Oxymetrin Uses, Dosage, Side Effects and more
Methylergometrine is an ergot alkaloid, which directly stimulates contractions of uterine and vascular smooth muscle.
Methylergometrine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result.
Synthetically prepared Oxytocin is identical to the natural occurring hormone from the posterior pituitary gland. Oxytocin causes contractions of the uterus, thus mimicking contractions of normal, spontaneous labor and transiently impeding uterine blood flow. Amplitude and duration of uterine contractions are increased, leading to dilation and effacement of the cervix. Oxytocin also stimulates the smooth muscle associated with the secretory epithelium of the lactating breast causing ejection of milk out of the mammary ductular system but having no direct effect on milk secretion.Oxytocin has only minimal cardiovascular and antidiuretic properties. Therefore, it can safely be administered to patients in whom a (further) increase in blood pressure must be avoided, as in the case of hypertension, toxemia, (pre-) eclampsia, solution placenta and uremia.
Oxytocin is a nonapeptide, pleiotropic hormone that exerts important physiological effects. It is most well known to stimulate parturition and lactation, but also has important physiological influences on metabolic and cardiovascular functions, sexual and maternal behaviour, pair bonding, social cognition, and fear conditioning.
It is worth noting that oxytocin receptors are not limited to the reproductive system but can be found in many peripheral tissues and in central nervous system structures including the brain stem and amygdala.
| Trade Name | Oxymetrin |
| Generic | Methylergometrine + Oxytocin |
| Type | Injection |
| Therapeutic Class | |
| Manufacturer | Zydus Cadila Healthcare Ltd |
| Available Country | India |
| Last Updated: | January 7, 2025 at 1:49 am |
Uses
Treatment and prophylaxis of postpartum and postabortal haemorrhage, Treatment and prophylaxis of postpartum and postabortal haemorrhage, Prophylaxis of postpartum haemorrhage
In Antepartum:
- Induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, (pre-) eclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is used;
- Stimulation or reinforcement of labor, as in selected cases of uterine inertia;
- As adjunctive therapy in the management of incomplete or inevitable abortion.
In Postpartum: Oxytocin is used to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.
Oxymetrin is also used to associated treatment for these conditions: Postpartum Haemorrhage (PPH), Uterine Atony, Uterine subinvolutionIncomplete Abortion, Inevitable abortion, Postpartum Bleeding, Reinforcement of labor
How Oxymetrin works
Methylergometrine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss.
Oxytocin plays a vital role in labour and delivery. The hormone is produced in the hypothalamus and is secreted from the paraventricular nucleus to the posterior pituitary where it is stored. It is then released in pulses during childbirth to induce uterine contractions.
The concentration of oxytocin receptors on the myometrium increases significantly during pregnancy and reaches a peak in early labor. Activation of oxytocin receptors on the myometrium triggers a downstream cascade that leads to increased intracellular calcium in uterine myofibrils which strengthens and increases the frequency of uterine contractions.
In humans, most hormones are regulated by negative feedback; however, oxytocin is one of the few that is regulated by positive feedback. The head of the fetus pushing on the cervix signals the release of oxytocin from the posterior pituitary of the mother. Oxytocin then travels to the uterus where it stimulates uterine contractions. The elicited uterine contractions will then stimulate the release of increasing amounts of oxytocin. This positive feedback loop will continue until parturition.
Since exogenously administered and endogenously secreted oxytocin result in the same effects on the female reproductive system, synthetic oxytocin may be used in specific instances during the antepartum and postpartum period to induce or improve uterine contractions.
Dosage
Intramuscular (Adult)-
- Treatment and prophylaxis of postpartum and postabortal haemorrhage: 200 mcg. May repeat every 2-4 hr. Max: 5 doses.
Intravenous (Adult)-
- Treatment and prophylaxis of postpartum and postabortal haemorrhage:As an emergency measure: 200 mcg by slow inj over at least 1 minute, may repeat every 2-4 hr, up to a max of 5 doses.
Oral (Adult)-
- Prophylaxis of postpartum haemorrhage:200 mcg 3-4 times daily in the puerperium for 2-7 days.
Induction or Stimulation of Labor:
- The standard solution for infusion of Oxytocin is prepared by adding the contents of one 1ml vial containing 10 units of Oxytocin to 1000 ml of infusion fluids. The combined solution containing 10 mU (1mU=0.001U) of Oxytocin/ml is rotated in the infusion bottle for thorough mixing.
- The initial dose should be 0.5-1 mU/min (equal to 3-6 ml of the dilute Oxytocin solution per hour). At 30-60 minutes intervals the dose should be gradually increased in increments of 1-2 mU/min until the desired contraction pattern has been established. Once the desired frequency of contractions has been reached and labor has progressed to 5-6 cm dilation, the dose may be reduced by similar increments.
- At term, higher infusion rates should be given with great care and rates exceeding 9-10 mU/min are rarely required.
- Before term, when the sensitivity of the uterus is lower because of a lower concentration of Oxytocin receptors, a higher infusion rate may be required.
Control of Postpartum Uterine Bleeding:
- Intravenous Infusion (Drip Method): To control postpartum bleeding, 10 to 40 units of Oxytocin may be added to the bottle, depending on the amount of infusion fluids solution remaining (maximum 40 units to 1000 ml). Adjust infusion rate to sustain uterine contraction and control uterine atony.
- Intramuscular Administration: 1 mL (10 units) of Oxytocin can be given after the delivery of the placenta.
Treatment of Incomplete or Inevitable Abortion:
- Intravenous infusion of 10 units of Oxytocin added to 500 ml of a 0.9% sodium chloride solution may help the uterus contract after a suction or sharp curettage for an incomplete, inevitable or elective abortion.
