tests for state registration.

When choosing drug analogues, you should pay attention to the name of the drug, namely the active substance. The analogue should be selected taking into account the dosage, course of treatment and dosage form. It is important to pay attention to the manufacturer and whether the chosen product is a medicinal product.

There are contraindications. Possible side effects. Before use, you should consult a specialist.

Adelphane-Esidrex tablets

Instructions for medical use of the drug

Indications for use

Arterial hypertension.

Release form

pills; blister 10, cardboard pack 5. tablets; blister 10, cardboard pack 2. tablets; blister 10, cardboard pack 25. tablets; blister 10, cardboard pack 3.

Pharmacodynamics

Adelfan-Ezidrex is a combination of three antihypertensive components that have different points of action and mutually complement each other's antihypertensive effects. Reserpine is a sympatholytic, causing depletion of catecholamine depots in the endings of postganglionic sympathetic fibers and in the central nervous system. As a result, the ability to deposit catecholamines is impaired for a fairly long period of time. Depletion of catecholamine reserves leads to disruption of impulse transmission in the endings of the sympathetic nerves, which, in turn, leads to a decrease in the tone of the sympathetic nervous system (while the activity of the parasympathetic nervous system does not change). Thus, reserpine reduces elevated blood pressure and heart rate. In addition, reserpine causes a sedative effect. Reserpine depletes reserves of other neurotransmitters, incl. serotonin, dopamine, neuropeptides in central and peripheral neurons. These effects of reserpine may play a role in its pharmacological effects and antihypertensive effects. After oral administration of reserpine, the antihypertensive effect develops slowly; the maximum effect is achieved only after 2–3 weeks and is maintained for a long time. Dihydralazine is an arterial vasodilator, reduces the tone of the smooth muscles of arterial vessels (mainly arterioles) and reduces peripheral vascular resistance. The mechanism of this action at the cellular level remains unclear. To a greater extent, vascular resistance decreases in the vessels of the heart, brain, kidneys and other internal organs, and to a lesser extent in the vessels of the skin and skeletal muscles. If the decrease in blood pressure is not pronounced, the blood flow in the dilated bloodstream generally increases. The preferential expansion of arterioles, rather than venules, reduces the severity of orthostatic hypotension and increases cardiac output. Vasodilation, leading to a decrease in blood pressure (to a greater extent in dBP than in sBP), is accompanied by a reflex increase in heart rate, stroke volume and cardiac output. The reflex increase in heart rate and cardiac output can be neutralized by combining dihydralazine with reserpine, which suppresses the sympathetic nervous system. Hydrochlorothiazide is a thiazide diuretic that acts in the cortical segment of the loop of Henle and the distal renal tubules. Inhibits the reabsorption of chlorine and sodium ions (due to antagonistic interaction with the transport enzyme Na + Cl-) and enhances the reabsorption of calcium ions (the mechanism is unknown). An increase in the amount and/or rate of entry of sodium and water ions into the cortical segment of the collecting ducts leads to an increase in the secretion and excretion of potassium and hydrogen ions. In patients with normal renal function, an increase in diuresis is observed after a single dose of hydrochlorothiazide at a dose of 12.5 mg. An increase in the urinary excretion of sodium and chlorine ions and a slightly less pronounced increase in the excretion of potassium ions depend on the dose of hydrochlorothiazide. After oral administration of hydrochlorothiazide, diuretic and natriuretic effects develop after 1–2 hours, reach a maximum after 4–6 hours and persist for 10–12 hours. Diuresis caused by thiazides initially leads to a decrease in blood volume, cardiac output and systemic blood pressure. Activation of the renin-angiotensin-aldosterone system is possible. With long-term use of hydrochlorothiazide, the maintenance of the hypotensive effect is probably ensured by a decrease in peripheral vascular resistance. Cardiac output returns to initial values, a slight decrease in plasma volume and an increase in plasma renin activity persist.

