Deferasirox (Monograph)

Drug class: Heavy Metal Antagonists

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Introduction

Heavy metal antagonist; chelating agent for iron.

Uses for Deferasirox

Chronic Iron Overload Due to Blood Transfusions

Treatment of chronic iron overload resulting from multiple transfusions (transfusional hemosiderosis) in patients ≥2 years of age (designated an orphan drug by FDA for this use). Safety and efficacy when administered with other iron chelation therapy not established. Experts generally consider deferasirox as an option for iron chelation therapy in patients with iron overload due to blood transfusions.

Chronic Iron Overload with Non-Transfusion Dependent Thalassemia

Treatment of chronic iron overload in patients ≥10 years of age with non-tranfusion-dependent thalassemia (NTDT), with a liver iron concentration (LIC) of at least 5 mg iron per gram of dry weight and serum ferritin level >300 mcg/L (designated an orphan drug by FDA for this use). Safety and efficacy when administered with other iron chelation therapy not established. The Thalassaemia International Federation generally recommends use of iron chelators, specifically deferasirox, for treatment of iron overload in patients with NTDT.

Deferasirox Dosage and Administration

General

Pretreatment Screening

• In patients with chronic iron overload resulting from multiple transfusions, determine baseline concentrations of serum ferritin. In patients with non-transfusion-dependent thalassemia (NTDT), determine baseline concentrations of serum ferritin and liver iron concentrations (LIC). The risk of toxicity may be increased when deferasirox is administered to patients with low iron burden or with only slightly elevated serum ferritin concentrations.

• Establish an accurate renal function baseline by obtaining duplicate serum creatinine values (due to variations in measurements) for calculation of an estimated glomerular filtration rate (eGFR) before therapy initiation.

• Obtain urinalyses and serum electrolyte concentrations to evaluate renal tubular function.

• Assess serum transaminase and bilirubin concentrations.

• Perform baseline auditory testing and ophthalmologic examinations (e.g., slit-lamp examinations, fundoscopy).

Patient Monitoring

• Monitor serum ferritin concentrations.

• Monitor blood counts.

• Monitor serum transaminase and bilirubin concentrations every 2 weeks during the first month of treatment, and monthly thereafter.

• In NTDT, measure the LIC by liver biopsy or by using an FDA-cleared or approved method every 6 months.

• Monitor all patients for changes in the eGFR and for renal tubular toxicity weekly during the first month of therapy or after dosage modification, and at least monthly thereafter. Increase monitoring frequency in patients with baseline renal disease, those at increased risk for renal failure, and in pediatric patients who are volume depleted. Obtain urinalyses and serum electrolyte concentrations to evaluate renal tubular function before any dosage increases.

• Ophthalmologic examination and auditory testing are recommended annually during treatment.

• Monitor for development of GI ulceration and hemorrhage.

Administration

Oral Administration

Available as tablets for oral suspension (e.g., Exjade), film-coated tablets for oral use (e.g., Jadenu), and granules for oral use (e.g., Jadenu Sprinkle).

Administer deferasirox tablets for oral suspension (e.g., Exjade) orally once daily on an empty stomach (≥30 minutes before eating), preferably at the same time each day.

Administer film-coated tablets or granules (e.g., Jadenu ) preparations orally once daily on an empty stomach (≥30 minutes before eating) or with a light meal (containing <7% fat and approximately 250 calories), preferably at the same time each day.

Tablets for Oral Suspension

Deferasirox tablets for oral suspension (e.g., Exjade) should not be chewed or swallowed whole.

Completely disperse tablets for oral suspension by stirring in water, orange juice, or apple juice. Disperse doses of <1 g in 105 mL (3.5 oz) and doses of ≥1 g in 210 mL (7 oz) of liquid. Use the suspension immediately following preparation. Following administration, resuspend any residue in a small volume of liquid and swallow.

Tablets

Swallow film-coated tablets (e.g., Jadenu) whole. If difficulty swallowing whole tablets, crush and mix deferasirox film-coated tablets with soft foods (e.g., yogurt, applesauce) immediately prior to administration. Do not store for future use.

Granules

Administer deferasirox granules for oral use (e.g., Jadenu Sprinkle) by sprinkling the full dose onto soft foods (e.g., yogurt, applesauce) immediately prior to use.

Dosage

Dosage conversion (i.e., about 30% reduction in dosage, rounded to the nearest whole tablet or whole sachet) required when switching from deferasirox tablets for oral suspension (e.g., Exjade) to film-coated tablets or granules (e.g., Jadenu) See Table 1.

