Adelphan-Ezidreks - instructions for use, doses, side effects, contraindications

Active substanceHydrochlorothiazide + Dihydralazine + ReserpineHydrochlorothiazide + Dihydralazine + Reserpine

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Dosage form: & nbsppills

Composition:1 tablet contains:
active ingredients - Reserpine 0.1025 mg, dihydralazine sulfate hydrated (on anhydrous basis 10 mg) 10.25 mg, hydrochlorothiazide 10.00 mg;
Excipients: mannitol 64.7525 mg, corn starch 46.981 mg, disodium edetate 0.70 mg, talc (magnesium hydroxysilicate) 5.834 mg, magnesium stearate (magnesium stearate) 1.38 mg.

Description:From white to almost white, round, flat tablets with beveled edges, without a casing, on one side marking CIBA, on the other side - the letters AhFc between them.

Pharmacotherapeutic group:Hypotensive combined agent (sympatholytic + arteriodilator + diuretic).

ATX: & nbsp

C.02.L.A.51 Reserpine and diuretics in combination with other drugs

Pharmacodynamics:Adelfan-Ezidreks is a combination of three antihypertensive components that have different points of application and mutually complementary antihypertensive effects of each other.
Reserpine - sympatholytic, causes depletion of the catecholamine depot in the endings of postganglionic sympathetic fibers and in the central nervous system (CNS). As a result, the ability to deposit catecholamines is disrupted for a fairly long period of time. Depletion of catecholamine stocks leads to impairment of impulse transmission in the endings of sympathetic nerves, which in turn leads to a decrease in the tone of the sympathetic nervous system (the activity of the parasympathetic nervous system does not change). In this way, reserpine reduces high blood pressure (BP) and heart rate (heart rate). Besides, reserpine causes sedation. Reserpine depletes the reserves of other neurotransmitters, incl. serotonin, dopamine, neuropeptides and adrenaline, in central and peripheral neurons. These effects of reserpine may play a role in the realization of its pharmacological effects and antihypertensive effects.
After taking reserpine, the antihypertensive effect develops slowly; The maximum effect is achieved only after 2-3 weeks and is maintained for a long time.
Dihydralazine - an arterial vasodilator, reduces the tone of the smooth muscles of arterial vessels (mostly arterioles) and reduces the overall peripheral vascular resistance. The mechanism of this action at the cellular level remains unclear. In a greater degree, the 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 of a pronounced nature, the blood flow in the enlarged bloodstream generally increases. The predominant expansion of arterioles, rather than venules, reduces the severity of orthostatic hypotension and contributes to an increase in cardiac output.
Vascular expansion, leading to a reduction in blood pressure (mostly diastolic than systolic), is accompanied by a reflex increase in heart rate, stroke volume and cardiac output. Reflex increase in heart rate and cardiac output can be leveled by combining dihydralazine with reserpine, which suppresses the sympathetic nervous system.
Hydrochlorothiazide is a thiazide diuretic, acting in the cortical segment of the Henle loop and the distal sections of the renal tubules.It inhibits the reabsorption of chloride and sodium ions (due to the antagonistic interaction with the transport enzyme Na⁺C^- ) and enhances the reabsorption of calcium ions (the mechanism is unknown). An increase in the amount and / or rate of intake of sodium and water ions into the cortical segment of the collecting tubes 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 intake of hydrochlorothiazide at a dose of 12.5 mg. The increase in urinary excretion of sodium and chlorine ions and a slightly less pronounced increase in excretion of potassium ions depend on the dose of hydrochlorothiazide. After taking hydrochlorothiazide, diuretic and natriuretic effects are inwardly developed through

1-2 hours, reach a maximum after 4-6 hours and persist for 10-12 hours. Diuresis caused by thiazides, first leads to a decrease in the volume of circulating plasma, cardiac output and systemic blood pressure. It is possible to activate the renin-angiotensin-aldosterone system. With prolonged use of hydrochlorothiazide, the maintenance of an antihypertensive effect is provided, probably, by decreasing the total peripheral vascular resistance.Cardiac output returns to baseline values, a small decrease in plasma volume and an increase in plasma renin activity persist.

