OXYTOCIN- oxytocin injection
JHP Pharmaceuticals, LLC
Oxytocin injection, USP is a sterile, clear, colorless aqueous solution of synthetic oxytocin, for intravenous infusion or intramuscular injection. Oxytocin 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, with the pH adjusted with acetic acid. Oxytocin 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. Oxytocin has the empirical formula C43H66N12O12S2 (molecular weight 1007.19). The structural formula is as follows:
Uterine motility depends on the formation of the contractile protein actomyosin under the influence of the Ca2+ -dependent phosphorylating enzyme myosin light-chain kinase. Oxytocin promotes contractions by increasing the intracellular Ca2+. Oxytocin has specific receptors in the myometrium and the receptor concentration increases greatly during pregnancy, reaching a maximum in early labor at term. The response to a given dose of oxytocin is very individualized and depends on the sensitivity of the uterus, which is determined by the oxytocin receptor concentration. However, the physician should be aware of the fact that oxytocin even in its pure form has inherent pressor and antidiuretic properties which may become manifest when large doses are administered. These properties are thought to be due to the fact that oxytocin and vasopressin differ in regard to only two of the eight amino acids (see PRECAUTIONS section).
Oxytocin is distributed throughout the extracellular fluid. Small amounts of the drug probably reach the fetal circulation. Oxytocin has a plasma half-life of about 1 to 6 minutes which is decreased in late pregnancy and during lactation. Following intravenous administration of oxytocin, uterine response occurs almost immediately and subsides within 1 hour. Following intramuscular injection of the drug, uterine response occurs within 3 to 5 minutes and persists for 2 to 3 hours. Its rapid removal from plasma is accomplished largely by the kidney and the liver. Only small amounts are excreted in urine unchanged.
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, oxytocin injection is not indicated for elective induction of labor.
Oxytocin injection 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.
Antepartum use of oxytocin injection is contraindicated in any of the following circumstances:
Oxytocin, when given for induction of labor or augmentation of uterine activity, should be administered only by the intravenous route and with adequate medical supervision in a hospital.
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.
There are no animal or human studies on the carcinogenicity and mutagenicity of this drug, nor is there any information on its effect on fertility.
Animal reproduction studies have not been conducted with oxytocin. There are no known indications for use in the first trimester of pregnancy other than in relation to spontaneous or induced abortion. Based on the wide experience with this drug and its chemical structure and pharmacological properties, it would not be expected to present a risk of fetal abnormalities when used as indicated.
See ADVERSE REACTIONS in the fetus or neonate.
See INDICATIONS AND USAGE section.
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|
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|
|Neonatal seizures have been reported with the use of oxytocin.|
For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or http://www.fda.gov/medwatch/.
Overdosage with oxytocin depends essentially on uterine hyperactivity whether or not due to hypersensitivity to this agent. Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions, or a resting tone of 15 to 20 mmHg or more between contractions can lead to tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, uteroplacental hypoperfusion, and variable deceleration of fetal heart, fetal hypoxia, hypercapnia, perinatal hepatic necrosis or death. Water intoxication with convulsions, which is caused by the inherent antidiuretic effect of oxytocin, is a serious complication that may occur if large doses (40 to 50 milliunits/minute) are infused for long periods. Management consists of immediate discontinuation of oxytocin and symptomatic and supportive therapy.
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.
Intravenous infusion (drip method) is the only acceptable method of parenteral administration of oxytocin injection 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 oxytocin infusion on a physiologic electrolyte solution, permitting the oxytocin infusion to be stopped abruptly without interrupting the electrolyte infusion. This is done in the following way.
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 oxytocin 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.
Intravenous infusion of 10 units of oxytocin injection 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 oxytocin 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.
Oxytocin Injection, USP, Synthetic is available as follows:
NDC 42023-140-25 Packages of twenty-five oversized 1 mL vials, each containing 10 units of oxytocin.
NDC 42023-141-01 A 10 mL multiple dose vial containing 10 units of oxytocin per mL (total = 100 units of oxytocin).
NDC 42023-141-25 Packages of twenty-five 10 mL multiple dose vials, each containing 10 units of oxytocin per mL (total = 100 units of oxytocin per vial).
Prescribing Information as of March 2013.
Manufactured and Distributed by: JHP Pharmaceuticals, LLC, Rochester, MI 48307
IV Infusion or IM
1 mL Single Dose Vial
|Labeler - JHP Pharmaceuticals, LLC (804894611)|