CARBOPROST TROMETHAMINE (Page 2 of 3)

Abortion

As with spontaneous abortion, a process which is sometimes incomplete, abortion induced by carboprost tromethamine may be expected to be incomplete in about 20% of cases.

Although the incidence of cervical trauma is extremely small, the cervix should always be carefully examined immediately post-abortion.

Use of carboprost tromethamine is associated with transient pyrexia that may be due to its effect on hypothalamic thermoregulation. Temperature elevations exceeding 2° F (1.1° C) were observed in approximately one-eighth of the patients who received the recommended dosage regimen. In all cases, temperature returned to normal when therapy ended.

Differentiation of post-abortion endometritis from drug-induced temperature elevations is difficult, but with increasing clinical experience, the distinctions become more obvious and are summarized below:

	Endometritis pyrexia	Pyrexia induced by Carboprost Tromethamine Injection
1.	Time of onset: Typically, on third post-abortional day (38° C or higher).	Within 1 to 16 hours after the first injection.
2.	Duration: Untreated pyrexia and infection continue and may give rise other pelvic infections.	Temperatures revert to pretreatment levels after discontinuation of therapy without any other treatment.
3.	Retention: Products of conception are often retained in the cervical os or uterine cavity.	Temperature elevation occurs whether or not tissue is retained.
4.	Histology: Endometrium is infiltrated with lymphocytes and some areas are necrotic and hemorrhagic.	Although the endometrial stroma may be edematous and vascular, it is not inflamed.
5.	The uterus: Often remains boggy and soft with tenderness over the fundus and pain on moving the cervix on bimanual examination.	Uterine involution normal and uterus is not tender.
6.	Discharge: Often associated with foul-smelling lochia and leukorrhea.	Lochia normal.
7.	Cervical culture: The culture of pathological organisms from the cervix or uterine cavity after abortion alone does not warrant the diagnosis of septic abortion in the absence of clinical evidence of sepsis. Pathogens have been cultured soon after abortion in patients with no infections. Persistent positive culture with clear clinical signs of infections are significant in the differential diagnosis.
8.	Blood count: Leukocytosis and differential white cell counts do not distinguish between endometritis and hyperthermia caused by carboprost tromethamine injection since total WBC’s may increase during infection and transient leukocytosis may also be drug-induced.

Fluids should be forced in patients with drug-induced fever and no clinical or bacteriological evidence of intrauterine infection. Any other simple empirical measures for temperature reduction are unnecessary because all fevers induced by carboprost tromethamine have been transient or self-limiting.

Postpartum Hemorrhage

Increased blood pressure. In the postpartum hemorrhage series, 5/115 (4%) of patients had an increase of blood pressure reported as a side effect. The degree of hypertension was moderate and it is not certain as to whether this was in fact due to a direct effect of carboprost tromethamine or a return to a status of pregnancy associated hypertension manifest by the correction of hypovolemic shock. In any event the cases reported did not require specific therapy for the elevated blood pressure.

Use in patients with chorioamnionitis. During the clinical trials with carboprost tromethamine, chorioamnionitis was identified as a complication contributing to postpartum uterine atony and hemorrhage in 8/115 (7%) of cases, 3 of which failed to respond to carboprost tromethamine. This complication during labor may have an inhibitory effect on the uterine response to carboprost tromethamine similar to what has been reported for other oxytocic agents.¹

¹ Duff, Sanders, and Gibbs; The course of labor in term patients with chorioamnionitis; Am. J. Obstet. Gynecol.; vol. 147, no. 4, October 15, 1983 pp 391–395.

Drug Interactions

Carboprost tromethamine may augment the activity of other oxytocic agents. Concomitant use with other oxytocic agents is not recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenic bioassay studies have not been conducted in animals with carboprost tromethamine due to the limited indications for use and short duration of administration. No evidence of mutagenicity was observed in the Micronucleus Test or Ames Assay.

Pregnancy: Teratogenic Effects:

Animal studies do not indicate that carboprost tromethamine is teratogenic, however, it has been shown to be embryotoxic in rats and rabbits and any dose which produces increased uterine tone could put the embryo or fetus at risk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

The adverse effects of carboprost tromethamine sterile solution are generally transient and reversible when therapy ends. The most frequent adverse reactions observed are related to its contractile effect on smooth muscle.

In patients studied, approximately two-thirds experienced vomiting and diarrhea, approximately one-third had nausea, one-eighth had a temperature increase greater than 2° F, and one-fourteenth experienced flushing.

The pretreatment or concurrent administration of antiemetic and antidiarrheal drugs decreases considerably the very high incidence of gastrointestinal effects common with all prostaglandins used for abortion. Their use should be considered an integral part of the management of patients undergoing abortion with carboprost tromethamine.

Of those patients experiencing a temperature elevation, approximately one-sixteenth had a clinical diagnosis of endometritis. The remaining temperature elevations returned to normal within several hours after the last injection.

Adverse effects observed during the use of carboprost tromethamine injection for abortion and for hemorrhage, not all of which are clearly drug related, in decreasing order of frequency include:

Vomiting	Nervousness
Diarrhea	Nosebleed
Nausea	Sleep disorders
Flushing or hot flashes	Dyspnea
Chills or shivering	Tightness in chest
Coughing	Wheezing
Headaches	Posterior cervical
Endometritis	perforation Weakness
Hiccough	Diaphoresis
Dysmenorrhea-like pain	Dizziness
Paresthesia	Blurred vision
Backache	Epigastric pain
Muscular pain	Excessive thirst
Breast tenderness	Twitching eyelids
Eye pain	Gagging, retching
Drowsiness	Dry throat
Dystonia	Sensation of choking
Asthma	Thyroid storm
Injection site pain	Syncope
Tinnitus	Palpitations
Vertigo	Rash
Vaso-vagal syndrome	Upper respiratory infection
Dryness of mouth
Hyperventilation	Leg cramps
Respiratory distress	Perforate uterus
	Perforated uterus
Hematemesis	Anxiety
Taste alterations	Chest pain
Urinary tract infection	Retained placental fragment
Septic shock
Torticollis	Shortness of breath
Lethargy	Fullness of throat
Hypertension	Uterine sacculation
Tachycardia	Faintness, light-headedness
Pulmonary edema
Endometritis from IUCD	Uterine rupture

The most common complications when carboprost tromethamine injection was utilized for abortion requiring additional treatment after discharge from the hospital were endometritis, retained placental fragments, and excessive uterine bleeding, occurring in about one in every 50 patients.

Post-marketing experience:

Hypersensitivity reactions (e.g. Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction, Angioedema).