Pharmacokinetics:Absorption and plasma concentrations
Reserpine is rapidly absorbed after ingestion. Systemic bioavailability is 50%.
Dihydralazine is rapidly absorbed after oral administration. In the blood plasma, dihydralazine is mainly in the form of unchanged dihydralazine and hydrazone substances formed as a result of the metabolism of the basic substance. Approximately 10% of dihydralazine is in the blood plasma in the form of hydralazine.
Hydrochlorothiazide after intake is absorbed by 60-80%. The time to reach the maximum concentration in the blood plasma is 1.5-3 hours. Changes in absorption due to food intake are not clinically important. In the range of therapeutic doses, the systemic bioavailability of hydrochlorothiazide is approximately proportional to the dose value. With regular administration of dihydralazine, its pharmacokinetics do not change.
Distribution
The relative volume of reserpine distribution averages 9.1 l / kg (fluctuations from 6.4 to 11.8 l / kg).The connection with plasma proteins is more than 96% (albumins and lipoproteins).
Hydrochlorothiazide accumulates in the erythrocytes. In the phase of elimination, its concentration in erythrocytes is 3-9 times higher than in the blood plasma. Connection with blood plasma proteins - 40-70%. The volume of distribution in the final phase of excretion is 3-6 l / kg (equivalent to 210-420 liters with a body weight of 70 kg).
Metabolism
Reserpine is metabolized in the intestine and liver. The main metabolites are methyl reserpate and trimethoxybenzoic acid.
Dihydralazine is metabolized to a large extent by oxidation (with the formation of hydrazones) and acetylation.
Hydrochlorothiazide is metabolized to a very small extent. Its only metabolite found in trace amounts is 2-amino-4-chloro-M-benzenedisulfonamide.
Excretion
Derivation of reserpine and its metabolites from plasma takes place in two phases: the half-life (TS) phase of phase I is 4.5 hours; Phase II is 271 hours. The average TS of unchanged substance is 33 hours. The total clearance of reserpine is on the average 245 ml / min. During the first 96 hours after ingestion, 8% of the dose is excreted by the kidneys, mainly in the form of metabolites, and 62% through the intestine, mostly unchanged.
TS of unchanged dihydralazine averages 4 hours. The total clearance is an average of 1450 ml / min. After oral administration, about 46% of the dose is taken within 24 hours, mainly in the form of metabolites, mainly through the intestine. About 0.5% of the dose is detected in the urine as an unchanged substance.
The removal of hydrochlorothiazide from plasma is biphasic: TS 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 almost exclusively performed by the kidneys. In general, 50-75% of the dose taken internally is excreted in the urine unchanged.
Pharmacokinetics in certain groups of patients (elderly age, renal failure, impaired liver function)
In elderly patients and patients with impaired renal function, clearance of hydrochlorothiazide significantly decreases, which leads to a significant increase in its concentration in blood plasma. The decrease in clearance, noted in elderly patients, is apparently associated with a decrease in kidney function. In patients with cirrhosis of the liver, there is no change in the pharmacokinetics of hydrochlorothiazide. In elderly patients and patients with impaired renal function, the average therapeutic doses of Adelfan-Ezidrex may be lower,than in younger patients with normal renal function.
In patients with impaired renal and / or liver function, cumulation of dihydralazine can be observed. In patients with renal insufficiency, there is a slowdown in the removal of reserpine, which, however, is compensated by an increase in its excretion through the intestine. In these cases, in order to avoid the cumulation of reserpine in the body, correction of a single dose of Adelphan-Ezidrex or an increase in the intervals between doses, taking into account the dynamics of blood pressure and tolerance, is required.

Indications:Arterial hypertension.

Contraindications:- Hypersensitivity to reserpine and indole derivatives, dihydralazine and derivative of hydrazinophthalazine, hydrochlorothiazide and sulfonamide derivative, as well as to auxiliary substances;
- Depression (currently or in anamnesis);
- Parkinson's disease;
- Epilepsy;
- Electroconvulsive therapy;
- Stomach ulcer and duodenal ulcer in the phase of exacerbation, ulcerative colitis;
- Pheochromocytoma;
- Concomitant use of MAO inhibitors (including 14 days before taking the drug);
- Systemic lupus erythematosus;
- Expressed tachycardia and heart failure on the background of high cardiac output (including with thyrotoxicosis);
- Heart failure due to obstruction of the outflow tract of the left ventricle (including the presence
aortic or mitral stenosis or constrictive pericarditis);
- Isolated right ventricular failure due to pulmonary hypertension ("pulmonary" heart);
- Dissecting aortic aneurysm;
- Anuria, marked renal failure (creatinine clearance less than 30 ml / min);
- Pregnancy.
Do not use the drug in persons under 18 years of age (efficacy and safety not established).