Pediatric Patients

Chronic Iron Overload Due to Blood Tranfusions

Only consider initiation of deferasirox for treatment of chronic iron overload due to blood transfusions in patients with evidence of transfusion overload based on a transfusion of ≥100 mL/kg of packed red blood cells (e.g., ≥20 units of packed red blood cells in patients weighing ≥40 kg), and a serum ferritin consistently >1000 mcg/L.

Initial dosages are recommendations for patients with an estimated glomerular filtration rate (eGFR) >60 mL/minute per 1.73 m².

Oral

Tablets for oral suspension (e.g., Exjade): Children ≥2 years of age: Initially, 20 mg/kg daily, rounded to the nearest whole-tablet dosage strength.

Adjust dosage every 3–6 months as needed based on trends in serum ferritin concentrations (monitor monthly). Adjust dosage in increments of 5 or 10 mg/kg daily according to the patient’s clinical response and therapeutic goals.

In pediatric patients not adequately controlled with dosages of 30 mg/kg daily (e.g., serum ferritin concentrations consistently >2500 mcg/L and not showing a downward trend over time), consider dosages up to 40 mg/kg daily. Dosages >40 mg/kg daily not recommended.

Consider dose reduction if serum ferritin falls below 1000 mcg/L at 2 consecutive visits, especially if the dose exceeds 25 mg/kg daily as tablets for oral suspension. To avoid overchelation, interrupt therapy if serum ferritin concentrations are <500 mcg/L and continue monthly monitoring. Increase monitoring frequencies in pediatric patients with acute illness causing volume depletion (e.g., vomiting, diarrhea, prolonged decreased oral intake).

Oral

Tablets and granules (e.g., Jadenu and Jadenu Sprinkle): Children ≥2 years of age: Initially, 14 mg/kg daily, rounded to the nearest whole-tablet or whole-sachet dosage strength.

Adjust dosage every 3–6 months as needed based on trends in serum ferritin concentrations (monitor monthly). Adjust dosage in increments of 3.5 or 7 mg/kg daily according to the patient’s clinical response and therapeutic goals.

In pediatric patients not adequately controlled with dosages of 21 mg/kg daily (e.g., serum ferritin concentrations consistently >2500 mcg/L and not showing a downward trend over time), consider dosages up to 28 mg/kg daily. Dosages >28 mg/kg daily not recommended.

Consider dose reduction if serum ferritin falls below 1000 mcg/L at 2 consecutive visits, especially if the dose exceeds 17.5 mg/kg daily as film-coated tablets or granules. To avoid overchelation, interrupt therapy if serum ferritin concentrations are <500 mcg/L and continue monthly monitoring. Increase monitoring frequencies in pediatric patients with acute illness causing volume depletion (e.g., vomiting, diarrhea, prolonged decreased oral intake).

Iron Overload in Non-Transfusion-Dependent Thalassemia (NTDT)

Only consider initiation of deferasirox for treatment of iron overload in non-transfusion dependent thalassemia (NTDT) in patients with an LIC ≥5 mg Fe/g dry weight and a serum ferritin >300 mcg/L.

Initial dosages are recommendations for patients with an eGFR >60 mL/minute per 1.73 m².

Oral

Tablets for oral suspension (e.g., Exjade): Children ≥10 years of age: Initially, 10 mg/kg daily, rounded to the nearest whole-tablet dosage strength.

Only consider initiation if LIC >5 mg Fe/g dry weight and serum ferritin concentration >300 mcg/L. Consider increasing dosage to 20 mg/kg daily after 4 weeks if baseline LIC >15 mg Fe/g dry weight.

Monitor ferritin concentrations monthly for over-chelation and interrupt therapy if serum ferritin decreases to <300 mcg/L. If serum ferritin <300 mcg/L, obtain LIC to determine if <3 mg Fe/g dry weight.

Monitor LIC every 6 months. After 6 months, adjust or continue current dosage based on LIC. If LIC is 3–7 mg Fe/g dry weight, continue therapy at dosage no greater than 10 mg/kg daily. Increase dosage to 20 mg/kg daily if LIC is >7 mg Fe/g dry weight. Dosages >20 mg/kg daily not recommended.

Increase monitoring frequencies in pediatric patients with acute illness causing volume depletion (e.g., vomiting, diarrhea, prolonged decreased oral intake).

Temporarily interrupt therapy if LIC <3 mg Fe/g dry weight. May restart when LIC >5 mg Fe/g dry weight.

