Oxytocin, a nonapeptide hormone secreted by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary (neurohypophysis) in mammals, indirectly stimulates contraction of uterine smooth muscle.
IV infusion of dilute solutions of oxytocin is the method of choice for inducing labor at term and stimulating uterine contractions during the first and second stages of labor.
Induction of labor with oxytocin infusion is indicated in term or near-term pregnancies associated with hypertension (e.g., preeclampsia, eclampsia, cardiovascular-renal disease), erythroblastosis fetalis, maternal or gestational diabetes mellitus, antepartum bleeding, or preterm, premature rupture of the membranes in which spontaneous labor does not ensue. Routine induction of labor with oxytocin may be indicated in prolonged pregnancies (greater than 42 weeks' gestation). Elective induction of labor merely for physician or patient convenience is not a valid indication for oxytocin use. In patients with eclampsia, if delivery is not imminent within 12 hours following an initial oxytocin infusion, some clinicians recommend cesarean section be done rather than continue administration of oxytocin.
Induction of labor also may be indicated in cases of uterine fetal death, fetal growth retardation, or static or decreasing maternal weight. However, in cases of missed abortion, intrauterine fetal death in late pregnancy, benign hydatidiform mole, or fetuses with anencephaly or erythroblastosis fetalis with hydrops or other congenital abnormalities incompatible with life, some clinicians recommend intravaginal dinoprostone because oxytocin may be relatively ineffective.
Pelvic adequacy and other maternal and fetal conditions (including fetal lung maturity) must be evaluated carefully whenever induction of labor is considered. Oxytocin should not be used to induce labor when the benefit-to-risk ratio for the mother or child favors surgical intervention. Induction of labor is contraindicated in cases of cephalopelvic disproportion, unfavorable fetal position or presentation (e.g., transverse lies), uterine or cervical scarring from previous cesarean section or major cervical or uterine surgery, fetal distress when delivery is not imminent, unengaged fetal head, when vaginal delivery is contraindicated (e.g., total placenta previa, vasa previa, cord presentation or prolapse, active genital herpes infection), or when uterine activity fails to progress adequately. Except in unusual circumstances requiring the clinician's judgment, the manufacturers warn that labor generally should not be induced with oxytocin when pregnancy is complicated by fetal distress, hydramnios, partial placenta previa, prematurity, borderline cephalopelvic disproportion, previous major surgery of the cervix or uterus (including cesarean section), overdistension of the uterus, grand multiparity, invasive cervical carcinoma, or history of uterine sepsis or traumatic delivery. Oxytocin should not be administered for prolonged periods in cases of severe toxemia.
During the first and second stages of labor, IV oxytocin infusion may be used to augment contractions if labor is prolonged or if dysfunctional uterine inertia occurs. Use of oxytocin is not recommended when labor is progressing normally during the first and second stages or when hypertonic patterns of labor occur, especially since response to the drug may be accentuated during the second stage of labor. In cases of uterine inertia, the drug should not be administered for prolonged periods (usually not more than 6-8 hours). Oxytocin should not be used to augment labor when vaginal delivery is contraindicated (e.g., total placenta previa).
Oxytocin infusions have been used to shorten the third stage of labor immediately following delivery of the infant (when the absence of additional fetuses is established), but some clinicians warn that oxytocics may inhibit, rather than assist in, expulsion of the placenta and increase the risk of hemorrhage and infection. If an oxytocic is used for this purpose, however, most clinicians recommend oxytocin.
Infusion of oxytocin is routinely used postpartum or following cesarean section to stimulate immediate contractions of the uterus and to control uterine bleeding. However, for the management of postpartum hemorrhage and uterine atony, most clinicians prefer ergonovine or methylergonovine to oxytocin unless an immediate contractile response is desired, because the amine ergot alkaloids produce more sustained contractions and higher uterine tonus than does oxytocin. Some clinicians prefer to manage postpartum bleeding with dilute IV oxytocin followed by an amine ergot alkaloid administered IM.
Other Uses of Parenteral Oxytocin
Oxytocin infusion has been used following prostaglandin or hypertonic abortifacients to shorten the induction-to-abortion time when these abortifacients are being used to induce second trimester abortions, to induce abortion when a patient has failed to respond to the abortifacient, or to induce abortion after membranes have ruptured. Oxytocin also has been used as an adjunct in cases of incomplete abortion when the placenta fails to abort spontaneously within 1 hour after abortion of the fetus; however, some clinicians maintain that oxytocin may hinder rather than assist in expulsion of the placenta. Because concurrent use of oxytocin with abortifacients may produce uterine contractions of such intensity that uterine rupture or cervical laceration may be more likely to occur, oxytocin usually should not be administered until the oxytocic effect of the abortifacient has subsided, and patients should be carefully monitored. Oxytocin, however, is routinely used in conjunction with hypertonic urea- and dinoprostone-induced abortions.
