Pitocin, Oxytocin Injection, USP, Synethetic  PARKE-DAVIS

Pitocin is a nonapeptide. It is standardized to contain 10 units of oxytocic hormone/mL and 0.5% of chorobutanol (a chloroform derivative) as a preservative.

The hormone is prepared synthetically to avoid contamination with vasopressin (ADH) and other small polypeptides with biologic activity.

Uterine motility depends on the formation of the contractile protein actomyosin under influence of the Ca2+-dependent phosophorylating enzyme myosin light-chain kinease.

Oxytocin promotes contractions by increasing the intracellular CA2+.

Oxytocin has specific receptor sites in the myometrium [muscle] and the receptor concentration increase greatly during pregnancy, reaching a maximum during early labor at term.

The physician should be aware of the fact the oxytocin even in its pure form has inherent pressor [blood pressure controlling properties] and antiduretics properties which may become manifest when large does are administered.

The response to a given dose of oxtocin is very individualized and depends on the sensitivity of the uterus, which is determined by the oxytocin receptor concentration. Small amount of the drug probably reach the fetus. Following intravenous administration of oxytocin, uterine response occurs almost immediately and subsides within 1 hour.

INDICATIONS AND USAGE

 Antepartum:

(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 interest of the 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 [spontaneous miscarriage].

Postpartum:

Pitocin is indicated to produce uterine contraction during the third state of labor and to control postpartum bleeding or hemorrhage. 

CONTRAINDICATIONS

1. Where there is significant cephalopelvic disproportion [baby’s head to big for mother’s pelvis]

2. In unfavorable fetal positions or presentation, such as transverse lies, which are undeliverable without conversion prior to delivery

3. In obstetric emergencies where the benefit-to-risk ration for either the fetu or the mother favors surgical intervention

4. In fetal distress were delivery is not imminent

5. Where adequate uterine activity fails to achieve satisfactory progress

6. Where the uterus is already hyperactive or hypertonic

7. 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

8. In patients with hypersensitivity to the drug.

 

PRECAUTIONS

General

1. All patients receiving intravenous oxytocin must be under continuous observation by trained personnel who have thorough knowledge of the drug and are qualified to identify complications.

A physician qualified to manage any complications should be immediately available. [note: same language used by ACOG in VBAC protocols]

Electronic fetal monitoring provides the best means for early detection of overdosage (see OVERDOSAGE section). However, it must be born 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.

2. 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 inpatients whose uteri are hypersensitive to oxytocin.

This fact must be considered by the physician in exercising his judgment regarding patient selection.

3. 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 sectioin, overdistention of the uterus, grand multiparity, or past history of uterine sepsis or of traumatic delivery.

[There is a] rare but definite potential for the drug to produce hypertonicity or tetanic spasm.

4. 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.

 Drug Interactions

Sever hypertension has been reported when oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.

Tertogenic Effects

Animal reproduction studies have not been conducted with oxytocin [i.e., no research has been done on the tertogenic effects of this synthetic drug].

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. [Note: Small amount of the drug probably reach the fetus.]

ADVERSE REACTIONS

The Following adverse reactions have been reported in the mother:

• Anaphylactic reaction
• Postpartum hemorrhage
• Cardiac arrhythmia
• Nausea
• Vomiting
• Premature ventricular contractions [irregular heartbeat]
• Pelvic hematoma [bleeding under the skin or in deep tissue]
• Subarachnoid hemorrhage [bleeding into the brain]
• Hypertensive episodes
• Rupture of the Uterus

Excessive dosage of 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 [loss of clotting factor] should be kept in mind when administering the drug.

Severe water intoxication with convulsions and coma has occurred, associated with a slow oyxtocin 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 use of {artificial} oxytocin {i.e. Pitocin] in the mother: 

Due to induced uterine motility: [abnormal length, strength or frequency of contractions]

• Bradycardia [abnormally slow heartbeat]
• Premature ventricular contractions and other [cardiac] arrythmias
• Permanent CNS or brain damage
• Fetal death
• Neonatal seizures
• Low Apgar scores at five minutes
• Neonatal jaundice
• Neonatal retinal hemorrhage

OVERDOSAGE

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 hyoperfusion [reduced blood flow thru placenta resulting in reduced oxygen to fetal and reduced ability to remove metabolic wastes], and
• variable decelerations of the fetal heart,
• fetal hypoxia [decreased level of oxygen in tissue],
• hypercapnia,
• perinatal hepatic [liver] necrosis
• death

Water intoxication with convulsions, which is caused by the inherent anti-diuretic effect of oxytocin, is a serious complication that may occur if large doses (40 to 50 milliunits/minute) are infused for long periods.

Studies of the concentration 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 labors. At term, higher infusion rates should be giving with great care and rates exceeding 9-10 mU/min are rarely required.

Monitoring

A. Electronically monitor the uterine activity and the fetal heart rate throughout the infusion of Pitocin. Attention should be paid to tonus, amplitude and the frequency of contractions, and to fetal heart rate in relation to uterine contractions. If uterine contractions become too powerful, the infusion can be abruptly stopped and oxytocin stimulation of the uterine musculature will soon wane (see PRECAUTIONS section).

B. Discontinue the infusion of Pitocin immediately in the event of hyperactivity and/or fetal distress. Administer oxygen to the mother, who preferably should be evaluated by the responsible physician and appropriate steps taken.

1996 Warner-Lambert Co. Revised December 1996

PARKE_DAVIS

Div of Warner-Lambert Co/ Morris Plains, NJ                                7950 4160G339