Ebrantil® (Ebrantil®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceUrapidilUrapidil
Similar drugsTo uncover
  • Urapidil Carino
    solution in / in 
    Karinofarm GmbH     Germany
  • Ebrantil®
    capsules inwards 
    Takeda GmbH     Germany
  • Ebrantil®
    solution in / in 
    Takeda GmbH     Germany
    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    Per 1 ml:

    Active substance:

    Urapidil hydrochloride

    5.47 mg

    (in terms of urapidil)

    5.00 mg

    Excipients:

    Propylene glycol

    100.00 mg

    Sodium hydrogen phosphate dihydrate

    0.42 mg

    Sodium dihydrogen phosphate dihydrate

    2.22 mg

    Water for injections

    up to 1.0 ml
    Description:Pa clear, colorless solution.
    Pharmacotherapeutic group:Alpha-blocker
    ATX: & nbsp

    C.02.C.A.06   Urapidil

    C.02.C.A   Alpha-blockers

    Pharmacodynamics:

    Ebrantil® refers to drugs that block postsynaptic alpha-1-adrenergic receptors, thereby reducing peripheral resistance. In addition, Egrantil® regulates the central mechanism of maintaining vascular tone and has a weak beta-adrenergic blocking effect. The heart rate (heart rate), cardiac output when it is administered does not change. Low cardiac output may be increased by decreasing vascular resistance. As a rule, Orthostatic phenomena do not cause Ebrantil®. Ebrantil® blocks vasoconstriction caused by alpha-2-adrenoreceptors, and does not cause reflex tachycardia due to vasodilation.

    Ebrantil® balances systolic and diastolic blood pressure (BP), reducing peripheral resistance and does not cause reflex tachycardia.

    Urapidil reduces pre- and postnagruzku on the heart, increases the efficiency of cardiac contraction, thus, in the absence of arrhythmia, the drug increases the reduced minute volume of the heart;

    Mechanism of action

    Ebrantil® has a central and peripheral mechanism of action.

    Primarily blocks peripheral postsynaptic alpha-1-adrenergic receptors, thus, the drug blocks the vasoconstrictive effect of catecholamines.

    In the central nervous system (CNS) urapidil affects the activity of the vasomotor center, which is manifested in the prevention of reflex increase (or decrease) in the tone of the sympathetic nervous system.

    Urapidil does not affect the parameters of carbohydrate metabolism, the exchange of uric acid and does not cause fluid retention in the body.

    Pharmacokinetics:

    After intravenous administration of 25 mg of urapidil, a two-phase decrease in drug concentration occurs: first, a rapid decrease (alpha phase), and then a slow (beta phase).

    The distribution period of the drug is about 35 minutes.

    The volume of distribution is 0.8 l / kg (0.6-1.2 l / kg). Most of the urapidil is metabolized in the liver. The main metabolite is the hydroxylated derivative in the 4-position of the benzene ring, which practically does not possess antihypertensive activity. O-demethylated metabolite is formed in very small amounts and is almost as active as urapidil, 50-70% of urapidil and its metabolites (15% in the form of an active drug) is excreted by the kidneys, the rest is excreted through the intestines in the form of metabolites (mainly in the form of inactive p-hydroxylated urapidil).

    The half-life after intravenous bolus administration is 2.7 hours (1.8-3.9 parts). Connection with blood plasma proteins - 80%. The relatively low degree of binding to blood plasma proteins explains that it is not known the possible interaction of urapidil with drugs strongly binding to plasma proteins.

    In elderly patients, as well as in patients with severe hepatic and / or renal insufficiency volume distribution and clearance of urapidil decreased, and the half-life increased.

    Urapidil penetrates through blood-brain and placental barriers.

    Indications:

    Hypertensive crisis, refractory and severe degree of arterial hypertension.

    Controlled arterial hypotension during and / or after surgery.

    Contraindications:

    Hypersensitivity to the drug, aortic stenosis, open Botallov duct, arteriovenous fistula (with the exception of the hemodynamically inactive dialysis shunt); age to 18 years, the period of breastfeeding (efficacy and safety not established).

