Deferasirox is a medication used for the treatment of chronic iron overload in conditions such as thalassemia and other chronic anemias. Iron overload can occur in patients who require frequent blood transfusions, as each transfusion introduces additional iron into the body. Over time, this can lead to a build-up of excess iron, which can be harmful to organs and tissues.

Deferasirox is an iron-chelating agent, meaning it binds to excess iron in the body and helps the body eliminate it. It is taken orally in the form of a tablet or a suspension. The medication works by forming a stable complex with iron, which is then excreted from the body through the feces.

Deferasirox (Exjade) is an oral iron-chelating agent that binds to the iron in the blood and removes it from the body via the kidneys. It is used in the treatment of patients with iron-overload states such as thalassemia and other hemolytic anemias.

Deferasirox (Exjade) Uses:

• Chronic iron overload due to blood transfusions:
  • Deferasirox is used in the treatment of chronic iron overload due to recurrent transfusions (e.g in Thalassemia/Aplastic Anemia etc) in patient older than 2 years.
• Chronic iron overload in non-transfusion-dependent thalassemia syndromes:
  • It is also used to treat chronic iron overload in patients with non-transfusion-dependent thalassemia syndromes (NTDT) in patients 10 years and older and with a liver iron concentration (LIC) of 5 mg or more iron per gram of liver dry weight (mg Fe/g dry weight) and a serum ferritin level > 300 mcg/L.
• Limitations of use:
  • It has not been established whether deferasirox is safe and efficacious when given in combination with other iron chelation therapies.
  • No controlled studies of deferasirox have been conducted in patients with myelodysplastic syndromes and chronic iron overload due to blood transfusions.

Deferasirox (Exjade) Dose in Adults

Note:

• When you're using a medication called deferasirox to manage too much iron in your body, it's important to use the smallest amount needed to lower the levels of a protein called ferritin and keep your iron levels where they should be.
• Your doctor will tell you exactly how much to take, and it's important to measure it precisely.
• This might mean using whole tablets or packets of granules to get the right amount.
• Following these instructions helps you manage the iron levels effectively.

Deferasirox (Exjade) Dose in the treatment of chronic iron overload due to blood transfusions: Oral:

For treating too much iron due to blood transfusions using a medicine called deferasirox:

Exjade:

• Start with 20 mg for every kilogram of your weight once a day.
• After that, adjust the dose every 3 to 6 months based on your blood test results. Increase or decrease by 5 or 10 mg for every kilogram of your weight.
• If your iron levels are still too high, your doctor might consider doses up to 40 mg for every kilogram of your weight. But don't go over this.
• If your iron levels get too low, your doctor might reduce the dose.

Jadenu:

• Begin with 14 mg for every kilogram of your weight once a day.
• Adjust the dose every 3 to 6 months based on your blood test results. Increase or decrease by 3.5 or 7 mg for every kilogram of your weight.
• If your iron levels are still too high, your doctor might consider doses up to 28 mg for every kilogram of your weight. But don't go over this.
• If your iron levels get too low, your doctor might reduce the dose.

Deferasirox (Exjade) Dose in treatment of chronic iron overload in non-transfusion-dependent thalassemia syndromes: Oral:

For treating chronic iron overload in non-transfusion-dependent thalassemia:

Exjade:

• Start: 10 mg for every kilogram of your weight once a day.
• Consider an increase to: 20 mg for every kilogram of your weight once a day after 4 weeks if your initial iron levels are high.
• Maintenance: Adjust based on monthly blood tests and iron concentration checks every 6 months.
  • If iron levels are too low (serum ferritin <300 mcg/L): Pause treatment and check iron concentration.
  • If iron concentration is:
    • Less than 3 mg Fe/g dry weight: Pause treatment, restart when it goes above 5 mg Fe/g.
    • Between 3 and 7 mg Fe/g dry weight: Continue with a dose of no more than 10 mg/kg/day.
    • More than 7 mg Fe/g dry weight: Increase the dose to a maximum of 20 mg/kg/day.

