Enzaprost®-F (Enzaprost®-F)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDinoprostDinoprost
Dosage form: & nbspsolution for intraamnial administration.
Composition:

1 ml contains

active substance: dinoprost-5 mg;

Excipients: sodium acetate trihydrate, water for injection.
Description:Transparent from colorless to slightly greenish-yellow liquid.
Pharmacotherapeutic group:Generic activity is a stimulant - prostaglandin F2 analogue is synthetic.
ATX: & nbsp

G.02.A.D.01   Dinoprost

Pharmacodynamics:

Natural prostaglandins (PG) belong to the class of fatty acids. The basis of their structure is the so-called prostonic acid, consisting of a 20-membered carbon chain, part of which is included in the cyclopentane ring. Depending on the state of the cyclopentane ring, the PG is divided into subgroups: prostaglandins A, B, C, D, E, F, etc. Their main biogenic precursor in the body is arachidonic acid, present in all organs and tissues. PGs do not accumulate, but are newly synthesized under the action of microsomal enzymes, such as cyclooxygenase, in response to mechanical or bacterial stimuli. The prostaglandins of the groups E and F ($), in particular,participate in the processes of ovulation and implantation, increase the contractile activity of the myometrium, and have a stimulating effect on the genus activity. During pregnancy, the synthesis of prostaglandins in the amnion, chorion and placenta is enhanced, thereby causing an increase in prostaglandin levels in the amniotic fluid and maternal blood.

In obstetric practice, 3 prostaglandins are used: PGE 1 (alprostadil), PGE 2 (dinoprostone) and PGF 2 alpha (dinoprost), causing a reduction in myometrium and "maturation" of the cervix. PGF 2 alpha is a reduced form of PGE 2, due to spontaneous conversion in vivo.

Mechanism of action. Dinoprost causes activation of phospholipase C, increases the permeability of cell membranes to calcium, thus contributing to an increase in the intracellular level of calcium ions, which leads to a reduction in myometrium. He also participates in the process of "maturation" of the cervix. PGF 2 alpha has an effect through certain, particularly sensitive to it receptors on cells of smooth muscle tissue, and their activity is regulated by specific receptors on the membranes of target cells.

Moreover, prostaglandins induce the formation of nexus, enhancing the transmission of signals in the myometrium and promoting the activation of receptors sensitive to oxytocin in the uterus.

Other actions. Local injection of prostaglandin leads to a pronounced softening of the connective tissue with "active" fibroblasts, characterized by a fine-grained loosening of the cytoplasm, an increase in the mitochondria of the vacuolated species, and an increase in the number of vesicular systems in the peripheral part of the cell. Simultaneously, the activity of collagenase doubles, the activity of elastase increases approximately 7-fold and a significant increase in the level of hyaluronidase occurs, all of these factors play an important role in the "maturation" (softening) of the cervix. Collagenases come mainly from neutrophilic granulocytes, which, after the administration of prostaglandins, also accumulate in large quantities in the cervical stroma as well as during normal timely delivery. Prostaglandin mediated increase in the activity of natural killer cells also contributes to the process of ejection of the fetus from the uterus.

As a result, prostaglandins can, on the one hand, promote the maturation of the cervix, and on the other hand, stimulate the process of expulsion of the fetus from the uterus. Both these effects are used in therapeutic practice.

Pharmacokinetics:

Suction: Dinoprost is slowly absorbed from the amniotic fluid into the systemic circulation. After intra-amniotic administration of a single dose of 40 mg, the maximum concentration in the blood plasma (Cmax) is -3-7 ng / ml.

Biotransformation: Enzymatic oxidation occurs mainly in the lungs and liver of the mother organism. Dinoprost is exposed to 15-OH-dehydrogenase with the formation of an intermediate ketone, which is oxidized to 2,3-nidor-6-keto-PGE 1 alpha.

Excretion: Primarily, the kidneys are in the form of metabolites, and about 5% through the intestine. The half-life (T1 / 2) of dinoprost from the amniotic fluid is 3-6 hours.

Indications:

Interruption of pregnancy in the second trimester in the following cases:

  • started spontaneous miscarriage (abortion in progress); intrauterine fetal death; severe fetal malformations and incompatible with life hereditary diseases in the fetus, diagnosed by ultrasound (ultrasound) or other modern methods of prenatal diagnosis;
  • The impossibility of conducting medical abortion in the first trimester of pregnancy due to complications and deterioration of the woman's health.

