Instructions for use Dinorik-Darnitsa film-coated tablets No. 10
Composition
active ingredients: 1 tablet contains atenolol 100 mg, chlorthalidone 25 mg;
excipients: heavy magnesium carbonate, potato starch, hypromellose, colloidal anhydrous silicon dioxide, talc, sodium lauryl sulfate, magnesium stearate, polyethylene glycol (macrogol 1500), titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white in color, with a biconvex surface, scored.
Pharmacotherapeutic group
Selective β-adrenergic blockers in combination with diuretics. ATC code C07C B03.
Pharmacological properties
Pharmacodynamics
Dinorik®-Darnitsa is a combined antihypertensive drug containing atenolol and chlorthalidone.
Atenolol is a cardioselective β1-adrenergic blocker. It has antihypertensive, antianginal and antiarrhythmic effects. It has no intrinsic sympathomimetic activity and membrane-stabilizing action. It blocks mainly β-adrenergic receptors of the heart and reduces the stimulating effect on the heart of the sympathetic nervous system and catecholamines circulating in the blood, as a result of which the automatism of the sinus node, heart rate, atrioventricular conduction slows down, myocardial contractility decreases, and myocardial oxygen demand decreases.
Chlorthalidone is a long-acting thiazide-like diuretic. Blocks the reabsorption of sodium ions, chlorine and, accordingly, water in the distal tubules of the nephron. Increases the excretion of potassium and magnesium ions from the body. Delays the excretion of calcium ions and uric acid. Reduces blood pressure by reducing the volume of circulating blood, reducing cardiac output, and reducing total peripheral vascular resistance with prolonged use.
The antihypertensive effect of the drug lasts for 24 hours after administration. Stabilization of the therapeutic effect occurs after 2 weeks of treatment with the drug.
Pharmacokinetics
Absorption. After oral administration, 50% of the atenolol dose is absorbed from the gastrointestinal tract; food intake does not significantly affect absorption. Maximum plasma concentration is reached after 2-4 hours. Chlorthalidone is absorbed quite rapidly after oral administration, with a bioavailability of almost 60%.
Distribution: Plasma protein binding of atenolol is approximately 6-16%. Chlorthalidone is 90% bound to plasma proteins and erythrocytes.
Metabolism and excretion. Atenolol is practically not metabolized in the liver. It is excreted mainly by the kidneys (90%). The half-life is 6-9 hours. Chlorthalidone is excreted in feces and urine. The half-life is 24-55 hours, in the elderly and with renal failure it increases.
Indication
Arterial hypertension.
Contraindication
Hypersensitivity to the active substances or to other components of the drug, severe sinus bradycardia, AV block II-III degree, sinoatrial block, sick sinus syndrome, acute heart failure, decompensated chronic heart failure, arterial hypotension, cardiogenic shock, severe peripheral circulatory disorders, metabolic acidosis, hypokalemia, hyponatremia, hypercalcemia, anuria, severe renal and/or hepatic failure, precoma associated with Addison's disease, untreated pheochromocytoma, intoxication with cardiac glycoside drugs, simultaneous use of lithium drugs, bronchial asthma, bronchoobstructive syndrome, gout. The drug is contraindicated in patients receiving verapamil within 48 hours.