Jadenu:

• Start: 7 mg for every kilogram of your weight once a day.
• Consider an increase to: 14 mg for every kilogram of your weight once a day after 4 weeks if your initial iron levels are high.
• Maintenance: Adjust based on monthly blood tests and iron concentration checks every 6 months.
  • If iron levels are too low (serum ferritin <300 mcg/L): Pause treatment and check iron concentration.
  • If iron concentration is:
    • Less than 3 mg Fe/g dry weight: Pause treatment, restart when it goes above 5 mg Fe/g.
    • Between 3 and 7 mg Fe/g dry weight: Continue with a dose of no more than 7 mg/kg/day.
    • More than 7 mg Fe/g dry weight: Increase the dose to a maximum of 14 mg/kg/day.

Deferasirox Dosage adjustment with concomitant medications:

Dosage Adjustment with Other Medications:

• Bile Acid Sequestrants (e.g., cholestyramine, colesevelam, colestipol) or Potent UGT Inducers (e.g., rifampin, phenytoin, phenobarbital, ritonavir):
  • Avoid using them together.
  • If you have to use them together, think about increasing the initial dose of deferasirox by 50%.
  • Keep an eye on your blood test results (serum ferritin) and how you're responding to the treatment.
• Conversion from Exjade to Jadenu:
  • If you're switching from Exjade to Jadenu, the dose for Jadenu should be around 30% lower than what you were taking with Exjade.

Deferasirox (Exjade) Dose in Childrens

Note:

• To manage iron overload effectively, it's important to use the smallest amount of deferasirox needed to lower ferritin levels and keep iron within the target range.
• There are two forms of deferasirox, Exjade (in tablet form) and Jadenu (in tablet and sprinkle sachet form), but they aren't exactly the same in terms of how the body absorbs them.
• So, it's crucial to calculate the dose precisely based on your doctor's guidance, rounding to the nearest whole tablet or sprinkle sachet size.
• This helps ensure you're getting the right amount for your treatment.

Deferasirox (Exjade) Dose in the treatment of chronic iron overload due to blood transfusion: 

Exjade (oral tablet for suspension):

• Start: 20 mg for every kilogram of the child's weight once a day.
• Adjustment: Change the dose every 3 to 6 months based on blood test results (serum ferritin). Increase or decrease by 5 or 10 mg for every kilogram of the child's weight.
• Usual range: 20 to 30 mg for every kilogram of the child's weight per day. For high ferritin levels that aren't improving, your doctor might consider up to 40 mg/kg/day, but not more.
• Adjust if needed:
  • If ferritin levels drop below 1,000 mcg/L at two consecutive visits: Think about reducing the dose, especially if it's over 25 mg/kg/day.
  • If ferritin drops below 500 mcg/L: Pause treatment and keep checking monthly.

Jadenu (oral tablet; sprinkle granules):

• Start: 14 mg for every kilogram of the child's weight once a day, rounding to the nearest whole tablet or sprinkle sachet.
• Adjustment: Change the dose every 3 to 6 months based on blood test results (serum ferritin). Increase or decrease by 3.5 or 7 mg for every kilogram of the child's weight.
• If not well controlled: If the child's iron levels remain too high at 21 mg/kg/day, your doctor might consider higher doses, but not more than 28 mg/kg/day.
• Adjust if needed:
  • If ferritin levels drop below 1,000 mcg/L at two consecutive visits: Think about reducing the dose, especially if it's over 17.5 mg/kg/day.
  • If ferritin drops below 500 mcg/L: Pause treatment and keep checking monthly.

Deferasirox (Exjade) Dose in the treatment of non-transfusion-dependent chronic iron overload; thalassemia syndromes (NTDT):

Exjade (oral tablet for suspension):

• Start: 10 mg for every kilogram of the child's weight once a day. If after 4 weeks, the initial iron levels in the liver are high, your doctor might increase the dose to 20 mg/kg once a day.
• Maintenance: Adjust based on monthly blood tests (serum ferritin) and iron concentration in the liver (LIC) every 6 months.
  • If ferritin levels are too low (less than 300 mcg/L): Pause treatment and check the LIC.
  • If LIC:
    • Less than 3 mg Fe/g dry weight: Pause treatment, restart when it goes above 5 mg Fe/g.
    • Between 3 and 7 mg Fe/g dry weight: Continue with a dose of no more than 10 mg/kg/day.
    • More than 7 mg Fe/g dry weight: Increase the dose to 20 mg/kg/day if not already; maximum daily dose: 20 mg/kg/day.