Oral

Tablets and granules (e.g., Jadenu and Jadenu Sprinkle): Children ≥10 years of age: Initially, 7 mg/kg daily, rounded to the nearest whole-tablet or whole-sachet dosage strength.

Only consider initiation if LIC >5 mg Fe/g dry weight and serum ferritin concentration >300 mcg/L. Consider increasing dosage to 14 mg/kg daily after 4 weeks if baseline LIC >15 mg Fe/g dry weight.

Monitor ferritin concentrations monthly for over-chelation and interrupt therapy if serum ferritin decreases to <300 mcg/L. If serum ferritin <300 mcg/L, obtain LIC to determine if <3 mg Fe/g dry weight.

Monitor LIC every 6 months. After 6 months, adjust or continue current dosage based on LIC. If LIC 3–7 mg Fe/g dry weight, continue therapy at dosage no greater than 7 mg/kg daily. Increase dosage to 14 mg/kg daily if LIC is >7 mg Fe/g dry weight. Dosages >14 mg/kg daily not recommended.

Increase monitoring frequencies in pediatric patients with acute illness causing volume depletion (e.g., vomiting, diarrhea, prolonged decreased oral intake.

Temporarily interrupt therapy if LIC <3 mg Fe/g dry weight. May restart when LIC >5 mg Fe/g dry weight.

Adults

Chronic Iron Overload Due to Blood Tranfusions

Only consider initiation of deferasirox for treatment of chronic iron overload due to blood transfusions in patients with evidence of transfusion overload based on a transfusion of ≥100 mL/kg of packed red blood cells (e.g., ≥20 units of packed red blood cells in patients weighing ≥40 kg), and a serum ferritin consistently >1000 mcg/L.

Initial dosages are recommendations for patients with an estimated glomerular filtration rate (eGFR) >60 mL/minute per 1.73 m².

Oral

Tablets for oral suspension (e.g., Exjade): Initially, 20 mg/kg daily, rounded to the nearest whole-tablet dosage strength.

Adjust dosage every 3–6 months as needed based on trends in serum ferritin concentrations (monitor monthly). Adjust dosage in increments of 5 or 10 mg/kg daily according to the patient’s clinical response and therapeutic goals.

In adults not adequately controlled with dosages of 30 mg/kg daily (e.g., serum ferritin concentrations consistently >2500 mcg/L and not showing a downward trend over time), consider dosages up to 40 mg/kg daily. Dosages >40 mg/kg daily not recommended.

Consider dose reduction if serum ferritin falls below 1000 mcg/L at 2 consecutive visits, especially if the dosage exceeds 25 mg/kg daily as tablets for oral suspension. To avoid overchelation, interrupt therapy if serum ferritin concentrations are <500 mcg/L and continue monthly monitoring.

Oral

Tablets and granules (e.g., Jadenu and Jadenu Sprinkle): Initially, 14 mg/kg daily, rounded to the nearest whole-tablet or whole-sachet dosage strength.

Adjust dosage every 3–6 months as needed based on trends in serum ferritin concentrations (monitor monthly). Adjust dosage in increments of 3.5 or 7 mg/kg daily according to the patient’s clinical response and therapeutic goals.

In adults not adequately controlled with dosages of 21 mg/kg daily (e.g., serum ferritin concentrations consistently >2500 mcg/L and not showing a downward trend over time), consider dosages up to 28 mg/kg daily. Dosages >28 mg/kg daily not recommended.

Consider dose reduction if serum ferritin falls below 1000 mcg/L at 2 consecutive visits, especially if the dosage exceeds 17.5 mg/kg daily as film-coated tablets or granules. To avoid overchelation, interrupt therapy if serum ferritin concentrations are <500 mcg/L and continue monthly monitoring.

Iron Overload in NTDT

Only consider initiation of deferasirox for treatment of iron overload in non-transfusion dependent thalassemia (NTDT) in patients with an LIC ≥5 mg Fe/g and a serum ferritin >300 mcg/L.

Initial dosages are recommendations for patients with an eGFR >60 mL/minute per 1.73 m².

Oral

Tablets for oral suspension (e.g., Exjade): Initially, 10 mg/kg daily, rounded to the nearest whole-tablet dosage strength.

Only consider initiation if LIC ≥5 mg Fe/g dry weight and serum ferritin concentration >300 mcg/L. Consider increasing dosage to 20 mg/kg daily after 4 weeks if baseline LIC >15 mg Fe/g dry weight.

Monitor ferritin concentrations monthly for overchelation and interrupt therapy if serum ferritin decreases to <300 mcg/L. If serum ferritin <300 mcg/L, obtain LIC to determine if <3 mg Fe/g dry weight.

