EXJADE (Deferasirox)

What Is EXJADE and What Is It Used For?

EXJADE (deferasirox) is an oral iron chelating medication that removes excess iron from the body. It is primarily prescribed for patients who develop chronic iron overload as a result of repeated blood transfusions for conditions such as beta-thalassemia, sickle cell disease, and myelodysplastic syndromes (MDS).

The human body has no natural mechanism for eliminating excess iron. When patients with certain blood disorders require regular blood transfusions, the iron contained in transfused red blood cells gradually accumulates in the body. Each unit of transfused blood contains approximately 200-250 mg of iron, and over time this accumulation can reach dangerously high levels. Without treatment, this excess iron deposits in vital organs, particularly the liver and heart, leading to potentially life-threatening organ damage including liver cirrhosis, heart failure, and endocrine dysfunction.

Deferasirox belongs to a class of medications known as iron chelators. The word "chelator" comes from the Greek word for "claw," which aptly describes how the drug works: two molecules of deferasirox bind to one iron atom (Fe3+) with high affinity, forming a stable complex. This iron-deferasirox complex is then excreted primarily through the feces, effectively removing excess iron from the body. Importantly, deferasirox has very low affinity for zinc and copper, meaning it selectively targets iron without significantly depleting other essential trace minerals.

EXJADE is used in several clinical scenarios. The primary indication is for the treatment of chronic iron overload caused by repeated blood transfusions in patients with beta-thalassemia major aged 6 years and older. Beta-thalassemia is a genetic blood disorder in which the body produces abnormal hemoglobin, resulting in severe anemia that requires lifelong transfusion support. Without adequate iron chelation, these patients face progressive organ damage that significantly shortens life expectancy.

Beyond beta-thalassemia, EXJADE is also approved for patients with other forms of transfusion-dependent anemia, including sickle cell disease and various types of myelodysplastic syndromes (MDS), when deferoxamine therapy is contraindicated or inadequate. For children aged 2-5 years with transfusion-dependent iron overload, EXJADE can be used when deferoxamine treatment is unsuitable. Additionally, EXJADE is indicated for patients aged 10 years and older with non-transfusion-dependent thalassemia syndromes who have developed clinically significant iron overload, where elevated iron absorption from the gut and the effects of ineffective red blood cell production contribute to iron accumulation even without regular transfusions.

What Should You Know Before Taking EXJADE?

Before starting EXJADE, your doctor needs to assess your kidney and liver function, review your current medications, and discuss potential risks. EXJADE is contraindicated in patients with moderate to severe kidney disease and should not be combined with other iron chelating agents.

Contraindications

EXJADE must not be used in certain situations. You should not take EXJADE if you are allergic to deferasirox or any of the other ingredients in the formulation. If you suspect you may have an allergy, consult your doctor before starting treatment. EXJADE is also contraindicated in patients with moderate or severe kidney disease, as the drug is primarily processed by the kidneys and can further impair renal function in those with pre-existing kidney problems.

Importantly, EXJADE should not be taken simultaneously with other iron chelating agents such as deferoxamine (Desferal) or deferiprone (Ferriprox). Combining iron chelators can increase the risk of adverse effects without necessarily improving iron removal. EXJADE is also not recommended for patients in advanced stages of myelodysplastic syndrome (MDS) or those with advanced cancer, as the risk-benefit ratio in these populations has not been adequately established.

Warnings and Precautions

Before and during treatment with EXJADE, there are several important warnings to be aware of. Discuss the following conditions with your doctor before starting the medication:

• Kidney disease: Even mild kidney impairment requires careful monitoring, as EXJADE can affect renal function. Report any significant decrease in urine output immediately.
• Liver disease: EXJADE can cause liver problems. Watch for signs such as drowsiness, upper right abdominal pain, yellowing of the skin or eyes, and dark-colored urine.
• Heart disease caused by iron overload: Patients with cardiac iron deposition need close cardiac monitoring during chelation therapy.
• Severe allergic reactions: Seek immediate medical attention if you experience severe rash, difficulty breathing, dizziness, or swelling of the face and throat.
• Severe skin reactions: Report any combination of rash, red skin, blistering on lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, or enlarged lymph nodes.
• Elevated blood ammonia: Difficulty thinking, reduced alertness, extreme drowsiness, or low energy may indicate high ammonia levels, which can be associated with liver or kidney problems.
• Gastrointestinal bleeding: Vomiting blood or passing black stools requires immediate medical evaluation.
• Low blood cell counts: Low platelet or white blood cell counts in your blood tests may require dose adjustment or discontinuation.
• Vision changes: Blurred or cloudy vision should be reported promptly, as EXJADE can affect eyesight.

