JADENU

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JADENU

Classes

Antidotes, Systemic
Chelating Agents

Administration
Oral Administration

Administer at approximately the same time every day. Do not administer with any aluminum-containing antacid products.
For patients converting from Exjade to Jadenu, the dose of Jadenu should be approximately 30% lower and rounded to the nearest whole tablet or sachet content for granules.

Oral Solid Formulations

Jadenu:
Administer on an empty stomach or with a light meal (less than 250 calories and less than 7% fat).
Tablets: For those who have difficulty swallowing whole tablets, the dose may be crushed and mixed with soft foods (e.g., yogurt, apple sauce). If crushed, the dose should be completely consumed immediately; DO NOT store for future use. Avoid use of commercial crushers with serrated surfaces when crushing the 90 mg tablet strength.
Sprinkle granules: Sprinkle granules on soft food (e.g., yogurt, apple sauce) immediately prior to use.

Oral Liquid Formulations

Exjade:
Administer on an empty stomach at least 30 minutes before food.
Tablets are for dispersion only and should not be chewed or swallowed whole. Completely disperse the tablets by stirring in water, orange juice, or apple juice until a fine suspension results.
Doses less than 1 g should be dispersed in at least 3.5 ounces of liquid and doses more than 1 g in at least 7 ounces of liquid.
After swallowing the suspension, any residue should be mixed in a small volume of liquid and swallowed.

Adverse Reactions
Severe

pancreatitis / Delayed / 0.1-1.0
peptic ulcer / Delayed / 0.1-1.0
GI bleeding / Delayed / 0.1-1.0
Fanconi syndrome / Delayed / 0.1-1.0
hearing loss / Delayed / 0.1-1.0
visual impairment / Early / 0.1-1.0
erythema multiforme / Delayed / 0-0.1
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / 0-0.1
optic neuritis / Delayed / 0-0.1
GI perforation / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

proteinuria / Delayed / 18.3-18.3
elevated hepatic enzymes / Delayed / 1.0-8.4
gastritis / Delayed / 0.1-1.0
hematuria / Delayed / 0-1.0
cataracts / Delayed / 0.1-1.0
edema / Delayed / 0.1-1.0
hypokalemia / Delayed / 0-1.0
esophagitis / Delayed / 0-0.1
cholelithiasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
glycosuria / Early / Incidence not known
neutropenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known

Mild

diarrhea / Early / 5.0-47.0
abdominal pain / Early / 21.3-28.0
nausea / Early / 2.0-26.0
vomiting / Early / 10.1-21.2
rash / Early / 2.0-13.0
fever / Early / 0.1-1.0
insomnia / Early / 0.1-1.0
fatigue / Early / 0.1-1.0
anxiety / Delayed / 0.1-1.0
dizziness / Early / 0.1-1.0
urticaria / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
alopecia / Delayed / Incidence not known
purpura / Delayed / Incidence not known

Boxed Warning
Nephrotoxicity, proteinuria, renal disease, renal failure, renal impairment

Deferasirox may cause fatal nephrotoxicity and is contraindicated for use in patients with renal failure or severe renal impairment with an eGFR less than 40 mL/minute/1.73 m2. In patients with moderate renal impairment (eGFR 40 to 60 mL/minute/1.73 m2), reduce the initial dose by 50%. Use caution in pediatric patients with eGFR 40 to 60 mL/minute/1.73 m2. If treatment is necessary, use the lowest effective dose and monitor renal function frequently. In clinical trials, deferasirox-treated patients experienced dose-dependent increases in serum creatinine and proteinuria. There have been postmarketing reports of renal impairment and acute renal failure leading to death in some patients and requiring dialysis in others. Most reported fatalities occurred in patients with multiple comorbidities and who were in an advanced stage of their hematological disorder. Pre-existing renal disease and concomitant use of other nephrotoxic drugs may increase the risk of acute kidney injury in adult and pediatric patients. Acute illnesses associated with volume depletion and overchelation may increase the risk of nephrotoxicity in pediatric patients. In pediatric patients, small decreases in eGFR can result in increases in deferasirox exposure, particularly in younger patients with smaller body surface areas (i.e., younger than 7 years of age). Renal tubular toxicity, including acquired Fanconi Syndrome, has been reported in patients treated with deferasirox, most commonly in pediatric patients with beta-thalassemia and serum ferritin concentrations less than 1,500 mcg/L. Prior to initiating treatment in any patient, obtain 2 SCr assessments and calculate eGFR (by appropriate method for age) to establish a reliable pre-treatment baseline. Additionally, obtain serum electrolytes and urinalyses to evaluate renal tubular function. Monitor SCr and eGFR weekly during the first month after initiation or modification of therapy and at least monthly thereafter. Monitor renal function more frequently in patients with pre-existing renal disease or decreased renal function. Dose reduction or interruption may be considered if abnormalities occur in markers of renal tubular function and/or as clinically indicated. Additionally, monitor renal function more frequently in pediatric patients during acute illnesses which can cause volume depletion such as vomiting, diarrhea, or prolonged decreased oral intake; in patients receiving Jadenu in the dosage range of 14 to 28 mg/kg/day or Exjade in the dosage range of 20 to 40 mg/kg/day; and when iron burden is approaching normal. Use the minimum effective dose to achieve and maintain a low iron burden. Interrupt deferasirox therapy in pediatric patients with volume depletion and resume when renal function and fluid volume have normalized.[31807] [59340]

