WARNINGS
Discontinue medication pending examination if there is
a sudden partial or complete loss of vision or if there
is sudden onset of proptosis, diplopia, or migraine. If
examination reveals papilledema or retinal vascular lesions,
medication should be withdrawn.
Because of the occasional occurrence of thrombophlebitis
and pulmonary embolism in patients taking progestogens,
the physician should be alert to the earliest manifestations
of the disease.
Several reports suggest an association between intrauterine
exposure to progestational drugs in the first trimester
of pregnancy and genital abnormalities in male and female
fetuses. The risk of hypospadias, 5 to 8 per 1,000 male
births in the general population, may be approximately
doubled with exposure to these drugs. There are insufficient
data to quantify the risk to exposed female fetuses, but
insofar as some of these drugs induce mild virilization
of the external genitalia of the female fetus, and because
of the increased association of hypospadias in the male
fetus, it is prudent to avoid the use of these drugs during
the first trimester of pregnancy.
PRECAUTIONS
GENERAL
PRECAUTIONS.
The pretreatment physical examination should include special
reference to breasts and pelvic organs, as well as a Papanicolaou
smear.
Because this drug may cause some degree of fluid retention,
conditions which might be influenced by this factor, such
as epilepsy, migraine, asthma, cardiac or renal dysfunctions,
require careful observation.
In cases of breakthrough bleeding, as in all cases of
irregular bleeding per vaginam, nonfunctional causes should
be borne in mind. In cases of undiagnosed vaginal bleeding,
adequate diagnostic measures are indicated.
Patients who have a history of psychic depression should
be carefully observed and the drug discontinued if the
depression recurs to a serious degree.
Any possible influence of prolonged progestogen therapy
on pituitary, ovarian, adrenal, hepatic, or uterine functions
awaits further study.
Data suggest that progestin therapy may have adverse effects
on lipid and carbohydrate metabolism. The choice of progestin,
its dose, and its regimen may be important in minimizing
these adverse effects, but these issues will require further
study before they are clarified. Women with hyperlipidemias
and/or diabetes should be monitored closely during progestin
therapy.
The age of the patient constitutes no absolute limiting
factor, although treatment with progestogens may mask
the onset of the climacteric.
The pathologist should be advised of progestogen therapy
when relevant specimens are submitted.
INFORMATION FOR THE PATIENT.
See text which appears at the end of this insert.
CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY.
Some beagle dogs treated with medroxyprogesterone acetate
developed mammary nodules. Although nodules occasionally
appeared in control animals, they were intermittent in
nature, whereas nodules in treated animals were larger
and more numerous, and persisted. There is no general
agreement as to whether the nodules are benign or malignant.
Their significance with respect to humans has not been
established.
PREGNANCY CATEGORY X.
Norethindrone acetate is contraindicated during pregnancy
as it may cause fetal harm when administered to pregnant
women. Several reports suggest an association between
intrauterine exposure to progestational drugs in the first
trimester of pregnancy and genital abnormalities in male
and female fetuses. Hypospadias occurs in about 5 to 8
per 1,000 male births and is about doubled with exposure
to these drugs. Some progestational drugs induce mild
virilization of the external genitalia of female fetuses.
NURSING MOTHERS.
Detectable amounts of progestogens have been identified
in the milk of mothers receiving them. The effect of this
on the nursing infant has not been determined.
PEDIATRIC USE.
Safety and effectiveness in pediatric patients have not
been established.
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