Oxytocin infusion has been used with success to evaluate the adequacy of fetal respiratory capabilities in high-risk pregnancies of greater than 31 weeks gestation†. By inducing uterine contractions, oxytocin transiently impedes uterine blood flow. If placental reserve is low, a late deceleration in fetal heart rate may occur following oxytocin administration, indicating chronic hypoxia (positive response). If fetal heart rate is unchanged (negative response) by the oxytocin challenge, adequate placental support is probably available. The test should be repeated in 1 week to reassess fetal response. A positive response indicates that there may be fetal distress and may be an indication for termination of pregnancy, especially if a lecithin-sphingomyelin ratio of greater than 1.5 can be demonstrated.
As an oxytocic, oxytocin should be given by IV infusion using a controlled-infusion device. Although oxytocin has been given IM, most clinicians believe this route of administration should not be used for augmentation or induction of labor because the effects it produces are unpredictable and difficult to control.
Prior to IV administration, the commercially available injection must be diluted. Generally, oxytocin infusions containing 10 milliunits/mL are used for induction or augmentation of labor. This solution may be prepared by adding 10 units (1 mL of the commercially available injection) to 1 L of 0.9% sodium chloride, lactated Ringer's, or 5% dextrose injection. Except under unusual circumstances, a physiologic electrolyte solution preferably should be used for preparing IV infusions of the drug intended for use in the induction or augmentation of labor. Infusions containing 20 milliunits/mL are used to produce intense uterine contractions and reduce postpartum bleeding, and as adjuncts to prostaglandin or hypertonic abortifacients. This solution may be prepared by adding 10 units (1 mL of the commercially available injection) to 500 mL of one of the above IV infusion solutions.
Standardized concentrations for oxytocin have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 250Multidisciplinary expert panels were convened to determine recommended standard concentrations. 250Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 250 For additional information on S4S (including updates that may be available), see [Web]. 250
Oxytocin dosage and rate of infusion are determined by uterine response. The drug should be discontinued if prolonged uterine contractions (greater than 90 seconds in duration) or rising intrauterine pressure occur or if uterine motility interferes with fetal heart rate; in addition, oxygen should be administered to the mother, who preferably should be in the lateral position, and other appropriate measures taken as necessary. For induction of labor, oxytocin usually is infused at an initial rate of 0.5-1 milliunit/minute. The infusion rate generally is increased in 1- to 2-milliunit/minute increments at 30- to 60-minute intervals until a response is observed. When the desired frequency of contractions is established (a uterine pattern comparable to spontaneous labor), without evidence of fetal distress, and labor has progressed to 5-6 cm dilation, the rate of oxytocin infusion may be reduced by similar increments. IV infusion rates up to 6 milliunits/minute have been shown to produce oxytocin concentrations in maternal plasma comparable to those associated with spontaneous labor. At term, higher rates of infusion should be employed with caution, and rates exceeding 9-10 milliunits/minute rarely are required. Before term, when uterine sensitivity to oxytocin is reduced secondary to decreased oxytocin receptors, higher infusion rates may be necessary.
To produce intense uterine contractions and reduce postpartum bleeding after expulsion of the placenta, a total of 10 units of oxytocin may be infused at a rate of 20-40 milliunits/minute after delivery of the infant(s) (when the absence of additional fetuses is established); rate is adjusted to maintain uterine contraction and control uterine atony. Most clinicians recommend that oxytocin not be given until after delivery of the placenta.
Other Uses of Parenteral Oxytocin
When used to shorten the induction-to-abortion time, to induce abortion in patients who have failed to abort following administration of second trimester abortifacients, or to induce abortion after membranes have ruptured, IV oxytocin infusions of 10-100 milliunits/minute have been used. However, it is recommended that cumulative dose in a 12-hour period not exceed 30 units because of the risk of water intoxication.
To evaluate fetal distress† using the oxytocin challenge test, 5-10 units of oxytocin (0.5-1.0 mL of the commercially available injection) is diluted with 1 L of 5% dextrose injection; the resultant solution contains 5-10 milliunits/mL. Initially the drug is infused IV in the mother at a rate of 0.5 milliunits/minute. The infusion rate may be gradually increased at 15- to 30-minute intervals to a maximum of 20 milliunits/minute. Fetal heart rate and uterine contractions should be monitored immediately before and during the oxytocin infusion. When 3 moderate uterine contractions occur within one 10-minute interval, the infusion should be discontinued and baseline and oxytocin-induced fetal heart rates should be compared. If no change in fetal heart rate occurs, the test should be repeated in 1 week. If a late deceleration in fetal heart rate occurs, termination of the pregnancy may be indicated.
