Terlipressin (Terlipressinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Hormones of the hypothalamus, pituitary gland, gonadotropins and their antagonists

Included in the formulation
  • Remestip®
    solution in / in 
    Ferring-Lechiva as     Czech Republic
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    H.01.B.A   Vasopressin and its analogues

    H.01.B.A.04   Terlipressin

    Pharmacodynamics:Synthetic polypeptide, inactive pro-drug, which in the body turns into lipressin, which has vasoconstrictor and hemostatic effects, similar to the effects of vasopressin - the hormone of the posterior lobe of the pituitary gland. Features of the structure of the molecule terlipressin (replacement in the molecule of natural vasopressin arginine in the 8th position on lysine, attachment to the amino group of the final cysteine ​​of 3 glycine residues) provide it with a vasoconstrictive effect with a reduced antidiuretic activity than in vasopressin. The most pronounced vasoconstrictive action terlipressin renders on arterioles, venules, veins and smooth muscles of visceral organs, which leads to a decrease in blood flow through the liver and a decrease in pressure in the portal system. Terlipressin stimulates the reduction of the smooth muscles of the esophagus, increases tone and strengthens the intestinal peristalsis. Strengthening the tone of the smooth muscles of the vessels, terlipressin also affects the smooth musculature of the uterus, activating the contractile activity of the myometrium, regardless of the presence of pregnancy.
    Pharmacokinetics:Terlipressin metabolized in the liver, kidneys and other tissues with the formation of active metabolites. The effect of terlipressin develops more slowly, but it is more prolonged than the action of lysine-vasopressin. The therapeutic concentration of active metabolites begins to be determined in the blood 30 minutes after the administration of terlipressin and reaches a maximum after 60-120 minutes. Half-life is about 40 minutes, the clearance is 9 ml / kg / min. and the volume of distribution is about 0.5 l / kg.

    Indications:
    • Bleeding from the gastrointestinal tract (varicose veins of the esophagus, stomach ulcers and duodenal ulcers).
    • Uterine bleeding (dysfunctional, with childbirth and abortion).
    • Bleeding associated with surgical interventions on the abdominal and pelvic organs.
    • Hepatorenal syndrome type 1.
    ICD-10

    IX.I80-I89.I85.0   Varicose veins of the esophagus with bleeding

    XI.K20-K31.K25.0   Gastric ulcer acute with bleeding

    XI.K20-K31.K25.4   Stomach ulcer chronic or unspecified with bleeding

    XI.K20-K31.K26.0   Duodenal ulcer acute with bleeding

    XI.K20-K31.K26.4   Duodenal ulcer chronic or unspecified with bleeding

    XI.K90-K93.K92.2   Gastrointestinal bleeding, unspecified

    XIV.N80-N98.N93   Other abnormal bleeding from the uterus and vagina

    XV.O60-O75.O67   Childbirth and delivery, complicated by bleeding during labor, not elsewhere classified

    XV.O60-O75.O72   Postpartum hemorrhage

    XVIII.R50-R69.R58   Bleeding, not elsewhere classified

    XIX.T80-T88.T81.0   Bleeding and hematoma complicating the procedure, not elsewhere classified

    Contraindications:
    • Hypersensitivity.
    • Epilepsy.
    • I trimester of pregnancy.
    • Toxicosis of pregnant women.
    • Childhood.

    Carefully:Special care should be taken when prescribing elderly patients with ischemic heart disease, unstable angina and recent acute myocardial infarction, severe arterial hypertension, septic shock with low cardiac output, heart rhythm disorders, bronchial asthma, and pregnancy more than 12 weeks.

    Pregnancy and lactation:Terlipressin causes an increase in the contractile activity of the myometrium and a decrease in blood flow in the uterus. At the gestational age of more than 12 weeks should be used only if the benefit to the mother exceeds the risk to the fetus. In pre-clinical studies of toxicity in rabbits, the introduction of terlipressin at a dose of 0.1 mg / kg from the 6th to the 18th day of gestation, spontaneous abortions and fetal malformations were observed. Adequate and well-controlled studies in humans have not been conducted.

