Oxytocin-Richter (Solution) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Contact Information

GEDEON RICHTER JSC (Hungary)

ATC Code

H01BB02 (Oxytocin)

Active Substance

Oxytocin (Rec.INN registered by WHO)

Dosage Form

Oxytocin-Richter

Solution for intravenous and intramuscular administration 5 IU/1 ml: amp. 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration colorless, transparent.

Excipients: glacial acetic acid, chlorobutanol hemihydrate, ethanol (96%), water for injections.

1 ml – ampoules made of colorless glass (Type I hydrolytic class) with a break point (5) – plastic contour packs (1) – cardboard boxes.

Clinical-Pharmacological Group

A drug that increases the tone and contractile activity of the myometrium

Pharmacotherapeutic Group

Hypothalamic and pituitary hormones and their analogues. Posterior pituitary lobe hormones. Oxytocin and its derivatives

Pharmacological Action

Oxytocin is a synthetic analogue of the peptide hormone of the posterior pituitary lobe. It has a uterotonic, labor-stimulating, and lactotropic effect.

It has a stimulating effect on the myometrium (especially at the end of pregnancy, during labor, and directly during delivery). Under the influence of oxytocin, the permeability of cell membranes to calcium ions (Ca²⁺) increases, the resting potential decreases, and their excitability increases (a decrease in the membrane potential leads to an increase in the frequency, intensity, and duration of contractions). In small doses, Oxytocin increases the frequency and amplitude of uterine contractions; in large doses or with repeated administration, it promotes an increase in uterine tone, frequency, and strength of its contractions (up to tetanic). It contracts the myoepithelial cells around the mammary gland alveoli, stimulates the flow of milk into the large ducts or sinuses, promoting increased milk secretion. It is practically devoid of vasoconstrictor and antidiuretic action (only in high doses), does not cause contraction of the muscles of the bladder and intestines.

The effect occurs within 1-2 minutes after intramuscular administration, lasting 20-30 minutes; after intravenous administration – within 0.5-1 minute.

Pharmacokinetics

Distribution

Plasma protein binding is low (30%). After intravenous administration, the effect of oxytocin on the uterus occurs almost instantly and lasts for 1 hour. After intramuscular administration, the myotonic effect of oxytocin occurs within the first 3-7 minutes and lasts for 2-3 hours. Similar to vasopressin, Oxytocin is distributed throughout the entire extracellular space. A small amount of oxytocin enters the fetal circulation.

Metabolism

Most of the oxytocin is rapidly metabolized in the liver and kidneys. During enzymatic hydrolysis, Oxytocin is inactivated primarily under the action of tissue oxytocinase, the concentration of which in blood plasma, target organs, and placenta increases during pregnancy.

Excretion

It is excreted mainly by the kidneys unchanged. T_1/2 is 1-6 minutes (decreases in late pregnancy and during lactation).

Pharmacokinetics in special patient groups

Renal impairment. Pharmacokinetic studies of oxytocin in patients with renal impairment have not been conducted. However, given the renal excretion of oxytocin and its antidiuretic effect, accumulation with increased and prolonged action is possible.

Hepatic impairment. Pharmacokinetic studies of oxytocin in patients with hepatic impairment have not been conducted. However, a change in the pharmacokinetics of oxytocin in patients with impaired liver function is unlikely, since during pregnancy the concentration of oxytocinase, which metabolizes Oxytocin, significantly increases in other organs and tissues (including the placenta). Therefore, impaired liver function cannot lead to significant changes in the metabolic clearance of oxytocin.

Indications

Adults aged 18 years and over

• For induction of labor for medical reasons (primary or secondary uterine inertia; need for premature delivery due to preeclampsia, Rh conflict, intrauterine fetal death; post-term pregnancy, premature rupture of membranes, management of labor in breech presentation);
• For the prevention and treatment of hypotonic uterine bleeding after medical or spontaneous abortion in the first trimester or termination of pregnancy in the second trimester, in the early postpartum period and to accelerate postpartum uterine involution;
• To enhance uterine contractility during cesarean section (after placental removal).

ICD codes

Dosage Regimen

For parenteral administration only: intravenous (slow bolus or drip), intramuscular, into the uterine wall. For intravenous drip administration, Oxytocin is preferably administered using an infusion pump with an adjustable infusion rate.

