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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
FERRIPROX (NDA-021825)
(DEFERIPRONE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
03/26/2025 (SUPPL-12)
5 Warnings and Precautions
5.1 Agranulocytosis and Neutropenia
Additions and/or revisions underlined:
. . .
For agranulocytosis (ANC less than 0.2 x 109/L) and severe neutropenia (0.2 x 109/L less than or equal to ANC less than 0.5 x 109/L):
Consider hospitalization and other management as clinically appropriate.
Do not resume FERRIPROX in patients who have developed agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia with FERRIPROX unless potential benefits outweigh potential risks.
. . .
11/30/2021 (SUPPL-10)
5 Warnings and Precautions
5.1 Agranulocytosis and NeutropeniaAdditions and/or revisions underlined:
Fatal agranulocytosis can occur with FERRIPROX use. FERRIPROX can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting FERRIPROX therapy and monitor it regularly while on therapy [see Dosage and Administration (2.1)].
Reduction in the frequency of ANC monitoring should be considered on an individual patient basis, according to the health care provider’s assessment of the patient’s understanding of the risk minimization measures required during therapy.
Interrupt FERRIPROX therapy if neutropenia develops (ANC < 1.5 x 109/L). Interrupt FERRIPROX if infection develops and monitor the ANC frequently.
Advise patients taking FERRIPROX to immediately interrupt therapy and report to their physician if they experience any symptoms indicative of infection.
The incidence of agranulocytosis was 1.7% of patients in pooled clinical trials of 642 patients with thalassemia syndromes and 1.5% of patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. The mechanism of FERRIPROX- associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of FERRIPROX, but there have been reports of agranulocytosis leading to death.
Implement a plan to monitor for and to manage agranulocytosis and neutropenia prior to initiating FERRIPROX treatment.
For agranulocytosis (ANC < 0.5 x 109/L):
Consider hospitalization and other management as clinically appropriate.
Do not resume FERRIPROX in patients who have developed agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia with FERRIPROX unless potential benefits outweigh potential risks.
For neutropenia (ANC < 1.5 x 109/L and > 0.5 x 109/L):
Instruct the patient to immediately discontinue FERRIPROX and all other medications with a potential to cause neutropenia.
Obtain a complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an absolute neutrophil count (ANC), and a platelet count daily until recovery (ANC greater than or equal to 1.5 x 109/L).
Additions and/or revisions underlined:
Decreased plasma zinc concentrations have been observed on FERRIPROX therapy. Monitor plasma zinc annually, and supplement in the event of a deficiency [see Dosage and Administration (2.1)].
6 Adverse Reactions
6.1 Clinical Trial ExperienceTable numbers have been revised; please refer to label
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEExtensive changes; please refer to label
Additions and/or revisions underlined:
Advise the patient to read the FDA-approved patient labeling (Medication Guide)
Instruct patients and their caregivers to store FERRIPROX at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature].
FERRIPROX Tablets (twice a day), 1,000 mg:
Advise patients to take the first dose of FERRIPROX Tablets (twice a day) in the morning and the second in the evening.
Advise patients to take FERRIPROX Tablets (twice a day) with food to reduce the risk of nausea and vomiting.
Advise patients to avoid alcohol while taking FERRIPROX Tablets (twice a day). Consumption of alcohol while taking FERRIPROX Tablets (twice a day) may result in more rapid release of deferiprone.
FERRIPROX Tablets (three times a day), 1,000 mg:
Store in the originally supplied bottle, closed tightly to protect from moisture.
Advise patients to take the first dose of FERRIPROX in the morning, the second dose at midday, and the third dose in the evening. Clinical experience suggests that taking FERRIPROX with meals may reduce nausea.
FERRIPROX Tablets, 500 mg:
Store in the originally supplied bottle, closed tightly to protect from moisture.
Advise patients to take the first dose of FERRIPROX in the morning, the second dose at midday, and the third dose in the evening. Clinical experience suggests that taking FERRIPROX with meals may reduce nausea.
If a dose of this medicine has been missed, take it as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not catch-up or double doses.
Inform patients of the risks of developing agranulocytosis and the need for regular blood testing before and during their treatment to monitor for decreases in their ANC. Instruct them to immediately interrupt therapy and report to their physician if they experience any symptoms of infection such as fever, sore throat or flu-like symptoms [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)] in order to check their ANC within 24 hours. Advise them if they are unable to reach their physician, seek care from another provider so as not to delay medical care.
Inform patients of the risk of abnormal liver transaminases and the need for regular blood testing before and during their treatment to monitor for increases in ALT [see Dosage and Administration (2.1) and Warnings and Precautions (5.2)].
Inform patients of the risk of zinc deficiency and the need for regular blood testing before and during their treatment to monitor for reductions in zinc [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)].
Advise patients to contact their physician in the event of overdose.
Inform patients that their urine might show a reddish/brown discoloration due to the excretion of the iron-deferiprone complex. This is a very common sign of the desired effect, and it is not harmful.