Jadenu (oral tablet, sprinkle granules):

• Start: 7 mg for every kilogram of the child's weight once a day. If after 4 weeks, the initial iron levels in the liver are high, your doctor might increase the dose to 14 mg/kg once a day.
• Maintenance: Adjust based on monthly blood tests (serum ferritin) and LIC every 6 months.
  • If ferritin levels are too low (less than 300 mcg/L): Pause treatment and check the LIC.
  • If LIC:
    • Less than 3 mg Fe/g dry weight: Pause treatment, restart when it goes above 5 mg Fe/g.
    • Between 3 and 7 mg Fe/g dry weight: Continue with a dose of no more than 7 mg/kg/day.
    • More than 7 mg Fe/g dry weight: Increase the dose to 14 mg/kg/day if not already; maximum daily dose: 14 mg/kg/day.

Conversion from Exjade to Jadenu:

• The dose for Jadenu should be around 30% lower than what you were taking with Exjade. Always round doses to the nearest whole tablet or sachet.

Dosing adjustment with other medications (bile acid sequestrants or UGT inducers):

• Avoid using them together.
• If you have to use them together, think about increasing the initial deferasirox dose by 50%.
• Keep an eye on your blood test results (serum ferritin) and how you're responding to the treatment.

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Deferasirox Dosing adjustment for toxicity:

In case of potential side effects or toxicity in children aged 2 years and older and adolescents receiving deferasirox:

• Auditory Disturbances: If there are issues with hearing, think about reducing the dose or temporarily stopping the treatment.
• Bone Marrow Suppression: If there is a drop in blood cell counts, stop the treatment. It can be resumed once the cause of the low blood cell counts is identified. However, if the platelet count is less than 50,000/mm, restarting is not recommended.
• Dermatologic Toxicity:
  • Severe Rash: Pause the treatment and consider reintroducing it at a lower dose, with future dose escalation. Short-term oral corticosteroids may be used.
  • Severe Skin Reactions (Stevens-Johnson syndrome, erythema multiforme): Stop the treatment and do not restart.
• Gastrointestinal Issues: If there is suspicion of gastrointestinal ulceration or bleeding, discontinue the treatment.
• Hearing Loss or Visual Disturbance: If there are concerns about hearing loss or vision problems, consider reducing the dose or temporarily stopping the treatment.

Deferasirox (Exjade) Pregnancy Risk Category: C

• In studies with animals, negative effects were noticed during pregnancy when using deferasirox.
• However, there's not a lot of information about how deferasirox affects pregnant women specifically, based on a study from 2011.

Use of deferasirox while breastfeeding

• We're not sure if deferasirox is found in breast milk.
• Because it could cause serious problems for the baby who's breastfeeding, the company suggests deciding whether to stop breastfeeding or stop taking the medication.
• This decision should consider how crucial the treatment is for the mother.

Deferasirox (Exjade) Dose in Kidney Disease:

Estimated Glomerular Filtration Rate (eGFR) Calculation:

• Use an appropriate prediction equation (e.g., CKD-EPI, MDRD method) to calculate eGFR.

Renal Impairment at Treatment Initiation:

• eGFR >60 mL/minute/1.73 m²: No need to change the dose.
• eGFR 40 to 60 mL/minute/1.73 m²: Initially, reduce the dose by 50%.
• eGFR <40 mL/minute/1.73 m²: Avoid using the medication.

Renal Toxicity During Treatment - Transfusional Iron Overload:

• If serum creatinine increases by ≥33% above the average baseline, repeat the test within 1 week.
• If still elevated by ≥33%:
  • Exjade: Reduce the daily dose by 10 mg/kg.
  • Jadenu: Reduce the daily dose by 7 mg/kg.
• eGFR <40 mL/minute/1.73 m²: Stop the treatment.