Hepatic decompensation, hepatic disease, hepatitis, hepatotoxicity

Deferasirox use has been associated with hepatotoxicity. Hepatic failure, sometimes fatal, has also been reported during postmarketing surveillance. Most of these occurred in patients older than 55 years of age. Many reports have also occurred in patients with significant comorbidities including liver cirrhosis and multi-organ failure. In one study, 4 patients discontinued deferasirox because of hepatic abnormalities (drug-induced hepatitis and increased serum transaminases). Fatal hepatotoxicity has also occurred in pediatric patients, usually in association with acute renal failure in patients at risk for overchelation during a volume depleting event. Avoid deferasirox use in patients with severe (Child-Pugh C) hepatic impairment. Reduce the starting dose in patients with moderate (Child-Pugh B) hepatic impairment. Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic disease may be at higher risk for hepatic toxicity. Monitor closely for signs and symptoms of hepatic decompensation. Monitor liver function tests (serum transaminases - AST, ALT, and bilirubin) before the initiation of treatment, every 2 weeks during the first month, and monthly thereafter. Monitor liver function more frequently in pediatric patients who are receiving Exjade in the dosage range of 20 to 40 mg/kg/day or Jadenu in the dosage range of 14 to 28 mg/kg/day and when iron burden is approaching normal; use the lowest minimum effective dose to achieve and maintain a low iron burden. If there are unexplained, persistent, or progressive increases in serum transaminase levels, consider dose modifications or interruption of treatment. Interrupt therapy in pediatric patients when acute liver failure or renal failure is suspected and during volume depletion. Hepatic disease may also dramatically alter enterohepatic recirculation of deferasirox, and may lead to a decrease in efficacy.

Anticoagulant therapy, corticosteroid therapy, GI bleeding, GI perforation, peptic ulcer disease

Treatment with deferasirox has been associated with serious, sometimes fatal, gastrointestinal (GI) adverse reactions, including GI bleeding, GI ulceration, and GI perforation. Fatal GI hemorrhages have been most frequently reported in patients 65 years of age or older who had advanced hematologic malignancies and/or low platelet counts. Use with caution in patients with known peptic ulcer disease. Non-fatal upper GI irritation, gastric ulceration, and GI hemorrhage have been reported in patients, including pediatric patients younger than 18 years of age, receiving deferasirox. In a cohort-based analysis of deferasirox pediatric pooled clinical trials, adverse reactions, such as gastrointestinal disorders, occurred 1.9-fold more frequently when the Exjade dose was more than 25 mg/kg/day and serum ferritin was less than 1,000 mcg/L compared to time periods when these simultaneous conditions were not met. Physicians and patients should remain alert for signs and symptoms of GI ulceration and hemorrhage during deferasirox therapy and promptly initiate additional evaluation and treatment if a serious GI adverse reaction is suspected. Use caution when administering deferasirox in combination with drugs that have ulcerogenic or hemorrhagic risk potential, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroid therapy, oral bisphosphonates, or anticoagulant therapy.

Common Brand Names

Exjade, Jadenu

Dea Class

Rx

Description

Tridentate iron chelator for once-daily oral administration
Used in the treatment of chronic iron overload associated with frequent blood transfusions and non-transfusion dependent thalassemia syndromes
Product label contains Black Box Warning regarding hepatic failure, renal failure, and GI bleeds

Dosage And Indications
For the treatment of chronic iron toxicity secondary to transfusional iron overload or non-transfusion-dependent thalassemia syndromes. For the treatment of chronic iron overload to transfusional iron overload.
NOTE: Evidence of chronic transfusional iron overload includes the transfusion of at least 100 mL/kg of packed red blood cells (e.g., at least 20 units of packed red blood cells for a 40 kg person or more in individuals weighing more than 40 kg), and a serum ferritin consistently more than 1,000 mcg/L.
Oral dosage (tablets for oral suspension) Adults

20 mg/kg/dose PO once daily, initially. Titrate dose by 5 or 10 mg/kg/dose every 3 to 6 months based on serum ferritin concentrations. Usual Max: 30 mg/kg/day. Max: 40 mg/kg/day. Round dose to the nearest whole tablet. Use the minimum effective dose to achieve a trend of decreasing ferritin and to maintain iron burden in the target range. Evaluate the need for ongoing chelation therapy for persons whose conditions no longer require regular blood transfusions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 2 to 17 years

20 mg/kg/dose PO once daily, initially. Titrate dose by 5 or 10 mg/kg/dose every 3 to 6 months based on serum ferritin concentrations. Usual Max: 30 mg/kg/day. Max: 40 mg/kg/day. Round dose to the nearest whole tablet. Use the minimum effective dose to achieve a trend of decreasing ferritin and to maintain iron burden in the target range. Evaluate the need for ongoing chelation therapy for persons whose conditions no longer require regular blood transfusions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (granules or tablets) Adults

