Instructions Ebrantyl solution for injection 50 mg ampoule 10 ml No. 5
Composition
active ingredient: urapidil;
1 ml of solution contains 5 mg of urapidil, corresponding to 5.47 mg of urapidil hydrochloride;
Excipients: propylene glycol; sodium hydrogen phosphate, dihydrate; sodium dihydrogen phosphate, dihydrate; water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent, colorless solution.
Pharmacotherapeutic group
Antihypertensive agent. Alpha-adrenergic receptor blockers. ATX 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 also 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 intravenous administration of 25 mg of urapidil, a two-phase decrease in the concentration of the drug in the blood is observed (initial distribution phase, terminal elimination phase). The half-life is approximately 35 minutes. The half-life of the drug from the blood serum after intravenous bolus administration is 2.7 hours (1.8-3.9 hours).
The binding of urapidil to plasma proteins (human serum) in vitro is 80%. This relatively low binding of urapidil to plasma proteins may explain why interactions between urapidil and drugs with high plasma protein binding 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 4th position of the phenolic 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 remainder, primarily para-hydroxylated urapidil, which has no antihypertensive effect, 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
Hypertensive crisis. Severe or very severe arterial hypertension. Refractory arterial hypertension. For controlled reduction of blood pressure in case of its increase during/or after surgery.
Contraindication
Hypersensitivity to any of the components of the drug. Aortic stenosis. Arteriovenous shunt (except for patients with hemodynamically insignificant dialysis shunt).
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), pulmonary embolism or cardiac dysfunction due to pericardial disorders; in children, as studies have not been conducted in this age group of patients; in patients with hepatic insufficiency; in patients with moderate or severe renal insufficiency; in elderly patients; in patients concomitantly using cimetidine (see section "Interaction with other medicinal products and other types of interactions").
In case of previous use of other antihypertensive drugs, urapidil injection should not be used until sufficient time has passed to detect the therapeutic effect of the previously used drug. The dose of Ebrantyl should be reduced accordingly. Excessively rapid fall in blood pressure may lead to bradycardia or cardiac arrest.
10 ml of Ebrantyl solution for injection contains 1000 mg of propylene glycol, which corresponds to 100 mg of propylene glycol in 1 ml of solution for injection.
This medicine should not be used during pregnancy or breast-feeding unless advised by your doctor. Additional tests may be performed while you are taking this medicine, as directed by your doctor.
This medication should not be used if you have liver or kidney disease unless recommended by your doctor. Additional tests may be performed while you are taking this medication as directed by your doctor.
The propylene glycol contained in this medicine may have the same effect as drinking alcohol and increase the chance of side effects.
The drug should not be used in children under 5 years of age.
The drug should be used only on the recommendation of a doctor. While taking this drug, additional tests may be performed as directed by a doctor.
Ebrantyl contains sodium, but less than 1 mmol (23 mg) sodium per 5 ml solution for injection, making it essentially sodium-free.
Ebrantyl contains sodium, but less than 1 mmol (23 mg) sodium per 10 ml solution for injection, which makes it essentially sodium-free.
Ability to influence reaction speed when driving vehicles or 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 increasing the dose/changing the medication, or when used with alcohol.
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.
Method of administration and doses
Hypertensive crisis, severe or very severe form of arterial hypertension, refractory hypertension.
1) Intravenous injection: 10–50 mg of urapidil should be administered slowly intravenously under constant monitoring of blood pressure. A decrease in blood pressure is observed within 5 minutes after injection. Parenteral therapy may be repeated if blood pressure increases again.
2) Slow intravenous drip infusion or continuous infusion using a perfusion machine.
The solution for drip infusion, intended to maintain blood pressure at the level achieved by injection, is prepared as follows:
Add 250 mg of Ebrantyl to 500 ml of a compatible infusion solution (e.g. 0.9% sodium chloride solution or 5% or 10% glucose solution).
If a perfusion device is used to administer the maintenance dose, 20 ml of the injection solution (100 mg of Ebrantyl) should be injected into the perfusion device syringe and diluted to a volume of 50 ml with a compatible infusion solution (see above).
The maximum permissible ratio is 4 mg of urapidil per 1 ml of infusion solution.
The rate of drip administration depends on the individual blood pressure response.
The recommended maximum initial rate is 2 mg/min.
The maintenance dose is an average of 9 mg/h, i.e. 250 mg of urapidil when added to 500 ml of infusion solution (1 mg = 44 drops = 2.2 ml).
Controlled blood pressure lowering to manage hypertensive episodes during/or after surgery.
Continuous infusion using a perfusor or drip infusion should be used to maintain blood pressure at the level achieved by injection.
Dosage regimen
Intravenous injection of urapidil 25 mg ( = 5 ml of solution for injection) | lowering blood pressure in 2 minutes | Stabilization of blood pressure with infusion Initial dose up to 6 mg over 1–2 min, then taper dose |
through 2 min | blood pressure does not change | |
Intravenous injection of urapidil 25 mg ( = 5 ml of solution for injection) | lowering blood pressure in 2 minutes | |
through 2 min | blood pressure does not change | |
Slow intravenous administration of urapidil 50 mg ( = 10 ml of solution for injection) | lowering blood pressure in 2 minutes | |
Ebrantyl, an intravenous solution, should be administered to the patient in the supine position by injection or infusion.
Single or repeated injections and intravenous drip infusions are possible.
Emergency parenteral therapy can be continued by switching to long-term treatment with Ebrantyl, modified-release capsules (initial recommended dose 2 x 60 mg), or other oral antihypertensive agents.
A treatment period of 7 days is considered safe from a toxicological point of view and is generally not exceeded during parenteral antihypertensive therapy. Parenteral therapy may be repeated if blood pressure re-elevates.
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 should be treated with caution with antihypertensive agents and therapy should be initiated at lower doses, as the sensitivity of elderly patients to these drugs is often altered.
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: Excessive hypotension can be relieved by elevating the lower extremities while lying down and replacing blood volume.
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., 0.5–1.0 mg of adrenaline diluted in 10 ml of 0.9% sodium chloride solution) is necessary.
Adverse reactions
Most of the side effects listed below are due to a sharp decrease in blood pressure, but clinical experience shows that they disappear within a few minutes, even after drip infusion. In case of severe side effects, the drug should be discontinued.
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), difficulty breathing, 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.
General disorders.
Uncommon: fatigue, changes at the injection site.
Research.
Uncommon: irregular heart rhythm.
Very rare: thrombocytopenia*.
From the nervous system.
Common: dizziness, headache.
From the psychological side.
Very rare: feeling restless.
From the reproductive system and mammary glands.
Very rare: priapism.
On the part of the respiratory system.
Rare: nasal congestion.
On the skin and subcutaneous tissue.
Uncommon: increased sweating.
Rare: hypersensitivity, including itching, skin redness, rash.
Not known: angioedema, urticaria.
* - 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.
If any adverse reactions occur, you should consult a doctor.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children!
Packaging
Ampoules of 5 ml or 10 ml. 5, or 10, or 50 ampoules in a cardboard box.
Vacation category
According to the recipe.
Producer
Takeda Austria GmbH, Austria
Location of the manufacturer and its business address
St. Peter-Strasse 25, 4020 Linz, Austria / St. Peter-Strasse 25, 4020 Linz, Austria