Renal Toxicity During Treatment - Non-transfusion-dependent Thalassemia Syndromes:

• If serum creatinine increases by ≥33% above the average baseline, repeat the test within 1 week.
• If still elevated by ≥33%:
  • Exjade: Pause therapy if the dose is 5 mg/kg; reduce the dose by 50% if the dose is 10 or 20 mg/kg.
  • Jadenu: Pause therapy if the dose is 3.5 mg/kg; reduce the dose by 50% if the dose is 7 or 14 mg/kg.
• All patients: eGFR <40 mL/minute/1.73 m²: Stop the treatment.

Deferasirox (Exjade) Dose in Liver Disease:

Hepatic Impairment at Treatment Initiation:

• Mild Impairment (Child-Pugh class A): No need to adjust the dose. Monitor closely for effectiveness and any side effects that may require a dose reduction.
• Moderate Impairment (Child-Pugh class B): Initially, reduce the dose by 50%. Keep a close eye on effectiveness and watch for any side effects that may require a further dose reduction.
• Severe Impairment (Child-Pugh class C): Avoid using the medication.

Hepatic Toxicity During Treatment:

• If there are severe or persistent increases in transaminases/bilirubin, consider reducing the dose or temporarily stopping the treatment. Regular monitoring is essential to manage potential liver-related issues.

Common Side Effects of Deferasirox (Exjade):

• Dermatologic:
  • Skin rash
• Gastrointestinal:
  • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
• Genitourinary:
  • Proteinuria
• Renal:
  • Increased serum creatinine

Less Common Side Effects of Deferasirox (Exjade):

• Cardiovascular:
  • Edema
• Central nervous system:
  • Anxiety
  • Dizziness
  • Fatigue
  • Sleep disorder
• Dermatologic:
  • Dyschromia
• Gastrointestinal:
  • Acute pancreatitis
  • Cholelithiasis
  • Duodenal ulcer
  • Gastric ulcer
  • Gastritis
  • Gastrointestinal hemorrhage
• Hepatic:
  • Increased serum alanine aminotransferase
• Ophthalmic:
  • Cataract
  • Maculopathy
• Otic:
  • Hearing loss (including high frequency)
• Renal:
  • Renal tubular disease
• Respiratory:
  • Pharyngolaryngeal pain
• Miscellaneous:
  • Fever

Frequency of Side effects not defined:

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Constipation
• Hepatic:
  • Increased serum bilirubin
• Infection:
  • Viral infection
• Neuromuscular & skeletal:
  • Arthralgia
  • Back pain
• Respiratory:
  • Cough
  • Nasopharyngitis
  • Pharyngitis
  • Respiratory tract infection

Contraindications to Deferasirox (Exjade):

• Avoid using deferasirox if you have a known allergy to it or any part of the medication, if your kidney function is very low (eGFR <40 mL/minute/1.73 m²), if your overall health is not good, if you have certain high-risk blood disorders or advanced cancers, or if your platelet counts are very low (<50,000/mm³).
• In Canada, additional reasons to avoid it include having a life expectancy of less than one year with certain blood disorders (MDS), low creatinine clearance (CrCl <60 mL/minute), or if you have other blood or non-blood cancers where chelation therapy isn't expected to help due to the fast progression of the disease.

Warnings and precautions

Auditory disturbances

• Rarely, decreased hearing and high-frequency hearing loss have been reported with deferasirox.
• Before starting the treatment and regularly (every 12 months) while using it, auditory testing is recommended.
• If any abnormalities develop, especially in pediatric patients taking doses higher than 25 mg/kg/day (Exjade) or 17.5 mg/kg/day (Jadenu) when serum ferritin is less than 1,000 mcg/L, closer monitoring and potential dose reduction or treatment interruption should be considered, although the exact link between the medication and auditory issues is not firmly established.