Interaction with other medicinal products and other types of interactions
with antihypertensive agents of various groups, tricyclic antidepressants, barbiturates, diuretics, phenothiazines, nitrates, peripheral vasodilators - increased hypotensive effect; with non-selective inhibitors of neuronal reuptake of monoamines - dangerous decrease in blood pressure; do not use simultaneously without medical supervision; with anesthetics, antiarrhythmics, blockers of "slow" calcium channels - increased severity of negative chrono-, ino- and dromotropic effects. This can cause severe arterial hypotension, severe bradycardia and heart failure. Blockers of "slow" calcium channels should not be used intravenously within 48 hours after discontinuation of β-blockers. A few days before anesthesia, it is necessary to stop taking the drug or choose an anesthetic agent with minimal negative inotropic effect; with cardiac glycosides – occurrence of tachy- or bradycardia, arrhythmias. Simultaneous use with digitalis preparations also increases the phenomenon of hypokalemia, therefore monitoring of laboratory parameters is required. Caution should be exercised when prescribing the drug to patients who take digitalis preparations together with an inadequate diet (which does not meet the body's need for potassium), or to those who have gastrointestinal diseases; with dihydropyridines – cardiac arrhythmia, worsening of heart failure in patients with chronic heart failure; with systemic glucocorticosteroids – cardiac arrhythmia due to significant loss of potassium; with reserpine, methyldopa, clonidine – occurrence of bradycardia. If Dinorik®-Darnitsa and clonidine are used simultaneously, clonidine can be discontinued only a few days after discontinuation of Dinorik®-Darnitsa; with nonsteroidal anti-inflammatory drugs, estrogens, α- and β-adrenomimetics, aminophylline, theophylline – weakening of the effect of atenolol, which is part of the drug; with propafenone – strengthening of the effect of atenolol, which is part of the drug; with nicotine – strengthening of the effect of atenolol as a result of a decrease in its metabolism and an increase in the level of the drug in the blood; with MAO inhibitors – strengthening of the effect of chlorthalidone, which is part of the drug; with cholestyramine – weakening of the effect of chlorthalidone, which is part of the drug; with drugs containing potassium – weakening of the effect of the latter; with drugs that depress the central nervous system – strengthening of the sedative effect; with lithium – strengthening of the effect of the latter; with narcotic analgesics – strengthening of the narcotic effect; dangerous inhibition; with adrenaline – strengthening of the vasopressor effect of adrenaline with subsequent bradycardia; with oral hypoglycemic agents, insulin - increased effect of the latter; with anticholinesterase agents, angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril) - increased blood potassium levels; with quinolones, cimetidine - increased bioavailability of atenolol; with lidocaine - increased concentration of lidocaine in blood plasma.
Alcohol potentiates the effect of the drug.
Application features
Treatment with the drug should be carried out under the supervision of a doctor.
Dinorik®-Darnitsa should not be prescribed for the treatment of angina attacks.
The hypotensive effect of the drug may be increased in post-sympathectomy patients.
When prescribing the drug to patients with pheochromocytoma, it is necessary to prescribe α-adrenoceptor blockers in advance to prevent the development of hypertensive crisis.
Dinorik®-Darnitsa should not be used in patients with untreated pheochromocytoma.
There have been reports of exacerbation of systemic lupus erythematosus.
Before surgery with general anesthesia, it may be necessary to stop taking the drug. In such cases, 48 hours should elapse between the last dose of the drug and anesthesia. If treatment is ongoing, caution should be exercised when using anesthetic agents - choose a drug for general anesthesia with minimal negative inotropic effect.
Hypersensitivity reactions may occur in patients with a history of bronchial asthma and who are receiving thiazides.
Even in patients without a history of heart failure, prolonged use of β-blockers may in some cases lead to heart failure. At the first signs of worsening heart failure, the drug should be discontinued and a doctor should be consulted.
During long-term thiazide therapy, patients experienced pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia, but general complications of hyperparathyroidism, such as nephrolithiasis, bone atrophy, and gastric ulcer, were not observed.
Use with caution in patients with impaired renal function. It is necessary to monitor the dynamics of their functional state, since the drug can provoke azotemia. Since atenolol is excreted by the kidneys, in severe renal impairment, the dose of the drug should be reduced. Given that a cumulative effect may develop with reduced renal insufficiency, and if renal function continues to deteriorate, treatment with Dinoric should be discontinued.
Use with caution in patients with impaired liver function. In patients with impaired liver function or progressive liver disease, a slight change in fluid and electrolyte balance may lead to hepatic coma.
Use with caution in patients with first-degree AV block, pulmonary emphysema, water and electrolyte imbalance, gastrointestinal diseases, diabetes mellitus, and hypoglycemia.
Concomitant use of calcium channel blockers may result in bradycardia, increased diastolic pressure, atrioventricular block, and death. Patients with pre-existing intraatrial conduction disorders or left ventricular dysfunction are particularly sensitive to the effects of the drug.