    Carefully:

    - Elderly age;

    - impaired liver and / or kidney function;

    - hypovolemia;

    - in patients with heart failure, which is caused by a violation of the mechanical function (for example, stenosis of the aortic or mitral valve), with pulmonary embolism or cardiac disorders due to pericardial diseases;

    - simultaneous use with cimetidine (see section "Interaction with other drugs");

    - simultaneous use with angiotensin-converting enzyme (ACE) inhibitors (clinical data of concomitant use with urapidil are limited).

    Pregnancy and lactation:

    The drug Ebrantil®, a solution for intravenous administration, is not recommended for use during pregnancy due to the fact that urapidil penetrates the placental barrier, except when the potential benefit to the mother exceeds the potential risk to the fetus.

    Clinical data on its use in the first and second trimesters of pregnancy are absent, data on the use of the drug in the third trimester are limited. Studies carried out on animals showed no signs of fetal damage.

    At present, it is not known whether urapidil with breast milk, so during treatment with urapidil, breastfeeding should be discontinued.

    Dosing and Administration:

    Ebrantil® is injected intravenously or by prolonged infusion, lying down.

    Hypertensive crisis, severe degree of hypertension, refractory hypertension

    1) Intravenous: 10-50 mg of Ebrantil® is slowly administered intravenously under the control of blood pressure (BP). Reduction of blood pressure is expected within 5 minutes after administration. Depending on the therapeutic effect, repeated administration of the Ebrantil® preparation is possible.

    2) Intravenous drip or continuous infusion with a perfusion pump. Maintenance dose: an average of 9 mg / h, i.e. 250 mg of Egrantil® (10 ampoules of 5 ml or 5 ampoules of 10 ml) in 500 ml of the infusion solution (1 mg = 44 drops = 2.2 ml). The maximum allowable ratio is 4 mg of the drug Egrantil® per 1 ml of solution for infusion.

    Recommended maximum initial speed: 2 mg / min.

    The rate of drip administration depends on the indices of the patient's blood pressure.

    Solution for drip infusion, designed to maintain blood pressure, is prepared as follows:

    Usually 250 mg of the drug (10 ampoules of 5 ml or 5 ampules of 10 ml) of Egrantil® are added to 500 ml of a solution for infusions, for example, saline, 5 or 10% dextrose (glucose) solution.

    If a perfusion pump is used to administer a maintenance dose, 100 mg of the preparation (4 ampoules of 5 ml or 2 ml of 10 ml each) of Ebrantil® is injected into the syringe of the perfusion pump and diluted to 50 ml with saline, 5 or 10% dextrose (glucose) .

    Controlled (controlled) reduction in blood pressure as it increases during and / or after surgery

    Continuous infusion with a perfusion pump or drip infusion is used to maintain blood pressure at a level,achieved by intravenous administration.

    Dosing scheme: see the figure.

    Notes

    If other antihypertensives have previously been used, then Ebrantil® can only be administered after a period of time sufficient to effect the previously administered drug (s). The dose of Ebrantil® should be adjusted accordingly.

    - When using antihypertensive drugs in elderly patients, care must be taken. The initial dose should be reduced compared to the recommended one, since the sensitivity in elderly patients to drugs of this series is often changed (the volume of distribution is reduced and the half-life is increased).

    The administration of the drug can be single or multiple. Injection administration of the drug can be combined with subsequent drip infusion. Parenteral therapy can be repeated with a new increase in blood pressure.

    Side effects:

    Most of the following side effects are due to a sharp drop in blood pressure, however, clinical experience shows that they disappear within a few minutes, even after a drip infusion of the drug Ebrantil®. Severe side effects may require discontinuation of treatment.

    The frequency of adverse events was determined in accordance with the classification of the World Health Organization: very often (≥10%); often (≥ 1% and <10%); infrequently (≥ 0.1% and <1%); rarely (≥ 0.01% and <0.1%); very rarely (<0.01%); frequency is unknown (can not be calculated based on available data).

    Disorders from the psyche:

    very rarely: excited state (feeling uneasy).

    Disorders from the central nervous system:

    often: dizziness, headache.

    Disorders from the cardiovascular system:

    infrequent: a feeling of palpitations, tachycardia, bradycardia, a feeling of constriction or pain in the chest (complaints of an anginous nature), dyspnea, arrhythmia, lowering of blood pressure when the position of the body changes, for example, when moving to a vertical position from the prone position (orthostatic hypotension).

