Oxtimon

Each mL contains: Oxytocin 10 units.
Oxytocin is a nonapeptide hormone having the property of causing the contraction of uterine smooth muscle and of the myoepithelial cells within the mammary glands. It is prepared by synthesis or obtained from the posterior lobe of the pituitary of healthy domestic animals used for food by man. Its oxytocic activity is not less than 400 USP units per mg. Store in airtight containers at 2 to 8 degrees celsius.

Pharmacotherapeutic group: Systemic hormonal preparations, excl. sex hormones and insulins, oxytocin and analogues.
Pharmacology: Pharmacodynamics: Mechanism of action: Oxytocin is a cyclic nonapeptide that is obtained by chemical synthesis. This synthetic form is identical to the natural hormone that is stored in the posterior pituitary and released into the systemic circulation in response to suckling and labour.
Oxytocin stimulates the smooth muscle of the uterus, more powerfully towards the end of pregnancy, during labour, and immediately postpartum. At these times, the oxytocin receptors in the myometrium are increased.
The oxytocin receptors are G-proteins coupled receptors. Activation of receptor by oxytocin triggers release of calcium from intracellular stores and thus leads to myometrial contraction.
Oxytocin elicits rhythmic contractions in upper segment of uterus, similar in frequency, force and duration to those observed during labour.
Being synthetic, oxytocin in this product does not contain vasopressin, but even in its pure form oxytocin possesses some weak intrinsic vasopressin-like antidiuretic activity.
Based on in vitro studies, prolonged exposure of oxytocin had been reported to cause desensitisation of oxytocin receptors probably due to down-regulation of oxytocin-binding sites, destabilisation of oxytocin receptors mRNA and internalisation of oxytocin receptors.
Plasma levels and onset/duration of effect: Intravenous infusion. When oxytocin is given by continuous i.v. infusion at doses appropriate for induction or enhancement of labour, the uterine response sets in gradually and usually reaches a steady state within 20 to 40 minutes. The corresponding plasma levels of oxytocin are comparable to those measured during spontaneous first-stage labour. For example, oxytocin plasma levels in 10 pregnant women at term receiving a 4 milliunits per minute intravenous infusion were 2 to 5 microunits/mL. Upon discontinuation of the infusion, or following a substantial reduction in the infusion rate, e.g. in the event of overstimulation, uterine activity declines rapidly but may continue at an adequate lower level.
Pharmacokinetics: Absorption: Plasma levels of oxytocin following intravenous infusion at 4 milliunits per minute in pregnant women at term were 2 to 5 microunits/mL.
Distribution: The steady-state volume of distribution determined in 6 healthy men after i.v. injection is 12.2 L or 0.17 L/kg. Plasma protein binding is negligible for oxytocin. It crosses the placenta in both directions. Oxytocin may be found in small quantities in mother's breast milk.
Biotransformation/Metabolism: Oxytocinase is a glycoprotein aminopeptidase that is produced during pregnancy and appears in the plasma. It is capable of degrading oxytocin. It is produced from both the mother and the foetus. Liver and kidney plays a major role in metabolising and clearing oxytocin from the plasma. Thus, liver, kidney and systemic circulation contribute to the biotransformation of oxytocin.
Elimination: Plasma half-life of oxytocin ranges from 3 to 20 minutes. The metabolites are excreted in urine whereas less than 1% of the oxytocin is excreted unchanged in urine. The metabolic clearance rate amounts to 20 mL/kg/min in the pregnant woman.
Renal impairment: No studies have been performed in renally impaired patients. However, considering the excretion of oxytocin and its reduced urinary excretion because of anti-diuretic properties, the possible accumulation of oxytocin can result in prolonged action.
Hepatic impairment: No studies have been performed in hepatically impaired patients. Pharmacokinetic alteration in patients with impaired hepatic function is unlikely since metabolising enzyme, oxytocinase, is not confined to liver alone and the oxytocinase levels in placenta during the term has significantly increased. Therefore, biotransformation of oxytocin in impaired hepatic function may not result in substantial changes in metabolic clearance of oxytocin.
Toxicology: Preclinical safety data: It reveals no special hazard for humans based on conventional studies of single dose acute toxicity, genotoxicity, and mutagenicity.

Oxytocin Injection may be used for: Induction of labour for medical reasons; stimulation of labour in hypotonic uterine inertia; during cesarean section following the delivery of the child; prevention and treatment of postpartum uterine atony and hemorrhage. Oxytocin Injection may also be indicated in early stages of pregnancy as an adjunctive therapy for the management of incomplete, inevitable or missed abortion.

