Pregnancy Category C.
There was no evidence of teratogenicity when terconazole was
administered orally up to 40 mg/kg/day (50x the recommended intravaginal human
dose of the 0.8% vaginal cream formulation, and 100x the intravaginal human
dose of the 0.4% vaginal cream formulation) in rats, or 20 mg/kg/day in rabbits,
or subcutaneously up to 20 mg/kg/day in rats.
Dosages
at or below 10 mg/kg/day produced no embryotoxicity; however, there was a
delay in fetal ossification at 10 mg/kg/day in rats. There was some evidence
of embryotoxicity in rabbits and rats at 20-40 mg/kg. In rats, this was reflected
as a decrease in litter size and number of viable young and reduced fetal
weight. There was also delay in ossification and an increased incidence of
skeletal variants.
The no-effect dose
of 10 mg/kg/day resulted in a mean peak plasma level of terconazole in pregnant
rats of 0.176 mcg/mL which exceeds by 44 times the mean peak plasma level
(0.004 mcg/mL) seen in normal subjects after intravaginal administration of
terconazole 0.4% vaginal cream, and by 30 times the mean peak plasma level
(0.006 mcg/mL) seen in normal subjects after intravaginal administration of
terconazole 0.8% vaginal cream. This safety assessment does not account for
possible exposure of the fetus through direct transfer to terconazole from
the irritated vagina by diffusion across amniotic membranes.
Since terconazole is absorbed from the human vagina, it should
not be used in the first trimester of pregnancy unless the physician considers
it essential to the welfare of the patient.
Terconazole Vaginal Cream 0.4%:
During controlled clinical studies conducted in the United
States, 521 patients with vulvovaginal candidiasis were treated with terconazole
0.4% vaginal cream. Based on comparative analyses with placebo, the adverse
experiences considered most likely related to terconazole 0.4% vaginal cream
were headache (26% vs. 17% with placebo) and body pain (2.1% vs. 0% with placebo).
Vulvovaginal burning (5.2%), itching (2.3%) or irritation (3.1%) occurred
less frequently with terconazole 0.4% vaginal cream than with the vehicle
placebo. Fever (1.7% vs. 0.5% with placebo) and chills (0.4% vs. 0.0% with
placebo) have also been reported. The therapy-related dropout rate was 1.9%.
The adverse drug experience on terconazole most frequently causing discontinuation
was vulvovaginal itching (0.6%), which was lower than the incidence for placebo
(0.9%).
Terconazole Vaginal Cream
0.8%:
During controlled
clinical studies conducted in the United States, patients with vulvovaginal
candidiasis were treated with terconazole 0.8% vaginal cream for three days.
Based on comparative analyses with placebo and a standard agent, the adverse
experiences considered most likely related to terconazole 0.8% vaginal cream
were headache (21% vs. 16% with placebo) and dysmenorrhea (6% vs. 2% with
placebo). Genital complaints in general, and burning and itching in particular,
occurred less frequently in the terconazole 0.8% vaginal cream 3 day regimen
(5% vs. 6%–9% with placebo). Other adverse experiences reported with
terconazole 0.8% vaginal cream were abdominal pain (3.4% vs. 1% with placebo)
and fever (1% vs. 0.3% with placebo). The therapy-related dropout rate was
2.0% for the terconazole 0.8% vaginal cream. The adverse drug experience most
frequently causing discontinuation of therapy was vulvovaginal itching, 0.7%
with the terconazole 0.8% vaginal cream group and 0.3% with the placebo group.
Terconazole Vaginal Cream 0.4%:
One full applicator (5 g) of Terconazole Vaginal Cream (20
mg terconazole) should be administered intravaginally once daily at bedtime
for seven consecutive days.
Terconazole Vaginal Cream 0.8%:
One full applicator (5 g) of Terconazole Vaginal Cream (40
mg terconazole) should be administered intravaginally once daily at bedtime
for three consecutive days.
Before prescribing
another course of therapy, the diagnosis should be reconfirmed by smears and/or
cultures and other pathogens commonly associated with vulvovaginitis ruled
out. The therapeutic effect of these products is not affected by menstruation.
| Mfd. for: Watson Laboratories, Inc.
Corona, CA 92880 USA | Mfd. by: Draxis Specialty Pharmaceuticals Inc.
Kirkland, Quebec, Canada H9H 4J4
or |
| | JOLLC
Manati, Puerto Rico 00674 |
| | |
| Printed in U.S.A. | Revised January 2010 |
