PROOFING COPY ■ Process Black (text & barcode) ■ PMS 3405 (color bar) ■ PMS 648 (logo) NDC 0703-6271-01 only Oxytocin Injection, USP Synthetic 10 units/1 mL 1 mL Single Dose Vial IV Infusion or IM Dosage: See Package Insert Note: Oversized Vial Sterile sicor™ SICOR Pharmaceuticals, Inc. Irvine, CA 92618 00335A Product Name: Oxytocin Injection, USP Part Number: Y29-003-35A Catalog Number: 6271-01 Labeling Component: Vial Label Drawing Specification Number: C-PK-LBL-2327, Rev. 1 Comments: Create labeling for new product. Initiated By: Robert Herndon Department: Regulatory Affairs Supercedes part number : New Label Labeling Approvals Signature Date Regulatory Affairs Mirabelle Pao Packaging Engineering Pete Montalvo Quality Assurance Kristina McIntyre Marketing Product Development Research and Development Other Approval Store at controlled room NDC 0703-6275-03 only For intravenous infusion or intramuscular injection. temperature 15°-30°C Oxytocin Each mL contains: Oxytocin activity equivalent to 10 USP (59°-86°F). Oxytocin Units; 5.25 mg Chlorobutanol, NF (hemihydrate); Do not permit to freeze. Injection, USP Water for Synthetic Injection q.s. 100 units/10 mL Acetic acid may LOT/EXP CODE (10 units/mL) have been added PLACE HOLDER for pH adjustment. (NO TEXT) 10 mL Multiple Dose Vial Sterile IMPRINTED ON-LINE sicor™ IV Infusion or IM Usual Dosage: SICOR Pharmaceuticals, Inc. 10 Vials See Package Irvine, CA 92618 Insert. 00338A PROOFING COPY ■ Process Black (text & barcode) ■ PMS 341 (color bar) ■ PMS 648 (logo) Store at controlled For intravenous infusion or intramuscular room temperature NDC 0703-6275-01 only injection. 15°-30°C (59°-86°F). Oxytocin Each mL contains: Oxytocin activity Do not permit to equivalent to 10 USP Oxytocin Units; freeze. Injection, USP 5.25 mg Chlorobutanol, NF Synthetic (hemihydrate); Water for Injection q.s. Acetic acid may have been 100 units/10 mL added for pH (10 units/mL) adjustment. Sterile 10 mL Multiple Dose Vial Usual IV Infusion or IM Dosage: sicor™ See Package SICOR Pharmaceuticals, Inc., Irvine, CA 92618 Insert. 00336A Product Name: Oxytocin Injection, USP Part Number: Y29-003-36A Catalog Number: 6275-01 Labeling Component: Vial Label Drawing Specification Number: C-PK-LBL-2322, Rev. 1 Comments: Revised Temp pee FDA letter. Initiated By: Robert Herndon Department: Regulatory Affairs Supercedes part number : New Label Labeling Approvals Signature Date Regulatory Affairs Mirabelle Pao Packaging Engineering Pete Montalvo Quality Assurance Kristina McIntyre Marketing Product Development Research and Development Other Approval Package Insert only Postpartum Oxytocin has been shown to have an intrinsic antidiuretic Oxytocin injection (synthetic) is indicated to produce effect, acting to increase water reabsorption from the glomerular filtrate. Consideration should, therefore, Oxytocin uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. be given to the possibility of water intoxication, Injection, USP particularly when oxytocin is administered continuously (Synthetic) CONTRAINDICATIONS by infusion and the patient is receiving fluids by FOR INTRAVENOUS INFUSION OR INTRAMUSCULAR USE mouth. Oxytocin injection (synthetic) is contraindicated in DESCRIPTION any of the following conditions: Drug Interactions Each mL of oxytocin injection, USP (synthetic), • Significant cephalopelvic disproportion; Severe hypertension has been reported when oxytocin intended for intravenous infusion or intramuscular was given three to four hours following prophylactic injection, possesses an oxytocic activity equivalent • Unfavorable fetal positions or presentations which administration of a vasoconstrictor in conjunction to 10 USP oxytocin units and contains 5.25 mg are undeliverable without conversion prior to with caudal block anesthesia. Cyclopropane Chlorobutanol, NF (hemihydrate). This product delivery, i.e., transverse lies; anesthesia may modify oxytocin’s cardiovascular may contain up to 12.5% decomposition products/ • In obstetrical emergencies where the benefit-to- effects, so as to produce unexpected results such impurities. Oxytocin injection (synthetic) is a sterile, risk ratio for either the fetus or the mother favors as hypotension. Maternal sinus bradycardia with clear, colorless solution of oxytocin in Water for surgical intervention; abnormal atrioventricular rhythms has also been Injection prepared by synthesis. Acetic acid may noted when oxytocin was used concomitantly with • In cases of fetal distress where delivery is not have been added for pH adjustment (pH 3.0-5.0) The cyclopropane anesthesia. structural formula is: imminent; Carcinogenesis, Mutagenesis, Impairment of • Prolonged use in uterine inertia or severe toxemia; H-Cys-Tyr-lle-Glu (NH2)-Asp(NH2)-Cys-Pro-Leu-Gly-NH2 