Remestip

Remestip contains the component terlipressin, which is an artificial analogue of the substance vasopressin (a natural hormone of the posterior pituitary lobe).

The therapeutic effect of terlipressin is based on a combination of specific effects of elements formed during its enzymatic breakdown. Among the noticeable properties of the substance are antihemorrhagic and powerful vasoconstrictors. Of the visible effects, the most noticeable is the reduction of blood flow within the parenchyma of internal organs, due to which there is a weakening of blood circulation within the liver and pressure in the portal vein.

Indications Remestipa

It is used for the following disorders:

• bleeding from the gastrointestinal tract - due to dilated esophageal veins due to varicose veins, as well as ulcerative lesions;
• bleeding occurring in the urogenital tract area - from the uterus, caused by functional disorders, abortion, childbirth and other reasons;
• bleeding caused by surgical procedures (eg, organs in the pelvic area or peritoneum).

Can be used locally in gynecological procedures involving the cervix.

Release form

The component is released in the form of an injection medicinal liquid - in ampoules with a capacity of 2 or 10 ml. There are 5 such ampoules in a pack.

Pharmacodynamics

Pharmacodynamic testing of the drug has shown that terlipressin, like other similar peptides, provokes the development of spasm of venules with arterioles mainly inside the parenchyma of internal organs, and in addition to this, contraction of the smooth muscles of the esophageal wall and increased tone along with intestinal peristalsis in general.

In addition to the effect on the smooth muscles of the vessels, the substance has a stimulating effect on the smooth muscles of the uterus, even in cases where the woman is not pregnant.

Tests of the drug's effects, conducted with the participation of humans and animals, have shown that it exhibits its highest activity inside the skin and internal organs.

No clinical symptoms of the antidiuretic effect of terlipressin were observed.

Pharmacokinetics

Terlipressin itself does not demonstrate activity relative to smooth muscles, but at the same time acts as a chemical depot for components with medicinal activity, formed during enzymatic cleavage. This effect develops at a slower rate than the effect of lysine-vasopressin, but has a longer duration.

Lysine vasopressin is often biologically converted within the kidneys, liver and other tissues.

The pharmacokinetics of the administered element is most fully described by a 2-component model. The half-life term is 40 minutes, the metabolic clearance rate is 9 ml/kg per minute, and the distribution volume values are 0.5 l/kg. The expected plasma lysine-vasopressin value is observed approximately half an hour after the administration of terlipressin. Cmax values are observed after 1-2 hours.

Dosing and administration

Initially, intravenous injections of 2 mg of the substance are administered at 4-hour intervals. This therapy must be continued until 24 hours have passed since the bleeding stopped (but this interval should be a maximum of 48 hours). After using the initial dose, it can be reduced to 1 mg at 4-hour intervals for individuals weighing <50 kg or if side effects develop.

Bleeding associated with varicose veins of the esophagus should be treated with a dose of 1000 mcg (for adults) at 4-6 hour intervals for 3-5 days. To prevent recurrence of bleeding, therapy is continued for another 1-2 days from the moment it stops. Remestip is administered by bolus, intravenous route or through a short infusion. The drug is administered undiluted or after dissolution with 0.9% NaCl.

For other types of gastrointestinal bleeding, the same dosage is used with the same time interval. The drug can be used to provide emergency care without being tied to surgical procedures - if there is a suspicion of bleeding in the upper gastrointestinal tract.

Bleeding that occurs in the area of internal organs in a child is stopped by introducing a portion of 8-20 mcg/kg with a 4-8-hour interval. The drug is used for the entire period of bleeding; to prevent relapses, the same measures are used as in adults. If the patient has sclerotic varicose veins inside the esophagus, a single bolus application of 20 mcg/kg is required.

Bleeding associated with the urogenital tract: due to the difference in the activity of endopeptidase in blood plasma and tissues, the limits of the dosage portion sizes are quite large - 0.2-1 mg; they should be used with a 4-6 hour break.

In case of uterine bleeding of a juvenile nature, dosages of 5-20 mcg/kg are used.

For local use in gynecological procedures involving the cervix, 400 mcg of the substance must be dissolved in 0.9% NaCl to obtain a volume of 10 ml. The product must be administered paracervically or intracervically. The therapeutic effect begins after 5-10 minutes. If necessary, the dose can be administered again or increased.

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Use Remestipa during pregnancy

The drug should not be used during pregnancy. It has been shown to cause uterine contractions and increased intrauterine pressure during early pregnancy, and can also weaken intrauterine blood flow. Tests on rabbits have shown fetal abnormalities and spontaneous abortions.

There is no information on whether the drug is excreted in breast milk. Excretion of the drug in milk has not been studied in animals. The risk of adverse effects on breast-fed infants cannot be excluded. The question of whether to stop breast-feeding or discontinue treatment must be decided taking into account all the risk and benefit factors of each decision.

Contraindications

Among the contraindications:

• severe sensitivity associated with the active component or any of the excipients of the drug;
• development of septic shock in individuals with poor cardiac output.

Side effects Remestipa

Side effects include:

• Cardiac disorders: arrhythmia or bradycardia are often observed, as well as manifestations of ischemia in the ECG. Sometimes tachycardia, heart failure, atrial fibrillation, ventricular extrasystoles, myocardial infarction, pain affecting the sternum, tachycardia of the pirouette variety and hyperhydration with pulmonary edema are observed;
• Vascular problems: mainly peripheral ischemia, peripheral vasoconstriction, epidermal pallor and decreased or increased blood pressure. Sometimes intestinal ischemia, flushes and peripheral cyanosis are observed;
• respiratory disorders: sometimes respiratory failure, bronchial spasm, difficulty breathing or breathing arrest, and pain during the breathing process are observed. Dyspnea occurs rarely;
• Gastrointestinal tract lesions: temporary diarrhea and transient abdominal pains of a spastic nature often occur. Sometimes transient vomiting or nausea are observed;
• disorders in the functioning of the nervous system: headaches often develop. Sometimes epileptic seizures are observed. Apoplexy occurs sporadically;
• problems with metabolic processes: sometimes, in the absence of control over fluid levels, hyponatremia appears;
• lesions of the subcutaneous layers and epidermis: sometimes lymphangitis or local skin necrosis occurs;
• disorders associated with the genitals: women often experience spasmodic pains affecting the lower abdominal area. Sometimes uterine ischemia develops or uterine tone increases;
• Problems in the injection area: often necrosis develops in such areas.

There is some data on the development of signs of intolerance.

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Overdose

It is forbidden to use doses higher than 2 mg in a 4-hour period, because in such cases severe side effects associated with the work of the cardiovascular system occur.

To control increasing blood pressure values (which may occur with the administration of Remestip), it is necessary to use sympatholytics or clonidine.

Atropine is used to eliminate bradycardia.

Interactions with other drugs

Terlipressin enhances the effect of non-selective β-blockers in reducing the severity of portal hypertension.

Combination with drugs that provoke bradycardia (including sufentanil and propofol) can cause the development of a severe form of this disease and a decrease in the severity of cardiac output.

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Storage conditions

Remestip should be stored in a place closed to small children at a temperature of 2-8°C. Freezing the substance is prohibited.

For 1 month, the medication can be kept at temperatures no higher than 25°C.

Shelf life

Remestip is approved for use for a period of 24 months from the date of manufacture of the drug.

Analogues

Analogues of the substance are the medications Adiupresin, Uropres, Minirin with Glipresin, and also D-void, H-desmopressin and Desmopressin.