Included as part of the "PRECAUTIONS" Section
Increased Risk Of Inflammatory Bowel Disease (IBD) Flare
Avoid use of ACCRUFER in patients with an active inflammatory bowel disease (IBD) flare, as there
is potential risk of increased inflammation in the gastrointestinal tract.
Excessive therapy with iron products can lead to excess storage of iron with the possibility of
iatrogenic hemosiderosis. Do not administer ACCRUFER to patients with evidence of iron overload or
patients receiving intravenous iron [see CONTRAINDICATIONS]. Assess iron parameters prior to
initiating ACCRUFER and monitor iron parameters while on therapy [see OVERDOSE and CLINICAL PHARMACOLOGY].
Risk Of Overdosage In Children Due To Accidental Injestion
Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under
6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison
control center immediately.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
Inform patients to take ACCRUFER as directed on an empty stomach, at least 1 hour before or 2
hours after meals. Instruct patients on concomitant medications that should be dosed apart from
ACCRUFER [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].
Advise patients that ACCRUFER may cause, flatulence, diarrhea, constipation, discolored feces,
abdominal pain, nausea, vomiting or abdominal bloating or discomfort. Advise patients to report
severe or persistent gastrointestinal symptoms or any allergic reactions to their physician [see ADVERSE REACTIONS].
Increased Risk Of IBD Flare
Advise patients that they should not use ACCRUFER if they are experiencing an IBD flare.
Iron Overload And Risk Of Accidental Overdose In Children
Inform patients to keep this product out of reach of children as accidental over dose of iron products
is a leading cause of fatal poisonings in children. In case of accidental overdose, advise them to call a
doctor or poison control center immediately [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
ACCRUFER is not absorbed systemically as an intact complex.
Carcinogenicity studies have not been conducted with ferric maltol.
Ferric maltol was mutagenic in vitro in reverse bacterial mutation (Ames) assays. Ferric maltol
increased revertant frequency in the absence and presence of metabolic activation.
Fertility studies have not been conducted with ferric maltol.
The carcinogenic potential of maltol has been evaluated in long-term animal toxicity studies in two
species: CD-1 mice and Sprague-Dawley rats. Maltol was not carcinogenic in a 18-month study in
mice at doses up to 400 mg/kg (approximately 5 times the human daily dose). Maltol was not
carcinogenic in a 2-year study in rats at doses up to 400 mg/kg (approximately 10 times the human
Maltol was mutagenic in vitro in reverse bacterial mutation (Ames) assays. Maltol increased revertant
frequency in the absence and presence of metabolic activation. Maltol was clastogenic in vivo in a
mouse micronucleus assay (increase in polychromatic erythrocytes) at intraperitoneal doses of 774
mg/kg. Absorbed maltol is rapidly conjugated with glucuronic acid. It is therefore unlikely that the
mutagenic activity of maltol would be expressed under the conditions of oral human intake.
In a multi-generation animal reproduction study in male and female rats, there were no effects on
mating, fertility, or early embryonic development at doses up to 400 mg/kg/day (approximately 10
times the human daily dose).
Use In Specific Populations
ACCRUFER is not absorbed systemically as an intact complex following oral administration, and
maternal use is not expected to result in fetal exposure to the drug [see CLINICAL PHARMACOLOGY].
In animal reproduction studies, oral administration of ferric or ferrous compounds to gravid CD1-mice
and Wistar-rats during organogenesis at doses 13 to 32 times the recommended human dose
resulted in no adverse developmental outcomes. An overdose of iron in pregnant women may carry a
risk for spontaneous abortion, gestational diabetes and fetal malformation.
In animal reproduction studies, oral administration of maltol to pregnant Crl: COBS-CD (SD) BR rats
during organogenesis at doses 6 times the recommended human dose resulted in no adverse
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%, respectively.
Disease-Associated Maternal and/or Embryo/Fetal Risk
Untreated iron deficiency anemia (IDA) in pregnancy is associated with adverse maternal outcomes
such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased
risk for preterm delivery and low birth weight.
In embryofetal development studies in mice and rats, pregnant animals received oral doses of ferric
or ferrous compounds (ferrous sulfate or ferric sodium pyrophosphate) of up to 160 mg/kg/day in
mice, or up to 200 mg/kg/day in rats, during the period of organogenesis. Administration of ferric or
ferrous compounds at doses 13 times (in mice) or 32 times (in rats) the recommended human dose
resulted in no maternal toxicity and no adverse developmental outcomes.
In a multigeneration reproductive and developmental study in rats, pregnant animals received oral
doses of maltol of 100, 200, and 400 mg/kg/day, during the period of organogenesis. Administration
of maltol at doses 6 times the recommended human dose resulted in no maternal toxicity and no
adverse developmental outcomes.
There are no data on the presence of ACCRUFER in human milk, the effects on the breastfed child,
or the effects on milk production. ACCRUFER is not absorbed systemically as an intact complex by
the mother following oral administration, and breastfeeding is not expected to result in exposure of
the child to ACCRUFER.
Safety and effectiveness of ACCRUFER have not been established in pediatric patients.
Of the 295 patients in the randomized trials of ACCRUFER, 39% of patients were aged 65 and older,
while 23% were aged 75 and older. No overall differences in safety or effectiveness were observed
between these patients and younger patients.