When oxytocin is administered in excessive dosage, with abortifacients or to sensitive patients, hyperstimulation of the uterus, with strong (hypertonic) and/or prolonged (tetanic) contractions, or a resting uterine tone of 15-20 mm H2O between contractions may occur, possibly resulting in uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, abruptio placentae, impaired uterine blood flow, amniotic fluid embolism, and fetal trauma including intracranial hemorrhage. Increased uterine motility also may cause adverse fetal effects, including sinus bradycardia, tachycardia, premature ventricular complexes and other arrhythmias, permanent CNS or brain damage, and death secondary to asphyxia. Excessive maternal dosage or administration of the drug to sensitive women also can cause uteroplacental hypoperfusion and variable deceleration of fetal heart rate, fetal hypoxia, perinatal hepatic necrosis, and fetal hypercapnia. Rare incidents of pelvic hematoma have been reported, but these were probably also related to the high incidence of operative vaginal deliveries in primiparas, the fragility of engorged pelvic veins (especially if varicosed), and faulty episiotomy repair.
When large amounts of oxytocin are administered, severe decreases in maternal systolic and diastolic blood pressure, increases in heart rate, systemic venous return and cardiac output, and arrhythmia may occur; these effects may be particularly hazardous to patients with valvular heart disease and those receiving spinal and epidural anesthesia.
Postpartum bleeding may be increased by administration of oxytocin; this effect may be related to reports of oxytocin-induced thrombocytopenia, afibrinogenemia, and hypoprothrombinemia. By carefully controlling delivery, the incidence of postpartum bleeding may be minimized.
Nausea, vomiting, maternal sinus bradycardia, and premature ventricular complexes reported in patients receiving oxytocin are probably related to labor and not the drug. The risk of neonatal hyperbilirubinemia appears to be about 1.6 times greater following oxytocin-induced labor than that following spontaneous labor, and neonatal jaundice has occurred. Other adverse neonatal effects from oxytocin-induced labor include retinal hemorrhage and low Apgar scores at 5 minutes.
Severe water intoxication with seizures, coma, and death has been reported following prolonged IV infusion of oxytocin with an excessive volume of fluid. Neonatal seizures also have been reported. Injudicious use of oxytocin has also resulted in maternal deaths secondary to hypertensive episodes and subarachnoid hemorrhage.
Anaphylactic and other allergic reactions have occurred in patients receiving oxytocin and may rarely be fatal.
Precautions and Contraindications
Parenteral oxytocin should be used only by qualified professional personnel in a hospital where intensive care and surgical facilities are immediately available. During administration of oxytocin, uterine contractions, fetal and maternal heart rate, maternal blood pressure, and, if possible, intrauterine pressure should be continuously monitored to avoid complications. If uterine hyperactivity occurs, oxytocin administration should be immediately discontinued; oxytocin-induced stimulation of uterine contractions usually decreases soon after discontinuance of the drug. Electronic monitoring of the fetus is the best method for early detection of oxytocin overdosage. However, accurate measurement of intrauterine pressure during contractions requires intrauterine pressure recording. Determination of fetal heart rate via a fetal scalp electrode is more dependable than via external monitoring.
Since oxytocin may produce some antidiuretic effects, some clinicians recommend restricting fluid intake, avoiding administration of low-sodium infusion fluids and high oxytocin doses for prolonged periods, and monitoring fluid intake and output during administration of the drug.
Oxytocin should not be given simultaneously by more than one route of administration. Oxytocin is contraindicated in patients with a history of hypersensitivity to the drug. For additional discussion on the precautions and contraindications associated with oxytocin, see Uses.
Mutagenicity and Carcinogenicity
The mutagenic and carcinogenic potentials of oxytocin have not been determined.201, 202, 203
Pregnancy, Fertility, and Lactation
Animal reproduction studies have not been performed with oxytocin;203 however, the manufacturers state that the drug is not indicated for use during the first or second trimester of pregnancy other than in relation to spontaneous or induced abortion.201, 202, 203 Based on wide experience with oxytocin and on its chemical and pharmacologic properties, the drug would not be expected to cause fetal abnormalities when used as indicated.201, 202, 203 Oxytocin can, however, cause nonteratogenic adverse effects.201, 202, 203 (See Cautions: Adverse Effects.)
It is not known whether oxytocin affects fertility.201, 202, 203
Oxytocin may be distributed in small quantities into milk.202 If oxytocin therapy is required postpartum (e.g., to control severe bleeding), commencement of nursing should be delayed for at least 1 day after the drug has been discontinued.202
Severe hypertension has been reported when oxytocin was given 3-4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia. Cyclopropane anesthesia may modify oxytocin's cardiovascular effects, producing less pronounced tachycardia but more severe hypotension than occurs with oxytocin alone; maternal sinus bradycardia with abnormal atrioventricular rhythms has been noted when oxytocin was used concomitantly with cyclopropane anesthesia. Oxytocin reportedly has delayed induction of thiopental (no longer commercially available in the US) anesthesia by producing venous spasm that caused peripheral pooling of thiopental; however, this interaction has not been conclusively established.