Suppression of bone marrow

• Cytopenias, which include serious conditions like agranulocytosis, neutropenia, thrombocytopenia, and worsening anemia, have been reported with deferasirox, and in some cases, these events were fatal.
• The risk might be higher for those with existing blood disorders.
• Regularly monitoring blood counts is crucial.
• If cytopenias develop, treatment should be interrupted, and it may resume once the cause of the condition is understood.
• Importantly, using deferasirox is not recommended if the platelet count is less than 50,000/mm³.

Dermatologic toxicities:

• Deferasirox may lead to skin rash, and the severity can vary based on the dose.
• Mild to moderate rashes might go away without stopping the treatment.
• However, for severe rashes, it's recommended to interrupt the treatment and think about restarting at a lower dose, gradually increasing it, and using oral steroids.
• In some cases, serious and life-threatening skin reactions like Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.
• If severe skin reactions are suspected, the treatment should be stopped immediately, and a thorough evaluation is necessary.
• Reintroducing the therapy is not advised in such cases.

Gastrointestinal events [US Boxed Warning]

• There's a serious warning about potential gastrointestinal (GI) issues with deferasirox.
• GI hemorrhages, including fatal cases, have been reported, especially in elderly patients with advanced blood cancers and low platelet counts.
• If there's suspicion of GI hemorrhage or ulceration, the treatment should be stopped.
• Nonfatal upper GI problems, like irritation, bleeding, and ulcers (sometimes leading to GI perforation, including fatal cases), have been observed.
• It's important to be cautious when using other medications that might increase the risk of GI problems, such as NSAIDs, corticosteroids, anticoagulants, and oral bisphosphonates.
• Patients should be closely monitored for any signs or symptoms of GI ulceration or bleeding, and immediate medical attention is crucial if any issues are suspected.

Hepatic failure: [US Boxed Warning]:

• There's a serious warning about the potential for liver problems with deferasirox.
• Hepatic injury and failure, including fatal cases, may happen.
• Regular monitoring of liver function is essential: at the start of treatment, every two weeks for the first month, and then at least monthly thereafter.
• Avoid using the medication in patients with severe (Child-Pugh class C) liver impairment; those with moderate (Child-Pugh class B) impairment should start with a reduced dose.
• Patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) impairment may have a higher risk of side effects.
• Hepatotoxicity may be more common in patients over 55 years old and those with significant health issues like liver cirrhosis and multiorgan failure.
• Acute liver injury and failure, sometimes fatal, have occurred in pediatric patients, especially those at risk of having too much iron and during states of low body fluid volume.
• If there's suspicion of liver or kidney injury, treatment should be interrupted, especially during times of low body fluid volume.
• Regular monitoring of liver and kidney function is particularly important in pediatric patients receiving certain doses when iron levels are approaching normal.
• Always use the minimum effective dose and consider dose reduction or treatment interruption if severe or persistent elevations in liver function tests occur.
• If there are any concerns about liver function, immediate medical attention is crucial.

Hypersensitivity

• Hypersensitivity reactions, including severe ones like anaphylaxis and angioedema, have been reported with deferasirox.
• These reactions typically happen within the first month of starting treatment.
• If a hypersensitivity reaction is severe, it's advised to discontinue the treatment.
• Importantly, patients who have had previous hypersensitivity reactions should not be reintroduced to deferasirox due to the risk of anaphylactic shock.
• If there are concerns about a severe allergic reaction, immediate medical attention is crucial.

Ocular disturbances:

• Rarely, deferasirox use has been associated with ocular disturbances, including lens opacities, cataracts, elevation of intraocular pressure, and retinal disorders.
• To monitor and address potential issues, it is recommended to undergo ophthalmic testing before starting the treatment and regularly (every 12 months) during its use.
• If abnormalities are detected during these tests, closer monitoring and considerations for dose reduction or treatment interruption may be necessary.