- Subsequent to intra-amniotic injection of hypertonic saline, prostaglandins, urea etc., for mid trimester elective abortion, the injection-to-abortion time may be shortened by infusion of Oxytocin at the rate of 10 to 20 mU (20 to 40 drops) per minute. The total dose should not exceed 30 units in a 12-hour period due to the risk of water intoxication.
Infusion Fluids-
- 0.9% Sodium Chloride solution
- 5% Dextrose-in-water solution
- Ringer’s solution
- Hartmann’s solution (Ringer-lactate)
Side Effects
Headache, dizziness, hallucinations; tinnitus; nausea, vomiting, foul taste, diarrhoea; hypertension, temporary chest pain, palpitations, bradycardia; nasal congestion, dyspnoea; diaphoresis; thrombophlebitis; haematuria; water intoxication; leg cramps; allergic reactions.
- Hypersensitivity to the drug may result in uterine hypertonicity, spasm, titanic contraction or rupture of the uterus.
- The possibility of increased blood loss and afbrinigenemia should be kept in mind when administering the drug.
- Severe water intoxication with convulsions and coma has occurred.
- Oxytocin may occasionally cause nausea, vomiting, haemorrhage or cardiac arrhythmias, anaphylactic reaction.
Toxicity
Signs and symptoms of overexposure: hypertension, seizures, headache, hypotension, nausea, and vomiting.
Administration of supratherapeutic doses of exogenous oxytocin can lead to myocardial ischemia, tachycardia, and arrhythmias. High doses can also lead to uterine spasms, hypertonicity, or rupture. Oxytocin has antidiuretic properties, thus, high daily doses (as a single dose or administered slowly over 24 hours) may lead to extreme water intoxication resulting in maternal seizures, coma, and even death. The risk of antidiuresis and water intoxication in the mother appears to be greater when fluids are given orally.
Precaution
Captivation of the placenta may occur if given during the 2nd or 3rd stage of labour prior to delivery of the placenta; use in this situation should only be done by a qualified personnel. Avoid prolonged use. Caution in patients with sepsis, hepatic or renal impairment. Lactation.
Oxytocin should not be administered in the following conditions: prematurity, borderline cephalopelvic disproportion, previous major surgery on the cervix or uterus including caesarean section, overdistention of the uterus, grand multiparity or invasive cervical carcinoma.
Interaction
Possible increase in serum levels and risk of severe vasoconstrictive effects with potent CYP3A4 inhibitors (e.g. erythromycin, troleandomycin, clarithromycin, ritonavir, indinavir, nelfinavir, delavirdine, ketoconazole, itraconazole, voriconazole) and less potent CYP3A4 inhibitors (e.g. saquinavir, nefazodone, fluconazole, fluoxetine, fluvoxamine, zileuton, clotrimazole).
Severe hypertension has been reported when Oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal-block anesthesia. Cyclopropane anesthesia may modify Oxytocin’s cardiovascular effects, so as to produce unexpected results such as hypotension. Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when Oxytocin was used concomitantly with cyclopropane anesthesia.
Volume of Distribution
- 56.1 ± 0 L
Elimination Route
Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.
Oxytocin is administered parenterally and is fully bioavailable. It takes approximately 40 minutes for oxytocin to reach steady-state concentrations in the plasma after parenteral administration.
Half Life
3.39 hours
The plasma half-life of oxytocin ranges from 1-6 minutes. The half-life is decreased in late pregnancy and during lactation.
Clearance
In a study that observed 10 women who were given oxytocin to induce labor, the mean metabolic clearance rate was 7.87 mL/min.
Elimination Route
Ergot alkaloids are mostly eliminated by hepatic metabolism and excretion, and the decrease in bioavailability following oral administration is probably a result of first-pass metabolism in the liver.
The enzyme oxytocinase is largely responsible for the metabolism and regulation of oxytocin levels in pregnancy; only a small percentage of the neurohormone is excreted in the urine unchanged.
Pregnancy & Breastfeeding use
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Pregnancy category C. It is not known whether Oxytocin is excreted in human milk
Contraindication
Hypertension, eclamptic or previously hypertensive patients, heart disease, venoatrial shunts, mitral valve stenosis, obliterative vascular disease. Do not use in cases of threatened spontaneous abortion. Pregnancy.
This drug is contraindicated in- significant cephalopelvic disproportion; unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, e.g., transverse lies; in obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention; in cases of fetal distress where delivery is not imminent; hypertonic uterine patterns; hypersensitivity to the drug. Prolonged use in uterine inertia or severe toxemia is contraindicated. Oxytocin should not be used in cases where vaginal delivery is not indicated.
Acute Overdose
Symptoms: Prolonged gangrene, numbness in extremities, acute nausea, vomiting, abdominal pain, respiratory depression, changes in BP, seizures.
Management: Symptomatic and supportive.
Overdosage with Oxytocin depends essentially on uterine hyperactivity whether or not due to hypersensitivity to this agent. Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions, or a resting tone of 15 to 20 mm H2O or more between contractions can lead to tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, utero-placental hypoperfusion, and variable deceleration of fetal heart, fetal hypoxia, hypercapnia, or death. Water intoxication with convulsions, which is caused by the inherent antidiuretic effect of Oxytocin, is a serious complication that may occur if large doses (40 to 50 mU/minute) are infused for long periods. Management consists of immediate discontinuation of Oxytocin and symptomatic and supportive therapy.
Storage Condition
Intramuscular: Store under refrigeration at 2-8° C. Protect from light.
Intravenous: Store under refrigeration at 2-8° C. Protect from light.
Oral: Store below 25° C.
Store in between 2 to 8° C, in dark & frost free place. Keep out of the reach of children.
