Oxytocin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Pitocin: 10 units/mL (1 mL, 10 mL, 50 mL) [contains chlorobutanol (chlorobutol)]

Generic: 10 units/mL (1 mL, 10 mL, 30 mL)

Pharmacology

Mechanism of Action

Oxytocin stimulates uterine contraction by activating G-protein-coupled receptors that trigger increases in intracellular calcium levels in uterine myofibrils. Oxytocin also increases local prostaglandin production, further stimulating uterine contraction.

Pharmacokinetics/Pharmacodynamics

Excretion

Urine (small amount unchanged)

Onset of Action

Uterine contractions: IM: 3 to 5 minutes; IV: ~1 minute

Duration of Action

IM: 2 to 3 hours; IV: 1 hour

Half-Life Elimination

1 to 6 minutes; decreased in late pregnancy and during lactation

Use: Labeled Indications

Antepartum: Induction of labor in patients with a medical indication (eg, Rh problems, maternal diabetes, preeclampsia, at or near term); stimulation or reinforcement of labor (as in selected cases of uterine inertia); adjunctive therapy in management of incomplete or inevitable abortion

Postpartum: To produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

Contraindications

Hypersensitivity to oxytocin or any component of the formulation; significant cephalopelvic disproportion; unfavorable fetal positions or presentations (such as transverse lies); fetal distress when delivery is not imminent; hypertonic or hyperactive uterus; contraindicated vaginal delivery (invasive cervical cancer, active genital herpes, prolapse of the cord, cord presentation, total placenta previa, or vasa previa); obstetrical emergencies where surgical intervention is favored; where adequate uterine activity fails to achieve satisfactory progress

Canadian labeling: Additional contraindications (not in US labeling): Severe toxemia; prematurity or unripe cervix; predisposition to uterine rupture (eg, grand multiparity, overdistention of the uterus, previous caesarian delivery, other surgery involving the uterus); prolonged use in uterine inertia; factors predisposing to thromboplastin or amniotic fluid embolism (eg, prolonged retention of dead fetus, placental abruption); serious medical or obstetric conditions and any condition in which fetal distress already occurs; inability of physician to be in attendance

Dosage and Administration

Dosing: Adult

Note: Dosage is determined by uterine response and must be individualized and initiated at a very low level for each patient.

Induction or stimulation of labor: IV: Administration requires the use of an infusion pump. The ideal dosing regimen has not been determined (Leduc 2013) and various protocols are available (ACOG 2009; Leduc 2013; Wei 2010). Discontinue the oxytocin infusion immediately in the event of uterine hyperactivity and/or fetal distress. If uterine contractions become too powerful, the infusion can be stopped abruptly.

Initial: 0.5 to 1 milliunits/minute; gradually increase dose in increments of 1 to 2 milliunits/minute every 30 to 60 minutes until desired contraction pattern is established; dose may be decreased by similar increments after desired frequency of contractions is reached and labor has progressed to 5 to 6 cm dilation. Higher infusion rates may be needed prior to term due to a lower sensitivity of the uterus. Infusion rates up to 6 milliunits/minute provide oxytocin levels similar to those with spontaneous labor; rates >9 to 10 milliunits/minute are rarely required.

Low-dose regimen (off-label dose): Initial 0.5 to 2 milliunits/minute, incrementally increase by 1 to 2 milliunits/minute every 15 to 40 minutes (ACOG 2009).

High-dose regimen (off-label dose): Initial 6 milliunits/minute, incrementally increase by 3 to 6 milliunits/minute every 15 to 40 minutes. Reduce the incremental increase to 3 milliunits/minute if hyperstimulation occurs; reduce the incremental increase to 1 milliunit/minute for recurrent hyperstimulation (ACOG 2009).

Postpartum uterine bleeding: Note: Oxytocin is used for both prevention and treatment of postpartum hemorrhage associated with uterine atony and vaginal or surgical delivery (Vallera 2017; WHO 2012). Due to desensitization of oxytocin receptors and changes in receptor density in the myometrium, larger doses may be needed in women undergoing a nonelective cesarean delivery if oxytocin was previously administered during labor; repeated doses may become ineffective (Dyer 2011; Vallera 2017). Oxytocin may be administered by slow IV bolus, IV infusion, or IM injection. Rapid IV bolus administration is associated with cardiovascular collapse (ACOG 183 2017; Vallera 2017); rapid IV boluses are not recommended for women with cardiovascular risk factors (Sentilhes 2016). In women not requiring treatment by IV infusion, administration via slow IV bolus may be preferred over IM injection for the prevention of postpartum hemorrhage based on a study evaluating oxytocin use following vaginal delivery (Adnan 2018).

IM: 10 units after delivery of the placenta

IV: Note: The optimal regimen has not been established (AWHONN 2015; Dyer 2011; Vallera 2017)

5 units (Sentilhes 2016) or 10 units (AWHONN 2015; Sentilhes 2016; WHO 2012) may be given initially and can be followed by a maintenance infusion of 10 units/hour (AWHONN 2015; Sentilhes 2016). Maximum cumulative dose: 40 units (Sentilhes 2016).

The dose may be administered using a standardized infusion containing 30 units in 500 mL NS or LR (AWHONN 2015; Sumikura 2016) or by adding 10 to 40 units to a running infusion solution depending on amount of infusion fluid remaining (maximum: 40 units in 1,000 mL of IV fluid); adjust infusion rate to sustain uterine contraction and control uterine atony.

Lower bolus doses (0.5 to 3 units) for the prevention of postpartum bleeding have also been evaluated in women undergoing elective cesarean delivery (Butwick 2010; Carvalho 2004).