Renal Failure: [US-Boxed Warning]

• Deferasirox comes with a serious warning about the risk of acute renal failure, which can be fatal, especially in patients with other health issues or advanced blood disorders.
• Before starting and when increasing the dose, evaluate the kidney function of all patients.
• Deferasirox is not recommended for adults and children with eGFR less than 40 mL/min/1.73 m².
• Monitor serum creatinine regularly, especially before starting treatment and at least monthly thereafter.
• For patients with existing kidney problems or a higher risk of acute renal failure, closely monitor renal function weekly for the first month and then at least monthly.
• Consider starting with a lower dose for patients with preexisting kidney disease.
• Increase the monitoring frequency if there's an increased risk of kidney problems, such as using other drugs that might harm the kidneys.
• The minimum effective dose should be used, and renal function should be frequently monitored.
• Adjust the dose based on improvement in kidney function.
• Initial dose reductions are necessary for patients with moderate renal impairment (eGFR 40 to 60 mL/min/1.73 m²), and caution is advised in pediatric patients with eGFR in this range.
• Acute kidney injury, including cases requiring dialysis and leading to fatal outcomes, has been reported, especially in patients with multiple health issues and advanced blood disorders.
• Deferasirox-treated patients may experience mild, nonprogressive increases in serum creatinine and proteinuria.
• Preexisting kidney disease and the use of other drugs harmful to the kidneys may increase the risk of acute kidney injury.
• In pediatric patients, small decreases in eGFR may result in increased deferasirox exposure, particularly in younger patients (<7 years old), and without proper management, this may worsen renal function.
• Renal tubular toxicity, including Fanconi Syndrome, has been reported, particularly in pediatric patients with beta-thalassemia and low serum ferritin levels.
• Therefore, regular evaluation of kidney function, electrolytes, and urinalysis is essential.
• Weekly monitoring is advised during the first month of treatment, after any treatment changes, and at least monthly thereafter.
• Serum ferritin levels should also be monitored monthly, especially to check for overchelation.
• Pediatric patients, particularly during illnesses causing fluid loss, should have their renal function closely monitored, and if needed, treatment should be interrupted until normal oral intake and fluid status are restored.

Deferasirox: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Agomelatine	Moderate CYP1A2 inhibitors may raise the serum Agomelatine concentration.
Anticoagulants	May increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Bisphosphonate Derivatives	May increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
CloZAPine	CloZAPine serum concentrations may be increased by CYP1A2 inhibitors (Moderate).
Corticosteroids	May increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Beclomethasone; Budesonide, Ciclesonide and Nasal; Desonide; Dexamethasone; Hydrocortisone; Hydrocortisone; Fluocinolone; Flunisolide; Fluocinolone; Fluticasone; Fluticasone; Fluocinolone; Fluticasone; Hydrocortisone; Loteprednol.
Corticosteroids (Systemic)	May increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
CYP1A2 Substrates (High Risk with Inhibitors).	Deferasirox can increase serum concentrations of CYP1A2 Substrates (High Risk with Inhibitors).
CYP2C8 Substrates (High Risk with Inhibitors).	Deferasirox can increase serum concentrations of CYP2C8 Substrates (High Risk with Inhibitors).
CYP3A4 Substrates - High risk with Inducers	Deferasirox can decrease serum concentrations of CYP3A4 Substrates (High Risk with Inducers).
Desloratadine	Moderate CYP2C8 inhibitors may raise the serum level of Desloratadine.
Nonsteroidal Anti-Inflammatory Drugs	May increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Repaglinide	Repaglinide serum concentrations may be increased by Deferasirox
Risk Factor D (Insist on therapy modification)
Bile Acid Sequestrants	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
Busulfan	The serum Busulfan concentration may be increased by deferasirox. Before starting busulfan, discontinue deferasirox for 2 to 3 days (approximately five half-lives). Monitor for elevated busulfan effects and concentrations if combined. Concomitant use may require reduced busulfan doses.
Fosphenytoin	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
PHENobarbital	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
Phenytoin	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
Pirfenidone	Moderate CYP1A2 inhibitors may cause an increase in the serum level of Pirfenidone. Management: Be cautious and closely monitor for pirfenidone toxicities in any combination. If CYP2C9 or 2C19, 2C6, 2C6, 2C6 or 2E1 are also inhibited (either by a CYP1A2 antagonist or a third drug), avoid pirfenidone and moderate CYP1A2 inhibitions.
Rasagiline	Moderate CYP1A2 inhibitors may cause a higher serum level of Rasagiline. Patients taking moderate CYP1A2 inhibitors should be limited to rasagiline at 0.5 mg per day.
RifAMPin	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
Ritonavir	May cause a decrease in serum concentrations of Deferasirox. Management: Do not combine deferasirox with other medications. If you must use the combination, increase your initial dose by 50%. Monitor serum ferritin levels and respond to clinical signs for guidance.
Selexipag	CYP2C8 Moderate Inhibitors may raise serum levels of active metabolites of Selexipag. CYP2C8 Moderate Inhibitors may increase Selexipag's serum concentration. Management: Consider a lower dose (e.g., one per day) when initiating selexipag for a patient who is taking a moderate CYP2C8 inhibitor. Consider reducing the dose of selexipag if you are initiating a moderate CYP2C8 inhibition in a patient taking selexipag.
TiZANidine	Moderate CYP1A2 inhibitors may cause an increase in serum TiZANidine. Management: Start tizanidine in adults at 2mg and increase by 2 to 4mg depending on the patient's response. Monitor for adverse reactions and increased effects of tizanidine.
Risk Factor X (Avoid Combination)
Alosetron	Moderate CYP1A2 inhibitors may cause a rise in serum Alosetron concentrations.
Aluminum Hydroxide	May decrease the therapeutic effects of Deferasirox.
Amodiaquine	Moderate CYP2C8 inhibitors may raise serum levels of Amodiaquine.
Theophylline	The serum concentration of Theophylline may be increased by Deferasirox.