Carefully:Patients who underwent myocardial infarction should not be prescribed Adelfan-Ezidrex® until the hemodynamic parameters are stabilized after myocardial infarction.
Adelfan-Ezidrex® should also be used with caution in patients with ischemic heart disease (CHD), including. with suspicion on it, heart failure, sinus bradycardia, conduction disorders. Care should be taken when prescribing Adelfan-Ezidrex® to patients with coronary and cerebral atherosclerosis, with peptic ulcer of the stomach and duodenum in history, with erosive gastritis and cholelithiasis,
electrolyte disorders, with porphyria, hepatic insufficiency, diabetes mellitus, hyperuricemia with clinical manifestations, gout, bronchial asthma, as well as elderly patients and taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, renin inhibitors; at carrying out of surgical interventions.

Pregnancy and lactation:Special studies to study the effect of Adelphan-Ezidrex® on reproductive performance have not been conducted. Determined that reserpine, dihydralazine and hydrochlorothiazide penetrate through the placental barrier. Hydrochlorothiazide accumulates in the amniotic fluid, reaching a maximum concentration in it, up to 19 times greater than in the plasma of the umbilical vein. The drug is contraindicated in pregnancy for the following reasons. Reserpine, in the case of his appointment before childbirth, can cause a newborn
pronounced drowsiness, swelling of the nasal mucosa and anorexia. The effect of thiazide diuretics, incl. hydrochlorothiazide, may cause fetal and newborn thrombocytopenia.Because thiazide diuretics do not prevent the onset of gestosis and do not affect
the severity of its manifestations (edema, proteinuria, arterial hypertension, preeclampsia, etc.), they should not be prescribed during pregnancy. Reserpine, dihydralazine and hydrochlorothiazide penetrate into breast milk. In a newborn reserpine can cause the reactions described above. Hydrochlorothiazide can suppress lactation. Apply Adelfan-Ezidrex® during breast-feeding is not recommended.

Dosing and Administration:The preparation Adelphan-Ezidrex® should be taken orally every day at the same time, with water. The dose of the drug should be selected individually. Treatment begins with the appointment of a minimal dose, which can be gradually (not more often than every 2-3 weeks) to increase, depending on the patient's response to treatment.
The daily dose, which is usually 1-2 tablets, should not be exceeded. The maximum daily dose of the drug should be divided into 2 divided doses. If adequate blood pressure control
the therapy can not be achieved, the treatment should be reviewed and, possibly, the drug of another pharmacotherapeutic group (beta-blocker, slow calcium channel blocker, ACE inhibitor) should be taken.
Use in patients with impaired renal function
In patients with impaired renal function, the frequency of drug intake or the interval between doses of the drug should be adjusted with caution, taking into account the dynamics of blood pressure and tolerability, in order to avoid excessive cumulation of the drug in the body. In patients with severe renal impairment (creatinine clearance <30 mL / min) who require diuretic therapy, it is preferable to use "loop" diuretics.
Use in patients with impaired liver function
In patients with a dysfunction of the liver, the dose of the drug or the interval between doses of the drug should be adjusted with caution, taking into account the dynamics of blood pressure and tolerance, in order to avoid excessive cumulation of the drug in the body.
Application in elderly patients
In elderly patients, the dose of the drug or the interval between doses of the drug should be adjusted with caution, taking into account the dynamics of blood pressure and tolerability.