Pharmacokinetics

Absorption and plasma concentrations Reserpine is rapidly absorbed after oral administration. Systemic bioavailability is 50%. Dihydralazine is rapidly absorbed after oral administration. In blood plasma, dihydralazine is found predominantly in the form of unchanged dihydralazine and hydrazone substances formed as a result of metabolism of the main substance. Approximately 10% of dihydralazine is found in the blood plasma in the form of hydralazine. Hydrochlorothiazide after oral administration is absorbed by 60–80%. The time to reach Cmax in blood plasma is 1.5–3 hours. Changes in absorption under the influence of food intake are not clinically significant. Over the therapeutic dose range, the systemic bioavailability of hydrochlorothiazide is approximately proportional to the dose. With regular use of hydrochlorothiazide, its pharmacokinetics do not change. Distribution The relative VSS of reserpine averages 9.1 l/kg (ranges from 6.4 to 11.8 l/kg). Binding to plasma proteins is more than 96% (albumin and lipoproteins). Hydrochlorothiazide accumulates in red blood cells. In the elimination phase, its concentration in erythrocytes is 3–9 times higher than in blood plasma. Binding to blood plasma proteins is 40–70%. VSS in the final elimination phase is 3–6 L/kg (equivalent to 210–420 L for a body weight of 70 kg). Metabolism Reserpine is metabolized in the intestines and liver. The main metabolites are methyl reserpate and trimethoxybenzoic acid. Dihydralazine is metabolized largely by oxidation (to form hydrazones) and acetylation. Hydrochlorothiazide is metabolized to a very small extent. Its only metabolite found in trace amounts is 2-amino-4-chloro-M-benzene disulfonamide. Excretion The removal of reserpine and its metabolites from blood plasma occurs in two phases: T1/2 of phase I is 4.5 hours; Phase II - 271 hours. The average T1/2 value of unchanged substance is 33 hours. The total clearance of reserpine averages 245 ml/min. During the first 96 hours after oral administration, 8% of the dose is excreted by the kidneys, mainly in the form of metabolites, and 62% through the intestines, mainly unchanged. T1/2 of unchanged dihydralazine averages 4 hours. Total clearance averages 1450 ml/min. After oral administration, about 46% of the dose taken is excreted within 24 hours, mainly in the form of metabolites, mainly through the intestines. About 0.5% of the dose taken is found in the urine as unchanged substance. The elimination of hydrochlorothiazide from plasma is two-phase: T1/2 of the initial phase is 2 hours, the final phase (10-12 hours after administration) is about 10 hours. In patients with normal renal function, excretion is carried out almost exclusively by the kidneys. In general, 50–75% of an oral dose is excreted unchanged in the urine. Pharmacokinetics in certain groups of patients (elderly age, renal failure, liver dysfunction) In elderly patients and patients with impaired renal function, the clearance of hydrochlorothiazide is significantly reduced, which leads to a significant increase in its concentration in the blood plasma. The decrease in clearance observed in elderly patients appears to be associated with decreased renal function. In patients with liver cirrhosis, no changes in the pharmacokinetics of hydrochlorothiazide are observed. In elderly patients and patients with impaired renal function, the average therapeutic dose of Adelfan-Ezidrex may be lower than in younger patients with normal renal function. In patients with impaired renal and/or liver function, accumulation of dihydralazine may occur. In patients with renal failure, there is a slowdown in the excretion of reserpine, which, however, is compensated by an increase in its excretion through the intestines. In these cases, in order to avoid the accumulation of reserpine in the body, it is necessary to adjust the single dose of Adelfan-Ezidrex or increase the intervals between doses, taking into account the dynamics of blood pressure and tolerability.

Use during pregnancy

The drug is contraindicated during pregnancy for the following reasons. Reserpine, if prescribed before childbirth, can cause severe drowsiness, swelling of the nasal mucosa and anorexia in the newborn. The effects of thiazide diuretics, incl. hydrochlorothiazide, led to thrombocytopenia in the fetus and newborn. Since thiazide diuretics do not prevent the occurrence or in any way affect the severity of toxicosis in pregnancy (edema, proteinuria, hypertension), they should not be prescribed for this indication. Reserpine, dihydralazine and hydrochlorothiazide pass into breast milk. In a newborn baby, reserpine can cause the reactions described above. Hydrochlorothiazide may suppress lactation. It is not recommended to use the drug Adelfan-Ezidrex during lactation.