ENZAPROST-F can be used only in obstetric-gynecological hospitals in the presence of an intensive care unit!

Contraindications:

  • allergic reactions to Enzaprost-F or other uterotonic medicines, including in the anamnesis;
  • bronchial asthma, including in the anamnesis; chronic obstructive pulmonary disease; lung disease in the acute stage; pulmonary tuberculosis,
  • ulcerative colitis; Crohn's disease;
  • thyrotoxicosis;
  • glaucoma;
  • acute infections;
  • acute inflammatory processes in the pelvic organs (for example, clinically pronounced chorionamnionitis, clinically pronounced cervicitis, which can contribute to cervical spasms [dystocia]); violation of the integrity of the amniotic membrane (increased risk of absorption of dinoprost in the vascular bed);
  • arterial hypertension;
  • sickle-cell anemia;
  • bleeding from the vagina of an unclear etiology;
  • significant disparity in the size of the pelvis and fetal head;
  • misconception of the fetus.

Carefully:

It is necessary to assess the benefit / risk ratio from the therapy under the following medical conditions:

The cardiovascular system:

  • acute conditions in heart diseases;
  • cardiovascular diseases now and in the anamnesis;
  • arterial hypotension (currently or in anamnesis).

Central nervous system:

  • epilepsy (currently or in anamnesis).

Diseases of the endocrine system and metabolism:

  • diabetes mellitus (currently or in anamnesis).

Gastrointestinal diseases:

  • acute liver disease (currently or anamnesis); jaundice (at present or in the anamnesis).

Genitourinary system:

  • acute kidney disease - currently or in history;
  • preeclampsia;
  • stenosis of the cervix;
  • malformations of the uterus;
  • uterine fibroids;
  • previous surgery on the uterus (increased risk of uterine rupture);
  • more than one kind in the anamnesis;
  • difficult or traumatic births in the anamnesis.

Others:

  • anemia in the anamnesis.

Pregnancy and lactation:

The drug is used to interrupt pregnancy in the second trimester - strictly according to indications and in a specialized hospital!

The effect of dinoprost on the fetus is not fully understood!
Dosing and Administration:

Premedication:

To reduce the number and severity of side effects, including to prevent or reduce the pain syndrome immediately before the administration of Enzaprost-F, it is advisable to perform a premedication by intravenous administration of one of the following combinations of drugs:

Combination

a

b

at

g

pethidine

100 mg

100 mg

100 mg

50 mg

promethazine

-

50 mg

50 mg

-

atropine

0.05 mg

-

0.5 mg

0.25 mg

diazepam

10 mg

-

-

-

The use of pethidine and atropine in the preparatory period is always desirable.

The drug can be administered intraamnially in two ways:

1) through the abdominal wall (transabdominal);

2) through the vaginal vault.

1) Transabdominal administration:

- Before starting the procedure with the help of ultrasound should determine the place of attachment of the placenta.

- Before the administration of the drug, the patient must empty the bladder.

- After treatment of the abdominal skin with antiseptics under local anesthesia, an amniocentesis is performed on the white belly line 3-4 fingers above the symphysis by means of a disposable needle for lumbar puncture (20G or 22G) away from the place of attachment of the placenta.

- Clear light amniotic fluid obtained by aspirating with a syringe indicates that the needle is in the amniotic cavity. In this case, 25 mg Enzaprost-F is injected into the amniotic cavity.

- If you need to re-introduce the drug, you can re-enter it after 8-12 hours through the plastic cannula used in the amniocentesis.

2) Introduction through the vaginal fornix

- Before administering the drug, the patient must empty the bladder.

- After examination of the vagina and its vaults, treatment with antiseptics is carried out.

- The cervix is ​​exposed in mirrors and fixed using bullet forceps.

- Entry into the amniotic cavity is carried out through the posterior or, more preferably, anterior arch.

- By aspirating several milliliters of amniotic fluid, make sure that the needle is in the correct position.

- When obtaining a transparent amniotic fluid in the amniotic cavity, 25 mg of Enzaprost-F is administered. This procedure can be repeated (as described above). The activity of the uterus should be constantly monitored by palpation or a tocograph, or by performing a periodic vaginal examination.

