Tachyben^® (Solution) Instructions for Use

Marketing Authorization Holder

Ever Neuro Pharma, GmbH (Austria)

Manufactured By

Cenexi (France)

Quality Control Release

EVER Neuro Pharma, GmbH (Austria)

ATC Code

C02CA06 (Urapidil)

Active Substance

Urapidil (Rec.INN)

Dosage Form

Tachyben®

Solution for intravenous administration 5 mg/1 ml: amp. 5 ml, 10 ml or 20 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless or slightly brownish in color.

Excipients: hydrochloric acid (37% w/w) – 1.272 mg, sodium dihydrogen phosphate dihydrate – 2.22 mg, disodium hydrogen phosphate dihydrate – 0.42 mg, propylene glycol – 100 mg, sodium hydroxide (4% w/w) – 0-0.8 µl (to pH 6.1±0.1), hydrochloric acid (3.7% w/w) – 0-0.8 µl (to pH 6.1±0.1), water for injections – up to 1 ml.

5 ml – ampoules of colorless glass (5) – contour cell packaging (1) – cardboard boxes.
10 ml – ampoules of colorless glass (5) – contour cell packaging (1) – cardboard boxes.
20 ml – ampoules of colorless glass (5) – contour cell packaging (1) – cardboard boxes.

Clinical-Pharmacological Group

Alpha₁-adrenergic blocker. Antihypertensive agent

Pharmacotherapeutic Group

Alpha-adrenergic blocker

Pharmacological Action

Antihypertensive agent. It has central and peripheral action. It blocks postsynaptic α₁-adrenoceptors, thereby reducing systemic vascular resistance (SVR). It regulates the central mechanism of vascular tone maintenance by stimulating serotonin 5-HT1A receptors of the vasomotor center (prevents reflex increase in sympathetic nervous system tone). Heart rate (HR) and cardiac output do not change. Low cardiac output may increase due to reduced SVR. Does not cause orthostatic phenomena. Stimulates presynaptic α₂-adrenoceptors.

It reduces systolic and diastolic blood pressure (BP) by decreasing SVR, does not cause reflex tachycardia. It reduces pre- and afterload on the heart, increases the efficiency of heart contraction, thus (in the absence of arrhythmia) increases the reduced minute cardiac volume.

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

Pharmacokinetics

After intravenous administration of 25 mg, a biphasic decrease in concentration is observed: first – a rapid (α-phase), then – a slow (β-phase) decrease. The distribution phase of urapidil is 35 min, V_d – 0.8 l/kg (0.6-1.2 l/kg). Plasma protein binding – 80%. Metabolized in the liver. The main metabolite is a hydroxylated derivative (at position 4 of the benzene ring), does not possess antihypertensive activity. The O-demethylated metabolite is formed in very small quantities and is as active as Urapidil. T_1/2 (after IV bolus administration) – 2.7 h (1.8-3.9 h). Excreted by the kidneys – 50-70% as unchanged substance and 15% as metabolites; through the intestine – as metabolites (mainly as inactive n-hydroxylated urapidil). In elderly patients and in severe hepatic and/or renal impairment, V_d and clearance are reduced, and T_1/2 is increased. Penetrates the blood-brain barrier (BBB) and placental barrier.

Indications

Hypertensive crisis, refractory arterial hypertension, stage III arterial hypertension, controlled arterial hypotension during and/or after surgery.

ICD codes

Dosage Regimen

Administered IV as a bolus or drip (long-term, in a lying position).

For hypertensive crisis, stage III arterial hypertension, refractory arterial hypertension: IV slowly 10-50 mg (under BP control; expected BP reduction within 5 min), repeated administration is possible. IV by infusion (drip or continuous) using a perfusion pump. Maintenance dose (on average) – 9 mg/h, i.e., 250 mg of urapidil in 500 ml of infusion solution (1 mg = 44 drops = 2.2 ml). The maximum permissible ratio is 4 mg of urapidil per 1 ml of infusion solution. Maximum initial rate – 2 mg/min (depending on BP).

For controlled arterial hypotension (during and/or after surgery): continuous infusion (using a perfusion pump) or drip to maintain BP achieved with IV administration. With IV administration of 25 mg: if BP decreases after 2 min – switch to infusion (6 mg over 1-2 min, then reduce the dose); if BP does not change after 2 min – repeat IV 25 mg and if BP decreases after 2 min – switch to infusion (6 mg over 1-2 min, then reduce the dose); if BP after repeated injection does not change after 2 min – IV slowly 50 mg and then, if BP decreases after 2 min, switch to infusion (6 mg over 1-2 min, then reduce the dose). If other antihypertensive agents were used previously, then Urapidil is administered after the time during which the previously administered agent should have taken effect. The dose of urapidil should be adjusted.

In elderly patients, the initial dose should be reduced compared to the recommended one. Administration can be single or multiple. Injections can be combined with subsequent drip infusion. Therapy is repeated upon repeated increase in BP.

Adverse Reactions

From the cardiovascular system sometimes – palpitations, tachycardia, bradycardia, feeling of pressure behind the breastbone, shortness of breath, arrhythmias.

From the digestive system often – nausea; sometimes – vomiting.

From the CNS often – dizziness, headache, fatigue; very rarely – anxiety.

Dermatological reactions sometimes – increased sweating.

Allergic reactions rarely – skin itching, skin redness, exanthema.

From the urinary system often – proteinuria; rarely – nephropathy, nephrotic syndrome.

From the reproductive system rarely – priapism.

Laboratory parameters very rarely – thrombocytopenia.

Contraindications

Aortic stenosis, patent ductus arteriosus, pregnancy, lactation period, children and adolescents under 18 years of age, hypersensitivity to urapidil.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during the lactation (breastfeeding) period.

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function.

Use in Renal Impairment

Should be used with caution in patients with impaired renal function.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Should be used with caution in patients with impaired liver and/or kidney function, with hypovolemia, and in the elderly.

A sharp drop in BP disappears within a few minutes after stopping the administration of urapidil.

Simultaneous use with oral antihypertensive agents is possible.

In hypovolemia, the hypotensive effect of urapidil is enhanced.

Drug Interactions

Other antihypertensive agents, including alpha-blockers, ethanol enhance the hypotensive effect of urapidil.

With simultaneous use of cimetidine, an increase in C_max of urapidil in plasma by 15% is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.