Urapidil

Pharmacological properties

urapidil leads to a decrease in systolic and diastolic pressure by reducing opss. heart rate remains virtually unchanged. cardiac output does not change; cardiac output, which decreases due to increased afterload, may increase.

Mechanism of action. Urapidil has a central and peripheral mechanism of action.

At the peripheral level, urapidil blocks mainly postsynaptic α₁-adrenoreceptors, thus suppressing the vasoconstrictor effect of catecholamines.

At the central level, urapidil modulates the activity of the center of blood circulation regulation, which prevents a reflex increase in the tone of the sympathetic nervous system or a decrease in the tone of the vascular bed.

Pharmacokinetics Absorption. After oral administration, more than 80–90% of urapidil is absorbed in the digestive tract. C_max in plasma, a sustained release dosage form is achieved 4-6 hours after use; T_½ from blood plasma is about 4.7 hours (3.3-7.6 hours).

After iv administration of 25 mg of urapidil, a two-phase decrease in the concentration of the drug in the blood was noted (initial phase of distribution, terminal phase of elimination). The half-life is about 35 minutes. T_½ the drug from the blood plasma after iv bolus injection is 2.7 hours (1.8-3.9 hours).

Bioavailability. The relative bioavailability when taking the drug in the form of capsules with prolonged release compared with the ingested p-rum is 92 (83–103)%. The absolute bioavailability of sustained release capsules compared with the iv standard is 72 (63–80)%.

Binding to plasma proteins of urapidil (human serum) in vitro - 80%. This relatively low binding to plasma proteins of urapidil may explain why the interactions of urapidil and drugs with strong binding to plasma proteins are still unknown.

Distribution. Distribution volume - 0.77 l / kg body weight. The substance crosses the BBB and the placenta.

Metabolism. Urapidil is metabolized primarily in the liver. The main metabolite, urapidil, hydroxylated in the 4th position of the benzene ring, does not show significant antihypertensive activity. O-dimethylated urapidyl - the metabolite practically exhibits the same biological activity as urapidil, but is formed in very small quantities.

Excretion and elimination. Elimination of urapidil and its metabolites in the human body is up to 50–70% renal, of which about 15% of the dose is pharmacologically active urapidil; the rest, primarily p-hydroxylated urapidil, which does not exhibit an antihypertensive effect, is excreted in feces.

In elderly patients, as well as patients with progressive liver and / or renal failure, the volume of distribution and clearance of urapidil are reduced, and T_½ from blood plasma increases.

Indications

Ebrantil capsules. ag.

Ebrantil, injection solution. Hypertensive crisis. Severe or very severe degree of hypertension. Refractory hypertension. A controlled decrease in blood pressure if it increases during / or after surgery.

Application

Ebrantil capsules. for a gradual decrease in hell, the recommended dose is 30 mg 2 times a day (2 capsules of Ebrantil 30 mg / day). in order to quickly reduce hell, treatment begins with a dose of 60 mg 2 times a day (2 capsules of ebrantil 60 mg / day).

The dose can be gradually adapted to individual needs. The maintenance dose range is 60–180 mg / day; the total daily dose is divided into 2 doses.

Capsules of the drug Ebrantil take 2 times a day in the morning and evening with meals, swallow whole, washed down with a small amount of liquid.

The drug Ebrantil is used for long-term treatment. Treatment of hypertension with a drug requires regular medical monitoring.

Special patient groups

Liver failure. Patients with hepatic insufficiency may require a reduction in the dose of Ebrantil.

Renal failure. Patients with moderate and severe renal failure may require a dose reduction of Ebrantil with prolonged treatment.

Elderly patients. Elderly patients may need to reduce the dose of Ebrantil with prolonged treatment.

Ebrantil injection

Hypertensive crisis, severe or very severe form of hypertension, refractory hypertension

1. I / O injection: 10-50 mg of urapidil is administered slowly in / in under constant monitoring of blood pressure. A decrease in blood pressure is noted within 5 minutes after the injection. Parenteral therapy can be repeated with a repeated increase in blood pressure.

2. Slow intravenous drip infusion or continuous infusion using a perfuser.

A solution for infusion, designed to maintain blood pressure at the level achieved by injection, is prepared as follows: add 250 mg of Ebrantil to 500 ml of a compatible solution for infusion (for example, 0.9% sodium chloride solution or p- RA glucose 5% or 10%).

If a perfuser is used to administer a maintenance dose, 20 ml of injection solution (100 mg of Ebrantil) is injected into the perfusion syringe and diluted to a volume of 50 ml with a compatible infusion solution (see above).

The maximum allowable ratio is 4 mg of urapidil per 1 ml of solution for infusion.

Speed ​​of administration: The rate of drip administration depends on the individual blood pressure response.

Recommended maximum starting speed: 2 mg / min.

Maintenance dose: an average of 9 mg / h, that is, 250 mg of urapidil when added to 500 ml of a solution for infusion (1 mg = 44 drops = 2.2 ml).

A controlled reduction in blood pressure to regulate hypertensive episodes during / or after surgery. Continuous infusion using a perfuser or drip infusion is used to maintain blood pressure at the level achieved by injection.

