Remestyp^® (Solution) Instructions for Use

Marketing Authorization Holder

Ferring-Leciva, a.s. (Czech Republic)

Manufactured By

Zentiva, k.s. (Czech Republic)

Labeled By

FERRING-LECIVA, a.s. (Czech Republic)

Or

ZENTIVA, k.s. (Czech Republic)

Quality Control Release

FERRING-LECIVA, a.s. (Czech Republic)

ATC Code

H01BA04 (Terlipressin)

Active Substance

Terlipressin (Rec.INN WHO registered)

Dosage Form

Remestyp®

Solution for intravenous administration 0.1 mg/1 ml: amp. 2 ml or 10 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless.

Excipients : sodium chloride – 9 mg, glacial acetic acid – 1.08 mg, sodium acetate trihydrate – 0.27 mg, water for injections – up to 1 ml.

2 ml – ampoules of colorless glass (5) in a set with an ampoule knife or scarifier – cardboard packs.
10 ml – ampoules of colorless glass (5) in a set with an ampoule knife or scarifier – cardboard packs.

Clinical-Pharmacological Group

Vasopressin analog. Vasoconstrictor

Pharmacotherapeutic Group

Posterior pituitary lobe hormone

Pharmacological Action

Vasopressin analog. It has an effect similar to that of the posterior pituitary hormone (vasopressin). It is a synthetic polypeptide that is an inactive prodrug and is biotransformed in the body into lypressin, which is a synthetic analog of vasopressin. Lypressin increases the tone of the smooth muscles of blood vessels and the gastrointestinal tract, causing a vasoconstrictor and hemostatic effect.

The main action of terlipressin is the contraction of arterioles, veins and venules of the visceral organs, which leads to a decrease in blood flow through the liver and a decrease in pressure in the portal system. Terlipressin, by contracting arterioles, veins and venules, stimulates the contraction of the smooth muscles of the esophagus, increases tone and enhances intestinal peristalsis. By enhancing the tone of the smooth muscles of blood vessels, Terlipressin also affects the smooth muscles of the uterus, increasing the contractile activity of the myometrium, regardless of the presence of pregnancy.

Pharmacokinetics

Terlipressin in its unchanged form does not affect the smooth muscles of the internal organs; during metabolism, active metabolites are formed that realize the pharmacological action of the drug. Unlike lysine-vasopressin, terlipressin is characterized by a slower onset and longer duration of pharmacological effect. Lysine-vasopressin is metabolized in the liver, kidneys and other tissues.

When administered intravenously, the pharmacokinetic profile can be represented by a two-component model. T_1/2 is about 40 min, clearance is about 9 ml/kg/min, V_d is about 0.5 l/kg. The concentration of lysine-vasopressin is determined in blood plasma 30 minutes after administration and reaches a maximum after 60-120 minutes.

Indications

Bleeding from the gastrointestinal tract, urinary and reproductive systems. Hepatorenal syndrome type I.

ICD codes

Dosage Regimen

Administer intravenously as a bolus injection or short-term infusion.

For control of acute variceal bleeding, administer a 2 mg bolus injection over one minute.

Repeat the 1 mg to 2 mg bolus dose every 4 to 6 hours until bleeding is controlled, for up to 72 hours.

For type 1 hepatorenal syndrome, administer a 0.5 mg to 1.0 mg bolus injection every 4 to 6 hours.

Alternatively, for hepatorenal syndrome, initiate therapy with a 0.5 mg intravenous bolus followed by a continuous infusion of 2 mg to 12 mg per 24 hours.

For gynecological hemorrhage, administer a 0.2 mg to 0.4 mg bolus; may repeat every 15 to 30 minutes as needed to control bleeding.

Adjust the dosage regimen individually based on clinical response and tolerability.

Monitor vital signs, electrolytes, and renal function closely during therapy.

Do not exceed the maximum recommended daily dose.

Adverse Reactions

Metabolism and nutrition disorders: infrequently – hyponatremia (in the absence of control of fluid intake).

Nervous system disorders often – headache.

Cardiac and vascular disorders often – bradycardia, peripheral vasoconstriction, peripheral tissue ischemia, facial skin pallor, arterial hypertension; infrequently – atrial fibrillation, ventricular extrasystole, tachycardia, angina pectoris, myocardial infarction, torsades de pointes ventricular tachycardia, heart failure, hypervolemia with development of pulmonary edema, intestinal ischemia, peripheral cyanosis, hot flashes.

Respiratory, thoracic and mediastinal disorders infrequently – respiratory distress syndrome, respiratory failure; rarely – dyspnea.

Gastrointestinal disorders often – transient abdominal cramping pain, transient diarrhea; rarely – transient nausea, transient vomiting.

Reproductive system and breast disorders increased uterine contractility, decreased uterine blood flow.

General disorders and administration site conditions skin pallor, skin necrosis, injection site necrosis.

Contraindications

Hypersensitivity to terlipressin; septic shock with low cardiac output; pregnancy, breastfeeding period; children and adolescents under 18 years of age.

With caution in elderly patients (over 70 years of age), with coronary artery disease, with unstable angina and recent acute myocardial infarction, severe arterial hypertension, with epilepsy or a history of seizures, respiratory failure, cerebrovascular diseases, coronary or peripheral vascular diseases (for example, with widespread atherosclerosis), with chronic renal failure, with septic shock (with normal or increased cardiac output), with cardiac arrhythmias, bronchial asthma, with simultaneous use of terlipressin with drugs that prolong the QT interval.

Use in Pregnancy and Lactation

The use of terlipressin during pregnancy is contraindicated. It is known that in early pregnancy, the use of terlipressin stimulates uterine contractile activity and increases uterine pressure, which leads to a decrease in uterine blood flow. Terlipressin may have a negative effect on the course of pregnancy and fetal development.

If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

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 chronic renal failure.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients (over 70 years of age).

Special Precautions

When using terlipressin, monitoring of water and electrolyte balance parameters is necessary. When used in high doses (0.8 mg and above), monitoring of blood pressure, heart rate and diuresis is necessary, especially when treating patients with arterial hypertension and heart disease.

In patients with liver cirrhosis and type I hepatorenal syndrome, daily monitoring of creatinine concentration is necessary to assess the effectiveness of the therapy.

Drug Interactions

With simultaneous use with oxytocin and methylergometrine, an increase in the contraction of the smooth muscles of the uterus and blood vessels is observed.

With simultaneous use, Terlipressin enhances the hypotensive effect of beta-blockers.

With simultaneous use with drugs that reduce heart rate, the risk of developing severe bradycardia increases.

Mixing terlipressin preparations with other medicinal products in the same syringe is not allowed!

Do not use dextrose (glucose) solution for diluting terlipressin preparations!

Storage Conditions

Store at 2°C (36°F) to 8°C (46°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.