Side effects:In the preparation of Adelfan-Ezidrex®, active substances are present in lower doses as compared to the monopreparations they comprise.In spite of this, when taking Adelfan-Ezidrex®, undesirable phenomena that are characteristic of individual components of the drug can be observed.
The following criteria were used to estimate the frequency: very often (>1/10); often (>1/100, <1/10); infrequently (>1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); including individual messages.
Reserpine
Disorders from the digestive system: often - Diarrhea, dry mouth, increased secretion of gastric juice; increased salivation; rarely - the formation of ulcers; rarely gastrointestinal bleeding.
Heart Disease: Frequent - Sinus bradycardia.
Disturbances from the respiratory system, chest, mediastinum: often - edema of the mucosa
Nasal membranes; dyspnea; rarely - nose bleed.
Mental disorders: often - Depression, nightmarish dreams; rarely - anxiety, decreased libido.
Disturbances from the nervous system: infrequently - dizziness, nervousness, rarely - Extrapyramidal disorders (including parkinsonism), violation of concentration of attention, stupor, confusion, postural disorders; rarely - cerebral edema, cerebrovascular disorders,
loss of consciousness.
Disturbances from the skin and subcutaneous tissues: rarely - eczema, itching; rarely - purple.
Disorders from the kidneys and urinary tract: very rare -disuria, glomerulonephritis.
Disorders from the metabolism and nutrition: often - increase in body weight; rarely - increased appetite.
Disorders from the side of the organ of vision: often - blurred vision, conjunctival hyperemia, lacrimation.
Hearing disorders and labyrinthine disturbances: very rare - hearing loss.
Violations of the genitals and breast cancer: rarely - violation of potency and ejaculation, galactorrhea, gynecomastia; rarely swelling of mammary glands.
Common violations: often - increased fatigue, peripheral edema.
Laboratory and instrumental data: rarely hyperprolactinemia.
Dihydralazine sulfate
Disturbances from the blood and lymphatic system: rarely anemia, leukopenia.
Disorders from the metabolism and nutrition: rarely - weight loss, anorexia.
Disorders of the psyche: rarely - agitation, a state of anxiety or anxiety, rarely - Depressed mood.
Disorders from the nervous system: very often - headache, rarely - peripheral neuritis; paresthesia (these side effects are eliminated with pyridoxine administration).
Heart Disease: Very Frequent - tachycardia, palpitation; often - pain behind the sternum; rarely - heart failure.
Vascular disorders: often -Three of blood to the skin of the face; marked decrease in blood pressure.
Disorders from the digestive system: often - Dyspeptic phenomena.
Disorders from the liver and bile ducts: rarely - jaundice, hepatitis.
Disturbances from musculoskeletal and connective tissue: often - arthralgia, rarely - lupus-like syndrome.
Common disorders: rarely fever, weakness.
Laboratory and instrumental data: rarely - increased activity of "liver" transaminases.
Hydrochlorothiazide
Disturbances from the blood and lymphatic system: rarely - thrombocytopenia, sometimes with purpura; rarely - agranulocytosis, oppression of bone marrow hematopoiesis, hemolytic anemia.
Immune system disorders: very rare hypersensitivity reactions.
Disorders from substance exchange and nutrition: very often - (mainly with the use of high doses) hypokalemia, increased concentration of lipids in the blood; often Hyponatremia, hypomagnesemia, hyperuricemia, decreased appetite; rarely - hypercalcemia, hyperglycemia, glucosuria, increased metabolic disorders in diabetes mellitus; very rarely - hypochloraemic alkalosis.
Disturbances from the nervous system: rarely - sleep disorders.
Disorders from the side of the organ of vision: rarely - visual impairment (especially in the first weeks of treatment).
Disorders from the heart: rarely - arrhythmia.
Vascular disorders: often - Orthostatic hypotension (which can be aggravated with simultaneous use of alcohol, anesthetics, sedatives).
Disturbances from the respiratory system, chest, mediastinum: very rarely - respiratory distress syndrome, pneumonitis, pulmonary edema.
Disorders from the digestive system: often - mild nausea and vomiting; rarely - discomfort in the abdomen, constipation, diarrhea; rarely - pancreatitis.
Disorders from the liver and bile ducts: rarely - cholestasis, jaundice.
Disturbances from the skin and subcutaneous tissues: often - urticaria, skin rash; rarely - Photosensitivity; rarely - necrotic vasculitis, toxic epidermal necrolysis, cutaneous manifestations of lupus-like syndrome, exacerbation of skin manifestations of systemic lupus erythematosus.
Violations of the genitals and breast: often - impotence.
On the background of therapy with hydrochlorothiazide, the following undesirable phenomena (frequency not established) were noted in clinical practice: pathology of kidney function (including acute renal failure); aplastic anemia, multi-form exudative erythema, muscle spasms, increased body temperature; asthenia, acute closed angle glaucoma.
If any of these side effects are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:Symptoms. Possible headache, dizziness, drowsiness, confusion, coma, extrapyramidal disorders, convulsions, paresthesia; resistant miosis.There may be nausea, vomiting, diarrhea. There was also reported the occurrence of tachycardia, a pronounced decrease in blood pressure (which may result in the development of collapse); sometimes about myocardial ischemia with such manifestations as angina and arrhythmias. There may be respiratory depression, violations of water-electrolyte balance, muscle weakness, muscle cramps (especially gastrocnemius), hypothermia; oliguria.
Treatment. If the patient is conscious, vomiting or rinsing of the stomach should be given, Activated carbon. With a marked decrease in blood pressure, the patient must be laid with raised legs; the introduction of plasma substitutes and correction of electrolyte disturbances; If necessary, with caution, you can introduce vasoactive drugs. In the case of diarrhea, an anticholinergic agent is administered. In the case of epilepsy or seizures, IV injection of anticonvulsants (eg, diazepam) is indicated. In the case of severe respiratory depression, artificial ventilation (IVL) is indicated. Observation of the patient after prima remedy should be at least 72 hours, incl. because of the long-acting reserpine.