Induction or enhancement of labour: Oxytocin Injection should be administered as an intravenous drip infusion or, preferably, by means of a variable-speed infusion pump. For drip infusion it is recommended that 10 I.U. of Oxytocin Injection be added to 1L of a physiologic electrolyte solution. For patients in whom infusion of sodium chloride must be avoided, 5% dextrose solution may be used as the diluent (see Precautions). To ensure even mixing, the bottle or bag must be turned upside down several times before use. The initial infusion rate should be set at 1-4 mU/min (2-8 drops/min). It may be gradually increased at intervals not shorter than 20 min, until a contraction pattern similar to that of normal labour is established. In pregnancy near term this can often be achieved with an infusion of less than 10 mU/min (20 drops/min), and the recommended maximum rate is 20 mU/min (40 drops/min). In the unusual event that higher rates are required, as may occur in the management of fetal death in utero or for induction of labour at an earlier stage of pregnancy, when the uterus is less sensitive to oxytocin, it is advisable to use a more concentrated Oxytocin Injection solution, e.g. 10 I.U. in 500 mL. When using a motor-driven infusion pump which delivers smaller volumes than those given by drip infusion, the concentration suitable for infusion with the recommended dosage range must be calculated according to the specifications of the pump. The frequency, strength and duration of contractions as well as the fetal heart must be carefully monitored throughout the infusion. Once an adequate level of uterine activity is attained, the infusion rate can often be reduced. In the event of uterine hyperactivity and/or fetal distress, the infusion must be discontinued immediately. If, in women who are at term or near term, regular contractions are not established after the infusion of a total amount of 5 I.U., it is recommended that the attempt to induce labour be ceased; it may be repeated on the following day, starting again from a rate of 1-4 mU/min.
Cesarean section: 5 I.U. by slow intravenous injection immediately after delivery.
Prevention of postpartum hemorrhage: The usual dose is 5 I.U slowly IV after delivery of the placenta. In women given Oxytocin Injection for induction or enhancement of labour, the infusion should be continued at an increased rate during the third stage of labour and for the next few hours thereafter.
Treatment of postpartum uterine hemorrhage: 5-10 I.U. IM or 5 I.U. slowly IV, followed in severe cases by intravenous infusion of a solution containing 5-20 I.U. of oxytocin in 500 mL of a non-hydrating diluent, run at the rate necessary to control uterine atony.
Incomplete, inevitable, or missed abortion: 5 I.U. IM or slowly IV, if necessary followed by intravenous infusion at a rate of 20-40 mU/min or higher.
Or as prescribed by the physician.

The fatal dose of Oxytocin Injection has not been established. Oxytocin Injection is subject to inactivation by proteolytic enzymes of the alimentary tract. Hence it is not absorbed from the intestine and is not likely to have toxic effects when ingested. The symptoms and consequences of overdosage are those mentioned under Side Effects. In addition, as a result of uterine overstimulation, placental abruption and/or amniotic fluid embolism have been reported.
When signs or symptoms of overdosage occur during continuous IV administration of Oxytocin Injection, the infusion must be discontinued at once and oxygen should be given to the mother. In cases of water intoxication it is essential to restrict fluid intake, promote diuresis, correct electrolyte imbalance, and control convulsions that may eventually occur, by judicious use of diazepam. In the case of coma, a free airway should be maintained with routine measures normally employed in the nursing of the unconscious patient.

Hypersensitivity to the drug.
Hypertonic uterine contractions, mechanical obstruction to delivery, fetal distress. Any condition in which for fetal or maternal reasons spontaneous labour is inadvisable and/or vaginal delivery is contraindicated, e.g. significant cephalopelvic disproportion, fetal malpresentation; placenta previa and vasa previa, placental abruption, cord presentation or prolapse, overdistension or impaired resistance of the uterus to rupture as in multiple pregnancy, polyhydramnios, grand multiparity and in the presence of a uterine scar resulting from major surgery including classical cesarean section. Oxytocin Injection should not be used for prolonged periods in patients with oxytocin-resistant uterine inertia, severe pre-eclamptic toxemia or severe cardiovascular disorders.