Use only in a hospital setting under medical supervision. Monitoring of uterine contractile activity, fetal condition, blood pressure, and the woman’s general condition is necessary.

A single dose for intramuscular administration, depending on the clinical situation, can range from 1 to 10 IU (from 0.4 ml to 2 ml); for intravenous administration – usually 5-10 IU (1-2 ml).

For induction and stimulation of labor for medical reasons

Oxytocin is administered only as an intravenous drip infusion.

Administration of oxytocin is contraindicated within the first 6 hours after the use of intravaginal forms of prostaglandins.

For intravenous infusion, 5 IU of oxytocin (1 ml) is diluted in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution. To ensure uniform mixing, the vial with oxytocin should be turned over several times before starting the infusion.

Administration of the drug begins at 5-8 drops/min for at least 20 minutes, followed by an increase in the infusion rate depending on the nature of labor by no more than 2-4 drops/min. The recommended maximum infusion rate is no more than 40 drops/min (20 mIU/min or 20 ml/min).

Careful monitoring of the frequency, strength, and duration of uterine contractions, and fetal heart rate is necessary until regular labor is achieved (3-4 uterine muscle contractions within 10 minutes, the uterus should relax between contractions).

After achieving an adequate level of uterine contraction activity, the infusion rate can be reduced. If hypertonic uterine muscle contractions and/or fetal distress occur, oxytocin administration must be stopped immediately. In exceptional cases, if higher doses of oxytocin are required (reduced uterine sensitivity to oxytocin in case of intrauterine fetal death or induction of labor at an earlier stage of pregnancy), it is advisable to administer oxytocin at a dose of 10 IU (2 ml) in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution.

During the infusion, constant monitoring of uterine contraction activity and fetal heart rate must be carried out. If excessively strong uterine muscle contractions occur, reducing the infusion rate quickly leads to a decrease in myometrial activity.

Prevention and treatment of hypotonic uterine bleeding after medical or spontaneous abortion in the first trimester of pregnancy or termination of pregnancy in the second trimester

After medical or spontaneous abortion in the first trimester of pregnancy, 5 IU of oxytocin is administered intravenously by slow bolus (over 5 minutes) diluted or 5-10 IU intramuscularly, if necessary – followed by an infusion of 5-10 IU of oxytocin in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution intravenously by drip, at a rate of 20-40 drops/min.

For incipient or incomplete abortion in the second trimester of pregnancy: 5 IU of oxytocin in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution intravenously by drip, at a rate of 20-40 drops/min.

Prevention of postpartum hypotonic uterine bleeding

In the third stage of labor (after placental separation) and in the early postpartum period: 5 IU of oxytocin (1 ml) in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution intravenously by drip or intravenously by slow bolus diluted (over 5 minutes).

As an alternative, administration of 5-10 IU (1-2 ml) intramuscularly is acceptable. For women who underwent labor stimulation, the oxytocin infusion should continue during the third stage of labor and for several hours of the postpartum period.

During cesarean section surgery (after fetal extraction and placental removal)

5 IU intravenously by slow bolus diluted.

To enhance uterine contractility

Into the uterine wall at a dose of 3-5 IU (0.6 ml -1 ml)

In the late postpartum period, intramuscular administration of oxytocin at a dose of 5 IU 1 or 2 times/day is recommended.

Treatment of postpartum hypotonic/atonic uterine bleeding

Oxytocin is administered at a dose of 5-10 IU (1-2 ml) in 500 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution intravenously by drip, at a rate of 60 drops/min (125 ml/h), in severe cases (with uterine atony – up to 20 IU (4 ml); or intravenously by slow bolus diluted, 5 IU each. The maximum daily dose is no more than 3 liters of solution containing Oxytocin (60 IU).

Prevention and treatment of uterine subinvolution in the postpartum period

2.5-5 IU of oxytocin (0.5 ml – 1 ml) intramuscularly 1-2 times/day.

Special patient groups

Children. The safety and efficacy of oxytocin in children aged 0 to 18 years have not been established. Data are not available.

Elderly patients. Not applicable. There are no indications for use.

Patients with renal impairment. Clinical studies of oxytocin in patients with renal impairment have not been conducted. However, due to the renal excretion of oxytocin and its antidiuretic effect, accumulation is possible in case of impaired renal function. Therefore, Oxytocin should be used with particular caution in patients with renal impairment.