Interaction:The antihypertensive effect of the drug Adelphan-Ezidrex is enhanced with the simultaneous administration of other antihypertensive drugs: guanethidine, alpha-methyldopa, beta-adrenoblockers, vasodilating agents, blockers of "slow" calcium channels; ACE inhibitors.
A number of interactions associated with individual components of the drug are also possible.
Reserpine

MAO inhibitors.
It is necessary to abolish MAO inhibitors at least 14 days before starting reserpine therapy. If it is necessary to administer MAO inhibitors to the patient who received reserpine, MAO inhibitors should be prescribed no less than 14 days after its cancellation. With simultaneous application of reserpine and MAO inhibitors, hyperactivity, hypertensive crisis are possible.
Drugs that depress the central nervous system.
Reserpine contributes to an increase in the inhibitory effect on the CNS of ethanol, funds for general anesthesia, some blockers of H1-histamine receptors, barbiturates and tricyclic antidepressants. It is necessary to carefully select a clinically effective dose of drugs that depress the central nervous system when they are administered together with reserpine. Reserpine weakens the action of levodopa.The simultaneous use of reserpine and tricyclic antidepressants can weaken the antihypertensive effect of reserpine.
Means for anesthesia and antiarrhythmic drugs.
Reserpine should be discontinued several days before the planned surgical intervention to avoid excessive BP reduction during general anesthesia. The appointment of reserpine in combination with antiarrhythmic drugs or cardiac glycosides can lead to sinus bradycardia.
Alpha- and beta-adrenomimetics.
Reserpine can enhance the effects of epinephrine (adrenaline). Care should be taken when using concomitantly with antitussives, drops in the nose, eye drops.