The induction of labour by means of oxytocin should be attempted only when strictly indicated for medical reasons. Administration should only be under hospital conditions and qualified medical supervision. When given for induction and enhancement of labour, Oxytocin Injection must only be administered as an intravenous infusion and never by intravenous bolus injection. Careful monitoring of fetal heart rate and uterine motility (frequency, strength, and duration of contractions) is essential, so that the dosage may be adjusted to individual response.
When Oxytocin Injection is given for induction or enhancement of labour, particular caution is required in the presence of borderline cephalopelvic disproportion, secondary uterine inertia, mild to moderate degrees of pregnancy-induced hypertension or cardiac disease and in patients above 35 years of age or with a history of lower-uterine-segment cesarean sections.
In the case of fetal death in utero, and/or in the presence of meconium-stained amniotic fluid, tumultuous labour must be avoided, as it may cause amniotic fluid embolism.
Because oxytocin possesses slight antidiuretic activity, its prolonged intravenous administration at high doses in conjunction with large volumes of fluid, as may be the case in the treatment of inevitable or missed abortion, or in the management of postpartum hemorrhage, may cause water intoxication associated with hyponatremia. To avoid this rare complication, the following precautions must be observed whenever high doses of oxytocin are administered over a long time; an electrolyte-containing diluent must be used (not dextrose); the volume of infused fluid should be kept low (by infusing oxytocin at a higher concentration than recommended for the induction or enhancement of labour at term); fluid intake by mouth must be restricted; a fluid balance chart should be kept, and serum electrolytes should be measured when electrolyte imbalance is suspected.
When Oxytocin Injection is used for prevention or treatment of uterine hemorrhage, rapid intravenous injection should be avoided, as it may cause an acute short-lasting drop in blood pressure. Prostaglandins may potentiate the uterotonic effect of oxytocin and vice versa; therefore, concomitant administration requires very careful monitoring. Some inhalation anesthetics, e.g. cyclopropane or halothane, may enhance the hypotensive effects of oxytocin and reduce its oxytocic action. Their concurrent use with oxytocin has also been reported to cause cardiac rhythm disturbances.
When given during or after caudal block anesthesia, oxytocin may potentiate the pressor effect of sympathomimetic vasoconstrictor agents.
Oxytocin Injection should not be infused via the same apparatus as blood or plasma, because the peptide linkages are rapidly inactivated by oxytocin-inactivating enzymes. Oxytocin Injection is incompatible with solutions containing sodium metabisulfite as a stabilizer.
Oxytocin Injection is compatible with the following infusions fluids, but due attention should be paid to the advisability of using electrolyte fluids in individual patients: Dextrose 5%, Sodium/potassium chloride (103 mmol Na and 51 mmol K), Laevulose 20%, Macrodex 6%, Sodium bicarbonate 1.39%, Sodium chloride 0.9%, Sodium lactate 1.72%, Rheomacrodex 10%, Ringer's solution.

Pregnancy: The induction of labour by means of oxytocin should be attempted only when strictly indicated for medical reasons.
Animal reproduction studies have not been conducted with oxytocin. Based on the wide experience with this drug and its chemical structure and pharmacological properties, it is not expected to present a risk of foetal abnormalities when used as indicated.
Breastfeeding: Oxytocin may be found in small quantities in mother's breast milk. However, oxytocin is not expected to cause harmful effects in the newborn because it passes into the alimentary tract where it undergoes rapid inactivation.

As there is a wide variation in uterine sensitivity, uterine spasm may be caused in some instances by what are normally considered to be low doses. When Oxytocin Injection is used by IV infusion for the induction or enhancement of labour, its administration at too high doses results in uterine overstimulation which may cause fetal distress, asphyxia, and death, or may lead to hypertonicity, tetanic contractions, soft tissue damage or rupture of the uterus. Water intoxication associated with maternal and neonatal hyponatremia has been reported in cases where high doses of oxytocin together with large amounts of electrolyte-free fluid have been administered over a prolonged period of time (see Precautions).
Symptoms of water intoxication include: Headache, anorexia, nausea, vomiting and abdominal pain.
Lethargy, drowsiness, unconsciousness and grand-mal type seizures.
Low blood electrolyte concentration.
Rapid intravenous bolus injection of oxytocin at doses amounting to several I.U. may result in acute short-lasting hypotension accompanied with flushing and reflex tachycardia. Oxytocin may occasionally cause nausea, vomiting or cardiac arrhythmias. In a few cases, skin rashes and anaphylactoid reactions associated with dyspnea, hypotension, or shock have been reported.

Interactions resulting in a concomitant use not recommended: Prostaglandins and their analogues: Prostaglandins and their analogues facilitate contraction of the myometrium hence oxytocin can potentiate the uterine action of prostaglandins and analogues and vice versa.
Drugs prolonging the QT interval: Oxytocin should be considered as potentially arrhythmogenic, particularly in patients with other risk factors for Torsades de Pointes such as drugs which prolong the QT interval or in patients with history of long QT syndrome.
Interactions to be considered: Inhalation anaesthetics: Inhalation anaesthetics (e.g. cyclopropane, halothane, sevoflurane, desflurane) have a relaxing effect on the uterus and produce a notable inhibition of uterine tone and thereby, may diminish the uterotonic effect of oxytocin. Their concurrent use with oxytocin has also been reported to cause cardiac rhythm disturbances.
Vasoconstrictors/Sympathomimetics: Oxytocin may enhance the vasopressor effects of vasoconstrictors and sympathomimetics, even those contained in local anaesthetics.
Caudal anaesthetics: When given during or after caudal block anaesthesia, oxytocin may potentiate the pressor effect of sympathomimetic vasoconstrictor agents.

Store at temperatures between 2-8°C. Do not freeze. Any portion of the content remaining should be discarded.

Drugs Acting on the Uterus

H01BB02 - oxytocin ; Belongs to the class of oxytocin and analogues. Used in posterior pituitary lobe hormone preparations.

Rx