Patients with hepatic impairment. Clinical studies of oxytocin in patients with hepatic impairment have not been conducted.

Adverse Reactions

The main adverse events noted in parturients with the use of oxytocin were hemodynamic side reactions – increased heart rate, decreased blood pressure; as well as myocardial ischemia, bronchospasm, hyperthermia, nausea and vomiting. In the fetus, adverse events such as hyperbilirubinemia and liver damage were observed.

Below are the adverse reactions grouped by system and organ according to the WHO classification of frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000); frequency unknown (cannot be estimated from the available data).

In parturients

Immune system disorders frequency unknown – anaphylaxis and other allergic reactions, with too rapid administration – bronchospasm (rarely – fatal outcome).

Metabolism and nutrition disorders frequency unknown – severe hyperhydration with prolonged intravenous administration with a large volume of fluid (antidiuretic effect of oxytocin), can also occur with 24-hour slow infusion of oxytocin, accompanied by convulsions and coma (rarely – fatal outcome).

Cardiac disorders frequency unknown – with use in high doses – arrhythmia, ventricular extrasystole, reflex tachycardia; with too rapid administration – bradycardia; myocardial ischemia, QT interval prolongation.

Vascular disorders rare – development of DIC syndrome; frequency unknown – severe arterial hypertension (in case of using vasopressor drugs), arterial hypotension (with simultaneous use with the anesthetic cyclopropane), shock, with too rapid administration – subarachnoid hemorrhage.

Respiratory, thoracic and mediastinal disorders frequency unknown – acute pulmonary edema without hyponatremia.

Gastrointestinal disorders frequency unknown – nausea, vomiting.

Reproductive system and breast disorders rare – pelvic organ hemorrhages, soft tissue tears of the genital tract; frequency unknown – with use in large doses or increased sensitivity – uterine hypertonus, cervical spasm, tetany, uterine rupture; increased bleeding in the postpartum period as a result of oxytocin-induced thrombocytopenia, afibrinogenemia, and hypoprothrombinemia.

Investigations frequency unknown – hyponatremia.

In the fetus or newborn

Frequency unknown as a consequence of maternal oxytocin administration – low Apgar score at 1 and 5 minutes; neonatal hyperbilirubinemia; with too rapid administration – decreased blood fibrinogen concentration; retinal hemorrhage; sinus bradycardia, tachycardia, ventricular extrasystole and other arrhythmias; CNS damage; hyponatremia; fetal death due to asphyxia.

Contraindications

• Hypersensitivity to oxytocin or any of the excipients of the drug;
• Severe cardiovascular diseases;
• Chronic renal failure;
• Discrepancy between the size of the mother’s pelvis and the fetus (anatomically or clinically narrow pelvis);
• Risk of uterine rupture due to its overdistension in polyhydramnios, multiple pregnancy, in multiparous women (more than 4 deliveries in history), especially in older women;
• Threatening uterine rupture;
• Presence of scars after previous cesarean section or other uterine surgeries;
• Uterine hypertonus (not occurring during labor), tendency to tetanic uterine contractions;
• Premature placental abruption, partial placenta previa or vasa previa (the entrance to the uterus is completely or partially blocked);
• Presentation or prolapse of the umbilical cord (the umbilical cord slips through the cervix before the baby is born);
• In the absence of clinical signs of cervical readiness for labor (immature cervix);
• Infectious diseases of the uterus;
• Oncological diseases of the uterus;
• Severe preeclampsia in the second half of pregnancy (preeclampsia, eclampsia);
• Premature birth;
• Transverse or oblique position of the fetus, face presentation of the fetus;
• Acute fetal hypoxia;
• Fetal distress.

The drug Oxytocin-Richter should not be administered within 6 hours after intravaginal administration of prostaglandins; long-term administration of the drug Oxytocin-Richter is not indicated in the absence of uterine sensitivity to oxytocin.