Embryo-Fetal toxicity
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least six months after the last dose [see Use in Specific Populations (8.1, 8.3)]. Advise males with female partners of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least three months after the last dose [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].
Lactation
Advise females not to breastfeed during treatment with FERRIPROX and for at least 2 weeks after the last dose [see Use in Specific Populations (8.2)].
04/30/2021 (SUPPL-8)
5 Warnings and Precautions
5.1 Agranulocytosis and Neutropenia(Additions and/or revisions underlined)
Fatal agranulocytosis can occur with FERRIPROX use. FERRIPROX can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting FERRIPROX therapy and monitor it weekly while on therapy.
Interrupt FERRIPROX therapy if neutropenia develops (ANC < 1.5 x 109/L). Interrupt FERRIPROX if infection develops and monitor the ANC frequently.
Advise patients taking FERRIPROX to immediately interrupt therapy and report to their physician if they experience any symptoms indicative of infection.
The incidence of agranulocytosis was 1.7% of patients in pooled clinical trials of 642 patients with thalassemia syndromes and 1.5% of patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias.
(Additions and/or revisions underlined)
In pooled clinical trials, 7.5% of 642 patients with thalassemia syndromes treated with FERRIPROX developed increased ALT values. Four (0.62%) FERRIPROX-treated subjects discontinued the drug due to increased serum ALT levels and 1 (0.16%) due to an increase in both ALT and AST. In pooled clinical trials, 7.7% of 196 patients with sickle cell disease or other anemias treated with FERRIPROX developed increased ALT values.
6 Adverse Reactions
6.1 Clinical Trial Experience(Extensive changes; please refer to label)
7 Drug Interactions
7.2 Effect of Other Drugs on FERRIPROX(Additions and/or revisions underlined)
UDP-Glucuronosyltransferases (UGT)
Avoid use of UGT1A6 inhibitors (e.g., diclofenac, probenecid, or silymarin (milk thistle)) with FERRIPROX [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3)].
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions underlined)
Risk Summary
In animal reproduction studies, oral administration of deferiprone to pregnant rats and rabbits during organogenesis at doses 33% and 49%, respectively, of the maximum recommended human dose (MRHD) resulted in structural abnormalities, embryo-fetal mortality and alterations to growth (see Data). The limited available data from deferiprone use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(Additions and/or revisions underlined)
What is FERRIPROX Tablets?
FERRIPROX Tablets is a prescription medicine used to treat iron overload from blood transfusions in adults and children 8 years of age and older with:
• thalassemia syndromes.
• sickle cell disease or other anemias.
It is not known if FERRIPROX Tablets is safe and effective to treat iron overload due to blood transfusions:
• in people with myelodysplastic syndrome or Diamond Blackfan anemia
• in children less than 8 years of age
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with FERRIPROX Tablets.
• There are 2 types of FERRIPROX Tablets that are taken on different schedules. Be sure you are taking the correct tablet and ask your healthcare provider if unsure.
• Take this FERRIPROX Tablets 3 times each day. Take your first dose in the morning, the second dose at midday, and the third dose in the evening.
The most common side effects of FERRIPROX Tablets in people with thalassemia include:
• nausea • vomiting • stomach-area (abdominal) pain
• joint pain • abnormal liver function tests • low white blood cells
The most common side effects of FERRIPROX Tablets in people with sickle cell disease or other anemias
include:
• fever • stomach-area (abdominal) pain • bone pain
• headache • vomiting • pain in arms or legs
• sickle cell anemia with crisis • back pain • abnormal liver function tests
• joint pain • mouth and throat pain • common cold
• low white blood cells • cough • nausea
• Store FERRIPROX Tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• Store FERRIPROX Tablets in the original bottle and tightly closed to protect from moisture.
(Newly added information)
Advise patients to take the first dose of FERRIPROX in the morning, the second dose at midday, and the third dose in the evening. Clinical experience suggests that taking FERRIPROX with meals may reduce nausea.
02/20/2020 (SUPPL-7)
8 Use in Specific Populations
8.1 Pregnancy(additions underlined)
In animal reproduction studies, oral administration of deferiprone to pregnant rats and rabbits during organogenesis at doses 33% and 49%, respectively, of the maximum recommended human dose (MRHD) resulted in structural abnormalities, embryo-fetal mortality and alterations to growth (see Data). The limited data from FERRIPROX use in pregnant women are insufficient to inform a drug- associated risk of major birth defects and miscarriage. Based on evidence of genotoxicity and developmental toxicity in animal studies, FERRIPROX can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
…
…
Contraception
Females
FERRIPROX can cause embryo-fetal harm when administered to a pregnant woman. Advise female patients of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least 6 months after the last dose.
Males
Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least 3 months after the last dose.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(section revised, additions underlined)
…
Inform patients that their blood will be checked to monitor liver function and zinc levels. A zinc supplement may be prescribed if zinc levels are low.
…
Embryo-Fetal toxicity
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise female patients of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least six months after the last dose.Advise males with female partners of reproductive potential to use effective contraception during treatment with FERRIPROX and at least three months after the last dose.