Contraindications for use

Hypersensitivity to reserpine and related substances, dihydralazine or other hydrazinophthalazines, hydrochlorothiazide or other sulfonamide derivatives, as well as to excipients; depression (current or history); Parkinson's disease; epilepsy; electroconvulsive therapy; peptic ulcer of the stomach and duodenum in the acute phase, ulcerative colitis; pheochromocytoma; concomitant or recent treatment with MAO inhibitors; systemic lupus erythematosus (idiopathic); severe tachycardia and heart failure against the background of high cardiac output (including with thyrotoxicosis); heart failure due to mechanical obstruction (including the presence of aortic or mitral stenosis or constrictive pericarditis); isolated right ventricular failure due to pulmonary hypertension (“pulmonary” heart); anuria, severe renal failure (creatinine Cl less than 30 ml/min); liver failure; refractory hypokalemia, hyponatremia, hypercalcemia, as well as hyperuricemia with clinical manifestations; pregnancy; age under 18 years (efficacy and safety have not been established). With caution - in cases where a sharp decrease in blood pressure should be avoided, because this can lead to a decrease in blood flow: patients who have had a myocardial infarction (should not be prescribed until the end of the stabilization period after a myocardial infarction); coronary and cerebral atherosclerosis (as in the case of prescribing any antihypertensive drugs with a pronounced hypotensive effect). The precautions outlined below apply not only to each component individually, but also to the drug Adelfan-Ezidrex as a whole. Reserpine - since reserpine increases motility and secretion in the gastrointestinal tract: a history of gastric and duodenal ulcers; erosive gastritis and cholelithiasis; heart failure, sinus bradycardia, conduction disorders; patients who have recently suffered a myocardial infarction. Dihydralazine sulfate - patients with suspected ischemic heart disease (tachycardia caused by dihydralazine can lead to an attack of angina pectoris and ECG changes indicating myocardial ischemia; in some cases, a connection between myocardial infarction and the use of dihydralazine could not be excluded). Hydrochlorothiazide patients taking ACEI (especially when taken together with potassium supplements or potassium-sparing diuretics); diabetes mellitus and gout (as with other thiazide diuretics).