14 mg/kg/dose PO once daily, initially. Titrate dose by 3.5 or 7 mg/kg/dose every 3 to 6 months based on serum ferritin concentrations. Usual Max: 21 mg/kg/day. Max: 28 mg/kg/day. Round dose to the nearest whole tablet or sachet. Use the minimum effective dose to achieve a trend of decreasing ferritin and to maintain iron burden in the target range. Evaluate the need for ongoing chelation therapy for persons whose conditions no longer require regular blood transfusions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 2 to 17 years

14 mg/kg/dose PO once daily, initially. Titrate dose by 3.5 or 7 mg/kg/dose every 3 to 6 months based on serum ferritin concentrations. Usual Max: 21 mg/kg/day. Max: 28 mg/kg/day. Round dose to the nearest whole tablet or sachet. Use the minimum effective dose to achieve a trend of decreasing ferritin and to maintain iron burden in the target range. Evaluate the need for ongoing chelation therapy for persons whose conditions no longer require regular blood transfusions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of chronic iron overload in non-transfusion-dependent thalassemia syndromes with a liver iron (Fe) concentration of at least 5 mg Fe/g of dry weight and serum ferritin more than 300 mcg/L. Oral dosage (tablets for oral suspension) Adults

10 mg/kg/dose PO once daily, initially. Consider increasing the dose to 20 mg/kg/day after 4 weeks if the baseline liver iron (Fe) concentration is more than 15 mg Fe/g of dry weight. Adjust dose after 6 months based on liver iron concentration. Max: 20 mg/kg/day. Round dose to the nearest whole tablet. Use the minimum effective dose to achieve a trend of decreasing ferritin. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 10 to 17 years

10 mg/kg/dose PO once daily, initially. Consider increasing the dose to 20 mg/kg/day after 4 weeks if the baseline liver iron (Fe) concentration is more than 15 mg Fe/g of dry weight. Adjust dose after 6 months based on liver iron concentration. Max: 20 mg/kg/day. Round dose to the nearest whole tablet. Use the minimum effective dose to achieve a trend of decreasing ferritin. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (granules or tablets) Adults

7 mg/kg/dose PO once daily, initially. Consider increasing the dose to 14 mg/kg/day after 4 weeks if the baseline liver iron (Fe) concentration is more than 15 mg Fe/g of dry weight. Adjust dose after 6 months based on liver iron concentration. Max: 14 mg/kg/day. Round dose to the nearest whole tablet or sachet. Use the minimum effective dose to achieve a trend of decreasing ferritin. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 10 to 17 years

7 mg/kg/dose PO once daily, initially. Consider increasing the dose to 14 mg/kg/day after 4 weeks if the baseline liver iron (Fe) concentration is more than 15 mg Fe/g of dry weight. Adjust dose after 6 months based on liver iron concentration. Max: 14 mg/kg/day. Round dose to the nearest whole tablet or sachet. Use the minimum effective dose to achieve a trend of decreasing ferritin. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Dosing Considerations
Hepatic Impairment

Child-Pugh A: No dosage adjustment necessary.
Child-Pugh B: Reduce the starting dose by 50%.
Child-Pugh C: Avoid use.

Renal Impairment

Use caution when administering to patients with renal disease, or renal impairment of any kind. Consider dose reduction or treatment interruption or discontinuation if elevated serum creatinine (SCr) measurements occur during treatment.
 
Dose modifications for patients with baseline renal impairment:
eGFR 40 to 60 mL/minute/1.73 m2: Decrease starting dose by 50%.
eGFR less than 40 mL/minute/1.73 m2: Use is contraindicated.
 
Dose modifications for decreases in renal function during treatment:
Transfusional iron overload
Adults: Decrease daily Exjade dose by 10 mg/kg/dose and daily Jadenu dose by 7 mg/kg/dose if two SCr measurements (separated by less than 1 week) are increased by 33% or more above average pretreatment levels.
Pediatric patients 2 to 17 years: Decrease daily Exjade dose by 10 mg/kg/dose and daily Jadenu dose by 7 mg/kg/dose if eGFR decreases by more than 33% below the average baseline measurement; repeat eGFR within 1 week. In the setting of decreased renal function, evaluate the risk benefit profile of continued deferasirox treatment. Titrate dosing based on renal injury. Interrupt therapy when acute renal failure is suspected in the presence of other risk factors such as volume depletion.
All patients (regardless of age): Discontinue therapy if eGFR decreases to less than 40 mL/minute/1.73 m2.
Non-transfusion dependent thalassemia syndromes
Adults: Interrupt therapy (if daily Exjade dose is 5 mg/kg/dose or daily Jadenu dose is 3.5 mg/kg/dose) or reduce dose by 50% (if daily Exjade dose is 10 to 20 mg/kg/dose or daily Jadenu dose is 7 to 14 mg/kg/dose) if two SCr measurements (separated by less than 1 week) are increased by 33% or more above average pretreatment levels.
Pediatric patients 10 to 17 years: Decrease daily Exjade dose by 5 mg/kg/dose and daily Jadenu dose by 3.5 mg/kg/dose if eGFR decreases by more than 33% below the average baseline measurement; repeat eGFR within 1 week. In the setting of decreased renal function, evaluate the risk benefit profile of continued deferasirox treatment. Titrate dosing based on renal injury. Interrupt therapy when acute renal failure is suspected in the presence of other risk factors such as volume depletion.
All patients (regardless of age): Discontinue therapy if eGFR decreases to less than 40 mL/minute/1.73 m2.