Substrates of P-glycoprotein (P-GS).
Reserpine may affect the concentration of drugs that are substrates of P-GP (colchicine, dabigatran etexilate, rivaroxaban, silodosin, topotecan).
Joint use of Adelphan-Ezidrex® and substrate preparations of P-GP should be avoided.
Injections of yobenguana (I¹³¹). The combined use of Adelphan®-Ezidrex® andI¹³¹ can lead to false-negative results of diagnostic studies.
Dihydralazine sulfate
The simultaneous use of tricyclic antidepressants, antipsychotics, as well as ethanol-containing drugs can enhance the hypotensive effect of dihydralazine. The administration of dihydralazine shortly before or shortly after administration of diazoxide may cause a marked decrease in blood pressure.
Hydrochlorothiazide
Lithium preparations. With the simultaneous use of hydrochlorothiazide and lithium preparations, an increase in the lithium content in the blood is possible, so in this case a systematic control of the concentration of lithium in the blood is necessary. In cases where lithium preparations cause polyuria, hydrochlorothiazide can cause a paradoxical antidiuretic effect.
Other antihypertensive drugs.
Thiazide diuretics increase the antihypertensive effect of other antihypertensive drugs (eg, muscle relaxant, piperidine, guanethidine, methyldopa, beta-blockers, "slow" calcium channel blockers, ACE inhibitors, angiotensin-II receptor blockers, renin inhibitors).
Muscle relaxants.
Hydrochlorothiazide can enhance the effects of muscle relaxants, for example, nondepolarizing muscle relaxants of peripheral action.
Drugs affecting the potassium content in the blood.
Hypokalemia caused by taking thiazide diuretics can be exacerbated by the simultaneous use of glucocorticoids (GK), adrenocorticotropic hormone (ATP), amphotericin, carbenoxolone, penicillin, acetylsalicylic acid or its derivatives and antiarrhythmic drugs.
Drugs affecting the sodium content in the blood.
Hyponatremia caused by the use of thiazide diuretics can be intensified with simultaneous use with antidepressants, antipsychotic, anticonvulsant drugs, carbamazepine, etc. Patients receiving Adelfan-Ezidrex® together with the above drugs should be informed of possible manifestations of hyponatremia and ensure regular monitoring of sodium ions.
Hypoglycemic agents.
When using hydrochlorothiazide in patients with diabetes mellitus, it may be necessary to correct insulin doses and hypoglycemic agents for oral administration.
Cardiac glycosides.
Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) can contribute to the development of disordersheart rhythm in patients receiving cardiac glycosides.
Non-steroidal anti-inflammatory drugs (NSAIDs).
Simultaneous administration of NSAIDs (acetylsalicylic acid derivatives, indomethacin) can weaken the diuretic and antihypertensive effects of hydrochlorothiazide.
Concomitant hypovolemia can provoke the development of acute renal failure.
H and M cholinoblockers.
H and M-holinoblokatory (incl. atropine, biperidene) can increase the bioavailability of hydrochlorothiazide, which is associated with a decrease in gastrointestinal peristalsis and gastric emptying rate. Accordingly, stimulators of motility of the gastrointestinal tract (cisapride) can reduce the bioavailability of hydrochlorothiazide.
Anion exchange resins.
The absorption of hydrochlorothiazide is disturbed in the presence of colestyramine and colestipol. Hydrochlorothiazide should be taken either 4 hours or 4-6 hours after taking these compounds.
Pressor amines.
Hydrochlorothiazide can reduce the effect of pressor amines (norepinephrine).
The simultaneous use of thiazide diuretics, including hydrochlorothiazide, may increase the risk of hypersensitivity reactions to allopurinol, increase the risk of side effects of amantadine, increase the hyperglycemic effect of diazoxide, reduce renal excretion of cytotoxic agents (including cyclophosphamide, methotrexate) and enhance their myelosuppressive effect.
Simultaneous intake of hydrochlorothiazide with vitamin D or calcium preparations can lead to an increase in the calcium content in the blood. With the simultaneous use of hydrochlorothiazide and cyclosporine, the risk of developing hyperuricemia and gout increases.
There are reports of the development of hemolytic anemia with simultaneous administration of hydrochlorothiazide and methyldopa preparations.
Joint use of thiazide diuretics with alcohol, barbiturates or narcotic analgesics may lead to the development of orthostatic hypotension.