Monitor LIC every 6 months. After 6 months, adjust or continue current dosage based on LIC. If LIC 3–7 mg Fe/g dry weight, continue therapy at dosage no greater than 10 mg/kg daily. Increase dosage to 20 mg/kg daily if LIC is >7 mg Fe/g dry weight. Dosages >20 mg/kg daily not recommended.

Oral

Tablets and granules (e.g., Jadenu and Jadenu Sprinkle): Initially, 7 mg/kg daily, rounded to the nearest whole-tablet dosage strength.

Only consider initiation if LIC ≥5 mg Fe/g dry weight and serum ferritin concentration >300 mcg/L. Consider increasing dosage to 14 mg/kg daily after 4 weeks if baseline LIC >15 mg Fe/g dry weight.

Monitor ferritin concentrations monthly for overchelation and interrupt therapy if serum ferritin decreases to <300 mcg/L If serum ferritin <300 mcg/L, obtain LIC to determine if <3 mg Fe/g dry weight.

Monitor LIC every 6 months. After 6 months, adjust or continue current dosage based on LIC. If LIC 3–7 mg Fe/g dry weight, continue therapy at dosage no greater than 7 mg/kg daily. Increase dosage to 14 mg/kg daily if LIC is >7 mg Fe/g dry weight. Dosages >14 mg/kg daily not recommended.

Dosage Modification for Adverse Renal Effects

Chronic Iron Overload Due to Blood Transfusions

Children 2–17 years of age treated with tablets for oral suspension (e.g., Exjade): Reduce dosage by 10 mg/kg per day if eGFR decreases by >33% below the average baseline measurement and repeat the eGFR within 1 week.

Children 2–17 years of age treated with film-coated tablets or granules (e.g., Jadenu ): Reduce dosage by 7 mg/kg if eGFR decreases by >33% below average baseline measurement and repeat eGFR within 1 week.

Adults treated with tablets for oral suspension (e.g., Exjade):If S_cr increases by ≥33% above average baseline measurement, repeat S_cr within 1 week, and if still elevated by ≥33%, reduce the dose by 10 mg/kg

Adults treated with film-coated tablets or granules (e.g., Jadenu ): If S_cr increases by ≥33% above average baseline measurement, repeat S_cr within 1 week, and if still elevated by ≥33%, reduce dose by 7 mg/kg.

In all patients, discontinue therapy if eGFR <40 mL/minute per 1.73m².

Iron Overload in NTDT

Children 10–17 years of age treated with tablets for oral suspension (e.g., Exjade): Reduce dosage by 5 mg/kg per day if eGFR decreases by >33% below the average baseline measurement and repeat eGFR within 1 week.

Children 10–17 years of age treated with film-coated tablets or granules (e.g., Jadenu ): Reduce dosage by 3.5 mg/kg if eGFR decreases by >33% below average baseline measurement and repeat eGFR within 1 week.

Adults treated with tablets for oral suspension (e.g., Exjade): If S_cr increases by ≥33% above average baseline measurement, repeat S_cr within 1 week, and if still elevated by ≥33%, interrupt therapy if dose is 5 mg/kg, or reduce by 50% if dose is 10 or 20 mg/kg.

Adults treated with film-coated tablets or granules (e.g., Jadenu ): If S_cr increases by ≥33% above average baseline measurement, repeat S_cr within 1 week, and if still elevated by ≥33%, interrupt therapy if dose is 3.5 mg/kg, or reduce by 50% if dose is 7 or 14 mg/kg.

In all patients, discontinue therapy if eGFR <40 mL/minute per 1.73m².

Dosage Modification for Concomitant Use of Bile Acid Sequestrants or UGT Inducers

If concomitant use of bile-acid sequestering agents (e.g., cholestyramine, colesevelam, colestipol) or potent UGT inducers (e.g., phenobarbital, phenytoin, rifampin, ritonavir) cannot be avoided, consider increasing initial deferasirox dosage by 50%. Make further dosage adjustments according to patient’s clinical response and serum ferritin concentrations.

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh A): No dosage adjustment necessary.

Moderate hepatic impairment (Child-Pugh B): Reduce starting dose by 50%.

Severe hepatic impairment (Child-Pugh C): Avoid use.

Renal Impairment

eGFR >60 mL/minute per 1.73 m²: No dosage adjustment necessary.

eGFR 40−60 mL/minute per 1.73 m²: Reduce starting dose by 50%. Exercise caution in pediatric patients; if treatment is needed, use the minimum effective dose and monitor renal function frequently.

eGFR <40 mL/minute per 1.73 m²: Use contraindicated.

