Oxytocin

Oxytocin is a nine-amino-acid neurohypophyseal peptide hormone. The FDA-approved product is oxytocin injection (Pitocin and generics), given intravenously or intramuscularly for obstetric indications. No FDA-approved oral, sublingual, buccal or nasal oxytocin product is marketed in the US. Lake Hills Pharmacy compounds oxytocin as a 503A pharmacy, pursuant to patient-specific prescriptions, in non-sterile preparations such as rapid dissolve tablets, alone or in combination.

• Pitocin (IV or IM), antepartum: to start or improve uterine contractions where there is a medical reason for induction or augmentation of labor, and as an adjunct in managing incomplete or inevitable abortion.
• Pitocin (IV or IM), postpartum: to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.
• No FDA-labeled indication or dose exists for oxytocin by the oral, sublingual or nasal routes. Prescribers use compounded non-parenteral oxytocin outside obstetrics, including in sexual health combinations; dosing is individualized by the prescriber.

Oxytocin binds the oxytocin receptor, a Gq-coupled receptor. Activation of phospholipase C raises intracellular calcium, contracting uterine smooth muscle and the myoepithelial cells of the breast (milk ejection). Uterine sensitivity rises sharply near term. Oxytocin also acts as a CNS neuropeptide involved in social and sexual behavior. Because it is structurally close to vasopressin, it has intrinsic antidiuretic activity at high doses.

After IV administration the plasma half-life is about 1 to 6 minutes, and uterine response begins almost at once. IM onset is 3 to 5 minutes. Oxytocin is cleared mainly by the liver and kidneys, and by placental oxytocinase during pregnancy; little is excreted unchanged in urine. As a peptide it is degraded by gastrointestinal proteases, so swallowed doses are largely inactivated. Absorption through the oral mucosa or nasal mucosa is limited and variable, and its pharmacokinetics by those routes are not well characterized.

• Hypersensitivity to oxytocin or any component of the preparation.
• Non-obstetric oral, sublingual or nasal preparations: pregnancy, possible pregnancy and lactation, given oxytocin's uterotonic and milk-ejection effects.
• Pitocin (obstetric) labeling also contraindicates use with significant cephalopelvic disproportion, unfavorable fetal position, obstetric emergencies favoring surgical delivery, fetal distress when delivery is not imminent, hypertonic or hyperactive uterine patterns, and conditions where vaginal delivery is contraindicated.

• Water intoxication: oxytocin's antidiuretic effect can cause fluid retention and hyponatremia, leading to seizures, coma and death, mainly with high doses given over long periods with large fluid volumes. Use caution in patients at risk of hyponatremia or with fluid-balance disorders.
• Cardiovascular: hypotension, reflex tachycardia, arrhythmias and myocardial ischemia are reported with IV use, especially rapid bolus; hypertensive episodes and subarachnoid hemorrhage are reported in obstetric use. Use caution with cardiovascular disease.
• Obstetric use: uterine hyperstimulation can cause uterine rupture and fetal harm; Pitocin should be given only in a hospital setting with qualified personnel.
• Hypersensitivity: anaphylaxis has been reported.

• Vasoconstrictors and sympathomimetics: severe hypertension has been reported when oxytocin was given after a prophylactic vasoconstrictor with caudal block anesthesia.
• Prostaglandins such as dinoprostone and misoprostol potentiate the uterotonic effect.
• Inhalation anesthetics such as halothane and cyclopropane may reduce the uterine response and have been associated with hypotension and arrhythmias.
• Drugs that cause fluid retention or hyponatremia (for example desmopressin, thiazide diuretics, carbamazepine, SSRIs) may add to oxytocin's antidiuretic effect.

Labeled maternal adverse reactions with parenteral use include nausea, vomiting, anaphylaxis, cardiac arrhythmias, premature ventricular contractions, hypertensive episodes, subarachnoid hemorrhage, postpartum hemorrhage, pelvic hematoma, uterine rupture and water intoxication. Fetal and neonatal effects in obstetric use include bradycardia, arrhythmias, jaundice and retinal hemorrhage. Safety data for chronic low-dose oral, sublingual or nasal use are limited; headache and nasal irritation are reported in nasal studies.

Oxytocin is a uterotonic. Outside obstetric care under medical supervision, it should not be used in pregnancy or in anyone who may become pregnant. Oxytocin acts on milk ejection and small amounts appear in human milk; non-obstetric compounded preparations are not for use during lactation.

In obstetric use, monitor uterine contractions, fetal heart rate, maternal blood pressure, and fluid intake and output. For non-obstetric preparations, confirm pregnancy status before starting in anyone who could be pregnant, and check serum sodium if symptoms of hyponatremia appear (headache, confusion, nausea, seizures). Monitor blood pressure and heart rate in patients with cardiovascular disease.

• Pitocin (oxytocin injection, USP) Prescribing Information.
• USP General Chapter <795> Pharmaceutical Compounding, Nonsterile Preparations.