Ebrantil iv solution is administered to the patient in a supine position, by injection or by infusion.

Single or repeated injections and iv drip infusions are possible. Injection is compatible with subsequent drip infusion. Emergency parenteral therapy can be continued by switching to long-term treatment with Ebrantil modified-release capsules (initial recommended dose: 2 x 60 mg) or other oral antihypertensive drugs. A treatment period of 7 days is considered safe from a toxicological point of view and, as a rule, is not exceeded with parenteral antihypertensive therapy. Parenteral therapy can be repeated with a repeated increase in blood pressure.

Contraindications

Hypersensitivity to the active substance or any of the excipients of the drug.

For Ebrantil, the solution for infusion is also aortic stenosis, arteriovenous shunt (with the exception of patients with hemodynamically insignificant dialysis shunt).

Side effects

Most of the following side effects are caused by a sharp decrease in hell, but clinical experience has shown that they disappear within a few minutes, even after a drip infusion. with severe side effects, discontinue use of the drug.

The frequency of occurrence is classified into the following categories: very often (≥1: 10), often (≥1: 100, 1:10), infrequently (≥1: 1000, 1: 100), rarely (≥1: 10,000, 1 : 1000), very rarely (1:10 000), unknown (the available data do not allow us to estimate the frequency).

On the part of the cardiovascular system: infrequently - palpitations, tachycardia, bradycardia, feeling of squeezing or pain behind the sternum (symptoms similar to angina pectoris), decreased blood pressure when changing the position of the body, for example, when standing up (orthostatic dysregulation).

From the digestive system: often - nausea; infrequently - vomiting, diarrhea, dry mouth.

General disorders and reactions at the injection site: infrequently - increased fatigue; very rarely - swelling due to increased fluid retention.

Research: very rarely - transient increase in the level of liver enzymes, thrombocytopenia *.

From the nervous system: often - dizziness, headache.

From the psyche: infrequently - sleep disturbances; very rarely - a feeling of anxiety.

From the kidneys and urinary tract: very rarely - frequent urination or an increase in the incidence of urinary incontinence.

From the reproductive system and mammary glands: very rarely - priapism.

From the respiratory system: infrequently - nasal congestion.

On the part of the skin and subcutaneous tissues: infrequently - allergic reactions, including itching, redness of the skin, rash; unknown - Quinckes edema, urticaria.

* In isolated cases, a decrease in platelet count due to the temporary use of the drug Ebrantil, but a causal relationship with the use of urapidil can not be established, for example, using immunological studies.

If any adverse reactions occur, consult a physician.

special instructions

With special care, the drug ebrantil should be used:

• with heart failure caused by mechanical functional disorders (for example, stenosis of the aortic or mitral valve), with pulmonary embolism or impaired cardiac activity due to pericardial disorders;
• in children, since studies for this age group of patients were not performed;
• patients with impaired liver function;
• patients with moderate or severe impaired renal function;
• elderly patients;
• patients who use cimetidine in parallel (see INTERACTIONS).

Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency should not use the drug in the form of capsules.

The capsule preparation contains sugar, which should be considered for patients with diabetes mellitus.

If previously used other antihypertensive drugs, urapidil injections should not be used until enough time has passed for the therapeutic effect of the previously used drug to be detected. The dose of Ebrantil should be accordingly reduced.

During pregnancy and breastfeeding. The drug is not recommended for use during pregnancy and lactation, since there is no relevant clinical data. The drug can be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Animal studies showed no signs of fetal damage.

It is not known whether urapidil passes into breast milk, so breastfeeding is not recommended during treatment with urapidil.

Children. There are no clinical data on the effectiveness and safety of the drug for the treatment of children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. In individual cases, adverse reactions from the central nervous system (dizziness) can affect the ability to drive vehicles or work with complex equipment. This is especially important at the beginning of treatment, when replacing a drug or when drinking alcohol.

Interactions

The antihypertensive effect of the drug ebrantil may be enhanced when combined with α-adrenergic blockers, vasodilators and other antihypertensive drugs, as well as with hypovolemia (diarrhea, vomiting) and with alcohol.

With the combined use of cimetidine C_max urapidil may increase by 15%.

Currently, information regarding combination therapy with ACE inhibitors is insufficient, therefore, such treatment is not recommended.

Incompatibility. The drug Ebrantil rr for injection should not be mixed with alkaline solutions for injection or infusion due to the darkening or precipitation of the lamellar precipitate in the solution due to the acidic properties of the solution for injection.

Overdose

Symptoms: on the part of the cardiovascular system - dizziness, orthostatic hypotension and collapse; on the part of the central nervous system - increased fatigue and a decrease in the rate of reactions.

Treatment: an excessive decrease in blood pressure can be reduced by raising the lower limbs in the supine position, replacing the bcc, in the absence of effect - the use of vasoconstrictors, which are administered iv slowly under the control of blood pressure. In very rare cases, iv administration of catecholamines is necessary (for example, 0.5–1.0 mg of adrenaline diluted in 10 ml of 0.9% sodium chloride solution).

Storage conditions

Capsules: in the original packaging at a temperature not exceeding 25 ° C.

Injection solution: at a temperature not exceeding 30 ° C.

UA / CVM / 1018/0009