General
Animal studies lasting several weeks at high doses have shown that prostaglandins
of the E and F series can induce proliferation of bone. Such effects have also
been noted in newborn infants who have received prostaglandin E1 during prolonged
treatment. There is no evidence that short term administration of HEMABATE Sterile
Solution can cause similar bone effects.
In patients with a history of asthma, hypo- or hypertension, cardiovascular,
renal, or hepatic disease, anemia, jaundice, diabetes, or epilepsy, HEMABATE
should be used cautiously.
As with any oxytocic agent, HEMABATE should be used with caution in patients
with compromised (scarred) uteri.
Abortion
As with spontaneous abortion, a process which is sometimes incomplete, abortion
induced by HEMABATE 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 HEMABATE 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 HEMABATE |
| 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 to 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. |
| Discharge: Often associated with foul-smelling lochia and leukorrhea. |
Lochia normal. |
| 7. Cervical culture: The culture of pathol ogicalorganisms
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 HEMABATE 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 HEMABATE 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 HEMABATE 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 HEMABATE,
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 HEMABATE. This complication during labor may have an inhibitory effect on
the uterine response to HEMABATE similar to what has been reported for other
oxytocic agents.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenic bioassay studies have not been conducted in animals with HEMABATE
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: Pregnancy Category C
Animal studies do not indicate that HEMABATE 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.
REFERENCES
1Duff, 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.
Last updated on RxList: 5/7/2008