With caution

• Women over 35 years of age;
• If the pregnancy was complicated (preeclampsia in the second half of pregnancy, diabetes mellitus diagnosed during pregnancy, arterial hypertension, hypothyroidism);
• If the gestational age is more than 40 weeks;
• In case of cardiovascular diseases (including hypertrophic cardiomyopathy, heart valve damage and/or coronary artery disease, including coronary artery spasm), to avoid significant changes in blood pressure and heart rate;
• Long QT syndrome;
• Administration of the drug to patients receiving antihypertensive drugs and drugs that cause QT interval prolongation;
• Against the background of using inhalational anesthetics (cyclopropane, halothane, sevoflurane, desflurane), sympathomimetics and vasoconstrictors;
• Concomitant use with methylergometrine preparations;
• Tendency to fluid retention in the body;
• Latex allergy.

Use in Pregnancy and Lactation

Pregnancy

Given the extensive experience of use, chemical structure, and pharmacological properties of the drug, when prescribed according to indications (for the purpose of induction or enhancement of labor), no risk of fetal malformations is expected. In the first trimester of pregnancy, Oxytocin is used only for spontaneous or artificial abortion.

Breastfeeding period

Oxytocin penetrates into breast milk in small amounts. However, there is no reason to believe that Oxytocin will have an undesirable effect on the newborn, since in this case it enters the digestive tract, where it undergoes rapid inactivation.

Use in Hepatic Impairment

Clinical studies of oxytocin in patients with hepatic impairment have not been conducted.

Use in Renal Impairment

Contraindicated in chronic renal failure.

Pediatric Use

The safety and efficacy of oxytocin in children aged 0 to 18 years have not been established. Data are not available.

Geriatric Use

Not applicable. There are no indications for use.

Special Precautions

Oxytocin should not be used to stimulate labor until the fetal head is engaged in the pelvis. Before initiating Oxytocin therapy, the expected beneficial effect should be weighed against the possibility, albeit rare, of developing uterine hypertonus and tetany.

Every patient receiving intravenous Oxytocin must be in a hospital under constant supervision by specialists experienced in using the drug and identifying complications. Immediate specialist medical assistance must be available if necessary. During drug administration, the frequency of uterine contractions, the maternal and fetal heart activity, and the mother’s blood pressure should be constantly monitored to avoid complications.

If signs of uterine hyperstimulation appear, the administration of oxytocin should be stopped immediately; as a result, the uterine contractions induced by the drug usually cease shortly thereafter.

When used appropriately, Oxytocin induces uterine contractions similar to those in spontaneous labor. Excessive stimulation of the uterus due to improper use of the drug is dangerous for both the mother and the fetus. Even with appropriate use and monitoring, uterine hypertonic contractions can occur due to increased sensitivity to oxytocin.

The risk of developing afibrinogenemia and increased blood loss should be considered.

Cases of maternal death due to hypersensitivity reactions, subarachnoid hemorrhage, uterine rupture, as well as fetal death due to various reasons associated with the parenteral administration of the drug for labor induction and stimulation in the first and second stages of labor have been reported.

Safety Regarding the Cardiovascular System and Cerebral Circulation

Oxytocin should be used with particular caution in patients suffering from cardiovascular diseases (e.g., hypertrophic cardiomyopathy, valvular heart disease and/or coronary artery disease, including coronary artery spasm) and those predisposed to myocardial ischemia, to avoid significant changes in blood pressure and heart rate.

Oxytocin should be prescribed cautiously to patients with long QT syndrome or related symptoms, and to patients taking drugs that prolong the QT interval.

Disseminated Intravascular Coagulation

In rare cases, pharmacological labor induction using uterotonic drugs, including Oxytocin, is associated with an increased risk of developing disseminated intravascular coagulation (DIC) in the postpartum period. This risk is directly related to pharmacological induction itself, not to the use of a specific drug. The risk is primarily increased in women with additional risk factors for DIC: age over 35, complicated pregnancy (e.g., gestational diabetes, arterial hypertension, hypothyroidism), gestational age over 40 weeks. In such women, Oxytocin and other medications should be used with caution.

Fluid Overload

Since Oxytocin has a weak antidiuretic effect, prolonged intravenous administration of high doses of the drug together with the infusion of large volumes of fluids (e.g., during treatment of inevitable or incomplete abortion or postpartum hemorrhage) can cause fluid overload accompanied by hyponatremia. When oxytocin is administered concurrently with intravenous fluids, a combined antidiuretic effect is observed, leading to hypervolemia with subsequent development of hemodynamic acute pulmonary edema without hyponatremia. To avoid these rare complications when administering high doses of oxytocin over a long period, the following precautions should be observed: use an electrolyte-containing solvent (not dextrose); fluid infusions should be given in small volumes (the infused volume should be as small as possible, i.e., administer oxytocin in a higher concentration); oral fluid intake should be restricted; fluid intake and output should be monitored; and if an electrolyte imbalance is suspected, laboratory monitoring of electrolyte levels is indicated.

