OVERDOSE
Signs and Symptoms: Toxic
effects accompanying acute overdosage of clomiphene citrate
tablets USP have not been reported. Signs and symptoms
of overdosage as a result of the use of more than the
recommended dose during clomiphene citrate tablets USP
therapy include nausea, vomiting, vasomotor flushes, visual
blurring, spots or flashes, scotomata, ovarian enlargement
with pelvic or abdominal pain. (See
CONTRAINDICATIONS
: Ovarian Cyst.)
Oral LD50: The acute oral LD50
of clomiphene citrate tablets USP is 1700 mg/kg in mice
and 5750 mg/kg in rats. The toxic dose in humans is not
known.
Dialysis: It is not known if
clomiphene citrate tablets USP is dialyzable.
Treatment: In the event of
overdose, appropriate supportive measures should be employed
in addition to gastrointestinal decontamination.
CONTRAINDICATIONS
Hypersensitivity
Clomiphene citrate tablets USP is contraindicated in
patients with a known hypersensitivity or allergy to clomiphene
citrate or to any of its ingredients.
Pregnancy
Clomiphene citrate tablets USP should not be administered
during pregnancy. Clomiphene citrate tablets USP may cause
fetal harm in animals (see Animal Fetotoxicity below).
Although no causative evidence of a deleterious effect
of clomiphene citrate tablets USP therapy on the human
fetus has been established, there have been reports of
birth anomalies which, during clinical studies, occurred
at an incidence within the range reported for the general
population (see ADVERSE REACTIONS, Fetal/Neonatal Anomalies
and Mortality).
To avoid inadvertent clomiphene citrate tablets USP administratton
during early pregnancy, appropriate tests should be utilized
during each treatment cycle to determine whether ovulation
occurs. The patient should be evaluated carefully to exclude
pregnancy, ovarian enlargement, or ovarian cyst formation
between each treatment cycle. The next course of clomiphene
citrate tablets USP therapy should be delayed until these
conditions have been excluded.
Fetal/Neonatal Anomalies and Mortality
The following fetal abnormalities have been reported
subsequent to pregnancies following ovulation induction
therapy with clomiphene citrate tablets USP during clinical
trials. Each of the following fetal abnormalities were
reported at a rate of <1% (experiences are listed in
order of decreasing frequency): Congenital heart lesions,
Down syndrome, club foot, congenital gut lesions, hypospadias,
microcephaly, harelip and cleft palate, congenital hip,
hemangioma, undescended testicles, polydactyly, conjoined
twins and teratomatous malformation, patent ductus arteriosus,
amaurosis, arteriovenous fistula, inguinal hernia, umbilical
hernia, syndactyly, pectus excavatum, myopathy, dermoid
cyst of scalp, omphalocele, spina bifida occulta, ichthyosis,
and persistent lingual frenulum. Neonatal death and fetal
death/stillbirth in infants with birth defects have also
been reported at a rate of < 1%. The overall incidence
of reported birth anomalies from pregnancies associated
with maternal clomiphene citrate tablets USP ingestion
during clinical studies was within the range of that reported
for the general population.
In addition, reports of birth anomalies have been received
during postmarketing surveillance of clomiphene citrate
tablets USP (see ADVERSE REACTIONS).
Animal Fetotoxicity: Oral administration
of clomiphene citrate to pregnant rats during organogenesis
at doses of 1 to 2 mg/kg/day resulted in hydramnion and
weak, edematous fetuses with wavy ribs and other temporary
bone changes. Doses of 8 mg/kg/day or more also caused
increased resorptions and dead fetuses, dystocia, and
delayed parturition, and 40 mg/kg/day resutted in increased
maternal mortality. Single doses of 50 mg/kg caused fetal
cataracts, while 200 mg/kg caused cleft palate.
Following injection of clomiphene citrate 2 mg/kg to
mice and rats during pregnancy, the offspring exhibited
metaplastic changes of the reproductive tract. Newborn
mice and rats injected during the first few days of life
also developed metaplastic changes in uterine and vaginal
mucosa, as well as premature vaginal opening and anovulatory
ovaries. These findings are similar to the abnormal reproductive
behavior and sterility described with other estrogens
and antiestrogens. In rabbits, some temporary bone alterations
were seen in fetuses from dams given oral doses of 20
or 40 mg/kg/day during pregnancy, but not following 8
mg/kg/day. No permanent malformations were observed in
those studies. Also, rhesus monkeys given oral doses of
1.5 to 4.5 mg/kg/day for various periods during pregnancy
did not have any abnormal offspring.
Liver Disease: Clomiphene citrate tablets
USP therapy is contraindicated in patients with liver
disease or a history of liver dysfunction (see also INDICATIONS
AND USAGE and ADVERSE REACTIONS).
Abnormal Uterine Bleeding: Clomiphene
citrate tablets USP is contraindicated in patients with
abnormal uterine bleeding of undetermined origin (see
INDICATIONS AND USAGE).
Ovarian Cysts: Clomiphene citrate tablets
USP is contraindicated in patients with ovarian cysts
or enlargement not due to polycystic ovarian syndrome
(see INDICATIONS AND USAGE and WARNINGS).
Other: Clomiphene citrate tablets USP
is contraindicated in patients with uncontrolled thyroid
or adrenal dysfunction or in the presence of an organic
intracranial lesion such as pituitary tumor (see INDICATIONS
AND USAGE).
|
|