Side effects

The components of the drug Adelfan-Ezidrex are present in it in lower doses, compared to doses of the same drugs prescribed for the treatment of arterial hypertension separately. However, the following undesirable effects may occur, which are characteristic of individual components of the drug. The following criteria were used to assess the frequency of adverse events: often (more than 10% of patients); sometimes (1–10%), rarely (0.001–1%); in some cases (less than 0.001% of patients). Reserpine From the gastrointestinal tract: sometimes - diarrhea, dry mouth, increased secretion of gastric juice, increased salivation; rarely - nausea, vomiting, increased appetite, ulceration; in some cases - gastrointestinal bleeding. From the cardiovascular system: sometimes - sinus bradycardia, edema; rarely - arrhythmia, chest pain, suggesting angina pectoris; orthostatic hypotension, flushing; in some cases - fainting, heart failure, cerebrovascular accident. From the respiratory system: sometimes - swelling of the nasal mucosa, shortness of breath; in some cases - nosebleeds. From the side of the central nervous system: sometimes - dizziness, depression, irritability, nightmares, increased fatigue; rarely - extrapyramidal disorders (including parkinsonism), headache, anxiety, impaired concentration, stupor, disorientation; in some cases - cerebral edema. From the genitourinary system: rarely - impaired potency and ejaculation; in some cases - dysuria, glomerulonephritis. From the endocrine system and metabolism: sometimes - weight gain; rarely - increased secretion of prolactin, galactorrhea, gynecomastia; in some cases - swelling of the mammary glands. From the senses: sometimes - blurred vision, conjunctival hyperemia, lacrimation; in some cases - hearing impairment. Other: rarely - eczema, itching, decreased libido; in some cases - purpura, anemia, thrombocytopenia. Dihydralazine sulfate From the cardiovascular system: often - tachycardia, palpitations; sometimes - flushing of the face, marked decrease in blood pressure, angina pectoris; rarely - edema, heart failure. From the gastrointestinal tract: sometimes - dyspeptic symptoms, nausea, vomiting, diarrhea. From the liver: rarely - jaundice, impaired liver function, hepatitis. From the central and peripheral nervous system: often - headache; sometimes - dizziness; rarely - agitation, anorexia, irritability, restlessness, anxiety, peripheral neuritis, paresthesia (these side effects are eliminated when pyridoxine is prescribed); in some cases - depressed mood. From the hematopoietic system: rarely - anemia, leukopenia, thrombocytopenia. Allergic and immunopathological reactions: rarely - lupus-like syndrome. Other: sometimes - arthralgia; rarely - weight loss, fever, weakness, skin rash, itching. Hydrochlorothiazide From the side of water-electrolyte balance and metabolism: often - mainly when using high doses, hypokalemia, increased levels of lipids in the blood; sometimes - hyponatremia, hypomagnesemia, hyperuricemia; rarely - hypercalcemia, hyperglycemia, glucosuria, increased metabolic disorders in diabetes mellitus; in some cases - hypochloremic alkalosis. Dermatological reactions: sometimes - urticaria, skin rash; rarely - photosensitivity; in some cases - necrotizing vasculitis, toxic epidermal necrolysis, skin manifestations of lupus-like syndrome, exacerbation of skin manifestations of lupus erythematosus. From the gastrointestinal tract, liver and pancreas: sometimes - loss of appetite, nausea, vomiting; rarely - discomfort, constipation, diarrhea, intrahepatic cholestasis, jaundice; in some cases - pancreatitis. From the cardiovascular system: sometimes - orthostatic hypotension (which can be aggravated by the simultaneous consumption of alcohol and the simultaneous use of anesthetics and sedatives); rarely - arrhythmia. From the central nervous system and sensory organs: rarely - headache, dizziness, sleep disturbances, depression, paresthesia; visual impairment (especially in the first weeks of treatment). From the hematopoietic system: rarely - thrombocytopenia, sometimes with purpura; in some cases - leukopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, hemolytic anemia. Other: sometimes - impotence; in some cases - hypersensitivity reactions, respiratory disorders, including pneumonitis and pulmonary edema.

Directions for use and doses

Inside, during meals and with water. The dose of the drug should be selected individually. Treatment begins with a minimum dose, which can be gradually (no more than every 2-3 weeks) increased, depending on the patient’s response to treatment. The daily dose is usually 1–3 tablets. The maximum daily dose is 3 tablets. The frequency of taking the drug is 2-3 times a day. If adequate blood pressure control cannot be achieved, treatment should be reconsidered and, possibly, switch to a drug from a different pharmacological group (beta-blocker, CCB, ACE inhibitor). Use in patients with impaired renal function, liver function, as well as elderly patients. The above doses are recommended for patients with normal renal function. In elderly patients, as well as patients with impaired liver function and/or mildly impaired renal function, the single dose of the drug or the interval between its prescriptions should be set with caution, taking into account the required clinical response to treatment and tolerability.

Overdose

Symptoms: possible headache, dizziness, drowsiness, confusion, coma, extrapyramidal disorders, convulsions, paresthesia, persistent miosis. Nausea, vomiting, and diarrhea may occur. The occurrence of tachycardia, a marked decrease in blood pressure, and collapse was also reported; sometimes - about myocardial ischemia with such manifestations as angina pectoris and arrhythmia. Respiratory depression, water and electrolyte imbalance, muscle weakness, muscle cramps (especially calf cramps), and oliguria may occur. Treatment: if the patient is conscious, induce vomiting or perform gastric lavage and prescribe activated charcoal. If there is a pronounced decrease in blood pressure, the patient must be placed with his legs elevated; the introduction of plasma substitutes and correction of electrolyte disturbances are indicated; if necessary, use vasoactive agents with caution. In case of diarrhea, an anticholinergic agent. In case of seizures, the use of anticonvulsants is indicated - slow intravenous administration of diazepam. In case of severe respiratory depression - mechanical ventilation. The duration of observation of the patient is at least 72 hours, since reserpine has a prolonged effect.