Monitoring During Treatment

Regular monitoring is a critical component of EXJADE therapy. Your doctor will schedule routine blood and urine tests throughout the course of treatment. These include measurement of serum ferritin levels to assess how effectively EXJADE is reducing iron burden, serum creatinine and urinary protein to monitor kidney function, and liver transaminases to evaluate liver health. In some cases, your doctor may request a kidney biopsy if significant kidney damage is suspected.

Magnetic Resonance Imaging (MRI) scans are used periodically to measure the amount of iron stored in the liver, providing a more accurate assessment than blood tests alone. Your doctor will use all of these results together to determine the optimal dose of EXJADE for your individual needs and to decide when treatment should be modified or discontinued.

As a precautionary measure, your vision and hearing will be tested annually during treatment, as iron chelation therapy has been associated with rare cases of visual and auditory disturbances.

Pregnancy and Breastfeeding

EXJADE is not recommended during pregnancy unless it is absolutely necessary and the potential benefit to the mother justifies the potential risk to the fetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medication.

Women who are currently using hormonal contraceptives (such as birth control pills, patches, or implants) should be aware that EXJADE may reduce their effectiveness. It is recommended to use an additional non-hormonal method of contraception (such as condoms) while taking EXJADE to prevent unintended pregnancy.

Breastfeeding is not recommended during treatment with EXJADE, as it is not known whether deferasirox passes into breast milk and could potentially affect the nursing infant.

Use in Elderly Patients

EXJADE can be used by patients aged 65 years and older at the same doses recommended for younger adults. However, elderly patients may experience more frequent side effects, particularly diarrhea, and should be monitored more closely by their healthcare provider. Dose adjustments may be necessary based on individual tolerability and kidney function, which naturally declines with age.

How Does EXJADE Interact with Other Drugs?

EXJADE interacts with numerous medications, including aluminum-containing antacids, cyclosporine, simvastatin, hormonal contraceptives, and certain anticonvulsants. Always inform your doctor of all medications you are taking before starting EXJADE therapy.

Drug interactions are a significant consideration with EXJADE treatment. Deferasirox is metabolized primarily through glucuronidation by the enzyme UGT1A1 and to a lesser extent by cytochrome P450 enzymes (CYP1A2, CYP2C8). It also inhibits CYP1A2, CYP2C8, and CYP3A4, and is an inhibitor of the drug transporter P-glycoprotein (P-gp). These pharmacological properties mean that EXJADE can affect the blood levels and effectiveness of many other medications, and vice versa.

Additional Interactions to Be Aware Of

Several other medication classes warrant caution when used together with EXJADE. NSAIDs and corticosteroids (such as aspirin, ibuprofen, and prednisone) increase the risk of gastrointestinal irritation and bleeding when combined with EXJADE. Patients taking these medications should be monitored more closely for gastrointestinal symptoms.

Oral bisphosphonates (used to treat osteoporosis) and anticoagulants (blood thinners) may also interact with EXJADE, requiring additional monitoring. Cholestyramine, used to lower cholesterol, can reduce the absorption of EXJADE and should be separated by several hours if both medications are necessary.

Paclitaxel (a chemotherapy agent), ritonavir (an HIV medication), clozapine (used for schizophrenia), tizanidine (a muscle relaxant), and ergotamine (used for migraines) all have clinically significant interactions with EXJADE. Always provide your healthcare team with a complete list of all prescription medications, over-the-counter drugs, and supplements you are taking before starting or changing EXJADE therapy.

What Is the Correct Dosage of EXJADE?

The dose of EXJADE is calculated based on body weight and adjusted according to serum ferritin levels and individual response. Treatment should be supervised by a physician experienced in managing iron overload conditions.

EXJADE dosing is individualized and requires careful medical supervision. The dose is calculated based on the patient's body weight and is adjusted over time according to the patient's response to treatment, as measured by serum ferritin levels and liver iron concentration. It is essential to follow your doctor's instructions precisely and to attend all scheduled monitoring appointments.

Adults and Adolescents (Transfusion-Dependent)

Non-Transfusion-Dependent Thalassemia (NTDT)

Children

EXJADE can be used in children and adolescents aged 2 years and older who receive regular blood transfusions, and in those aged 10 years and older with non-transfusion-dependent thalassemia. The dose is calculated in the same way as for adults, based on body weight, and is adjusted as the child grows. EXJADE is not recommended for children under 2 years of age.

How to Take EXJADE

EXJADE film-coated tablets should be taken once daily, at approximately the same time each day, with water. The tablets can be taken on an empty stomach or with a light meal. Taking EXJADE at a consistent time helps maintain steady drug levels and makes it easier to remember your daily dose.