Anaphylaxis in Women with Latex Allergy

There are reports of anaphylaxis following oxytocin administration in women with a known latex allergy. Due to the existing structural homology between oxytocin and latex, latex allergy/intolerance may be an important predisposing risk factor for the development of anaphylaxis following oxytocin administration.

Excipients

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

This medicine contains a small amount of ethanol (alcohol), less than 100 mg per 5 IU.

Effect on Ability to Drive and Use Machines

Oxytocin does not affect the ability to drive vehicles, operate machinery, or engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

.

Overdose

The maximum dose of oxytocin has not been established. Oxytocin is inactivated by proteolytic enzymes in the digestive tract. Consequently, it is not absorbed in the intestines, and the development of toxic effects from oral intake is unlikely.

Symptoms of overdose depend mainly on the sensitivity of the uterus to oxytocin and are not related to the presence of hypersensitivity to the drug. With hyperstimulation, strong (hypertonic) or prolonged (tetanic) contractions occur, or an increase in resting uterine tone (between contractions) to 15-20 mm H₂O or more, leading to incoordinate labor, rupture of the uterine body or cervix, vagina, postpartum hemorrhage, utero-placental insufficiency, fetal bradycardia, fetal hypoxia, hypercapnia, and death.

With prolonged administration of high doses of the drug (40-50 mL/min), a serious adverse reaction in the form of fluid overload and convulsions may develop, which is due to the antidiuretic effect of oxytocin.

Treatment: If signs or symptoms of overdose occur during continuous intravenous infusion of oxytocin, the infusion must be stopped immediately and oxygen administered to the mother. In case of fluid overload, it is important to restrict fluid intake, promote diuresis, correct electrolyte balance, and control convulsions that may develop over time. In case of coma, airway patency must be maintained using standard methods employed for the care of an unconscious patient.

Drug Interactions

Pharmaceutical incompatibility of Oxytocin-Richter with other intravenously administered drugs is possible.

Concomitant use is contraindicated

Prostaglandins and their analogues

Prostaglandins and their analogues also promote myometrial contraction and, therefore, may enhance the stimulatory effect of oxytocin on the uterine muscles and vice versa. Thus, Oxytocin can be used no less than 6 hours after prostaglandin administration.

Concomitant use is not recommended

Medicinal products that prolong the QT interval

Oxytocin may potentially cause arrhythmia, especially in patients with other risk factors for polymorphic ventricular tachycardia of the ‘torsades de pointes’ type, i.e., in patients taking medicinal products that prolong the QT interval, or in patients with a history of long QT syndrome.

Caudal anesthesia – Vasoconstrictors

Oxytocin can enhance the vasoconstrictive effects of vasoconstrictors and sympathomimetics, even those contained in local anesthetics. Cases of severe arterial hypertension have been described when oxytocin was administered 3-4 hours after prophylactic use of vasoconstrictors in conjunction with caudal anesthesia.

Inhalational anesthetics (e.g., cyclopropane, halothane, sevoflurane, desflurane, enflurane)

Inhalational anesthetics have a relaxing effect on the uterus and cause a noticeable decrease in uterine tone, thus reducing the stimulatory effect of oxytocin. Cases of cardiac arrhythmia have been reported with the concomitant use of inhalational anesthetics and oxytocin.

During anesthesia with cyclopropane, enflurane, halothane, and isoflurane, the effect of oxytocin on the cardiovascular system may be altered, and unforeseen arterial hypotension may develop. Cases of maternal sinus bradycardia and abnormal atrioventricular rhythm have been described with oxytocin administration during cyclopropane anesthesia.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature between 2°C (35.6°F) and 15°C (59°F).

Shelf Life

The shelf life is 3 years. Do not use the drug after the expiration date.

The prepared solution should be used within (maximum) 8 hours after preparation.

Dispensing Status

The drug is dispensed by prescription.

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.