Drug Interactions

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Acetaminophen; Aspirin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with deferasirox can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If deferasirox is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Deferasirox is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Ibuprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of oxycodone as needed. If deferasirox is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Albuterol; Budesonide: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Alclometasone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Alendronate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including alendronate.
Alendronate; Cholecalciferol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including alendronate.
Aluminum Hydroxide: (Moderate) Although deferasirox has a lower affinity for aluminum than for iron, deferasirox may also increase the excretion of aluminum. Because deferasirox may bind to aluminum instead of iron, aluminum containing antacids should not be administered concurrently in order to avoid a possible decreased efficacy of either therapy.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Although deferasirox has a lower affinity for aluminum than for iron, deferasirox may also increase the excretion of aluminum. Because deferasirox may bind to aluminum instead of iron, aluminum containing antacids should not be administered concurrently in order to avoid a possible decreased efficacy of either therapy.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Although deferasirox has a lower affinity for aluminum than for iron, deferasirox may also increase the excretion of aluminum. Because deferasirox may bind to aluminum instead of iron, aluminum containing antacids should not be administered concurrently in order to avoid a possible decreased efficacy of either therapy.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Although deferasirox has a lower affinity for aluminum than for iron, deferasirox may also increase the excretion of aluminum. Because deferasirox may bind to aluminum instead of iron, aluminum containing antacids should not be administered concurrently in order to avoid a possible decreased efficacy of either therapy.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Although deferasirox has a lower affinity for aluminum than for iron, deferasirox may also increase the excretion of aluminum. Because deferasirox may bind to aluminum instead of iron, aluminum containing antacids should not be administered concurrently in order to avoid a possible decreased efficacy of either therapy.
Amikacin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Aminoglycosides: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Amiodarone: (Moderate) Deferasirox inhibits CYP2C8. Amiodarone is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and amiodarone are not available, a similar interaction may occur. The dose of amiodarone may need to be decreased if coadministered with deferasirox.
Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Atorvastatin: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Celecoxib: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly. (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Antithrombin III: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Apalutamide: (Moderate) Monitor serum ferritin levels and clinical response to deferasirox if coadministration with apalutamide is necessary. Deferasirox is a substrate of UGT1A1 and 1A3. Apalutamide may be a UGT inducer.
Aprepitant, Fosaprepitant: (Major) Use caution if deferasirox and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Deferasirox is a moderate CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for weak-to-moderate inducers.
Argatroban: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Aspirin, ASA: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Caffeine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Carisoprodol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Dipyridamole: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Omeprazole: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Aspirin, ASA; Oxycodone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of oxycodone as needed. If deferasirox is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atogepant: (Major) Avoid use of atogepant and deferasirox when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with deferasirox. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and deferasirox is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Azelastine; Fluticasone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Bedaquiline: (Major) Avoid concurrent use of deferasirox with bedaquiline. Deferasirox is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Bendamustine: (Major) Consider the use of an alternative therapy if deferasirox treatment is needed in patients receiving bendamustine. Deferasirox may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and deferasirox is a CYP1A2 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with deferasirox may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of deferasirox may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If deferasirox is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Deferasirox is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Betibeglogene Autotemcel: (Major) Avoid use of deferasirox for 6 months after betibeglogene autotemcel infusion due to risk of myelosuppression. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators (i.e., deferoxamine). Phlebotomy can be used instead of iron chelation, when appropriate.
Bismuth Subsalicylate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Bivalirudin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and deferasirox are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; deferasirox is a moderate inducer of CYP3A4.
Budesonide: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Budesonide; Formoterol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Bupivacaine; Lidocaine: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
Bupivacaine; Meloxicam: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Busulfan: (Major) Discontinue iron chelating agents (e.g., deferasirox) well in advance of busulfan administration. Decreased clearance of busulfan was observed with concomitant use with deferasirox. The mechanism of this interaction is not fully elucidated.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Celecoxib: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Celecoxib; Tramadol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with deferasirox can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If deferasirox is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Deferasirox is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Cholestyramine: (Major) The concomitant administration of deferasirox and cholestyramine may result in decreased systemic exposure to deferasirox. In healthy volunteers, the administration of cholesytramine after a single dose of deferasirox resulted in a 45% decrease in deferasirox exposure (AUC). Avoid the concomitant use of cholestyramine with deferasirox if possible. If cholestyramine and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin levels and clinical responses for further dose modification.
Choline Salicylate; Magnesium Salicylate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Clindamycin: (Moderate) Concomitant use of deferasirox and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Avoid use of clindamycin in pediatric patients (2 to 17 years) who develop decreases in renal function while receiving deferasirox.
Clobetasol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with deferasirox due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and deferasirox is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Colesevelam: (Major) The concomitant administration of deferasirox and colesevelam may result in decreased systemic exposure to deferasirox. Avoid the concomitant use if possible. If colesevelam and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox to 30 mg/kg. Monitor serum ferritin levels and clinical responses for further dose modification.
Colestipol: (Major) The concomitant administration of deferasirox and colestipol may result in decreased systemic exposure to deferasirox. Avoid the concomitant use if possible. If colestipol and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox to 30 mg/kg. Monitor serum ferritin levels and clinical responses for further dose modification.