Geriatric Use

No specific dosage adjustments; however, manufacturer states that geriatric patients experienced more adverse reactions compared to younger adults. Careful selection of dosage necessary; initiate at lower end of the dosing range.

Cautions for Deferasirox

Contraindications

• eGFR <40 mL/minute per 1.73 m²

• Poor performance status

• High-risk myelodysplastic syndrome

• Advanced malignancy

• Platelet counts <50,000/mm³

• Known hypersensitivity to deferasirox or any ingredient in the formulation

Warnings/Precautions

Warnings

Renal Effects

Renal effects including acute renal failure (sometimes fatal or requiring dialysis), dose-related increases in S_cr, and renal tubulopathy reported (See Boxed Warning). Most fatalities occurred in patients with multiple comorbid conditions and in advanced stages of hematologic disease. Most cases of renal tubulopathy, including Fanconi syndrome, occurred in children and adolescents with β-thalassemia and serum ferritin concentrations <1500 mcg/L. Baseline renal disease and concomitant nephrotoxic medications may increase risk. Small decreases in eGFR in pediatric patients, particularly in those with a small body-surface area (e.g., patients <7 years of age), can result in increased deferasirox exposure and subsequent worsening renal function.

Assess renal glomerular and tubular function at baseline, and before any dosage increases. Assess serum electrolytes and urinalysis in all patients. Assess serum ferritin concentrations monthly. Monitor for changes in eGFR and for renal tubular toxicity weekly during the first month of therapy or after dosage modification, and thereafter at least once monthly. Monitor renal function more frequently if renal disease at baseline or if renal function decreased.

Interrupt therapy during periods of acute illness in pediatric patients that may result in volume depletion (e.g., diarrhea, vomiting, prolonged reduced oral intake). Increase monitoring during periods of acute illness. Resume therapy based on renal function assessments when oral intake and volume status have normalized; avoid concomitant use of nephrotoxic agents. Use minimum effective dose, and assess tubular and glomerular function more frequently. Consider dosage reduction or interruption or discontinuance of therapy if renal function worsens or as clinically indicated.

Hepatic Effects

Hepatic abnormalities, including hepatic failure (sometimes fatal), drug-induced hepatitis, hepatic dysfunction, and increased serum transaminases, reported (See Boxed Warning). Most cases of hepatic failure occurred in individuals >55 years of age and in those with serious comorbid conditions (e.g., hepatic cirrhosis, multiorgan failure); however, some occurred in pediatric patients. In pediatric patients, liver failure occurred in conjunction with acute kidney injury during volume depletion.

Closely monitor liver function tests (serum transaminase and bilirubin concentrations) during treatment; consider dosage reduction or interruption of therapy if severe, persistent, progressive, or unexplained elevations occur. Assess serum transaminase and bilirubin concentrations before initiation of therapy, every 2 weeks during the first month of treatment, and monthly thereafter.

Monitor liver and renal function more frequently in pediatric patients receiving deferasirox tablets for oral suspension (e.g., Exjade) dosages of 20−40 mg/kg daily or dosages of 14–28 mg/kg daily as film-coated tablets or granules (e.g., Jadenu) and when iron burden approaching normal levels. Interrupt treatment in pediatric patients if acute liver or kidney injury occurs, and during episodes of acute illness (e.g., vomiting, diarrhea, decreased oral intake) when volume depleted. Avoid use in severe (Child-Pugh C) hepatic impairment; reduce starting dose in moderate (Child-Puge B) hepatic impairment.

GI Effects

GI hemorrhage (sometimes fatal) reported (See Boxed Warning). Most fatalities occurred in geriatric patients with advanced hematologic malignancies and/or low platelet counts. Nonfatal upper GI irritation, ulceration (some complicated by perforation), and hemorrhage also reported in patients, including children and adolescents.

Be alert for signs and symptoms of GI ulceration and hemorrhage during deferasirox therapy. Promptly initiate additional evaluation and treatment if a serious adverse GI effect is suspected. Use deferasirox and drugs with ulcerogenic or hemorrhagic potential (e.g., anticoagulants, oral bisphosphonates, corticosteroids, NSAIAs) concomitantly with caution.

Bone Marrow Suppression

Cytopenias (sometimes fatal), including agranulocytosis, worsening anemia, neutropenia, and thrombocytopenia, reported. Preexisting hematologic disorders may increase risk of bone marrow failure. Monitor blood counts.