Special instructions:Reserpine
When signs of depression appear, the drug should be immediately discontinued, since there is a risk of suicidal actions. Depression induced by reserpine (especially in cases of high doses of Adelphan-Ezidrex®) can be quite severe, up to suicidal attempts.It can persist for several months after drug withdrawal.
Reserpine should be discontinued at least 7 days before electroconvulsive therapy.
The cancellation of reserpine before surgery is not a guarantee that the operation does not reduce blood pressure, so it is necessary to alert the surgeon / anesthesiologist that the patient is taking reserpine. There have been cases of lowering blood pressure in patients who received rauvolfia preparations. The use of reserpine affects the results of the determination in urine of 17-ketosteroids and 17-hydroxycorticosteroids by a colorimetric method, leading to an underestimation of these results.
Dihydralazine
Caution should be exercised in patients with suspected ischemic heart disease (CHD). Caused by dihydralazine
tachycardia can lead to an attack of angina and changes in the electrocardiogram (ECG), indicative of myocardial ischemia. In some cases, the connection of myocardial infarction with the intake of dihydralazine was not excluded.
During the surgical intervention, patients who received dihydralazine may experience a marked decrease in blood pressure.
The use of dihydralazine can lead to a delay in sodium and water in the body and, consequently, the development of edema and a decrease in diuresis.
It is required to systematically monitor the condition of patients with impaired liver function, given the possibility of rare, but serious side effects. At present, there are few reports of cases of lupus-like syndrome associated with the intake of dihydralazine. The mild forms of this syndrome are manifested by arthralgia, sometimes accompanied by fever and skin rashes; with the withdrawal of the drug, these symptoms pass by themselves. In more severe cases, the clinical picture is similar to that of systemic lupus erythematosus; complete disappearance of symptoms can be achieved only with long-term treatment with glucocorticoids. The frequency of this syndrome is directly related to the dose and duration of treatment. In this regard, for the implementation of long-term maintenance therapy, it is recommended to use the minimum effective dose.
During treatment with dihydralazine, it seems advisable to determine the antinuclear factor in blood plasmaevery 6 months. If an antinuclear factor is detected, its titres should be systematically determined. If clinical manifestations of lupus-like syndrome develop, the drug should be immediately withdrawn.
Hydrochlorothiazide
Therapy with thiazide diuretics can lead to the development of hypokalemia or aggravate existing hypokalemia. Thiazide diuretics should be taken with caution in the presence of hypokalemia, in the elderly, in patients with ascites (due to cirrhosis of the liver). Prior to the initiation of hydrochlorothiazide therapy, correction of existing water electrolyte disturbances is recommended. With the purpose of timely detection of possible violations of water-electrolyte balance during therapy, it is necessary to regularly determine the content of electrolytes in plasma (especially potassium).
The level of excretion of potassium by the kidneys with the admission of thiazide diuretics is dose-dependent. The control of the potassium content in the blood should be carried out before the drug is prescribed, the first months of therapy every 3-4 weeks, then every 4-6 months in the absence of hypokalemia-provoking factors (vomiting, diarrhea, renal dysfunction).
Joint ingestion of potassium and thiazide diuretics is possible in patients receiving cardiac glycosides in patients with ischemic heart disease (if they do not receive ACE inhibitors), in patients receiving high doses of beta-adrenomimetics and in patients with a serum potassium concentration of less than 3 mmol / l. The administration of the drug should be avoided, especially in combination with potassium preparations or with potassium-sparing diuretics, patients taking ACE inhibitors, angiotensin II receptor blockers, direct renin inhibitors, unless the expected benefit exceeds the estimated risk.
In the event that hypokalemia that occurs when taking hydrochlorothiazide is accompanied by muscle weakness, paresthesia, changes in ECG, therapy with thiazide diuretics should be discarded.
Therapy with thiazide diuretics can lead to the development of hyponatremia or aggravate the existing hyponatraemia.
Some cases of development of neurologic symptoms in patients with hyponatremia (nausea, asthenia, disorientation, apathy) were noted.
Thiazide diuretics cause a decrease in calcium excretion.With long-term therapy with thiazide diuretics, parathyroid gland dysfunction may occur, accompanied by hypercalcemia and hypophosphatemia.
In the case of hypercalcemia, additional tests are needed to clarify the diagnosis. Thiazide diuretics cause an increase in urinary excretion of magnesium, which can lead to hypomagnesemia. When used in high doses hydrochlorothiazide can cause a decrease in glucose tolerance and lead to an increase in plasma concentrations of cholesterol, triglycerides and uric acid.
When applied to ascites, which has developed against cirrhosis of the liver, thiazide diuretics (like other diuretics) can provoke the development of hepatic encephalopathy and hepatorenal syndrome.
There is evidence that against the background of taking hydrochlorothiazide and sulfonamide, idiosyncrasy may develop, manifested by acute transient myopia and acute closed-angle glaucoma. This pathology manifests itself in a few hours or weeks after the start of the drug, the symptoms include: decreased visual acuity, pain in the eye. In the absence of adequate treatment, acute closed-angle glaucoma can lead to loss of vision.It is necessary to quickly abolish Adelfan-Ezidreks. If intraocular pressure remains elevated, surgical intervention may be required.
Presumptive factors for the development of acute angle-closure glaucoma is the presence in the history of allergy to sulfonamides or penicillins.

Effect on the ability to drive transp. cf. and fur:The drug Adelphan-Ezidrex can disrupt the patient's ability to respond quickly, especially at the beginning of treatment. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Pills.

Packaging:10 tablets per blister PVC / Al.
For 1, 2, 3, 5 or 25 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:At a temperature of no higher than 30 ° C. Protect from light and moisture.
Keep out of the reach of children.
List B.

Shelf life:4 years.
The drug should not be used after the expiration date marked with <EXP> on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014280 / 01

Date of registration:01.12.2009/18.11.2013

Expiration Date:Unlimited

Date of cancellation:2016-07-29

The owner of the registration certificate:Sandoz Private LimitedSandoz Private Limited India

Manufacturer: & nbsp

SANDOZ PRIVATE, Limited India

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp04.02.2017

Illustrated instructions

Instructions

Adelphan Ezidreks® (Adelphane-Esidrex®)