Included as part of the PRECAUTIONS section.
Pressor Effect With Concomitant Oxytocic Drugs
Serious postpartum hypertension has been described in
patients who received both a vasopressor (i.e., methoxamine, phenylephrine,
ephedrine) and an oxytocic (i.e., methylergonovine, ergonovine) [see DRUG
INTERACTIONS]. Some of these patients experienced a stroke. Carefully
monitor the blood pressure of individuals who have received both ephedrine and
Tolerance And Tachyphylaxis
Data indicate that repeated administration of ephedrine
can result in tachyphylaxis. Clinicians treating anesthesia-induced hypotension
with CORPHEDRA should be aware of the possibility of tachyphylaxis and should
be prepared with an alternative pressor to mitigate unacceptable
Risk Of Hypertension When Used Prophylactically
When used to prevent hypotension, ephedrine has been
associated with an increased incidence of hypertension compared with when
ephedrine is used to treat hypotension.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Two-year feeding studies in rats and mice conducted under
the National Toxicology Program (NTP) demonstrated no evidence of carcinogenic
potential with ephedrine sulfate at doses up to 10 mg/kg/day and 27 mg/kg/day
(approximately 2 times and 3 times the maximum human recommended dose on a mg/m²
Ephedrine sulfate tested negative in the in vitro
bacterial reverse mutation assay, the in vitro mouse lymphoma assay, the in
vitro sister chromatid exchange, and the in vitro chromosomal aberration assay.
Impairment Of Fertility
Studies to evaluate the effect of ephedrine on fertility
have not been conducted.
Use In Specific Populations
Limited published data on the
use of ephedrine sulfate are insufficient to determine a drug associated risk
of major birth defects or miscarriage. However, there are clinical
considerations [see Clinical Considerations]. Animal reproduction
studies have not been conducted with ephedrine sulfate.
The estimated background risk
of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse
outcomes. In the U.S. general population, the estimated background risk of
major birth defects and miscarriage in clinically recognized pregnancies is 2
to 4% and 15 to 20%, respectively.
Cases of potential metabolic
acidosis in newborns at delivery with maternal ephedrine exposure have been
reported in the literature. These reports describe umbilical artery pH of
≤ 7.2 at the time of delivery [see CLINICAL PHARMACOLOGY].
Monitoring of the newborn for signs and symptoms of metabolic acidosis may be
required. Monitoring of infant's acid-base status is warranted to ensure that
an episode of acidosis is acute and reversible.
Limited published literature
reports that ephedrine is present in human milk. However, no information is
available on the effects of the drug on the breastfed infant or the effects of
the drug on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother's clinical need for
CORPHEDRA and any potential adverse effects on the breastfed child from
CORPHEDRA or from the underlying maternal condition.
Safety and effectiveness in
pediatric patients have not been established.
Clinical studies of ephedrine
did not include sufficient numbers of subjects aged 65 and over to determine
whether they respond differently from younger subjects. Other reported clinical
experience has not identified differences in responses between the elderly and
In general, dose selection for
an elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug therapy. This drug
is known to be substantially excreted by the kidney, and the risk of adverse
reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care
should be taken in dose selection, and it may be useful to monitor renal
Ephedrine and its metabolite are excreted in urine. In
patients with renal impairment, excretion of ephedrine is likely to be affected
with a corresponding increase in elimination half-life, which will lead to slow
elimination of ephedrine and consequently prolonged pharmacological effect and
potentially adverse reactions. Monitor patients with renal impairment carefully
after the initial bolus dose for adverse events.