Dosing and uses of Ferriprox (deferiprone)
Adult dosage forms and strengths
tablet
- 500mg
Transfusional Iron Overload
Iron chelator indicated for treatment of transfusional iron overload caused by thalassemia syndromes when current chelation therapy is inadequate
Approval based on serum ferritin level reduction; no controlled trials demonstrating a direct treatment benefit (eg, improvement in disease-related symptoms, functioning, or increased survival)
25-33 mg/kg PO TID (ie, total daily dosage range 75-99 mg/kg/day)
Round dose to nearest 250 mg (half-tablet)
Monitoring and dose adjustments
- Monitor serum ferritin concentration every 2-3 months to assess the effects on body iron stores
- Dose adjustments should be tailored to the individual patient’s response and therapeutic goals (maintenance or reduction of body iron burden)
- If the serum ferritin falls consistently <500 mcg/L, consider temporarily interrupting therapy
Siderosis (Orphan)
Orphan designation for treatment of superficial siderosis
Orphan sponsor
- ApoPharma, Inc; 200 Barmac Drive; Canada
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Safety and effectiveness in elderly individuals have not been established
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
Ferriprox (deferiprone) adverse (side) effects
>10%
Chromaturia (14.6%)
Nausea (12.6%)
Abdominal pain/discomfort (10.4%)
1-10%
Arthralgia (9.8%)
Vomiting (9.8%)
Increased ALT (7.5%)
Decreased neutrophil count (7.3%)
Neutropenia (6.2%)
Increased appetite (4%)
Diarrhea (3%)
Headache (2.5%)
Dyspepsia (2%)
Back pain (2%)
Extremity pain (1.9%)
Increased weight (1.9%)
Agranulocytosis (1.7%)
Arthropathy (1.4%)
Increased AST (1.2%)
Decreased appetite (1.1%)
Warnings
Black box warnings
Can cause agranulocytosis that can lead to serious infections and death; neutropenia may precede agranulocytosis
Measure absolute neutrophil count (ANC) before initiating and monitor weekly while on therapy
Interrupt treatment if infection develops and monitor ANC more frequently
Advise patients taking to report immediately any symptoms indicative of infection
Contraindications
Hypersensitivity; Henoch-Schönlein purpura, urticaria, and periorbital edema with skin rash have been reported
Cautions
Fatal agranulocytosis can occur; interrupt therapy if neutropenia develops (ANC <1.5 x 10^9/L)
If infection occurs, interrupt therapy and monitor the ANC more frequently
Pregnancy; can cause fetal harm; women should be advised of the potential hazard to the fetus and to avoid pregnancy while on this drug
Monitor serum ferritin concentration every 2-3 months to assess the effects on body iron stores
Avoid coadministration with other drugs known to cause neutropenia or agranulocytosis; however, if this is not possible, closely monitor the absolute neutrophil count
Allow at least a 4-hour interval between deferiprone and mineral supplements, and antacids that contain polyvalent cations (eg, iron, aluminum, zinc) to avoid binding and malabsorption of supplements
Caution is administered with UGT 1A6 inhibitor (eg, silymarin [milk thistle])
Thorough QT interval studies have not been conducted
Pregnancy and lactation
Pregnancy category: D; can cause fetal harm when administered to pregnant women
In animal studies, administration during organogenesis resulted in embryofetal death and malformations at doses lower than equivalent human clinical doses
There are no studies in pregnant women, and available human data are limited
Lactation: Unknown whether distributed in breast milk; because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ferriprox (deferiprone)
Mechanism of action
Chelating agent with an affinity for ferric ion (iron III); binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable over a wide range of pH values
Has a lower binding affinity for other metals (eg, copper, aluminum, zinc) than for iron
Metabolism
Primarily eliminated via metabolism to the 3-O-glucuronide (lacks iron binding capability)
UGT 1A6 is primarily responsible for glucuronidation
Elimination
Half-life: 1.9 hr
Excretion: 75-90% excreted within 24 hr in urine as metabolite
Absorption
Absorption: Rapidly absorbed from upper GI within 5-10 minutes of PO administration
Peak Plasma Time: 1 hr (fasting); 2 hr (with food)
Peak Plasma Concentration: 20 mcg/mL
AUC: 53 mcg•hr/mL
Food decreases Cmax by 38% and AUC by 10%, but magnitude of exposure change does not warrant dose adjustment
Distribution
Protein Bound: <10%
Vd: 1.6 L/kg (in patients with thalassemia); 1 L/kg (in healthy subjects)