Adjunctive treatment of abortion: IV:

Incomplete, inevitable, or elective abortion: 10 units as an IV infusion after suction or a sharp curettage (used to help contract the uterus)

Midtrimester elective abortion: 10 to 20 milliunits/minute; maximum total dose: 30 units/12 hours (may decrease injection to abortion time)

Reconstitution

IV:

Induction or stimulation of labor: Add oxytocin 10 units to NS or LR 1,000 mL to yield a solution containing oxytocin 10 milliunits/mL or 30 units in 500 mL NS or LR (AWHONN 2015). Rotate solution to mix.

Postpartum uterine bleeding: Add oxytocin 10 to 40 units to running IV infusion (maximum: 40 units to 1,000 mL) or 30 units in 500 mL NS or LR (AWHONN 2015; Sumikura 2016).

Adjunctive management of abortion: Add oxytocin 10 units to 500 mL of a physiologic saline solution or D5W.

Administration

Induction or stimulation of labor: Administer as an IV infusion (drip method) by use of an infusion pump; accurate control of the rate of infusion flow is essential.

Incomplete or inevitable abortion: Administer by IV infusion

Postpartum uterine bleeding: Administer by IV or IM. IM administration may be used when IV access is not available (AWHONN 2015). IV push is not recommended; rapid IV bolus administration is associated with cardiovascular collapse (ACOG 183 2017; Vallera 2017). Slow IV injections (5 or 10 units over 1 minute) are preferred for women without cardiovascular risk factors; very slow injections (≥5 minutes) are preferred for women with cardiovascular risk factors (Sentilhes 2016).

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Carboprost Tromethamine: May enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Avoid combination

Dinoprostone: May enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: Concomitant use of dinoprostone and oxytocin is not recommended. If used sequentially, monitor uterine activity closely. Administer oxytocin 30 minutes after removing dinoprostone vaginal insert and 6 to 12 hours after the application of dinoprostone gel. Consider therapy modification

EPHEDrine (Nasal): Oxytocin may enhance the hypertensive effect of EPHEDrine (Nasal). Monitor therapy

EPHEDrine (Systemic): Oxytocin may enhance the hypertensive effect of EPHEDrine (Systemic). Monitor therapy

Gemeprost: May enhance the adverse/toxic effect of Oxytocin. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

MiSOPROStol: May enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of misoprostol recommends avoiding concomitant use with oxytocin. Misoprostol may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Adverse Reactions

Frequency not defined:

Cardiovascular: Cardiac arrhythmia, hypertensive crisis, hypotension (Dyer 2011), subarachnoid hemorrhage, tachycardia (Dyer 2011), ventricular premature contractions

Endocrine & metabolic: Water intoxication (severe water intoxication with seizure and coma is associated with a slow oxytocin infusion over 24 hours)

Gastrointestinal: Nausea, vomiting

Genitourinary: Postpartum hemorrhage, uterine rupture

Hematologic & oncologic: Pelvic hematoma

Hypersensitivity: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Antidiuretic effect: May produce intrinsic antidiuretic effect (ie, water intoxication). Severe water intoxication with convulsions, coma, and death may occur, particularly with large doses (40 to 50 milliunits/minute) or when given as a slow infusion over 24 hours and if the patient is receiving fluids by mouth.
• Cardiovascular effects: Arrhythmias, hypotension, myocardial ischemia, peripheral vasodilation, and tachycardia have been reported following administration. The risk of adverse events is influenced by dose and route of administration and is increased in women with cardiovascular disease. Use with extreme caution in hemodynamically unstable patients (Dyer 2011).
• Maternal deaths: Maternal deaths caused by hypertensive episodes, subarachnoid hemorrhage, or rupture of the uterus and fetal deaths have occurred with oxytocic medications when used for induction of labor or for augmentation in the first and second stages of labor.
• Uterine effects: High doses or hypersensitivity to oxytocin may cause uterine hypertonicity, spasm, tetanic contraction, or rupture of the uterus.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: To be used for medical rather than elective induction of labor. Oxytocin is used to initiate or improve uterine contractions in order to achieve a vaginal delivery; it should only be used when medically needed for fetal or maternal reasons. Medical indications for labor induction may include Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interest of mother or fetus, or premature rupture of membranes when delivery is indicated. Use is generally not recommended in the following conditions: Fetal distress, hydramnios, partial placenta previa, prematurity, borderline cephalopelvic disproportion, or conditions where there is a predisposition for uterine rupture (eg, previous major surgery on cervix or uterus, cesarean section, overdistention of the uterus, grand multiparity, past history of uterine sepsis or traumatic delivery).
• Appropriate use: Abortion: For the adjunctive management of abortion in the first trimester, curettage is generally considered primary therapy. Oxytocin infusion in second trimester abortion will often be effective; however, other therapy may be required.
• Trained personnel: IV preparations should be administered by adequately trained individuals familiar with its use and able to identify complications; continuous observation is necessary for all patients.

Monitoring Parameters

Fluid intake and output during administration, uterine activity (tonus, amplitude, and frequency of contractions), maternal blood pressure; fetal heart rate in relation to uterine contractions.

Pregnancy

Pregnancy Considerations

[US Boxed Warning]: To be used for medical rather than elective induction of labor.

Small amounts of exogenous oxytocin are expected to reach the fetal circulation. When used as indicated, teratogenic effects would not be expected. Nonteratogenic adverse reactions are reported in the neonate as well as the mother.

Patient Education

What is this drug used for?

• It is used to start labor.
• It is used to stop or treat bleeding that happens after a birth or an abortion.
• It is used to end a pregnancy.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Vomiting or nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like soaking one pad an hour
• Abnormal heartbeat
• Difficult urination
• Severe headache
• Dizziness
• Passing out
• Vision changes
• Slow heartbeat
• Seizures
• Severe abdominal pain
• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.