The drug should not be used in patients with broncho-obstructive syndrome and other bronchospastic diseases. However, since the drug is a selective β1-adrenoblocker, it can be used with caution in patients of this category in the absence of response to treatment or tolerance of other antihypertensive therapy. Since the selectivity of β1-adrenoblockers is not absolute, the drug should be used in the lowest possible doses and with the possibility of using β2-adrenomimetics. If the dosage needs to be increased, the dose should be divided to achieve lower maximum levels of the drug in the blood.
The drug should not be used before conducting studies on parathyroid function, since thiazides reduce calcium excretion.
Consideration should be given to discontinuing treatment or to closely monitoring patients suspected of developing thyrotoxicosis, as β-blockers may mask some clinical symptoms of hyperthyroidism, such as tachycardia. Abrupt discontinuation of therapy may precipitate an exacerbation of the disease.
Even in the absence of existing angina, discontinuation of the drug should be carried out under the supervision of a physician gradually, reducing the dose over 7-10 days and limiting physical activity to a minimum.
In the event of withdrawal syndrome, treatment with the drug should be resumed.
Creatinine levels should be measured periodically in patients with impaired renal function.
Plasma and urine electrolyte levels should be determined periodically to detect possible electrolyte imbalance, especially in patients with intractable vomiting or receiving parenteral fluids. Signs or symptoms of fluid and electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, nervousness, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Potassium levels should be determined periodically, especially in elderly patients, in patients taking digitalis preparations for the treatment of heart failure, in patients with an unbalanced diet or in patients with complaints of digestive tract disorders. Hypokalemia may develop especially in patients with accelerated diuresis, in the presence of severe cirrhosis or during concomitant use of corticosteroids or adrenocorticotropic hormone. The intake of electrolytes orally may also contribute to the development of hypokalemia.
Hypokalemia can be corrected or treated by taking potassium supplements or eating foods high in potassium.
Any chloride deficiency during thiazide therapy is usually minor and does not require specific treatment except in exceptional circumstances (e.g., liver or kidney disease).
Some patients receiving thiazide therapy may experience hyperuricemia or acute gout.
Dilutional hyponatremia may occur in patients with edema in hot weather. Appropriate therapy is fluid restriction rather than salt restriction, except in rare cases when hyponatremia is life-threatening.
This medicinal product contains 8 mg sodium lauryl sulfate. Caution should be exercised when used in patients on a controlled sodium diet.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, caution should be exercised when driving vehicles and working with complex mechanisms, and in case of dizziness, refrain from potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.
Use during pregnancy or breastfeeding
Do not use the medicine during pregnancy or breastfeeding.
Method of administration and doses
The dosage of the drug and the duration of treatment are determined by the doctor individually, depending on the therapeutic effect obtained.
Dinorik®-Darnitsa tablets are prescribed to adults orally. Take without chewing, with water, before meals once a day (in the morning).
The dosage regimen is given in terms of atenolol.
In arterial hypertension, the initial dose is 50 mg (1/2 tablet) per day. In the absence of clinical effect, the dose can be increased to 100 mg (1 tablet) per day. Further increase in dose in most cases does not lead to a decrease in blood pressure. If necessary, use other antihypertensive agents.
The greatest therapeutic effect is observed after 1-2 weeks of treatment. Withdrawal of the drug should be carried out gradually, since the development of withdrawal syndrome is possible with sudden cessation of the drug.
Elderly patients require a lower dose of the drug (based on atenolol), which is determined by the doctor.
Patients with impaired renal function.
In patients with impaired renal function, the dosage regimen depends on the degree of reduction in glomerular filtration and creatinine clearance (see table).
| Creatinine clearance (ml/min) | Maximum dose |
| 15-35 | 50 mg daily or 100 mg every other day |
| < 15 | 50 mg every other day |
| hemodialysis | 50 mg daily immediately after dialysis |
Children
The drug should not be used in pediatric practice.
