Instructions for use Ebrantyl modified-release hard capsules 60 mg No. 50
Composition
active ingredient: urapidil;
1 capsule of Ebrantyl 30 mg contains 30 mg of urapidil;
1 capsule of Ebrantyl 60 mg contains 60 mg of urapidil;
excipients: methacrylate copolymer (type B); diethyl phthalate; talc; hypromellose; fumaric acid; ethyl cellulose; hypromellose phthalate; stearic acid; spherical sugar;
shell for 30 mg capsules: gelatin; titanium dioxide (E 171); iron oxide yellow (E 172); purified water; black ink (for marking);
capsule shell for 60 mg: gelatin; titanium dioxide (E 171); erythrosine (E 127); indigo carmine (E 132); red iron oxide (E 172); purified water; black ink (for marking).
Dosage form
The extended-release capsules are hard.
Main physicochemical properties:
30 mg capsules: hard gelatin capsules (No. 4) with an opaque yellow body and a yellow cap with the inscription “Ebr 30” printed in black on the body. The contents of the capsules are yellow granules;
60 mg capsules: hard gelatin capsules (No. 2) with an opaque pink body and a bright red cap with the inscription “Ebr 60” printed in black on the body. The contents of the capsules are yellow granules.
Pharmacotherapeutic group
Antihypertensive agent. Alpha-adrenergic receptor blockers. ATC code C02C A06.
Pharmacological properties
Pharmacodynamics.
Urapidil leads to a decrease in systolic and diastolic blood pressure by reducing peripheral resistance.
Heart rate remains virtually unchanged. Cardiac output remains unchanged; cardiac output, which is reduced as a result of increased afterload, may increase.
Mechanism of action: Urapidil has central and peripheral mechanisms of action.
At the peripheral level, urapidil blocks mainly postsynaptic alpha-1-adrenoreceptors, thus inhibiting the vasoconstrictor effect of catecholamines.
At the central level, urapidil modulates the activity of the circulatory regulation center; which prevents a reflex increase in the tone of the sympathetic nervous system or a decrease in sympathetic tone.
Pharmacokinetics.
Absorption: After oral administration, more than 80–90% of urapidil is absorbed from the gastrointestinal tract. Peak plasma concentrations of the extended-release formulation are reached 4–6 hours after administration; the plasma elimination half-life is approximately 4.7 hours (3.3–7.6 hours).
Bioavailability: The relative bioavailability of the extended-release capsules compared to the oral solution is 92 (83–103)%. The absolute bioavailability of the extended-release capsules compared to the intravenous standard is 72 (63–80)%.
The in vitro binding of urapidil to plasma proteins (human serum) is 80%. This relatively low plasma protein binding of urapidil may explain why interactions between urapidil and highly protein-bound medicinal products are still unknown.
Distribution: Volume of distribution is 0.77 l/kg body weight. The substance crosses the blood-brain barrier and crosses the placenta.
Metabolism. Urapidil is metabolized mainly in the liver. The main metabolite is hydroxylated urapidil at the 4-position of the benzene ring, which does not have significant antihypertensive activity. The O-dimethylated metabolite of urapidil has practically the same biological activity as urapidil, but is formed in very small quantities.
Excretion and elimination. Elimination of urapidil and its metabolites in humans is up to 50–70% renal, of which about 15% of the administered dose is pharmacologically active urapidil; the rest, primarily hypotensive para-hydroxylated urapidil, is excreted in the feces.
Special groups: In elderly patients and patients with progressive hepatic and/or renal insufficiency, the volume of distribution and clearance of urapidil are reduced, and the plasma half-life is prolonged.
Indication
Arterial hypertension.
Contraindication
Hypersensitivity to the active substance or to any of the excipients.
Interaction with other medicinal products and other types of interactions
The hypotensive effect of Ebrantyl may be enhanced by concomitant use with alpha-adrenergic blockers, vasodilators and other antihypertensive drugs, as well as by hypovolemia (e.g., diarrhea, vomiting) and alcohol consumption.
Concomitant use of cimetidine may increase the maximum serum level of urapidil by 15%.
Currently, there is insufficient information on combination therapy with ACE inhibitors, so this treatment is not recommended.
Application features
Ebrantyl should be used with extreme caution:
in heart failure caused by mechanical functional disorders (e.g., aortic or mitral valve stenosis), in pulmonary embolism, or in cardiac dysfunction due to pericardial disorders;
children, as studies have not been conducted for this age group of patients;
patients with moderate or severe renal dysfunction;
elderly patients;
patients who are concomitantly taking cimetidine (see section "Interaction with other medicinal products and other types of interactions").
