Dilatrand

Dilatrend is a drug that non-selectively blocks the action of β-adrenoreceptors. In addition, it selectively blocks the activity of α-receptors. It does not have an endogenous sympathomimetic effect. It reduces the systemic preload of the heart by selectively blocking the activity of α-adrenoreceptors.

With non-selective blockade of β-adrenergic receptors, there is suppression of the renal RAS activity (reduction of renin activity in the plasma), as well as a decrease in the level of heart rate, blood pressure and intensity of cardiac output. When blocking α-receptors, the drug exhibits peripheral vasodilation, which reduces vascular resistance. [ 1 ]

Indications Dilatrand

It is used to reduce elevated blood pressure (in monotherapy or in combination with other antihypertensive drugs), and also in chronic forms of cardiovascular dysfunction and stable angina.

Release form

The medicinal substance is released in tablets with a volume of 12.5 or 25 mg; there are 30 such tablets inside a cell plate.

Pharmacodynamics

The combination of blocking β-receptor activity and vasodilation leads to the development of the following effects: [ 2 ]

• in people with coronary heart disease, it prevents the development of pain and myocardial ischemia;
• in people with elevated blood pressure values – reduces these indicators;
• In individuals with left ventricular dysfunction or blood flow insufficiency, it helps improve hemodynamics, increase the left ventricular ejection fraction and reduce its size.

The drug does not change lipid metabolism processes. [ 3 ]

Pharmacokinetics

The bioavailability values of the drug are 25%. The Cmax level with oral administration is recorded after 1 hour. The drug is linear with respect to blood parameters and the administered portion. The degree of bioavailability is not tied to food intake.

Dilatrend is a highly lipophilic component. About 98-99% of the substance is synthesized with protein. The half-life is in the range of 6-10 hours. The first intrahepatic passage rate is 60-75%. The distribution volume is 2 l/kg. Intraplasmic clearance is 590 ml per minute.

Intrahepatic metabolism of Dilatrend is realized by glucuronidation, as well as oxidation relative to the phenolic ring. During dimethylation and hydroxylation of the aromatic ring, 3 metabolic elements with β-blocking activity are formed. In preclinical processes, it was determined that the activity of 4'-hydroxyphenol is 13 times higher than the effect of Dilatrend. Blood indices of metabolic components are approximately ten times lower than the level of Dilatrend. The remaining 2 metabolic elements (hydroxycarbazole) have an intense antioxidant and adrenoblocking effect. Their antioxidant properties are 30-80 times stronger than the activity of Dilatrend.

Elimination of the drug occurs with bile (and then with feces); a small portion is excreted through the kidneys.

Elderly people have higher LS levels (50% higher). Bioavailability levels of the substance in people with liver cirrhosis are four times higher, and the level in the blood is five times higher than in people without this disorder.

In some patients with renal insufficiency (CC - below ≤20 ml per minute) and elevated blood pressure, an increase in blood LS indicators is determined (40-55%).

Dosing and administration

Dilatrend should be taken orally, without reference to food intake. In case of cardiovascular insufficiency in the patient, the drug should be taken with food (to enhance absorption, which reduces the likelihood of orthostatic collapse).

For people with high blood pressure.

The medication should be taken 1-2 times a day. The initial dose for an adult is 12.5 mg per day during the first 1-2 days.

The daily maintenance dose is 25 mg. If necessary, the dosage can be gradually increased (with a minimum 14-day interval) to reach the maximum daily dose of 50 mg.

Elderly people should initially be administered 12.5 mg of the drug once a day. In some cases, this dosage can be used further.

In case of increased blood pressure, no more than 50 mg of the medication can be used per day.

For people with stable angina.

During the first 1-2 days, adults take 25 mg of the drug (split the dose into 2 doses). The size of the maintenance dose per day is 50 mg (25 mg is used for 1 dose). A maximum of 0.1 g of Dilatrend is allowed per day (for 2 doses).

Elderly people initially take 12.5 mg once a day (the first 1-2 days). Later, the patient is transferred to a maintenance dose (50 mg for 2 doses). The indicated dosage is the maximum for elderly people.

Chronic cardiovascular insufficiency.

The drug is used as an auxiliary substance together with the use of ACE inhibitors, digitalis drugs, diuretics, and vasodilators.

To use the drug, the patient must be in a stable condition during the last month before switching to therapy with Cardvedilol. Among other important conditions are heart rate indicators not higher than 50 beats per minute, and systolic blood pressure level - higher than 85 mm Hg.

At first, 6.25 mg of the drug is used once a day. If there are no complications from using the drug, the dose may be gradually increased (with a minimum 14-day break) in the following regimen: from 6.25 mg taken twice a day to 12.5 mg/day taken twice a day, and then to 25 mg taken twice a day.

