Deferasirox

Deferasirox is a prescription medication used for the treatment of transfusional hemosiderosis and non-transfusion-dependent thalassemia.

• Deferasirox is available under the following different brand names: Exjade, Jadenu, Jadenu Sprinkle

Adult and pediatric dosage

Tablet for oral suspension (Exjade)

• 125mg
• 250mg
• 500mg

Oral tablet (Jadenu)

• 90mg
• 180mg
• 360mg

Oral granules (Jadenu Sprinkle)

• 90mg
• 180mg
• 360mg

Transfusional Hemosiderosis

Adult dosage

• Exjade: 20 mg/kg orally every day; may increase by 5- to 10-mg increments based on serum ferritin; if not controlled on 30 mg/kg/day (ie, serum ferritin persistently above 2500 mcg/L), may increase up to 40 mg/kg every day  
• Jadenu: 14 mg/kg orally every day (round to nearest whole tablet); adjust dose in 3.5-7 mg/kg according to response and goals; if not adequately controlled on 21 mg/kg/day (serum ferritin levels persistently above 2500 mcg/L), may increase to 28 mg/kg/day; do not exceed 28 mg/kg

Pediatric dosage

• Children below 2 years: Safety and efficacy not established
• Children above 2 years
  • Exjade: 20 mg/kg orally every day; may increase by 5- to 10-mg increments based on serum ferritin; if not controlled on 30 mg/kg/day (ie, serum ferritin persistently above 2500 mcg/L), may increase up to 40 mg/kg every day
  • Jadenu: 14 mg/kg orally every day (round to nearest whole tablet); adjust dose in 3.5-7 mg/kg according to response and goals; if not adequately controlled with doses of 21 mg/kg/day (serum ferritin levels persistently above 2500 mcg/L), may increase up to 28 mg/kg/day ; do not exceed 28 mg/kg

Nontransfusion-Dependent Thalassemia

Adult dosage

• Exjade: 10 mg/kg orally every day (calculate dose to nearest tablet size); if LIC above 15 mg Fe/g dw after 4 weeks, consider increasing dose by 5-10 mg/kg up to 20 mg/kg/day
• Jadenu: 7 mg/kg orally every day (calculate dose to nearest whole tablet); if LIC above 7 mg Fe/g dw after 6 months, increase dose by 3.5-7 mg/kg up to 14 mg/kg/day; do not exceed 14 mg/kg/day
• Pediatric dosage
  • Children below 10 years: Safety and efficacy not established
  • Children above 10 years
  • Exjade: 10 mg/kg orally every day (calculate dose to nearest tablet size); if LIC above 15 mg Fe/g dw after 4 weeks, consider increasing dose by 5-10 mg/kg up to 20 mg/kg/day
  • Jadenu: 7 mg/kg orally every day (calculate dose to nearest whole tablet); if LIC above 7 mg Fe/g dw after 6 months, increase dose by 3.5-7 mg/kg up to 14 mg/kg/day; do not exceed 14 mg/kg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Deferasirox include:

• nausea,
• vomiting,
• stomach/abdominal pain,
• diarrhea,
• dizziness,
• anxiety,
• tired feeling,
• sleep problems (insomnia),
• rash,
• discolored skin,
• headache,
• fever,
• cough,
• sinus pain, or
• runny or stuffy nose.

Serious side effects of Deferasirox include:

• problems with vision or hearing;
• kidney problems--little or no urination, swelling in the feet or ankles, feeling tired or short of breath;
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• low blood cell counts--fever, chills, mouth sores, skin sores, pale skin, easy bruising, unusual bleeding, cold hands, and feet, feeling light-headed or short of breath; or
• signs of stomach bleeding--bloody or tarry stools, coughing up blood, or vomit that looks like coffee grounds.

Rare side effects of Deferasirox include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Deferasirox has severe interactions with no other drugs.
• Deferasirox has serious interactions with the following drugs:
  • pacritinib
  • tucatinib
• Deferasirox has moderate interactions with at least 227 other drugs.
• Deferasirox has minor interactions with the following drugs:
  • cevimeline
  • docetaxel
  • donepezil
  • doxorubicin liposomal
  • dutasteride
  • galantamine
  • imipramine
  • oxybutynin
  • pioglitazone
  • saxagliptin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Hypersensitivity
• Estimated GFR below 40 ml/min/1.73 m² or serum creatinine above 2 x ULN
• Poor performance status and high-risk myelodysplastic syndromes or advanced malignancies
• Platelet counts below 50 x10^9/L

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Deferasirox?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Deferasirox?”