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take Ebrantyl.
The drug contains sugar, which should be taken into account by patients with diabetes.
Use during pregnancy or breastfeeding
Women of childbearing age.
Ebrantyl is not recommended for women of childbearing age who are not using contraception.
Pregnancy.
There are no or limited amount of data from the use of urapidil in pregnant women.
Animal studies have shown reproductive toxicity.
Urapidil crosses the placenta.
Ebrantyl should not be used during pregnancy unless treatment with urapidil is necessary due to the clinical condition of the woman.
Lactation.
It is not known whether urapidil passes into breast milk.
A risk to the newborn/infant cannot be excluded.
Ebrantyl should not be used during lactation.
Fertility.
No clinical studies have been conducted on the effects on male and female fertility. Animal studies have shown that urapidil affects fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
In individual cases, some central nervous system side effects (dizziness) may affect the ability to drive or operate machinery. This is especially important at the beginning of treatment, when changing medications, or when used with alcohol.
Method of administration and doses
To gradually reduce blood pressure, start treatment with a dose of 30 mg 2 times a day (2 capsules of Ebrantyl, 30 mg capsules per day).
To quickly reduce blood pressure, start treatment with a dose of 60 mg 2 times a day (2 capsules of Ebrantyl, 60 mg capsules per day).
The dose can be gradually adjusted to individual needs. The maintenance dose range is 60–180 mg urapidil per day, the total amount should be divided into 2 individual doses.
Ebrantyl capsules should be taken in the morning and evening, during meals, and swallowed whole with a small amount of liquid.
Ebrantyl is suitable for long-term use. Treatment of arterial hypertension with this drug requires regular medical monitoring.
Special patient groups.
Hepatic impairment: Patients with hepatic impairment may require a reduced dose of Ebrantyl.
Renal impairment: Patients with moderate to severe renal impairment may require a reduction in the dose of Ebrantyl during long-term treatment.
Elderly patients: Elderly patients may require a reduced dose of Ebrantyl during long-term treatment.
Children
There are no clinical data on the efficacy and safety of the drug for the treatment of children.
Overdose
Symptoms:
Cardiovascular system: dizziness, orthostatic hypotension, collapse;
Central nervous system: increased fatigue and impaired reaction speed.
Treatment. In case of excessive decrease in blood pressure, it is necessary to place the patient in a horizontal position with a low head and begin infusion therapy to increase the volume of circulating blood.
If these measures prove insufficient, vasoconstrictors can be administered slowly intravenously under blood pressure monitoring.
In very rare cases, intravenous injection of catecholamines (e.g., 0.5–1 mg of adrenaline diluted in 10 ml of 0.9% sodium chloride solution) is necessary.
Side effects
Adverse effects are classified according to the frequency of occurrence into the following categories:
very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), not known (frequency cannot be estimated from the available data).
From the cardiovascular system.
Uncommon: palpitations, tachycardia, bradycardia, feeling of pressure or pain behind the sternum (symptoms similar to angina pectoris), decrease in blood pressure when changing body position, for example when getting up from a lying position (orthostatic dysregulation).
From the digestive tract.
Common: nausea.
Uncommon: vomiting, diarrhoea, dry mouth.
General disorders.
Uncommon: increased fatigue.
Very rare: edema due to increased fluid retention.
Research.
Very rare: transient increase in liver enzymes, thrombocytopenia*.
From the nervous system.
Common: dizziness, headache.
From the psychological side.
Uncommon: sleep disorders.
Very rare: feeling restless.
From the kidneys and urinary tract.
Very rare: increased frequency of urination or increased incidence of urinary incontinence.
From the reproductive system and mammary glands.
Very rare: priapism.
On the part of the respiratory system.
Uncommon: nasal congestion.
On the part of the skin and subcutaneous tissues.
Uncommon: hypersensitivity (including itching, redness of the skin, rash).
* - In isolated cases, a decrease in platelet count was noted in temporal association with the use of the drug Ebrantyl, although a causal relationship with the use of urapidil cannot be established, for example, using immunological studies.
Expiration date
18 months.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children!
Packaging
50 or 100 capsules in a bottle. 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Takeda GmbH, production site Oranienburg, Germany/Takeda GmbH Betriebsstätte Oranienburg, Germany.
Address
Lehnitzstrasse 70-98, 16515 Oranienburg, Germany.