Lactation
Advise females not to breastfeed during treatment with FERRIPROX and for at least 2 weeks after the last dose.
…
07/25/2019 (SUPPL-4)
5 Warnings and Precautions
5.2 Embryofetal Toxicity(additions are underlined)
Based on evidence of genotoxicity and developmental toxicity in animal studies, FERRIPROX can cause fetal harm when administered to a pregnant woman. The limited available data on the use of FERRIPROX in pregnant women are insufficient to inform risk. In animal studies, administration of deferiprone during the period of organogenesis resulted in embryofetal death and malformations at doses lower than equivalent human clinical doses.
Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use highly effective contraception during treatment with FERRIPROX. Six months of contraception is recommended after cessation of therapy. Advise males of reproductive potential to use effective contraception during treatment with FERRIPROX. Three months of contraception is recommended after cessation of therapy.
(renaming of subsection title)
(renaming of subsection title)
6 Adverse Reactions
(additions are underlined)
The following clinically significant adverse reactions are described below and elsewhere in the labeling:
Agranulocytosis/Neutropenia
Liver Enzyme Elevations
Zinc Deficiency
7 Drug Interactions
7.2 UDP-Glucuronosyltransferases (UGTs)(additions are underlined)
Avoid use of UGT1A6 inhibitors (e.g., diclofenac, probenecid, or silymarin (milk thistle)) with FERRIPROX.
8 Use in Specific Populations
8.1 Pregnancy(Pregnancy and Lactation Labeling Rule (PLLR) conversion)
Risk Summary
Limited available data with FERRIPROX use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. FERRIPROX can cause fetal harm when administered to a pregnant woman. based on genotoxicity and developmental toxicity in animal studies.
In animal reproduction studies, administration of deferiprone to pregnant animals during the period of organogenesis resulted in adverse developmental outcomes including embryofetal death and malformations in rats and rabbits at doses much lower than the MRHD (maximum recommended human dose) based on body surface area. Advise women of the 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 of miscarriage is 2-4% and 15-20%, respectively.
Data
Human Data
Post-marketing data available from 39 pregnancies of FERRIPROX-treated patients and 10 pregnancies of partners of FERRIPROX- treated patients are as follows:
Of the 39 pregnancies in FERRIPROX-treated patients, 23 resulted in healthy newborns, 6 ended in spontaneous abortion, 9 had unknown outcomes, and 1 infant was born with anal atresia, nephroptosis, ventricular septal defect, hemivertebra and urethral fistula.
Of the 10 pregnancies in partners of FERRIPROX-treated patients, 5 resulted in healthy newborns, 1 resulted in a healthy newborn with slight hypospadias, 1 was electively terminated, 1 resulted in the intrauterine death of twins, and 2 had unknown outcomes.
Animal Data
During organogenesis, pregnant rats and rabbits received deferiprone at oral doses of 0, 30, 80 or 200 mg/kg/day, and 0, 10, 50, or 150 mg/kg/day, respectively. The daily dose was administered as two equal divided doses approximately 7 hours apart. Doses of 200 mg/kg/day in rats and 150 mg/kg/day in rabbits, approximately 33% and 49% of the MRHD, respectively, resulted in increased post-implantation loss and reduced fetal weights in the presence of maternal toxicity (reduced maternal body weight and body weight gain in both rats and rabbits; abnormal large placenta at low incidence in rats). The 200 mg/kg/day dose in rats resulted in external, visceral and skeletal fetal malformations (absent eye bulge, cranial meningocele, domed head, limb malrotation, protruding tongue, anal atresia, cleft palate, internal hydrocephaly, anophthalmia, misshapen bones of the face and naso-pharyngeal tract, and fused bones in the axial skeleton). The dose of 150 mg/kg/day in rabbits resulted in external fetal malformations (partially opened eyes) and minor blood vessel and skeletal variations.
In rats, malformations including micrognathia and persistent ductus arteriosus could be observed in the absence of maternal toxicity at doses equal to or greater than 30 and 80 mg/kg/day, approximately 5% and 13% of the MHRD, respectively.
(Pregnancy and Lactation Labeling Rule (PLLR) conversion)
Risk Summary
There is no information regarding the presence of deferiprone in human milk, the effects on the breastfed child, or the effects on milk production.
Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for deferiprone in animal studies, advise patients not to breastfeed during FERRIPROX treatment and for 2 weeks after the last dose.
(newly added subsection)
FERRIPROX can cause fetal harm when administered to a pregnant female.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating FERRIPROX therapy.
Contraception
Females
Advise females of reproductive potential to avoid pregnancy during treatment with FERRIPROX and 6 months of contraception is recommended after cessation of therapy. Advise females to immediately report pregnancy.
Males
Advise males with female sexual partners of reproductive potential to use effective contraception during treatment with FERRIPROX and 3 months of contraception is recommended after cessation of therapy
(additions are underlined)
Clinical studies of FERRIPROX 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 younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(extensive revisions; please refer to labeling)