For patients who cannot swallow whole tablets, the film-coated tablets may be crushed and sprinkled on soft food such as yogurt or applesauce. The food should be consumed immediately and completely. Do not store the crushed tablet mixture for later use.

Missed Dose

If you forget to take a dose of EXJADE, take it as soon as you remember on the same day. Take your next dose at the scheduled time. Do not take a double dose the next day to make up for a missed dose. Consistent daily dosing is important for effective iron chelation, but missing a single dose occasionally will not significantly impact the overall treatment outcome.

Overdose

If you or someone else has taken too much EXJADE, contact your doctor or go to the nearest hospital emergency department immediately. Bring the medication packaging with you to show the healthcare providers. Symptoms of overdose may include abdominal pain, diarrhea, nausea, and vomiting, as well as potential kidney or liver toxicity that may be serious. Immediate medical attention is essential, as supportive care and monitoring of organ function will be required.

What Are the Side Effects of EXJADE?

Like all medicines, EXJADE can cause side effects, although not everyone experiences them. The most common side effects are gastrointestinal symptoms and changes in kidney or liver function tests. Most side effects are mild to moderate and typically resolve within the first few days to weeks of treatment.

Understanding the potential side effects of EXJADE is important for recognizing when to seek medical attention. Side effects are categorized by their frequency of occurrence in clinical trials and post-marketing surveillance. While most side effects are manageable, some can be serious and require immediate medical evaluation.

Managing Common Side Effects

Many of the gastrointestinal side effects of EXJADE, including nausea, diarrhea, and abdominal discomfort, are most pronounced during the initial weeks of therapy and tend to improve as the body adjusts to the medication. Taking EXJADE with a light meal rather than on an empty stomach may help reduce gastrointestinal symptoms in some patients. Staying well hydrated is important, particularly if diarrhea occurs.

Skin rash and itching typically resolve spontaneously or with simple measures. However, if a rash becomes severe, spreads widely, or is accompanied by blistering, fever, or other systemic symptoms, it is essential to seek immediate medical attention, as this could indicate a serious dermatologic reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Elderly patients (aged 65 years and older) may experience side effects more frequently, especially diarrhea, compared to younger patients. More frequent monitoring and proactive dose adjustments are recommended in this age group.

How Should You Store EXJADE?

Store EXJADE at room temperature, out of the sight and reach of children. Do not use the medication after the expiration date printed on the packaging.

Proper storage of EXJADE is important to maintain the effectiveness and safety of the medication. Keep the tablets in their original blister packaging until ready to use. Store the medication at room temperature and protect it from moisture and excessive heat. Do not use any packaging that appears damaged or has been previously opened.

Check the expiration date (marked as "EXP" on the blister pack and carton) before taking each dose. The expiration date refers to the last day of the indicated month. Do not use EXJADE after this date, as the stability and potency of the active ingredient cannot be guaranteed beyond the expiration date.

Do not dispose of unused medications via household waste or by flushing them down the drain. Ask your pharmacist about appropriate medication disposal programs in your area. Proper disposal of unused medications helps protect the environment and prevents accidental ingestion by others.

What Does EXJADE Contain?

EXJADE film-coated tablets contain deferasirox as the active ingredient, available in 90 mg, 180 mg, and 360 mg strengths. The tablets contain less than 1 mmol of sodium (23 mg) per tablet, making them essentially sodium-free.

The active substance in EXJADE is deferasirox. Each film-coated tablet contains either 90 mg, 180 mg, or 360 mg of deferasirox, depending on the strength prescribed.

The inactive ingredients (excipients) include microcrystalline cellulose, crospovidone, povidone, magnesium stearate, colloidal anhydrous silicon dioxide, and poloxamer. The film coating of the tablet contains hypromellose, titanium dioxide (E171), macrogol 4000, talc, and indigo carmine aluminum lake (E132), which gives the tablet its characteristic blue color.

Tablet Appearance

EXJADE film-coated tablets are oval and biconvex in shape. They can be identified by their color and imprint:

• 90 mg: Light blue tablet, imprinted with "90" on one side and "NVR" on the other
• 180 mg: Medium blue tablet, imprinted with "180" on one side and "NVR" on the other
• 360 mg: Dark blue tablet, imprinted with "360" on one side and "NVR" on the other

EXJADE is supplied in blister packs containing 30 or 90 film-coated tablets. Multi-packs containing 300 tablets (10 packs of 30) are also available. Not all pack sizes or strengths may be marketed in every country.

Frequently Asked Questions About EXJADE