    If you need to use the drug during lactation, breastfeeding should be discontinued.

    Action category for the fetus by FDA - FROM.
    Dosing and Administration:Terlipressin is intended for intravenous administration in the form of bolus injections or short-term infusion.

    Bleeding from the digestive tract (gastric and duodenal ulcers, varicose veins of the esophagus): 1.0 mg at intervals of 4-6 h until bleeding stops and in the next 3-5 days. To prevent repeated bleeding terlipressin is canceled only after a complete absence of bleeding within 24-48 hours. It can be used in the provision of first aid if there is a suspicion of bleeding from the gastrointestinal tract.

    Bleeding during surgery on the abdominal and pelvic organs: intravenously sprayed or drip 0.2 to 1.0 mg every 4 to 6 hours, depending on the activity of tissue endopeptidases.

    Uterine bleeding (dysfunctional, at birth and interruption of pregnancy): 0.4 mg is added to 6 ml of 0.9% sodium chloride solution and injected para- and / or intracervical in 5-10 minutes before the beginning of surgery. If necessary, the dose may be increased or decreased. In juvenile uterine bleeding, the recommended dose is 5-20 μg / kg of the body weight of the patient.

    Hepatorenal syndrome type 1: 1 mg 3-4 times a day. Treatment should continue until the level of creatinine in the plasma is normalized (less than 130 μmol / l), on average - 10 days. If the creatinine level does not decrease by more than 30% within 3 days, further administration of terlipressin is not advisable.

    Side effects:From the side of the cardiovascular system: often - increased blood pressure, bradycardia, rarely - myocardial infarction, heart failure, supraventricular tachycardia, atrial fibrillation, stenocardia, changes in the ECG, polymorphic ventricular tachycardia such as "pirouette", ventricular fibrillation.

    From the respiratory system: rarely - shortness of breath, bronchospasm.

    From the digestive system: often - abdominal pain, enhancement peristalsis of the intestine until the onset of colic, nausea, vomiting, diarrhea; rarely - gastrointestinal bleeding.

    From the nervous system: often - a headache.

    From the musculoskeletal system: often - pain and cramps in the limbs; rarely rhabdomyolysis.

    From the skin: rarely - skin itching, local necrosis at the injection site, peripheral cyanosis.

    Other: often - pale skin; rarely - hyponatremia, hypokalemia, hypomagnesemia

    Overdose:A dose of more than 2 mg, injected within 4 hours, increases the risk of developing severe hemodynamic disorders (do not exceed the recommended dose). For relief of hypertension is prescribed clonidine, with a heart rate of less than 50 beats / min - atropine.

    Interaction:It is not allowed to mix terlipressin with other drugs in one syringe! Do not use glucose solution to dilute terlipressin!

    When used simultaneously with oxytocin and methylergometrin intensifies vasoconstrictive and uterotonic action.

    Enhances antihypertensive effect nonselective beta-blockers.

    When used simultaneously with drugs that reduce heart rate, the risk of developing severe bradycardia increases.

    Caution is necessary when combined with drugs, lengthening interval QT.

    Special instructions:Do not exceed the recommended dose of terlipressin! It should be avoided by intramuscular injection to prevent the occurrence of local necrosis.

    When using terlipressin, it is necessary to monitor the parameters of the water-electrolyte balance.

    When doses above 800 mcg are used, it is necessary to monitor blood pressure, heart rate and diuresis, especially in the treatment of patients with hypertension, heart disease and elderly patients.

    The drug terlipressin does not replace the measures to restore the volume of circulating blood in patients with bleeding.

    In patients with cirrhosis and hepatorenal syndrome type 1, daily monitoring of the level of creatinine is needed to assess the effectiveness of the therapy.

    Studies of the effect of terlipressin on the ability to drive vehicles and mechanisms,requiring increased concentration of attention, was not conducted.

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