Interactions with other drugs

The hypotensive effect of Adelfan-Ezidrex is enhanced by simultaneous use of other antihypertensive drugs: guanethidine, alpha-methyldopa, beta-blockers, vasodilators, CCBs, ACE inhibitors. A number of interactions associated with individual components of the drug are also possible. Reserpine. It is necessary to discontinue MAO inhibitors at least 14 days before starting reserpine therapy. If it is necessary to prescribe MAO inhibitors to a patient receiving reserpine, MAO inhibitors should be prescribed no less than 14 days after discontinuation of reserpine. With the simultaneous use of reserpine and MAO inhibitors, hyperactivity and hypertensive crisis are possible. Reserpine enhances the depressant effect on the central nervous system of alcohol, general anesthesia, some antihistamines, barbiturates and tricyclic antidepressants. Reserpine weakens the effect of levodopa. The simultaneous use of reserpine and tricyclic antidepressants may weaken the hypotensive effect of reserpine. Reserpine should be discontinued several days before elective surgery to avoid an excessive decrease in blood pressure during general anesthesia. Prescribing reserpine in combination with antiarrhythmic drugs or digitalis drugs can lead to sinus bradycardia. Reserpine may enhance the effects of epinephrine (adrenaline) or other sympathomimetic substances (caution should be exercised when used simultaneously with antitussives containing them, nasal drops, eye drops). Dihydralazine sulfate. The simultaneous use of tricyclic antidepressants, antipsychotics, and ethanol-containing drugs may enhance the hypotensive effect of dihydralazine. Administration of dihydralazine shortly before or shortly after administration of diazoxide may cause a marked decrease in blood pressure. Hydrochlorothiazide. With the simultaneous use of hydrochlorothiazide and lithium preparations, an increase in the concentration of lithium in the blood is possible, therefore, in this case, systematic monitoring of the concentration of lithium in the blood is necessary. In cases where lithium preparations cause polyuria, hydrochlorothiazide may cause a paradoxical antidiuretic effect. Hydrochlorothiazide may enhance the effects of non-depolarizing muscle relaxants. The hypokalemic effect caused by diuretics may be enhanced by the simultaneous use of GCS, ACTH, amphotericin, carbenoxolone. Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) may contribute to the development of cardiac arrhythmias in patients receiving cardiac glycosides. When using hydrochlorothiazide in patients with diabetes mellitus, dose adjustment of insulin and oral hypoglycemic agents may be required. Co-administration of NSAIDs (including indomethacin) may weaken the diuretic, natriuretic and antihypertensive effects of hydrochlorothiazide. There are isolated reports of deterioration of renal function in predisposed patients. The absorption of hydrochlorothiazide is impaired in the presence of anion exchange resins. Absorption of hydrochlorothiazide from the gastrointestinal tract with simultaneous single use of cholestyramine and colestipol is reduced by 85 and 43%, respectively, due to binding to these compounds. Simultaneous use of thiazide diuretics, incl. hydrochlorothiazide, may increase the risk of hypersensitivity reactions to allopurinol, increase the risk of side effects of amantadine, enhance the hyperglycemic effect of diazoxide, reduce the renal excretion of cytotoxic drugs (including cyclophosphamide, methotrexate) and enhance their myelosuppressive effect. Anticholinergic drugs (including atropine, biperiden) can increase the bioavailability of hydrochlorothiazide, which is associated with a decrease in gastrointestinal motility and the rate of gastric emptying. Concomitant use of hydrochlorothiazide with vitamin D or calcium supplements may lead to increased calcium levels in the blood. With simultaneous use of hydrochlorothiazide and cyclosporine, the risk of developing hyperuricemia and gout increases. There are reports of the development of hemolytic anemia while taking hydrochlorothiazide and methyldopa drugs. Since hyponatremia may occur when hydrochlorothiazide is administered with carbamazepine, patients receiving Adelfan-Ezidrex with carbamazepine should be advised of the possible manifestations of hyponatremia and ensure appropriate monitoring.