Overdose
Symptoms: bradycardia, AV block II-III degree, acute heart failure, arterial hypotension, respiratory disorders, arrhythmias, loss of consciousness, hypoglycemia, bronchospasm, convulsions, increased drowsiness, dizziness, nausea, hypovolemia, electrolyte disturbances with cardiac arrhythmias and muscle spasms.
Treatment: the drug should be canceled. Control and correction of vital body functions should be carried out. In addition to gastric lavage and the use of adsorbents, if necessary, the following measures are recommended: excessive bradycardia can be eliminated by intravenous administration of 1-2 mg of atropine (if ineffective, isoproterenol) and/or the installation of a pacemaker. If necessary, 10 mg of glucagon can be administered intravenously as a bolus. This procedure can be repeated if necessary or followed by intravenous administration of glucagon at a rate of 1-10 mg/h depending on the response. In the absence of a response to glucagon or in the absence of glucagon itself, dobutamine can be administered intravenously at a dose of 5-10 μg/kg/min, isoprenaline intravenously drip at a dose of 10-25 μg at a rate of 5 μg/min. Dobutamine, due to its positive inotropic effect, can also be used to treat hypotension and acute heart failure. The doses indicated are unlikely to be sufficient to control the cardiac symptoms associated with β-blockade in cases of significant overdose. Therefore, if necessary, the dose of dobutamine may be increased until the desired response is achieved according to the patient's clinical condition.
Maintain normal fluid and electrolyte balance in the body. In case of arterial hypotension - administration of plasma or plasma substitutes. Relieve bronchospasm with bronchodilators.
Fluids and electrolytes should be administered in case of significant diuresis.
Adverse reactions
From the organs of vision: conjunctivitis, dry eyes, decreased tear secretion, visual impairment, xanthopsia.
On the part of the respiratory system, chest organs and mediastinum: cough, stridor, bronchospasm in patients with bronchial asthma or in patients with a tendency to bronchial obstruction, shortness of breath.
Gastrointestinal: dyspepsia, nausea, vomiting, constipation, diarrhea, dry mouth, anorexia, abdominal pain, gastric irritation, spasms, thrombosis of mesenteric arterial vessels, ischemic colitis.
From the liver and biliary tract: hepatotoxicity, liver dysfunction, intrahepatic cholestasis, cholestatic jaundice, pancreatitis, increased levels of liver enzymes, bilirubin.
Renal and urinary disorders: interstitial nephritis.
On the part of the endocrine system: worsening of diabetes mellitus.
From the nervous system: headache, weakness, fatigue, drowsiness, lethargy, dizziness, short-term memory loss, paresthesia, muscle cramps.
Psychiatric: sleep disturbances, nightmares, mood changes, depression, psychosis, hallucinations, disorientation, confusion, loss of consciousness, agitation, impaired concentration, aggressiveness.
From the cardiovascular system: bradycardia, atrioventricular conduction disorders, arrhythmia, palpitations, in patients with angina pectoris there may be an increase in attacks, symptoms of heart failure, a feeling of coldness in the extremities, orthostatic hypotension, which may be associated with syncope, Raynaud's syndrome, necrotizing vasculitis, sick sinus syndrome, lupus-like syndrome.
From the blood and lymphatic system: purpura, thrombocytopenia, leukopenia, aplastic anemia, agranulocytosis, eosinophilia, neutropenia, pancytopenia.
Skin and subcutaneous tissue disorders: pruritus, skin rash, erythematous rash, erythema, purpura, alopecia, psoriatic rash, exacerbation of psoriasis, photosensitivity, toxic epidermal necrolysis, Lyell's syndrome.
From the reproductive system and mammary gland function: impotence, Peyronie's disease.
General disorders: fever accompanied by pain and sore throat, muscle weakness, muscle cramps, leg pain, increased sweating, withdrawal syndrome.
Laboratory indicators: hyperuricemia, hyponatremia, hypokalemia, hypercalcemia, hypochloremic alkalosis, hyperglycemia, glucosuria, impaired glucose tolerance, increased serum transaminase levels, bilirubin, hypercholesterolemia, hypertriglyceridemia, formation of antinuclear antibodies.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a contour blister pack; 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