Cyclosporine: (Moderate) The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. Although not specifically studied, reduced serum concentrations may also occur in patients taking other CYP3A4 substrates such as cyclosporine. If these drugs are used together, monitor patients for a decrease in the effects of cyclosporine.
Dabigatran: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as deferasirox. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dalteparin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Daprodustat: (Major) Reduce the initial daprodustat dose by half during concomitant use of deferasirox unless the daprodustat dose is already 1 mg. Monitor hemoglobin and further adjust the daprodustat dose as appropriate. Concomitant use may increase daprodustat exposure and the risk for daprodustat-related adverse reactions. Daprodustat is a CYP2C8 substrate and deferasirox is a moderate CYP2C8 inhibitor. Concomitant use with a moderate CYP2C8 inhibitor is expected to increase daprodustat overall exposure by approximately 4-fold.
Dapsone: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with deferasirox, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Deflazacort: (Major) Avoid concomitant use of deflazacort and deferasirox. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; deferasirox is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone. Additionally, coadministration may increase the risk of GI toxicity. Gastric ulceration and GI bleeding have been reported in patients taking deferasirox; corticosteroids increase the risk of peptic ulcers or gastric hemorrhage.
Desirudin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Desogestrel; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Dexamethasone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Diclofenac: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Diclofenac; Misoprostol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Diflunisal: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Diphenhydramine; Ibuprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Diphenhydramine; Naproxen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Doravirine: (Minor) Concurrent administration of doravirine and deferasirox may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; deferasirox is a weak CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and deferasirox may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; deferasirox is a weak CYP3A4 inducer.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with deferasirox is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; deferasirox is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Drospirenone: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Drospirenone; Estetrol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Drospirenone; Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Drospirenone; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Edoxaban: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with deferasirox. Deferasirox is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response.
Enoxaparin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Estradiol; Levonorgestrel: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Estradiol; Norethindrone: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Estradiol; Norgestimate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Ethinyl Estradiol; Norelgestromin: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Ethinyl Estradiol; Norgestrel: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Etodolac: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Etonogestrel: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Etonogestrel; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Ezetimibe; Simvastatin: (Moderate) The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. Although not specifically studied, reduced serum concentrations may also occur in patients taking other CYP3A4 substrates such as simvastatin. If these drugs are used together, monitor patients for a decrease in the effects of simvastatin.
Fenoprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concomitant use of deferasirox is necessary. If deferasirox is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like deferasirox with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and deferasirox is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; deferasirox is a moderate CYP1A2 inhibitor. Concomitant use with another moderate CYP1A2 inhibitor increased fezolinetant overall exposure by 360%.
Flurbiprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Fluticasone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Fluticasone; Salmeterol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Fluticasone; Vilanterol: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Fluvastatin: (Moderate) Deferasirox inhibits CYP2C8. Fluvastatin is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and fluvastatin are not available, a similar interaction may occur. The dose of fluvastatin may need to be decreased if coadministered with deferasirox.
Fondaparinux: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Food: (Moderate) The bioavailability (AUC) of deferasirox was variably increased when administered with food. Deferasirox should be taken on an empty stomach 30 minutes before eating. Deferasirox tablets for oral suspension can be dispersed in water, orange juice, or apple juice.
Fosphenytoin: (Major) Deferasirox undergoes UGT metabolism, and phenytoin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and phenytoin or fosphenytoin are not available, a similar interaction may occur. Avoid the concomitant use of phenytoin or fosphenytoin and deferasirox if possible. If coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Gentamicin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Guanfacine: (Major) Deferasirox may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if deferasirox is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If deferasirox is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and deferasirox is a moderate CYP3A4 inducer.
Heparin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly. (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of hydrocodone as needed. If deferasirox is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Ibandronate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including ibandronate.
Ibuprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Ibuprofen; Famotidine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Ibuprofen; Oxycodone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of oxycodone as needed. If deferasirox is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ibuprofen; Pseudoephedrine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Indomethacin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with deferasirox may result in decreased serum concentrations of isavuconazonium and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4; deferasirox is an inducer of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Deferasirox undergoes UGT metabolism, and rifampin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Avoid the concomitant use of rifampin and deferasirox if possible. If rifampin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Isoniazid, INH; Rifampin: (Major) Deferasirox undergoes UGT metabolism, and rifampin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Avoid the concomitant use of rifampin and deferasirox if possible. If rifampin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Ketoprofen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Ketorolac: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Leuprolide; Norethindrone: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Levonorgestrel: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Lidocaine: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
Lidocaine; Epinephrine: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
Lidocaine; Prilocaine: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
Lopinavir; Ritonavir: (Major) Deferasirox undergoes UGT metabolism, and ritonavir is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and ritonavir are not available, a similar interaction may occur. Avoid the concomitant use of ritonavir and deferasirox if possible. If ritonavir and defe

rasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Lumateperone: (Major) Avoid coadministration of lumateperone and deferasirox as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; deferasirox is a weak CYP3A4 inducer.
Magnesium Salicylate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with deferasirox is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and deferasirox is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
Meclofenamate Sodium: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Mefenamic Acid: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Meloxicam: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Metformin; Repaglinide: (Moderate) Repaglinide is metabolized by CYP2C8 and deferasirox is a CYP2C8 inhibitor. Co-administration of deferasirox (30 mg/kg/day for 4 days) and repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide systemic exposure (AUC) to 2.3-fold of control and an increase in Cmax of 62%. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Methenamine; Sodium Salicylate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Methylprednisolone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Midazolam: (Moderate) The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. If these drugs are used together, monitor patients for a decrease in the effects of midazolam.
Nabumetone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with deferasirox is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and deferasirox is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with deferasirox. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and deferasirox is a weak CYP3A inducer.
Naproxen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Naproxen; Esomeprazole: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Naproxen; Pseudoephedrine: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Neratinib: (Major) Avoid concomitant use of deferasirox with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and deferasirox is a moderate CYP3A4 inducer. The effect of moderate CYP3A4 induction on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inducer decreased neratinib exposure by 87% and decreased exposure to active metabolites M6 and M7 by 37% to 49%. Because of the significant impact on neratinib exposure from strong CYP3A4 induction, the potential impact on neratinib efficacy from concomitant use with moderate CYP3A4 inducers should be considered as they may also significantly decrease neratinib exposure.
Niacin; Simvastatin: (Moderate) The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. Although not specifically studied, reduced serum concentrations may also occur in patients taking other CYP3A4 substrates such as simvastatin. If these drugs are used together, monitor patients for a decrease in the effects of simvastatin.
Nirmatrelvir; Ritonavir: (Major) Deferasirox undergoes UGT metabolism, and ritonavir is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and ritonavir are not available, a similar interaction may occur. Avoid the concomitant use of ritonavir and deferasirox if possible. If ritonavir and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of deferasirox is necessary. Concomitant use of nirmatrelvir and deferasirox may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and deferasirox is a weak CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with deferasirox due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Coadministration with a CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Non-Ionic Contrast Media: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including radiopaque contrast agents, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Nonsteroidal antiinflammatory drugs: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Norethindrone: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Norethindrone; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Norgestimate; Ethinyl Estradiol: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Norgestrel: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Oxaprozin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of oxycodone as needed. If deferasirox is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Deferasirox inhibits CYP2C8. Paclitaxel is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and paclitaxel are not available, a similar interaction may occur. The dose of paclitaxel may need to be decreased if coadministered with deferasirox.
Paromomycin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Pentosan: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Phenobarbital: (Major) Deferasirox undergoes UGT metabolism, and phenobarbital is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and phenobarbital are not available, a similar interaction may occur. Avoid the concomitant use of phenobarbital and deferasirox if possible. If phenobarbital and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Deferasirox undergoes UGT metabolism, and phenobarbital is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and phenobarbital are not available, a similar interaction may occur. Avoid the concomitant use of phenobarbital and deferasirox if possible. If phenobarbital and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Phenytoin: (Major) Deferasirox undergoes UGT metabolism, and phenytoin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and phenytoin are not available, a similar interaction may occur. Avoid the concomitant use of phenytoin and deferasirox if possible. If phenytoin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Piroxicam: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Plazomicin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Pomalidomide: (Major) Avoid the concomitant use of pomalidomide and deferasirox; significantly increased pomalidomide exposure may occur increasing the risk of pomalidomide adverse events. If concomitant use is unavoidable, decrease the pomalidomide dose by 50% and monitor for pomalidomide adverse events. Pomalidomide is a CYP1A2 substrate and deferasirox inhibits CYP1A2. In healthy volunteers, the Cmax and AUC values for pomalidomide were increased by 24% and 125%, respectively, when pomalidomide was co-administered with a strong CYP1A2 inhibitor. Additionally, the AUC value of a sensitive CYP1A2 substrate about doubled when deferasirox was co-administered with a sensitive CYP1A2 substrate in healthy volunteers.
Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with deferasirox, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Prednisolone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Prednisone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Rasagiline: (Major) Do not exceed a rasagiline dose of 0.5 mg once daily when coadministered with deferasirox. Coadministration may result in increased rasagiline concentrations. Rasagiline is primarily metabolized by CYP1A2; deferasirox is a moderate CYP1A2 inhibitor. When rasagiline was administered with a strong CYP1A2 inhibitor, the AUC of rasagiline increased by 83%.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Repaglinide: (Moderate) Repaglinide is metabolized by CYP2C8 and deferasirox is a CYP2C8 inhibitor. Co-administration of deferasirox (30 mg/kg/day for 4 days) and repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide systemic exposure (AUC) to 2.3-fold of control and an increase in Cmax of 62%. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Rifampin: (Major) Deferasirox undergoes UGT metabolism, and rifampin is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Avoid the concomitant use of rifampin and deferasirox if possible. If rifampin and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Riluzole: (Moderate) Coadministration of riluzole with deferasirox may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and deferasirox is a CYP1A2 inhibitor.
Risedronate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including risedronate.
Ritonavir: (Major) Deferasirox undergoes UGT metabolism, and ritonavir is a potent inducer of this enzyme system. The concomitant administration of deferasirox (single dose of 30 mg/kg) and the potent UGT inducer rifampin (i.e., rifampicin 600 mg/day for 9 days) resulted in a decrease in deferasirox AUC by 44%. Although specific drug interaction studies of deferasirox and ritonavir are not available, a similar interaction may occur. Avoid the concomitant use of ritonavir and deferasirox if possible. If ritonavir and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin concentrations and clinical response for further modifications.
Rivaroxaban: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Salicylates: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Salsalate: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Coadministration of deferasirox, a CYP3A4 inducer with segesterone, a CYP3A4 substrate may result in decreased serum concentrations of segesterone and loss of contraceptive efficacy; an alternate or additional form of contraception should be considered. The concomitant administration of another CYP3A4 substrate and deferasirox resulted in a decrease in the peak serum concentration and exposure by 23% and 17%, respectively, in healthy volunteers. (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness.
Selexipag: (Major) Reduce selexipag dose to once daily when coadministered with deferasirox due to increased exposure to the active metabolite of selexipag, which may cause side effects. Selexipag is a CYP2C8 substrate, and deferasirox is a moderate CYP2C8 inhibitor.
Simvastatin: (Moderate) The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. Although not specifically studied, reduced serum concentrations may also occur in patients taking other CYP3A4 substrates such as simvastatin. If these drugs are used together, monitor patients for a decrease in the effects of simvastatin.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of deferasirox. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and deferasirox is a weak CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with deferasirox. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a substrate of CYP3A4 and CYP2C8; deferasirox is an inducer of CYP3A4 and an inhibitor of CYP2C8.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with deferasirox. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a substrate of CYP3A4 and CYP2C8; deferasirox is an inducer of CYP3A4 and an inhibitor of CYP2C8. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as deferasirox. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and deferasirox; sonidegib levels may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate deferasirox is a CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that the sonidegib geometric mean steady-state AUC (0-24 hours) would decrease by 56% in cancer patients who received 14 days of sonidegib 200 mg/day with a moderate CYP3A inducer. Additionally, the PBPK model predicts that the sonidegib geometric mean steady-state AUC (0-24 hours) would decrease by 69% in cancer patients who received sonidegib 200 mg/day with a moderate CYP3A inducer for 4 months.
Streptomycin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if deferasirox must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with deferasirox is necessary; consider increasing the dose of sufentanil injection as needed. If deferasirox is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sulindac: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Sumatriptan; Naproxen: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Tacrolimus: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including tacrolimus, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Telmisartan; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as deferasirox, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Tobramycin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
Tolmetin: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Trandolapril; Verapamil: (Moderate) Deferasirox inhibits CYP2C8. Verapamil is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and verapamil are not available, a similar interaction may occur. The dose of verapamil may need to be decreased if coadministered with deferasirox.
Triamcinolone: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Tucatinib: (Moderate) Closely monitor for tucatinib-related adverse reactions if coadministration with deferasirox is necessary due to the risk of increased tucatinib exposure. Tucatinib is a CYP2C8 substrate and deferasirox is a moderate CYP2C8 inhibitor.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with deferasirox as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; deferasirox is a weak CYP3A4 inducer.
Ulipristal: (Moderate) Deferasirox is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with deferasirox. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking deferasirox.
Valdecoxib: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Vancomycin: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including vancomycin, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Verapamil: (Moderate) Deferasirox inhibits CYP2C8. Verapamil is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and verapamil are not available, a similar interaction may occur. The dose of verapamil may need to be decreased if coadministered with deferasirox.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with deferasirox is necessary as concurrent use may increase or decrease the exposure of warfarin leading to increased bleeding risk or reduced efficacy. Deferasirox is a CYP1A2 inhibitor and warfarin is a CYP1A2 substrate. Additionally, deferasirox is a weak CYP3A4 inducer and warfarin is a CYP3A4 substrate. Finally, because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when giving with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as deferasirox. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamic effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.

