PITOCIN

Pitocin (oxytocin injection, USP) is a sterile, clear, colorless aqueous solution of synthetic oxytocin, for intravenous infusion or intramuscular injection. Pitocin is a nonapeptide found in pituitary extracts from mammals. It is standardized to contain 10 units of oxytocic hormone/mL and contains 0.5% Chlorobutanol, a chloroform derivative as a preservative, 1.65 mg acetic acid and 0.16 mg ammonium acetate as buffers, and with the pH adjusted with acetic acid to achieve a targeted pH of 3.5. Pitocin may contain up to 16% of total impurities. The hormone is prepared synthetically to avoid possible contamination with vasopressin (ADH) and other small polypeptides with biologic activity. Pitocin has the empirical formula C 43 H 66 N 12 O 12 S 2 (molecular weight 1007.19). The structural formula is as follows: Chemical Structure

IMPORTANT NOTICE Elective induction of labor is defined as the initiation of labor in a pregnant individual who has no medical indications for induction. Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor. Antepartum: Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. 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, preeclampsia at or near term, when delivery is in the best interests 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) as 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: Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The dosage of oxytocin is determined by the uterine response and must therefore be individualized and initiated at a very low level. The following dosage information is based upon various regimens and indications in general use. A. Induction or Stimulation of Labor Intravenous infusion (drip method) is the only acceptable method of parenteral administration of Pitocin for the induction or stimulation of labor. Accurate control of the rate of infusion is essential and is best accomplished by an infusion pump. It is convenient to piggyback the Pitocin infusion on a physiologic electrolyte solution, permitting the Pitocin infusion to be stopped abruptly without interrupting the electrolyte infusion. This is done in the following way. 1. Preparation a. The standard solution for infusion of Pitocin is prepared by adding the contents of one 1-mL vial containing 10 units of oxytocin to 1000 mL of 0.9% aqueous sodium chloride or Ringer's lactate. The combined solution containing 10 milliunits (mU) of oxytocin/mL is rotated in the infusion bottle for thorough mixing. b. Establish the infusion with a separate bottle of physiologic electrolyte solution not containing Pitocin. c. Attach (piggyback) the Pitocin-containing bottle with the infusion pump to the infusion line as close to the infusion site as possible. 2. Administration 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 minute 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. Studies of the concentrations of oxytocin in the maternal plasma during Pitocin infusion have shown that infusion rates up to 6 mU/min give the same oxytocin levels that are found in spontaneous labor. 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. 3. Monitoring a. Electronically monitor the uterine activity and the fetal heart rate throughout the infusion of Pitocin. Attention should be given to tonus, amplitude and frequency of contractions, and to the fetal heart rate in relation to uterine contractions. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane (see PRECAUTIONS section). b. Discontinue the infusion of Pitocin immediately in the event of uterine hyperactivity and/or fetal distress. Administer oxygen to the mother, who preferably should be put in a lateral position. The condition of mother and fetus should immediately be evaluated by the responsible physician and appropriate steps taken. B. Control of Postpartum Uterine Bleeding 1. Intravenous infusion (drip method). If the patient has an intravenous infusion running, 10 to 40 units of oxytocin may be added to the bottle, depending on the amount of electrolyte or dextrose solution remaining (maximum 40 units to 1000 mL). Adjust the infusion rate to sustain uterine contraction and control uterine atony. 2. Intramuscular administration. (One mL) Ten (10) units of Pitocin can be given after the delivery of the placenta. C. Treatment of Incomplete, Inevitable, or Elective Abortion Intravenous infusion of 10 units of Pitocin added to 500 mL of a physiologic saline solution or 5% dextrose-in-water 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 midtrimester elective abortion, the injection-to-abortion time may be shortened by infusion of Pitocin at the rate of 10 to 20 milliunits (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.

Antepartum use of Pitocin is contraindicated in any of the following circumstances: Where there is significant cephalopelvic disproportion; In unfavorable fetal positions or presentations, such as transverse lies, which are undeliverable without conversion prior to delivery; In obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention; In fetal distress where delivery is not imminent; Where adequate uterine activity fails to achieve satisfactory progress; Where the uterus is already hyperactive or hypertonic; In cases where vaginal delivery is contraindicated, such as invasive cervical carcinoma, active herpes genitalis, total placenta previa, vasa previa, and cord presentation or prolapse of the cord; In patients with hypersensitivity to the drug.

The following adverse reactions have been reported in the mother: Anaphylactic reaction Premature ventricular contractions Postpartum hemorrhage Pelvic hematoma Cardiac arrhythmia Subarachnoid hemorrhage Fatal afibrinogenemia Hypertensive episodes Nausea Rupture of the uterus Vomiting 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, 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 neonate: Due to induced uterine motility: Due to use of oxytocin in the mother: Bradycardia Low Apgar scores at five minutes Premature ventricular contractions and other arrhythmias Neonatal jaundice Permanent CNS or brain damage Neonatal retinal hemorrhage Fetal death Neonatal seizures have been reported with the use of Pitocin. For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Endo at 1-800-828-9393 or FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch.

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.

STORAGE Store between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.)