oxytocin injection King Pharmaceuticals, Inc.
Pitocin® (Oxytocin Injection, USP) Synthetic
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, with the pH adjusted with
acetic acid. 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 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).
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.
INDICATIONS AND USAGE
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.
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.
is indicated to produce uterine contractions during the third stage
of labor and to control postpartum bleeding or hemorrhage.
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
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.
Pitocin, 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.
All patients receiving intravenous oxytocin must be under continuous
observation by trained personnel who have a thorough knowledge of
the drug and are qualified to identify complications. A physician
qualified to manage any complications should be immediately available.
Electronic fetal monitoring provides the best means for early detection
of overdosage (see OVERDOSAGE section). However, it must be borne
in mind that only intrauterine pressure recording can accurately measure
the intrauterine pressure during contractions. A fetal scalp electrode
provides a more dependable recording of the fetal heart rate than
any external monitoring system.
When properly administered, oxytocin should stimulate uterine
contractions comparable to those seen in normal labor. Overstimulation
of the uterus by improper administration can be hazardous to both
mother and fetus. Even with proper administration and adequate supervision,
hypertonic contractions can occur in patients whose uteri are hypersensitive
to oxytocin. This fact must be considered by the physician in exercising
his judgment regarding patient selection.
Except in unusual circumstances, oxytocin should not be administered
in the following conditions: fetal distress, hydramnios, partial placenta
previa, prematurity, borderline cephalopelvic disproportion, and any
condition in which there is a predisposition for uterine rupture,
such as previous major surgery on the cervix or uterus including cesarean
section, overdistention of the uterus, grand multiparity, or past
history of uterine sepsis or of traumatic delivery. Because of the
variability of the combinations of factors which may be present in
the conditions listed above, the definition of “unusual circumstances”
must be left to the judgment of the physician. The decision can be
made only by carefully weighing the potential benefits which oxytocin
can provide in a given case against rare but definite potential for
the drug to produce hypertonicity or tetanic spasm.
Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage,
rupture of the uterus, and fetal deaths due to various causes have
been reported associated with the use of parenteral oxytocic drugs
for induction of labor or for augmentation in the first and second
stages of labor.
Oxytocin has been shown to have an intrinsic antidiuretic effect,
acting to increase water reabsorption from the glomerular filtrate.
Consideration should, therefore, be given to the possibility of water
intoxication, particularly when oxytocin is administered continuously
by infusion and the patient is receiving fluids by mouth.
When oxytocin is used for induction or reinforcement of
already existent labor, patients should be carefully selected. Pelvic
adequacy must be considered and maternal and fetal conditions evaluated
before use of the drug.
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
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.
The following adverse reactions have been reported
in the mother:
Premature ventricular contractions
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
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:
Low Apgar scores at five minutes
Premature ventricular contractions and
Permanent CNS or brain damage
Neonatal retinal hemorrhage
Neonatal seizures have been reported
with the use of Pitocin.
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 mm H2O 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.
DOSAGE AND ADMINISTRATION
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.
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.
Establish the infusion with a separate bottle of physiologic
electrolyte solution not containing Pitocin.
Attach (piggyback) the Pitocin-containing bottle with the infusion
pump to the infusion line as close to the infusion site as possible.
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.
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).
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
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.
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.
Pitocin (Oxytocin Injection, USP) Synthetic is available
Packages of twenty-five oversized 1-mL Steri-Vials®, each containing 10 units of oxytocin.
60793–267–01 A 10 mL multiple-dose Steri-Vial® containing 10 units of oxytocin per mL (total = 100 units of oxytocin).
Store at 15°–25°C (59°–77°F).
Seitchik J, Castillo M: Oxytocin augmentation of dysfunctional
labor. I. Clinical data. Am J Obstet
Gynecol 1982; 144:899–905.
Seitchik J, Castillo M: Oxytocin augmentation of dysfunctional
labor. II. Multiparous patients. Am J
Obstet Gynecol 1983; 145:777–780.
Fuchs A, Goeschen K, Husslein P, et al: Oxytocin and the initiation
of human parturition. III. Plasma concentrations of oxytocin and 13,
14-dihydro-15-keto-prostaglandin F2a in spontaneous and oxytocin-induced
labor at term. Am J Obstet Gynecol 1983; 145:497–502.
Seitchik J, Amico J, et al: Oxytocin augmentation of dysfunctional
labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol 1984; 150:225–228.
American College of Obstetricians and Gynecologists: ACOG Technical
Bulletin Number 110—November 1987: Induction and augmentation
Prescribing Information as of March 2007.
Manufactured and Distributed by: King Pharmaceuticals,
Inc., Bristol, TN 37620
HUMAN PRESCRIPTION DRUG
Item Code (Source)
Route of Administration
Name (Active Moiety)
10 UNITS In 1 MILLILITER
contains a VIAL
This package is contained within the PACKAGE (60793-265-25)