How Supplied

Deferasirox/Exjade Oral Tab for Susp: 125mg, 250mg, 500mg
Deferasirox/Jadenu Oral Gran: 90mg, 180mg, 360mg
Deferasirox/Jadenu Oral Tab: 90mg, 180mg, 360mg

Maximum Dosage
Adults

28 mg/kg/day PO for Jadenu; 40 mg/kg/day PO for Exjade.

Geriatric

28 mg/kg/day PO for Jadenu; 40 mg/kg/day PO for Exjade.

Adolescents

28 mg/kg/day PO for Jadenu; 40 mg/kg/day PO for Exjade.

Children

2 to 12 years: 28 mg/kg/day PO for Jadenu; 40 mg/kg/day PO Exjade.
younger than 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Deferasirox is an orally active iron chelator that binds selectively to Fe3+. It is a tridentate ligand that requires two molecules of itself to form a stable complex with each iron atom. The efficiency of chelation of this compound is defined as the ratio of the amount of iron actually excreted to the amount of iron that could have been theoretically bound. In one clinical study, this capacity was calculated to be 20.5% in patients receiving a 20 mg/kg oral dose; one oral dose of deferasirox appears to be four to five times more effective than parenterally administered deferoxamine in promoting the excretion of chelatable iron from hepatocellular iron stores. This suggests that deferasirox chelates excess iron that enters the reticuloendothelial system as insoluble ferritin rather than iron required for enzyme activity. This may explain the lack of enzyme-related adverse effects seen with deferasirox treatment. At recommended doses, deferasirox is able to prevent net iron accumulation in most patients transfused with 12—15 ml packed red blood cells/kg/day.
 
Deferasirox is highly selective for iron, while it does not appear to promote dietary absorption of iron. Although deferasirox has very low affinity for zinc and copper, there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. These transient decreases may, however, be clinically irrelevant. The iron complex of deferasirox appears to be inert and is excreted to a large extent in the feces, rather than being redistributed.

Pharmacokinetics

Deferasirox is administered orally. It is highly (about 99%) protein bound, binding almost exclusively to serum albumin. Only 5% is confined to the blood cells in humans. The volume of distribution at steady state (Vss) is 14.37 +/- 2.69 L in adults. The main metabolic pathway is glucuronidation, with subsequent biliary excretion. Deconjugation of glucuronidates in the intestine and subsequent reabsorption (enterohepatic recycling) is likely to occur. Glucuronidation is carried out by UGT1A1 and to a lesser extent by UGT1A3. CYP450-catalyzed (oxidative) metabolism appears to be minor in humans (about 8%). No evidence for induction or inhibition of enzymes at therapeutic doses has been observed. Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% of the dose). The mean elimination half-life ranged from 8 to 16 hours following oral administration. In clinical evaluation, the total body iron elimination rate (range 7.7 to 28.5 mg iron/day) in patients treated with deferasirox was similar to values in patients receiving deferoxamine.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C8, CYP1A2, CYP2A6, CYP2D6, CYP2C19, UGT1A1, UGT1A3
UGT1A1 is the primary enzyme involved in glucuronidation of deferasirox, and UGT1A3 is involved to a lesser extent. If a concomitantly administered drug undergoes selective metabolism by UGT1A1, competition for drug metabolism will exist, possibly resulting in the reduced clearance of deferasirox. During in vivo studies, deferasirox inhibited the actions of CYP1A2 and CYP2C8, and was an inducer of CYP3A4. In vitro studies showed inhibition of CYP2A6, CYP2D6, and CYP2C19.

Oral Route

Deferasirox is well absorbed and circulates in the plasma for several hours after once daily dosing. Maximum plasma concentration (Cmax) is reached in about 1.5 to 4 hours. After administration of a single dose, the Cmax and AUC of deferasirox increase in an approximate linear fashion under steady-state conditions. Deferasirox tablets for oral suspension have an absolute bioavailability of 70%, while the bioavailability of the tablet and sprinkle granules is 36% and 52% more, respectively. The bioavailability of deferasirox oral suspension is variably increased when taken with a meal; therefore, this formulation must be taken on an empty stomach 30 minutes before eating. Exposure (AUC) and Cmax of the oral tablets when administered with a low-fat meal are similar to fasting conditions; however, when administered with a high-fat meal the AUC and Cmax are increased by 18% and 29%, respectively. The AUC and Cmax of the granule formulation after a low-fat meal or soft foods were also similar to that under fasting conditions. When administered with a high-fat meal, the AUC of the granules increased by 18% with no changes in Cmax compared to fasting condition. The oral tablets and granules may be administered either on an empty stomach or with a light meal (less than 250 calories and less than 7% fat). After multiple dosing, exposure to deferasirox increases by an accumulation factor of 1.3 to 2.3.

Pregnancy And Lactation
Pregnancy

There are no adequate and well-controlled studies with the use of deferasirox in pregnant women to inform about drug-associated risks. In animal studies, the administration of deferasirox resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses less than the recommended human doses. Deferasirox should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

There are no data available on the presence of deferasirox or its metabolites in human milk, the effects on the breast-fed infant, or the effects on milk production. In animal studies, deferasirox and its metabolites were excreted in rat milk. Due to the potential for serious adverse reactions in the nursing infant from deferasirox, a decision should be made whether to discontinue breast-feeding or discontinue deferasirox, taking into account the mother's clinical need for deferasirox.