Interrupt therapy in patients who develop unexplained cytopenia until cause is determined. Use of deferasirox contraindicated if platelets <50,000/mm³.

Age-related Toxicity

Serious adverse reactions (sometimes fatal) reported, particularly in patients with advanced age, complications from underlying conditions, or very advanced disease. Monitor geriatric patients more frequently.

Serious (some fatal) adverse reactions reported in pediatric patients; frequently associated with volume depletion or dosages of deferasirox tablets for oral suspension (e.g., Exjade) of 20–40 mg/kg daily (equivalent to dosages of 14-28 mg/kg daily as film-coated tablets or granules [e.g., Jadenu]) when iron burden approaching normal values. Monitor more frequently if volume depletion occurs and when using dosages of tablets for oral suspension (e.g., Exjade) of 20–40 mg/kg daily or Jadenu preparations of 14-28 mg/kg daily as film-coated tablets or granules and iron burden is approaching normal. During episodes of volume depletion, interrupt treatment. May resume when volume status and kidney function are normalized.

Ocular and Otic Effects

Ocular toxicity, including lens opacities, cataracts, increased IOP, and retinal disorders, reported rarely. Ototoxicity, including high frequency hearing loss and decreased hearing, reported rarely. The frequency of adverse auditory reactions was increased among pediatric patients who received tablets for oral suspension (e.g., Exjade) doses greater than 25 mg/kg daily (equivalent to 17.5 mg/kg daily as film-coated tablets or granules [e.g., Jadenu]) when serum ferritin was less than 1000 mcg/L.

Ophthalmologic examination (e.g., slit-lamp examinations, fundoscopy) and auditory testing recommended prior to initiation of therapy and every 12 months thereafter. Monitor more frequently if disturbances observed. Consider dosage reduction or interruption of therapy if ocular and/or otic effects occur.

Overchelation

Measure serum ferritin concentrations monthly in transfusional iron overload.

Higher rates of renal adverse events reported in children receiving deferasirox tablets for oral suspension (e.g., Exjade) at dosages greater than 25 mg/kg daily (equivalent to 17.5 mg/kg daily as film-coated tablets or granules [e.g.,Jadenu]) when serum ferritin concentrations <1000 mcg/L. Consider dosage reduction or more frequent monitoring of serum ferritin and renal and hepatic function.

Consider dosage reduction if serum ferritin <1000 mcg/L at 2 consecutive visits, especially if deferasirox tablets for oral suspension (e.g., Exjade) dosage exceeds 25 mg/kg daily or exceeds 17.5 mg/kg daily as film-coated tablets or granules (e.g., Jadenu) . If serum ferritin concentrations <500 mcg/L, temporarily interrupt treatment and continue monthly monitoring. Evaluate continued need for chelation if not requiring regular transfusions.

In NTDT, measure LIC by liver biopsy or by using an FDA-cleared or approved method every 6 months during treatment. Temporarily interrupt treatment when the LIC is <3 mg Fe/g dry weight. Measure serum ferritin concentrations monthly; if serum ferritin <300 mcg/L, interrupt treatment and obtain confirmatory LIC.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis and angioedema, reported. Serious sensitivity reactions usually occur within the first month of therapy. If reactions are severe, discontinue the drug and institute appropriate medical therapy. Deferasirox is contraindicated in patients with known hypersensitivity to the drug and should not be reintroduced in patients who have experienced previous hypersensitivity reactions because of the risk of anaphylactic shock.

Dermatologic Effects

Life-threatening or fatal severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), reported. Cases of erythema multiforme also reported. Monitor for signs and symptoms of severe skin reactions, and discontinue treatment if they occur. Do not reintroduce therapy.

For mild to moderate rashes, continue therapy without dosage adjustment; rashes of this type frequently resolve spontaneously.

In severe cases, temporarily interrupt therapy. Reinitiate deferasirox at a lower dosage and gradually increase the dosage following resolution of the rash.

Specific Populations

Pregnancy

No data available to inform drug-associated risk of use in humans; decreases in offspring viability and increases in renal anomalies observed in animals at doses less than or similar to the equivalent human dose. Use only during pregnancy if benefits outweigh potential risks.

Lactation

Distributed into milk in rats; not known whether the drug is distributed into human milk. Discontinue nursing or the drug.

Females and Males of Reproductive Potential

Patients should use nonhormonal methods of contraception while receiving deferasirox; may reduce efficacy of hormonal contraception.

Pediatric Use

Safety and efficacy for transfusional iron overload not established in children <2 years of age.

Safety and efficacy for chronic iron overload in NTDT syndromes not established in children <10 years of age.

