Deferiprone

V03A - All other therapeutic products ATC V03AC02 Small molecule approved 1999 Oral Natural product Black-box warning

JFDA label: Ferriprox Tab

⚠ Black-Box Warning

Agranulocytosis/Neutropenia:

Mechanism of Action

— Unknown

Indications

Approved

Transfusional iron overload

Contraindications

Source: Lexicomp

Hypersensitivity to deferiprone or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Common Headache

Hepatobiliary disorders (2)

Common Increased serum ALT · increased serum AST

Renal and urinary disorders (1)

Very Common Urine discoloration

Blood and lymphatic system disorders (2)

Common agranulocytosis · Neutropenia

Gastrointestinal disorders (9)

Very Common Nausea

Common abdominal distress · abdominal pain · decreased appetite · diarrhea · dyspepsia · increased appetite · Vomiting · weight gain

Musculoskeletal and connective tissue disorders (4)

Common Arthralgia · arthropathy · back pain · limb pain

Dosing

Source: Lexicomp

Note: Round dose to the nearest 250 mg (or 1/2 tablet) or 2.5 mL (oral solution). If serum ferritin falls consistently below 500 mcg/L, consider temporary treatment interruption. Transfusional iron overload: Oral: Initial: 25 mg/kg 3 times/day (75 mg/kg/day); individualize dose based on response and therapeutic goal; maximum dose: 33 mg/kg 3 times/day (99 mg/kg/day)

Refer to adult dosing. Begin at the low end of dosing range.

There are no dosage adjustments provided in the manufacturer’s labeling.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied in patients with severe impairment).

Warnings & Precautions

Source: Lexicomp

Agranulocytosis//Neutropenia

May cause agranulocytosis, which could lead to serious infections (some fatal). Agranulocytosis may be preceded by neutropenia; monitor absolute neutrophil count (ANC) prior to treatment initiation and weekly during therapy. If infection develops, interrupt treatment and monitor ANC more frequently. Patients should promptly report any symptoms which may indicate infection. Interrupt treatment if neutropenia (ANC 3) develops; withhold any other medications which may also be associated with neutropenia; monitor CBC, corrected WBC, ANC, and platelets daily until ANC recovery. If ANC 3, consider hospitalization (and other clinically appropriate management); do not resume or rechallenge unless the potential benefits outweigh potential risks. Neutropenia and agranulocytosis were generally reversible upon discontinuation. The mechanism for deferiprone-induced agranulocytosis is not known. Avoid concurrent use with other agents associated with neutropenia (or agranulocytosis).

Hepatotoxicity

Elevations in ALT values have been observed; monitor ALT and consider treatment interruption for persistent elevations.

Hypersensitivity

Hypersensitivity reactions have been reported (eg, Henoch-Schönlein purpura [immunoglobulin A vasculitis], urticaria, and periorbital edema with skin rash).

Zinc deficiency

Lower plasma zinc concentrations have been observed; monitor zinc levels and supplement if necessary.

Pregnancy & Lactation

Pregnancy

FDA category D

Adverse effects have been observed in animal reproduction studies. Although there is limited data in humans, deferiprone may cause fetal harm if administered during pregnancy. During treatment with deferiprone in women of reproductive potential, pregnancy should be avoided.

Lactation

It is not known if deferiprone is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	Serum ferritin (every 2-3 months); ANC (at baseline and weekly during treatment); if ANC 3, monitor CBC, WBC (corrected for nucleated RBCs), ANC, and platelets daily until ANC recovery; ALT (monthly); zinc levels; signs or symptoms of infection

Chemistry & Properties

Formula	C7H9NO2
Molecular weight	139.15 g/mol
IUPAC name	3-hydroxy-1,2-dimethylpyridin-4-one
CAS	30652-11-0
PubChem CID	2972
InChIKey	`TZXKOCQBRNJULO-UHFFFAOYSA-N`
logP	0.4 (XLogP 0.5)
Polar surface area	42.23 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.56
Lipinski violations	0

SMILES

Cc1c(O)c(=O)ccn1C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.021 h
Volume of distribution	0.905 L/kg
Protein binding	9.6%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abemaciclib	major
Acalabrutinib	major
Adalimumab	major
Aflibercept	major
Aldesleukin	major
Alemtuzumab	major
Allopurinol	major
Altretamine	major
Anakinra	major
Antilymphocyte immunoglobulin (horse)	major
Antithymocyte immunoglobulin (rabbit)	major
Arsenic trioxide	major
Auranofin	major
Aurothioglucose	major
Avapritinib	major
Axicabtagene ciloleucel	major
Azacitidine	major
Azathioprine	major
Baricitinib	major
Belantamab mafodotin	major
Belatacept	major
Belinostat	major
Bendamustine	major
Bevacizumab	major
Bexarotene	major
Bleomycin	major
Blinatumomab	major
Bortezomib	major
Bosutinib	major
Brentuximab vedotin	major
Brexucabtagene autoleucel	major
Busulfan	major
Cabazitaxel	major
Capecitabine	major
Carbamazepine	major
Carboplatin	major
Carfilzomib	major
Carmustine	major
Certolizumab pegol	major
Chlorambucil	major

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Ferriprox Tab	Tablet 500 mg	100 tab	Sadeq Drug Store	130.720