- If induction of abortion is ineffective, the administration of Enzaprost-F can be repeated after 8-12 hours and, if necessary, supplemented with oxytocin infusion. If the miscarriage does not occur within 12 hours, the patient's condition should be controlled even more carefully (pulse determination, measurement of body temperature, number of white blood cells).

WHEN RECEIVING IN BLOODAL ASPIRAT OR WATERPROOF WITH BLOOD ADJUSTMENT, ENZAPROST-F CAN NOT BE INTRODUCED!

INDUCED ABORTS USING ENZAPROST-F PREPARATION IS POSSIBLE TO BE CARRIED OUT ONLY IN THE OBSTACLE-GYNECOLOGICAL STATIONARY WHEN THE INTESIVE THERAPY IS AVAILABLE!

Side effects:

Often observed: diarrhea (about 16%); nausea (about 25%); pain (including spastic nature) in the abdomen (about 25%); vomiting (about 57%).

Less common are the following side effects:

From the cardiovascular system: spasms of peripheral vessels; bradycardia; temporary increase or decrease in blood pressure; tachycardia; atrioventricular block of the second degree; ventricular arrhythmia; feeling of constriction or pain in the sternum; development and aggravation of heart failure.

From the respiratory system: bronchospasm; hyperventilation of the lungs.

From the central nervous system: diplopia; miosis; paresthesia; dizziness; general weakness; euphoria.

From the gastrointestinal tract: hiccough, intestinal paralysis.

From the genitourinary system: urination disorders (urinary incontinence, dysuria, urinary retention, atony or bladder hypertension); hematuria; painful contractions associated with increased uterine contractility.

Other side effects: burning in the eyes; pain in the legs, back and shoulders; increase in the number of leukocytes.

Very rarely observed (<1%):

From the respiratory system: a prolonged cough.

From the central nervous system: headache; drowsiness; sense of anxiety.

Other side effects: allergic reactions; chills or intensified sweating; body trembling, transient fever; hyperemia of the face; petechiae, nosebleeds; feeling of thirst; polydipsia; muscle spasms.

Possible: hypovolemic shock; heart failure; dyspnea; loss of consciousness; DIC-syndrome; pulmonary embolism; thrombophlebitis of pelvic veins; uterine rupture; postpartum infection.

Overdose:

Clinical signs of an overdose:

The phenomena observed with the administration of the drug in the recommended dose, but in a much more pronounced degree: nausea, vomiting and diarrhea.

Treatment of overdose:

Special therapy: if necessary, surgical dissection an amniotic bladder (a reservoir containing a drug).

Supportive therapy: Particular importance is given to intravenous infusion therapy.

Interaction:

The combined use of Enzaprost-F with oxytocin and ergometrine enhances their effect, so there may be an increase in the number of side effects.

Furosemide inhibits the metabolism and excretion of the metabolites of dinoprost in the kidneys. Progesterone reduces the acute toxicity of the drug.

Special instructions:

Accidental ingestion of the drug into the blood can cause nausea, vomiting, bronchospasm, spasm of peripheral vessels, fainting, general weakness, increased blood pressure, a sense of panic. However, due to the fact that dinoprost is rapidly metabolized, these phenomena are transient (lasting from 15 to 30 min) and in most cases do not require additional therapy.

After the termination of pregnancy, an appropriate examination is necessary to confirm the completeness of the abortion, becausethe remains of the fetal egg may require surgical intervention!

Form release / dosage:

Solution for intraamnial administration 5 mg / ml.

Packaging:1 ml per ampoule of colorless glass (hydrolytic class I) with a break point. 5 ampoules per contour cell box (pallet) made of PVC. 1 pallet together with instructions for use in a cardboard box.
Storage conditions:

Store at temperatures between 5 ° C and 15 ° C.

Keep out of the reach of children in the place.

Shelf life:

3 years.

Do not use the product after the expiration date printed on the package.
Terms of leave from pharmacies:For hospitals
Registration number:П N014872 / 01
Date of registration:13.10.2008
The owner of the registration certificate:HINOIN Pharmaceutical and Chemical Products Plant, ZAO HINOIN Pharmaceutical and Chemical Products Plant, ZAO Hungary
Manufacturer: & nbsp
Representation: & nbspHINOIN Pharmaceutical and Chemical Products Plant ZAOHINOIN Pharmaceutical and Chemical Products Plant ZAO
Information update date: & nbsp10.01.16
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