Cautions

• Coadministration with aluminum-containing antacids decreases absorption
• Concomitant cholestyramine (see Dosage Modifications)
• Risk of hepatic failure, some with the fatal outcome; most occurred with age above 55 years and with comorbid conditions (eg, liver cirrhosis, multiorgan failure); (see Black Box Warnings)
• Consider dose reduction or closer monitoring of renal and hepatic function, and serum ferritin levels during periods when patients are receiving doses above 25 mg/kg/day while their serum ferritin values were below 1,000 mcg/L; use minimum effective dose to maintain the low iron burden
• The frequency of auditory adverse events irrespective of causality may increase among pediatric patients who receive doses above 25 mg/kg/day when serum ferritin is below 1,000 mcg/L
• Acute liver injury and failure, including fatal outcomes, have occurred in pediatric; liver failure has occurred in association with acute kidney injury in pediatric patients at risk for over chelation during a volume depleting event; interrupt therapy when acute liver injury or acute kidney injury is suspected and during volume depletion; monitor liver and renal function more frequently in pediatric patients who are receiving doses in the 20-40 mg/kg/day range and when the iron burden is approaching normal; use minimum effective dose to achieve and maintain a low iron burden
• Avoid use with severe (Child-Pugh C) hepatic impairment; closely monitor with mild or moderate hepatic impairment and decrease initial dose by 50%
• Consider discontinuation if auditory/ocular disturbances occur
• GI perforation and hemorrhage, including deaths reported, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts; nonfatal upper GI irritation, ulceration, and hemorrhage reported; monitor for signs and symptoms of GI ulceration and hemorrhage during therapy and promptly initiate evaluation and treatment if serious GI adverse event is suspected; risk of gastrointestinal hemorrhage may be increased when administering in combination with drugs that have ulcerogenic or hemorrhagic potentials, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral bisphosphonates, or anticoagulants; there have been reports of ulcers complicated with gastrointestinal perforation (including fatal outcome; see Black Box Warnings)
• Neutropenia, agranulocytosis, and thrombocytopenia, including fatal events, reported; preexisting hematologic disorders may increase this risk
• Elderly: Monitor closely for toxicity due to the greater frequency of decreased hepatic, renal, and/or cardiac function
• Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) and erythema multiforme reported
• Rashes may occur during treatment; for rashes of mild to moderate severity, therapy may be continued without dose adjustment; rash often resolves spontaneously; in severe cases, interrupt treatment; may consider reintroduction at a lower dose after resolution of the rash
• Should not reintroduce patients that have experienced previous hypersensitivity reactions on deferasirox products; may cause anaphylactic shock
• Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) which could be life-threatening or fatal reported during therapy; cases of multiforme observed; advise patients of signs and symptoms of severe skin reactions, and closely monitor; if any severe skin reactions suspected, discontinue the drug immediately and do not reintroduce therapy
• Auditory disturbances (e.g., high-frequency hearing loss, decreased hearing) and ocular disturbances (lens opacities, cataracts, increased IOP, retinal disorders) reported
• Minimize risk of over chelation of iron by monitoring serum ferritin levels monthly to assess the patient’s response to therapy; when used for nontransfusion-dependent thalassemia, also measure LIC q6Months
• Renal failure (see Black Box Warnings)
  • Evaluate renal glomerular and tubular function before initiating therapy or increasing dose; use prediction equations validated for use in adult and pediatric patients to estimate GFR; obtain serum electrolytes and urinalysis in all patients to evaluate the renal tubular function
  • Risk of acute renal failure, fatal in some patients and requiring dialysis in others
  • Dose reduction or interruption may be considered if abnormalities occur in levels of markers of renal tubular function and/or as clinically indicated
  • Exercise caution in pediatric patients with eGFR of 40-60 mL/minute/1.73 m²; if treatment is needed use minimum effective dose and monitor renal function frequently; individualize dose titration based on improvement in renal injury; for patients with renal impairment (eGFR 40–60 mL/min/1.73 m²) reduce starting dose by 50%
  • Therapy can cause acute kidney injury including renal failure requiring dialysis that has resulted in fatal outcomes; renal tubular toxicity, including acquired Fanconi Syndrome, reported in patients receiving therapy, most commonly in pediatric patients with beta-thalassemia and serum ferritin levels below 1,500 mcg/L
  • In pediatric patients, interrupt therapy during acute illnesses which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor renal function more frequently; promptly correct fluid deficits to prevent renal injury; resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal
  • Most fatalities reported with advanced stage hematologic disorder
  • Monitor serum Cr level and CBC
  • Closely monitor renal function if CrCl 40-60 mL/min, particularly in cases where there are additional risk factors that may impair renal function (e.g., concomitant medications, dehydration, severe infections)
  • Renal tubulopathy was reported; the majority of reports were in children and adolescents with beta-thalassemia and serum ferritin levels below 1500 mcg/L

Pregnancy and Lactation

• There are no studies with use in pregnant women to inform drug-associated risks; administration of deferasirox to rats during pregnancy resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses that were about or less than recommended human dose on an mg/ m² basis; no fetal effects were noted in pregnant rabbits at doses equivalent to the human recommended dose on an mg/ m² basis; the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
• Contraception
  • Counsel patients to use non-hormonal method(s) of contraception since the drug can render hormonal contraceptives ineffective
• Lactation
  • No data are available regarding the presence of drug or their metabolites in human milk, effects on the breastfed infant, or on milk production; drug and their metabolites is excreted in rat milk; because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account importance of the drug to mother