Fertility • Hypertonic uterine patterns; 1 2 3 4 5 6 7 8 9 There are no animal or human studies on the • Patients with hypersensitivity to the drug; carcinogenicity and mutagenicity of this drug, nor is CLINICAL PHARMACOLOGY • Induction or augmentation of labor in those cases there any information on its effect on fertility. Oxytocin injection (synthetic) acts on the smooth where vaginal delivery is contraindicated, such Pregnancy Category C muscle of the uterus to stimulate contractions; as cord presentation or prolapse, total placenta There are no known indications for use in the first response depends on the uterine threshold of previa, and vasa previa. excitability. It exerts a selective action on the smooth and second trimester of pregnancy other than in musculature of the uterus, particularly toward the WARNINGS relation to spontaneous or induced abortion. Based end of the pregnancy, during labor and immediately on the wide experience with this drug and its following delivery. Oxytocin stimulates rhythmic Oxytocin injection (synthetic), when given for chemical structure and pharmacological properties, contractions of the uterus, increases the frequency induction of labor or stimulation of labor, must be it would not be expected to present a risk of fetal of existing contractions and raises the tone of the administered only by the intravenous route and with abnormalities when used as indicated. adequate medical supervision in a hospital. uterine musculature. Synthetic oxytocin does not Nonteratogenic Effects possess the cardiovascular effects, such as elevation PRECAUTIONS of blood pressure, as exhibited by vasopressin found See ADVERSE REACTIONS in the fetus or infant. in posterior pituitary injection. General Labor and Delivery All patients receiving intravenous oxytocin must be INDICATIONS AND USAGE See INDICATIONS AND USAGE section. under continuous observation by trained personnel Nursing Mothers IMPORTANT NOTICE with a thorough knowledge of the drug and qualified Oxytocin injection, USP (synthetic) is indicated to identify complications. A physician qualified to It is not known whether this drug is excreted in for the medical rather than the elective induction manage any complications should be immediately human milk. Because many drugs are excreted of labor. Available data and information are available. in human milk, caution should be exercised when inadequate to define the benefits to risks When properly administered, oxytocin should stimulate oxytocin is administered to a nursing woman. considerations in the use of the drug product for uterine contractions similar to those seen in normal ADVERSE REACTIONS elective induction. Elective induction of labor is labor. Overstimulation of the uterus by improper defined as the initiation of labor for convenience administration can be hazardous to both mother and The following adverse reactions have been reported in an individual with term pregnancy who is free of fetus. Even with proper administration and adequate in the mother: medical indications. supervision, hypertonic contractions can occur in Anaphylactic reaction Nausea patients whose uteri are hypersensitive to oxytocin. Postpartum hemorrhage Vomiting Except in unusual circumstances, oxytocin should Antepartum not be administered in the following conditions: Cardiac arrhythmia Premature ventricular Oxytocin injection (synthetic) is indicated for the prematurity, borderline cephalopelvic disproportion, contractions initiation or improvement of uterine contractions, previous major surgery on the cervix or uterus including where this is desirable and considered suitable, in Fatal afibrinogenemia Pelvic hematoma Caesarean section, overdistension of the uterus, grand order to achieve early vaginal delivery for fetal or multiparity or invasive cervical carcinoma. Because of Excessive dosage or hypersensitivity to the drug maternal reasons. It is indicated for (1) induction of the variability of the combinations of factors which may result in uterine hypertonicity, spasm, tetanic labor in patients with a medical indication for the may be present in the conditions listed above, the contraction, or rupture of the uterus. initiation of labor, such as Rh problems, maternal definition of “unusual circumstances” must be left to The possibility of increased blood loss and diabetes, preeclampsia at or near term, when the judgment of the physician. The decision can only afibrinogenemia should be kept in mind when delivery is in the best interests of mother and fetus be made by carefully weighing the potential benefits administering the drug. or when membranes are prematurely ruptured and which oxytocin can provide in a given case against delivery is indicated; (2) stimulation