Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term.


METHODS
Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM).


RESULTS
All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg.


CONCLUSIONS
The MTD was calculated to be at 200 microg carbetocin.
van Dongen
P W
PW
Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands.
Verbruggen
M M
MM
de Groot
A N
AN
van Roosmalen
J
J
Sporken
J M
JM
Schulz
M
M
D015746:Abdominal Pain / Q000139:chemically induced; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D007273:Injections, Intramuscular; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010121:Oxytocin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018457:Placenta, Retained / Q000139:chemically induced; D006473:Postpartum Hemorrhage / Q000517:prevention & control*; D011247:Pregnancy; D014839:Vomiting / Q000139:chemically induced
D010120:Oxytocics; D010121:Oxytocin; C020731:carbetocin