Monitoring parameters:

Transfusional Iron Overload:

• Serum Ferritin: Check baseline levels and monitor monthly thereafter. Also, assess with dose increases.
• CBC with Differential: Monthly monitoring.
• Serum Electrolytes: Baseline measurement and assessment with dose increases.
• Renal Function: Evaluate serum creatinine in duplicate at baseline, eGFR at baseline, and monitor weekly during the first month and then monthly.
• Liver Function: Assess serum transaminases (ALT/AST) and bilirubin at baseline, every 2 weeks for the first month, and then at least monthly and with dose increases.
• Urinalysis: Conduct baseline and follow-up assessments, including urine protein on a monthly basis.
• Cumulative RBC Units: Keep a record of the total number of red blood cell units received.

Non-Transfusion-Dependent Thalassemia Syndromes:

• Liver Iron Concentration: Baseline assessment, then every 6 months and as clinically indicated.
• Serum Ferritin: Two measurements at least a month apart before treatment, followed by monthly monitoring.
• CBC with Differential: Monthly check.
• Serum Electrolytes: Baseline measurement and with dose increases.
• Renal Function: Evaluate serum creatinine in duplicate at baseline, eGFR at baseline, and monitor weekly during the first month, then monthly and with dose increases.
• Liver Function: Assess serum transaminases (ALT/AST) and bilirubin at baseline, every 2 weeks for the first month, and then at least monthly and with dose increases.
• Urinalysis: Conduct baseline and follow-up assessments.

All Patients:

• Blood Glucose: More frequent monitoring for patients with diabetes.
• Auditory Examination: Baseline, annual checks, and before dose increases.
• Ophthalmic Examination: Including slit-lamp examinations and dilated fundoscopy; baseline, annually, and prior to dose increases.
• Renal Tubular Toxicity: Monitor for changes in eGFR weekly during the first month.
• Liver and Renal Function: Frequent monitoring in pediatric patients receiving specific doses and when iron burden is approaching normal.
• Toxicity Monitoring: More frequent for elderly patients, pediatric patients experiencing volume depletion or overchelation, and those receiving concomitant nephrotoxic drugs.
• Dermatologic Toxicity, GI Ulcers, Hemorrhage, Hypersensitivity: Watch for signs and symptoms regularly.

How to administer Deferasirox (Exjade)?

Oral Administration:

• Timing: Take as directed by your healthcare provider.
• Antacids: Do not take Deferasirox simultaneously with aluminum-containing antacids.