Systemic exposure of deferasirox in children <6 years of age is lower than that in adults.

Geriatric Use

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. Monitor geriatric patients closely for early signs and/or symptoms of adverse reactions that may require dosage adjustment.

Higher incidence of adverse reactions occurred with deferasirox therapy in geriatric patients ≥65 years of age than in younger adults. Majority of these patients had myelodysplastic syndrome (MDS).

Hepatic Impairment

Average deferasirox total exposure increased by 16 and 76%, respectively, in patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment compared to those with normal hepatic function.

Renal Impairment

Approximately 50% higher mean deferasirox plasma concentrations in patients with MDS and eGFR 40–60 mL/minute per 1.73 m² compared to patients with MDS and eGFR >60 mL/minute per 1.73 m².

Common Adverse Effects

Adverse effects (>5%) in patients with transfusional iron overload: diarrhea, vomiting, nausea, abdominal pain, rash, increases in serum creatinine concentration.

Adverse effects (>5%) in patients with NTDT syndromes: diarrhea, rash, nausea.

Drug Interactions

Metabolized principally by UGT1A1 and to a lesser extent by UGT1A3; CYP isoenzymes appear to play minor role.

Inhibits CYP isoenzymes 3A4, 2C8, 1A2, 2A6, 2D6, and 2C19 in vitro. Clinical importance of inhibition of CYP isoenzymes 1A2, 2A6, 2D6, and 2C19 unknown.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP3A4 substrates: Potential pharmacokinetic interaction. Deferasirox inhibits CYP3A4 activity in vitro; however, deferasirox may also induce CYP3A4, resulting in decreased plasma concentrations of drugs metabolized by CYP3A4. Closely monitor for reduced efficacy of CYP3A4 substrates if used concomitantly.

CYP2C8 substrates: Potential pharmacokinetic interaction. Deferasirox inhibits CYP2C8 activity; may increase plasma concentrations of drugs metabolized by CYP2C8. Use with caution.

CYP1A2 substrates: Potential pharmacokinetic interaction. Deferasirox inhibits CYP1A2; may increase plasma concentration of CYP1A2 substrate. Avoid concomitant use of theophylline or other CYP1A2 substrates with narrow therapeutic index (e.g, tizanidine). Monitor for signs of CYP1A2-mediated toxicity if used concomitantly with deferasirox.

Drugs Affecting Uridine 5’-Diphosphate Glucuronosyltransferase (UGT) Enzymes

Potent UGT inducers: Potential pharmacokinetic interaction (decreased AUC of deferasirox, possibility of reduced efficacy). Avoid concomitant use of deferasirox and potent UGT inducers. If concomitant use cannot be avoided, consider increasing the initial dosage of deferasirox by 50%. Monitor serum ferritin concentrations and clinical response carefully to determine need for further dosage adjustment.

Drugs with Ulcerogenic or Hemorrhagic Effects

Potential pharmacologic interaction (risk of GI ulceration or bleeding). Use concomitantly with caution.

Specific Drugs

Deferasirox Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentrations usually attained within 1.5–4 hours.

Absolute oral bioavailability of deferasirox tablets for oral suspension (Exjade) is 70%.

Comparative bioavailability of Jadenu tablets and Jadenu Sprinkle granules 36% and 52% greater than Exjade, respectively.

Food

Food variably increases bioavailability of Exjade .

Bioavailability of Jadenu when administered with a light meal (containing <7% fat and approximately 250 calories) similar to fasting conditions.

Special Populations

Systemic exposure to deferasirox is lower in children and adolescents than in adults. In children <6 years of age, systemic exposure about 50% lower than in adults.

Pharmacokinetics not specifically studied in geriatric patients ≥65 years of age.

Distribution

Extent

5% distributed into RBCs.

Distributed into milk in rats; not known whether the drug is distributed into human milk.

Plasma Protein Binding

Approximately 99% (mainly albumin).

Elimination

Metabolism

Metabolized principally in the liver via glucuronidation by UGT1A1 and to a lesser extent by UGT1A3.

Deconjugation of glucuronide metabolites and subsequent enterohepatic recirculation are likely to occur.

Minimally metabolized (8%) by oxidative CYP enzymes.

Elimination Route

Deferasirox and its metabolites eliminated principally in feces via bile (84%) and to a lesser extent in urine (8%).

Half-life

8–16 hours.

Special Populations

Clearance in females is moderately lower (i.e., 17.5%) than that in males.

Stability

Storage

Oral

Tablets for Oral Suspension

20-25°C (excursions permitted between 15–30°C).