People weighing ≤85 kg can take no more than 50 mg of the drug per day (in 2 doses); people weighing ≥85 kg - 0.1 g per day (in 2 doses). In the latter case - except for situations with severe cardiovascular insufficiency. The portion should be increased under the close supervision of a doctor.

At the beginning of treatment, some aggravation of symptoms of cardiovascular insufficiency is possible (especially in people using large doses of diuretics or if the disease is severe). In this case, you do not need to cancel the medicine - just refuse to increase its dose.

During therapy, the patient's condition should be monitored by a therapist or cardiologist. Before increasing the dose of the drug, the patient should be additionally examined, determining weight, liver function, heart rate, blood pressure and heart rate. If symptoms of decompensation or delayed fluid excretion appear, symptomatic actions are required (increasing the dose of diuretics). The dosage of Dilatrend should not be increased (until the patient's condition stabilizes).

In some cases, it is necessary to reduce the dose of the drug or temporarily discontinue therapy (in this case, titration of the dosage can be performed).

When temporarily discontinuing the medication, it is necessary to resume taking it with a minimum dose (1-time administration of 6.25 mg per day). The dosage is increased gradually, according to the scheme indicated above.

It should be taken into account that the use of the drug by elderly people should be carried out under constant supervision of a doctor, since they have increased sensitivity to Dilatrend.

The drug is discontinued by gradually reducing the dosage over a period of 1-2 weeks.

• Application for children

Carvedidol should not be prescribed in pediatrics (individuals under 18 years of age), since there is only limited information regarding its medicinal efficacy and safety in this group.

Use Dilatrand during pregnancy

Dilatrend is contraindicated for use in breastfeeding or pregnant patients.

Animal testing has not revealed any teratogenic activity of the drug, but clinical trials investigating the safety of its administration to such patients have not been sufficiently conducted.

The drug can reduce the level of blood circulation inside the placenta, which leads to the death of the fetus in the womb or premature birth. In case of using the drug, the newborn or fetus may develop hypoglycemia, bradycardia, hypothermia, pulmonary insufficiency and cardiorespiratory complications.

The use of the drug during pregnancy is allowed only in situations where the probable benefit is more expected than the risks of complications for the fetus. The drug taken by the pregnant woman should be discontinued 2-3 days before the expected birth. If this condition is not met, it is necessary to monitor the condition of the newborn for the first 2-3 days.

The drug is lipophilic; animal testing has shown that the drug molecule and its metabolites can be excreted in breast milk. Therefore, breastfeeding should be avoided during therapy.

Contraindications

Among the contraindications:

• cardiovascular insufficiency in decompensated form;
• chronic bronchopulmonary pathologies of an obstructive nature;
• cardiogenic shock or BA;
• having 2-3 stage AV block;
• bradycardia (heart rate is ≤50 beats per minute);
• severe allergy to the active ingredient or other components of the drug;
• SSSU (also cardiac SA block);
• spontaneous angina;
• untreated pheochromocytoma;
• use in combination with parenteral vascular administration of verapamil or diltiazem;
• severe hypotension with systolic blood pressure readings below 85 mm Hg;
• peripheral vascular disease;
• glucose-galactose malabsorption, hereditary hypolactasia, and Lapp lactase deficiency.

Side effects Dilatrand

Main side effects:

• problems with hematopoietic processes: mild thrombocytopenia;
• metabolic disorders: hypercholesterolemia, -glycemia or -volemia, fluid retention and peripheral edema. Hyperglycemia is usually observed in diabetics;
• CNS dysfunction: paresthesia, dizziness, syncope, depression, sleep disorders and headaches;
• damage to the visual organs: deterioration of lacrimation, visual disturbance and irritation in the eye area;
• symptoms associated with the urinary tract: urinary dysfunction, peripheral edema and renal failure;
• gastrointestinal disorders: constipation, vomiting, xerostomia, nausea, abdominal pain, diarrhea and increased transaminase levels;
• problems with sexual function: impotence or swelling in the genital area;
• disorders of the cardiovascular system: peripheral blood flow disorder, bradycardia or orthostatic collapse;
• damage to the function of the musculoskeletal system: pain in the limbs;
• respiratory disorders: dry nasal mucosa and dyspnea (obstruction) in people with COPD;
• problems with the subcutaneous layer and epidermis: itching, urticaria, allergic exanthema and manifestations similar to psoriasis and lichen planus. If the patient suffers from psoriasis, he may experience worsening of epidermal symptoms;
• other: systemic weakness;
• rarely: AV block, angina pectoris and exacerbation of manifestations of pathologies associated with peripheral vessels (intermittent claudication, Raynaud's disease, etc.).

The use of Dilatrend may lead to the development of a latent form of diabetes mellitus or worsening of existing diabetes, as well as to insufficient control of serum glucose levels.

In case of drug titration, myocardial contractile function may be weakened (rarely).