Jadenu Granules:

• Timing: Administer on an empty stomach or with a light meal, at the same time each day.
• Administration: Sprinkle granules on soft food (e.g., yogurt or applesauce) immediately before taking.

Jadenu Tablets:

• Timing: Swallow with water or other liquids at the same time each day.
• Administration: Take on an empty stomach or with a light meal (contains <7% fat content and ~250 calories).
• Difficulty Swallowing: If swallowing whole tablets is challenging, you may crush them and mix with soft foods (e.g., yogurt, applesauce); consume immediately (do not store).

Exjade Tablets for Suspension:

• Administration: Create an oral suspension; do not chew or swallow tablets whole.
• Preparation: Completely disperse tablets in water, orange juice, or apple juice (use 105 mL for total doses <1 g; 210 mL for doses ≥1 g).
• Stir and Drink: Stir to form a fine suspension and drink the entire contents. Rinse any remaining residue with more fluid.
• Avoid Dispersion in: Milk (slowed dissolution) or carbonated drinks (foaming).
• Timing: Administer at the same time each day on an empty stomach, at least 30 minutes before food.

Mechanism of action of Deferasirox (Exjade):

• Deferasirox is a medication that helps remove excess iron from the body.
• It works by attaching to iron and creating a compound that the body can get rid of, mostly through bowel movements.
• This way, it helps reduce the amount of iron in the body, particularly in situations where there is an overload of iron due to frequent blood transfusions.
• By binding to iron, Deferasirox supports the elimination of this excess iron, which is essential for people who have conditions like thalassemia or other disorders requiring regular blood transfusions.

Distribution:

• In adults, Deferasirox is distributed in the body at an average of 14.37 ± 2.69 liters.

Protein Binding:

• It binds to serum albumin, a protein in the blood, at a very high rate, approximately 99%.

Metabolism:

• Deferasirox undergoes metabolic processes in the liver, primarily through glucuronidation by UGT1A1 and UGT1A3.
• There is also minor involvement of oxidation by CYP450.
• The medication goes through a cycle of being reabsorbed in the intestines and returned to the liver (enterohepatic recirculation).

Bioavailability:

• Depending on the form of the medication, bioavailability varies.
• Tablets for oral suspension have a bioavailability of 70%, tablets have 36% greater bioavailability than tablets for oral suspension, and granules have 52% greater bioavailability than tablets for oral suspension.

Half-life elimination:

• Deferasirox stays in the body for a duration of 8 to 16 hours before it is eliminated.

Time to Peak, Plasma:

• The time it takes to reach the maximum concentration in the blood is approximately 1.5 to 4 hours for tablets and tablets for oral suspension.

Excretion:

• The majority of Deferasirox is excreted through the feces (84%), with a smaller portion eliminated in the urine (8%).

International Brand Names of Deferasirox:

• Exjade
• Jadenu
• Jadenu Sprinkle
• APO-Deferasirox
• PMS-Deferasirox
• SANDOZ Deferasirox
• TARO-Deferasirox
• TEVA-Deferasirox
• Androrasirox
• Asunra
• Clearon
• Difirax
• Egychelaton
• Exjade
• Feresirrox
• Jadenu

Deferasirox Brand Names in Pakistan:

Deferasirox tablets 100 mg in Pakistan
Asunra	Novartis Pharma (Pak) Ltd

Deferasirox Tablets 400 mg in Pakistan
Asunra	Novartis Pharma (Pak) Ltd

Deferasirox Tablets efr 100 mg in Pakistan
Dasirox	Consolidated Chemical Laboratories (Pvt) Ltd.

Deferasirox Tablets efr 250 mg in Pakistan
Oderox	A. J. Mirza Pharma (Pvt) Ltd

Deferasirox Tablets efr 400 mg in Pakistan
Dasirox	Consolidated Chemical Laboratories (Pvt) Ltd.

Deferasirox Tablets efr 500 mg in Pakistan
Oderox	A. J. Mirza Pharma (Pvt) Ltd