Exogenous oxytocin elicits all the pharmacologic responses usually produced by endogenous oxytocin.
Oxytocin indirectly stimulates contraction of uterine smooth muscle by increasing the sodium permeability of uterine myofibrils. High estrogen concentrations lower the threshold for uterine response to oxytocin. Uterine response to oxytocin increases with the duration of pregnancy and is greater in patients who are in labor than those not in labor; only very large doses elicit contractions in early pregnancy. Contractions produced in the term uterus by oxytocin are similar to those occurring during spontaneous labor. In the term uterus, oxytocin increases the amplitude and frequency of uterine contractions which in turn tend to decrease cervical activity producing dilation and effacement of the cervix and to transiently impede uterine blood flow.
Oxytocin contracts myoepithelial cells surrounding the alveoli of the breasts, forcing milk from the alveoli into the larger ducts and thus facilitating milk ejection. The drug possesses no galactopoietic properties.
Oxytocin produces vasodilation of vascular smooth muscle, increasing renal, coronary, and cerebral blood flow. Blood pressure is usually unchanged, but following IV administration of very large doses or undiluted solutions, blood pressure may decrease transiently, and tachycardia and an increase in cardiac output may be reflexly induced. Any initial fall in blood pressure is usually followed by a small but sustained increase in blood pressure.
In contrast to vasopressin, oxytocin has minimal antidiuretic effects; however, water intoxication may occur when oxytocin is administered with an excessive volume of electrolyte-free IV fluids and/or at too rapid a rate.
Oxytocin is destroyed by chymotrypsin in the GI tract. Uterine response occurs almost immediately and subsides within 1 hour following IV administration of oxytocin. Following IM injection of the drug, uterine response occurs within 3-5 minutes and persists for 2-3 hours. Following intranasal application of 10-20 units of oxytocin (nasal preparations are no longer commercially available in the US), contractions of myoepithelial tissue surrounding the alveoli of the breasts begin within a few minutes and continue for 20 minutes; IV oxytocin produces the same effect with a dose of 100-200 milliunits.
Like vasopressin, oxytocin is distributed throughout the extracellular fluid. Small amounts of oxytocin probably reach the fetal circulation.
Oxytocin has a plasma half-life of about 3-5 minutes. Most of the drug is rapidly destroyed in the liver and kidneys. Oxytocinase, a circulating enzyme produced early in pregnancy, is also capable of inactivating the polypeptide. Only small amounts of oxytocin are excreted in urine unchanged.
Oxytocin is a nonapeptide hormone secreted by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary (neurohypophysis) in mammals. Commercially available oxytocin preparations are prepared synthetically. Although the highly purified synthetic preparations are substantially free from the pressor and antidiuretic principles of the posterior pituitary, even these preparations may contain some impurities with inherent pressor and antidiuretic properties which may be manifested following administration of large doses. The potency of oxytocin is standardized according to its vasodepressor activity in chickens (which closely parallels oxytocic activity) and is expressed in USP Posterior Pituitary units. Each unit is equivalent to about 2-2.2 mcg of the pure hormone.
Oxytocin occurs as a white powder and is soluble in water. During manufacture, the pH of commercially available oxytocin injection is adjusted to 2.5-4.5 with acetic acid.
Oxytocin injection should be stored at temperatures less than 15-25°C but should not be frozen. Pitocin® should be refrigerated at 2-8°C but may be exposed to temperatures ranging from 15-25°C for up to 30 days; Pitocin® exposed to this latter temperature range for longer periods should be discarded.
Oxytocin injection appears to be compatible with most IV infusion fluids but is reported to be physically incompatible with fibrinolysin, norepinephrine bitartrate, prochlorperazine edisylate, and warfarin sodium. Oxytocin injection has also been reported to be incompatible with various other drugs, but the compatibility depends on several factors (e.g., the concentration of the drugs, resulting pH, temperature). Specialized references should be consulted for more specific compatibility information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 10 units/mL* | Oxytocin Injection | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
201. Wyeth. Oxytocin injection (synthetic) prescribing information. In: Physicians' desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:2771-2.
202. Sandoz. Syntocinon® (oxytocin) injection prescribing information. In: Physicians' desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:2296-7.
203. Parke-Davis. Pitocin® (oxytocin) synthetic injection prescribing information. Morris Plains, NJ; 1994 May.
250. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]