OXYTOCIN

Each mL of Oxytocin Injection, USP (synthetic), intended for intravenous infusion or intramuscular injection, possesses an oxytocic activity equivalent to 10 USP Oxytocin Units and contains chlorobutanol anhydrous (chloral derivative) 0.5%. This product may contain up to 12.5% decomposition products/impurities. Oxytocin injection (synthetic) is a sterile, clear, colorless solution of oxytocin in Water for Injection prepared by synthesis. Acetic acid may have been added for pH adjustment (pH 3.0-5.0). The structural formula is: structure

IMPORTANT NOTICE: Oxytocin Injection, USP (synthetic) is indicated for the medical rather than the elective induction of labor. Available data and information are inadequate to define the benefits to risks considerations in the use of the drug product for elective induction. Elective induction of labor is defined as the initiation of labor for convenience in an individual with a term pregnancy who is free of medical indications. Antepartum Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons. It is indicated for (1) 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 interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Antepartum Oxytocin injection (synthetic) is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable, in order to achieve early vaginal delivery for fetal or maternal reasons. It is indicated for (1) 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 interest of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

Dosage of oxytocin is determined by uterine response. The following dosage information is based upon the various regimens and indications in general use. Induction or Stimulation of Labor Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor. Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane. An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances. To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent. The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion. The initial dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor. The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored. The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and fetus must be evaluated by the responsible physician. Control of Postpartum Uterine Bleeding Intravenous Infusion ( Drip Method )—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony. Intramuscular Administration —1 mL (10 units) of oxytocin can be given after delivery of the placenta. Treatment of Incomplete or Inevitable Abortion Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Induction or Stimulation of Labor Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor. Accurate control of the rate of infusion flow is essential. An infusion pump or other such device and frequent monitoring of strength of contractions and fetal heart rate are necessary for the safe administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane. An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances. To prepare the usual solution for intravenous infusion–one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent. The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion. The initial dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor. The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored. The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or fetal distress. Oxygen should be administered to the mother. The mother and fetus must be evaluated by the responsible physician. Control of Postpartum Uterine Bleeding Intravenous Infusion ( Drip Method )—To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating diluent and run at a rate necessary to control uterine atony. Intramuscular Administration —1 mL (10 units) of oxytocin can be given after delivery of the placenta. Treatment of Incomplete or Inevitable Abortion Intravenous infusion with physiologic saline solution, 500 mL, or 5% dextrose in physiologic saline solution to which 10 units of oxytocin have been added should be infused at a rate of 20 to 40 drops/minute. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Oxytocin injection (synthetic) is contraindicated in any of the following conditions: Significant cephalopelvic disproportion; Unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, i.e., 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; Prolonged use in uterine inertia or severe toxemia; Hypertonic uterine patterns; Patients with hypersensitivity to the drug; Induction or augmentation of labor in those cases where vaginal delivery is contraindicated, such as cord presentation or prolapse, total placenta previa, and vasa previa.

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following adverse reactions have been reported in the mother: Anaphylactic reaction Postpartum hemorrhage Cardiac arrhythmia Fatal afibrinogenemia Nausea Vomiting Premature ventricular contractions Pelvic hematoma Excessive dosage or hypersensitivity to the drug may result in uterine hypertonicity, spasm, tetanic contraction or rupture of the uterus. The possibility of increased blood loss and afibrinogenemia should be kept in mind when administering the drug. Severe water intoxication with convulsions and coma has occurred, and is associated with a slow oxytocin infusion over a 24-hour period. Maternal death due to oxytocin-induced water intoxication has been reported. The following adverse reactions have been reported in the fetus or infant: Due to induced uterine mobility: Bradycardia Premature ventricular contractions and other arrhythmias Permanent CNS or brain damage Fetal death Due to use of oxytocin in the mother: Neonatal retinal hemorrhage Low Apgar scores at five minutes Neonatal jaundice