Overdose

In case of poisoning with Dilatrend, the development of heart failure, bradycardia, vomiting, severe hypotension, bronchial spasm, respiratory disorders, cardiogenic shock and convulsions, as well as cardiac arrest and loss of consciousness are possible.

During therapy, it is necessary to monitor the functioning of vital body systems. Persons with poisoning should be in intensive care (if necessary).

Supporting actions:

• to prevent severe bradycardia – administer 0.5-2 mg of atropine intravenously;
• to maintain cardiovascular function – use of glucagon (by intravenous jet method 1-10 mg, and then intravenous infusion 2-5 mg per hour).

Sympathomimetics are also used - dobutamine, isoprenaline or epinephrine. The portion size is selected taking into account the patient's weight.

In case of refractory bradycardia, in addition to taking medications, cardiac electrical stimulation is performed.

To prevent bronchial spasm, β-sympathomimetics are administered via intravenous infusion or inhalation; in addition, aminophylline can be used intravenously.

To stop seizures, diazepam should be administered intravenously (at a low rate).

Hemodialysis will be ineffective because Dilatrend is synthesized at high speed with blood protein.

In severe cases of intoxication, supportive procedures are performed for a long time, since the redistribution and excretion of the drug slows down. The duration of treatment is determined by the patient's condition (it is performed until the condition stabilizes).

Interactions with other drugs

Antiarrhythmic agents and Ca antagonists.

Administration with diltiazem, amiodarone or verapamil causes hypotension and bradycardia. People using such combinations should have their blood pressure monitored and ECG studies performed.

The synergistic effect that develops when using Dilatrend with Ca antagonists may lead to a disorder of cardiac AV conduction, which causes decompensation.

Careful monitoring of patients combining the drug with subtype I antiarrhythmic agents or amiodarone is necessary. There are reports of bradycardia and ventricular fibrillation, as well as cardiac arrest, at the initial stage of treatment with Dilatrend in patients taking amiodarone.

With parenteral use of antiarrhythmic drugs, cardiovascular insufficiency may be observed (antiarrhythmic drugs of subtypes Ia or Ic).

Bradycardia has been reported with the combination of the drug and reserpine, guanfacine, methyldopa, guanethidine, or MAOIs (excluding MAOI-B agents). Heart rhythm should be monitored with such use regimens.

The drug should not be administered together with dihydropyridines, as this may provoke cardiovascular failure and severe hypotension.

Nitrates lead to a decrease in blood pressure when combined with drugs.

Simultaneous administration of the drug and digoxin leads to an increase in the equilibrium values of digoxin with digitoxin (by 16 and 13%). It is necessary to monitor the blood level of digoxin at the beginning of therapy and at the end of the selection of the maintenance dose.

The drug potentiates the antihypertensive activity of drugs from other pharmacological categories (barbiturates, vasodilators, phenothiazines, as well as tricyclics, alcohol and α1-ending antagonists).

Combining drugs and cyclosporine requires monitoring the blood levels of the latter, because they may increase.

Antidiabetic agents, including insulin.

The drug is able to neutralize the manifestations of hypoglycemia; the activity of insulin and hypoglycemic drugs may be enhanced when using the drug, which is why it is necessary to constantly monitor serum glucose levels in such people.

When using a combination with clonidine and there is a need to discontinue both drugs, first stop the administration of Dilatrend, and then gradually reduce the dose of clonidine.

If anesthesia is required via inhalation, negative inotropic and antihypertensive interactions between anesthetics and the drug must be taken into account.

The therapeutic effect of drugs is weakened when combined with substances that retain Na and fluid in the body (corticosteroids, anti-inflammatory analgesics and estrogens).

People using cimetidine, erythromycin, ketoconazole with barbiturates, verapamil and fluoxetine with haloperidol or rifampicin (substances that induce or inhibit the action of hemoprotein P450 enzymes) should be under the supervision of a doctor, since the drug level may increase (with the introduction of inhibitors) or decrease (with the use of inducers).

Combination with ergotamine leads to the development of a significant vasoconstrictor effect.

Combination with substances that lead to neuromuscular blockade causes potentiation of neuromuscular impulses.

Use together with sympathomimetics (α- or β-adrenergic agonists) increases the likelihood of increased blood pressure or the development of severe bradycardia.

Storage conditions

Dilatrend should be stored in a dark place, out of the reach of small children. Temperature indicators are in the range of 15-25°C.

Shelf life

Dilatrend can be used for a period of 24 months from the date of manufacture of the therapeutic substance.

Analogues

Analogues of the drug are the drugs Coriol and Akridilol with Corvasan, as well as Dilatrend.

Reviews

Dilatrend receives good reviews from medical professionals - it is considered quite effective in the treatment of heart failure, as well as in the control of AV conduction and atrial fibrillation. In addition, it receives good reviews as a treatment for elevated blood pressure, which increases its medicinal value.