Included as part of the PRECAUTIONS section.
Serious hypersensitivity reactions, including
anaphylactic-type reactions, some of which have been life-threatening and
fatal, have been reported in patients receiving parenteral iron products. Patients
may present with shock, clinically significant hypotension, loss of
consciousness, and/or collapse. Monitor patients for signs and symptoms of
hypersensitivity during and after hemodialysis until clinically stable.
Personnel and therapies should be immediately available for the treatment of
serious hypersensitivity reactions. [see ADVERSE REACTIONS]
Hypersensitivity reactions have been reported in 1 (0.3%)
of 292 patients receiving Triferic in two randomized clinical trials.
Iron Laboratory Testing
Determine iron status on pre-dialysis blood samples.
Post-dialysis serum iron parameters may overestimate serum iron and transferrin
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Studies examining the carcinogenic potential of ferric
pyrophosphate citrate have not been conducted.
Ferric pyrophosphate citrate was clastogenic in the in
vitro chromosomal aberration assay in CHO cells in the presence of metabolic
activation. Ferric pyrophosphate citrate was not mutagenic in the in vitro bacterial
reverse mutation (Ames) test or clastogenic in the in vitro chromosomal
aberration assay in CHO cells in the absence of metabolic activation or in the in
vivo mouse micronucleus assay.
In a combined male and female fertility study in rats,
ferric pyrophosphate citrate was administered intravenously over one hour three
times per week at doses of up to 40 mg/kg. No adverse effects on fertility or
reproduction were noted.
Use In Specific Populations
There are no available data on Triferic use in pregnant
women to inform a drug-associated risk of major birth defects and miscarriage.
In pregnant rats and rabbits, ferric pyrophosphate citrate caused adverse
developmental outcomes at maternally toxic dose levels that were higher than
the maximum theoretical amount of iron transferred to patients from Triferic.
Use Triferic during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
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 2-4% and 15-20%,
In a fertility and early embryonic development study in
female rats, the maternally toxic ferric pyrophosphate citrate dose of 40 mg/kg
administered three times per week by intravenous (IV) infusion was not toxic to
the developing embryo. In embryo-fetal developmental toxicity studies, ferric
pyrophosphate citrate was administered during the period of organogenesis as a
one-hour IV infusion to pregnant rats and rabbits. No maternal or developmental
toxicity was observed at doses up to 30 mg/kg/day in rats and 20 mg/kg/day in
rabbits. Maternally toxic doses affected embryo-fetal development, resulting in
post-implantation loss due to early resorptions, abnormal placentae, decreased
fetal body weight and fetal head and vertebral malformations at 90 mg/kg/day in
rats and vertebral malformations at 40 mg/kg/day in rabbits.
A pre-and post-natal development study was conducted in
pregnant rats with intravenous doses of ferric pyrophosphate citrate up to 90
mg/kg/day. The maternally toxic dose of 90 mg/kg/day resulted in reductions in
the number of live offspring and lower offspring body weights. There were no
adverse effects on survival of offspring at doses up to 30 mg/kg/day, or on
behavior, sexual maturation or reproductive parameters of offspring at any dose
There is no information regarding the presence of
Triferic in human milk, the effects on the breastfed child, or the effect on
milk production. The developmental and health benefits of breastfeeding should
be considered along with the mother's clinical need for Triferic and any potential
adverse effects on the breastfed child from Triferic or from the underlying
Females And Males Of Reproductive Potential
Triferic may cause fetal harm when administered to
pregnant women. Advise females of reproductive potential to use effective
contraception measures to prevent pregnancy during treatment with Triferic and
for at least 2 weeks following completion of therapy.
Safety and effectiveness have not been established in
In controlled clinical trials, 99 (28.6%) patients ≥
65 years of age were treated with Triferic. No overall differences in safety
and efficacy were observed between older and younger patients in these trials [see