Protect from moisture.

Film-Coated Tablets

20–25°C (excursions permitted between 15–30°C).

Protect from moisture.

Granules

20–25°C (excursions permitted between 15–30°C).

Protect from moisture.

Actions

• Chelates iron by binding ferric ions and forming a stable, soluble complex.

• A tridentate ligand with high binding affinity for iron in a 2:1 ratio (2 ligand molecules binding 1 iron atom).

• At dosages of 10, 20, and 40 mg/kg daily as tablets for oral suspension, deferasirox is capable of sequestering 0.1, 0.3, and 0.4 mg of iron, respectively, per kg of body weight daily.

• Demonstrates 2–5 times higher potency than deferoxamine in mobilizing and excreting tissue iron.

• Reduces liver iron burden; preliminary data suggest that deferasirox also mobilizes cardiac iron stores.

• Chelates zinc and copper, but with very low binding affinity. Decreased concentrations of zinc and copper reported in humans during therapy; however, clinical importance of this effect unknown.

• Deferasirox has potential to chelate with aluminum, but has lower binding affinity for aluminum than for iron.

Advice to Patients

• Advise the patient to take tablets for oral suspension (e.g., Exjade) once daily on an empty stomach at least 30 minutes before eating, preferably at the same time every day. Advise the patient that film-coated tablets or granules (e.g., Jadenu) may be taken on an empty stomach or with a light meal.

• Advise the patient to avoid chewing or swallowing tablets for oral suspension (Exjade) whole; instead, completely disperse the tablets in water, orange juice, or apple juice, and drink the mixture immediately after mixing. Disperse doses of less than 1 g in 105 ml (3.5 oz) and doses of 1 g or more in 210 ml (7 oz) of liquid. Advise the patient to disperse any residue in a small amount of liquid and swallow.

• Advise patients who have difficulty swallowing whole tablets that film-coated tablets (e.g., Jadenu) may be crushed and mixed with soft foods (e.g., yogurt, applesauce) immediately prior to use and administered orally. Advise against the use of commercial crushers with serrated surfaces for crushing a single 90 mg tablet. Advise patients to immediately and completely consume the dose and not store it for future use.

• Advise the patient to open the deferasirox granules for oral use (e.g., Jadenu Sprinkle) sachets and sprinkle the entire dose onto soft foods (e.g., yogurt, applesauce) immediately prior to administration.

• Potential for drug to cause dizziness; use caution when driving or operating machinery until effects on individual are known.

• Importance of discontinuing the drug and informing the healthcare provider if a severe hypersensitivity reaction occurs.

• Risk of renal effects (e.g., renal failure). Importance of regular monitoring of renal function, and notifying the provider if symptoms of renal failure occur.

• Risk of hepatic effects (e.g., hepatitis, hepatic failure). Importance of regular monitoring of liver function, and notifying the healthcare provider if symptoms of hepatic failure occur.

• Advise patients that serious allergic reactions (including throat swelling) have been reported with deferasirox, usually within the first month of treatment. Advise patients that if a serious allergic reaction occurs, to stop taking deferasirox and seek immediate medical attention.

• Advise caregivers of pediatric patients to contact their healthcare providers during episodes of acute illness, particularly if the patient has not been drinking fluids or if the patient has a fever, vomiting, or diarrhea.

• Advise patients of reproductive potential to use nonhormonal methods of contraception while taking deferasirox, since the drug may decrease the efficacy of hormonal contraceptives.

• Risk of GI ulcers or bleeding when deferasirox is used concomitantly with drugs that have ulcerogenic or hemorrhagic potential such as anticoagulants, oral bisphosphonates, corticosteroids, or nonsteroidal anti-inflammatory agents (NSAIAs). Inform patients of the signs and symptoms of GI ulceration and bleeding; advise patients to contact their provider if symptoms of heartburn occur, but to seek immediate medical attention if symptoms of GI hemorrhage occur.

• Risk of blood disorders. Importance of regular monitoring of blood cell counts.

• Risk of auditory and ocular disturbances. Importance of regular auditory testing and ophthalmologic examinations. Advise patients to contact their healthcare provider if visual or auditory changes occur while taking deferasirox.

• Risk of rash or severe skin reactions. Advise patients that if severe skin reactions or a severe rash occurs, to stop taking deferasirox and seek medical attention.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aluminum-containing antacids) and herbal supplements, as well as any concomitant illnesses (e.g., history of kidney or liver disease).

• Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Deferasirox is available only from designated specialty pharmacies.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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