Special instructions for use

If signs of depression appear, the drug should be discontinued immediately, as there is a risk of suicidal actions. Depression provoked by reserpine (especially in cases of high doses of Adelfan-Ezidrex) can be severe enough to provoke suicidal actions. It may persist for several months after discontinuation of the drug. The use of dihydralazine can lead to sodium and water retention in the body and, consequently, to the development of edema and decreased diuresis. It is required to systematically monitor the condition of patients with impaired liver function, taking into account the possibility of rare but serious side effects of dihydralazine from the liver. It should also be taken into account that even minor disturbances in water and electrolyte balance caused by a thiazide diuretic can provoke hepatic coma, especially in patients with liver cirrhosis. Currently, there are a small number of case reports of lupus-like syndrome associated with dihydralazine. Mild forms of this syndrome are manifested by arthralgia, sometimes accompanied by fever and skin rashes; when the drug is discontinued, these symptoms go away on their own. In more severe cases, the clinical picture is similar to that of systemic lupus erythematosus. Complete disappearance of symptoms can only be achieved with long-term treatment with GCS. The incidence of this syndrome is directly dependent on the dose and duration of treatment. In this regard, for long-term maintenance therapy it is recommended to use the minimum effective doses. During treatment with dihydralazine, it seems advisable to determine antinuclear factor in blood plasma every 6 months. If an antinuclear factor is detected, its titers should be systematically determined. If clinical manifestations of lupus-like syndrome develop, the drug should be discontinued immediately. Reserpine should be discontinued at least 7 days before electroconvulsive therapy. Discontinuation of reserpine before surgery does not guarantee that hemodynamic instability will not occur during surgery. It is important to warn the anesthesiologist that the patient is taking reserpine, so that he takes this into account when managing the patient (there are known cases of decreased blood pressure in patients receiving rauwolfia drugs). During surgery, patients receiving dihydralazine may experience a marked decrease in blood pressure. Hypokalemia develops with the use of hydrochlorothiazide. Hypokalemia may sensitize the myocardium or enhance the cardiac response to the toxic effects of digitalis drugs. The risk of hypokalemia is increased with liver cirrhosis, rapidly developing diuresis, insufficient intake of potassium from food, concomitant therapy with corticosteroids, beta-adrenergic stimulants or ACTH. In order to timely identify possible electrolyte imbalances, it is necessary to determine the content of electrolytes in plasma at the beginning of treatment and at certain intervals during treatment. Nonspecific manifestations of electrolyte imbalance observed in a number of cases were dry mouth, thirst, weakness, drowsiness, anxiety, muscle pain and cramps, muscle weakness, decreased blood pressure, oliguria, tachycardia, nausea. Thiazide diuretics cause a decrease in calcium excretion. In several patients who received thiazide diuretics for a long time, pathological changes in the parathyroid gland were detected, accompanied by hypercalcemia and hypophosphatemia. If hypercalcemia is detected, additional examinations are required to clarify the diagnosis. There were no complications that are usually associated with hyperparathyroidism, such as the formation of renal stones, bone resorption, or peptic ulcers. Thiazide diuretics cause increased urinary excretion of magnesium, which can lead to hypomagnesemia. When used in high doses, thiazide diuretics can cause a decrease in glucose tolerance and lead to increased plasma concentrations of cholesterol, triglycerides and uric acid. The use of reserpine affects the results of determination of 17-ketosteroids and 17-hydroxycorticosteroids in urine by the colorimetric method, leading to an underestimation of these results. Impact on the ability to drive vehicles and operate machinery. Adelfan-Ezidrex may impair the patient's ability to react quickly, especially at the beginning of treatment. As with the prescription of other antihypertensive drugs, patients driving vehicles and machinery should be warned about the possibility of a decrease in the speed of psychomotor reactions and the need to exercise caution.

Storage conditions

List B.: In a place protected from light and moisture, at a temperature not exceeding 30 °C.

Best before date

48 months

ATX classification:

C Cardiovascular system

C02 Antihypertensive drugs

C02L Antihypertensive drugs in combination with diuretics

C02LA Rauwolfia alkaloids in combination with diuretics

C02LA51 Reserpine and diuretics in combination with other drugs

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.