    Disturbances from respiratory system, chest and mediastinum:

    rarely: nasal congestion.

    Disorders from the gastro-intestinal tract:

    often: nausea;

    infrequently: vomiting.

    Disturbances from the skin and subcutaneous tissue

    infrequently: increased sweating;

    rarely: allergic reactions, such as itchy skin, reddening of the skin, exanthema;

    unknown: angioedema, hives.

    Disorders from the urinary system:

    often: proteinuria;

    rarely: nephropathy, nephrotic syndrome.

    Disorders from the reproductive system and mammary glands:

    rarely: priapism.

    Systemic disorders and disorders at the site of administration:

    infrequently: increased fatigue.

    Deviations from the norm revealed in laboratory and instrumental studies:

    very rarely: thrombocytopenia *;

    infrequent: heart rhythm disturbance.

    * Very rarely a decrease in the number of platelets during the application of urapidil. However, it was impossible to establish any causal relationship with therapy with the drug Ebrantil®, for example, through immunohematological studies.

    Overdose:

    Symptoms: dizziness, orthostatic collapse, fatigue, retardation.

    Treatment: With a sharp drop in blood pressure, it is necessary to raise the patient's legs and begin infusion therapy to increase the volume of circulating blood.If these measures are ineffective, infusion of vasoconstrictors, under the control of arterial pressure, can begin. In very rare cases, intravenous administration of catecholamines (0.5-1.0 mg epinephrine (epinephrine) diluted in 10 ml of physiological solution) is necessary.

    Interaction:

    The antihypertensive effect of urapidil can be enhanced by joint admission with alpha-adrenoblockers, vasodilators or other antihypertensive agents, as well as in conditions associated with a decrease in body fluid (diarrhea, vomiting) and with the intake of ethanol (alcohol).

    With simultaneous administration of cimetidine, the maximum concentration of urapidil in the blood plasma can increase by 15%.

    It is not recommended to use with angiotensin converting enzyme inhibitors, since data on such a combination is not enough.

    Special instructions:

    Possible simultaneous use with other used orally antihypertensive drugs.

    There are no clinical data on the use of the drug in children under 18 years of age.

    If previously prescribed antihypertensive drugs, the drug Egrantil®, solution for intravenous administration, should not apply until sufficient time has elapsed to develop the effect of taking the previous drug (s) drug (s). The dosage of the drug Ebrantil® should be appropriately reduced.

    An excessively rapid drop in blood pressure can cause bradycardia or cardiac arrest.

    In elderly patients, use with caution and initially inject in small doses, since sensitivity in elderly patients is higher or changed to such drugs.

    Patients on a controlled sodium diet should take into account that the drug Ehrrantil®, an intravenous solution, contains sodium in an amount not exceeding 1 mmol (23 mg) in 5 ml of the drug and 2 mmol (46 mg) in 10 ml of the preparation.

    There are cases of the development of prolonged erection and priapism against the background of therapy with alpha1-adrenergic blockers. If the erection persists for more than 4 hours, you should immediately seek medical help. If priapism therapy has not been carried out immediately, it can lead to damage to the tissues of the penis and an irreversible loss of potency.

    Effect on the ability to drive transp. cf. and fur:

    The drug may affect the ability to drive vehicles or work with various mechanisms. This is especially true at the beginning of treatment, with an increase in the dose of the drug or the replacement of the drug, as well as the use of alcohol during the treatment period.

    Form release / dosage:

    Solution for intravenous administration, 5 mg / ml.

    Packaging:

    5 ml of the drug are placed in an ampoule of neutral colorless glass (type I, Hept. F.) with a break point and two marking strips.

    10 ml of the drug are placed in an ampoule of neutral colorless glass (type I, Hept. F.) with a break point and a marking strip.

    For 5 ampoules in a plastic contour acheive box is placed in a cardboard box with instructions for use.
    Storage conditions:

    Store at a temperature not exceeding 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-001751/09
    Date of registration:10.03.2009 / 04.07.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:Takeda GmbHTakeda GmbH Germany
    Manufacturer: & nbsp
    Representation: & nbspTakeda Pharmaceuticals Ltd.Takeda Pharmaceuticals Ltd.
    Information update date: & nbsp11.01.2017
    Illustrated instructions
    Instructions
    Up