What is Deferasirox used for?

**Introduction to Deferasirox**

Deferasirox, known by its trade names such as Exjade and Jadenu, is an oral iron chelator developed to manage chronic iron overload in patients. This condition is often a consequence of frequent blood transfusions, which are commonly required by individuals suffering from beta-thalassemia, sickle cell anemia, and other chronic anemias. Iron overload can lead to severe organ damage if not managed properly, making Deferasirox a crucial medication for these patients.

Deferasirox works by binding to excess iron in the blood, allowing it to be excreted from the body, thus preventing the accumulation of iron in vital organs such as the heart and liver. The drug was developed by Novartis and gained approval from the U.S. Food and Drug Administration (FDA) in 2005 for the treatment of transfusional hemosiderosis. Since then, ongoing research has continued to explore the effectiveness and safety profile of Deferasirox, aiming to refine its use and better understand its long-term effects on patients.

**Deferasirox Mechanism of Action**

The mechanism of action of Deferasirox revolves around its ability to chelate iron. Deferasirox binds to ferric iron (Fe3+) with high affinity, forming a complex that is water-soluble and can be excreted via the feces. The drug’s structure allows it to bind to iron in a 2:1 ratio, meaning two molecules of Deferasirox can bind to one molecule of iron, effectively neutralizing its potential to cause harm.

Deferasirox specifically targets non-transferrin-bound iron (NTBI) and labile plasma iron (LPI), which are particularly toxic forms of iron that circulate freely in the bloodstream. By chelating these iron species, Deferasirox reduces their ability to catalyze the formation of harmful free radicals, which can damage cellular components and promote fibrosis in organs. This mechanism helps mitigate the risk of organ dysfunction and failure associated with chronic iron overload.

**How to Use Deferasirox**

Deferasirox is administered orally, which is a significant convenience compared to other iron chelators that require intravenous or subcutaneous delivery. The drug comes in two formulations: dispersible tablets (Exjade) and film-coated tablets (Jadenu).

For Exjade, the tablets should be dissolved in a liquid (water, apple juice, or orange juice) and consumed once a day on an empty stomach, at least 30 minutes before food. The starting dose is typically based on the patient’s body weight and the severity of iron overload, adjusted over time based on regular monitoring of serum ferritin levels and other indicators of iron burden.

Jadenu, on the other hand, offers a film-coated tablet that can be taken with or without a light meal, making it a more flexible option for patients. The standard dose and adjustments remain similar to Exjade, tailored according to the patient’s response and tolerance.

The onset of Deferasirox's action is gradual, with noticeable reductions in iron levels typically occurring over months of consistent use. Therefore, patients are advised to maintain regular follow-ups with their healthcare providers to monitor their iron levels and adjust their dosages accordingly.

**What are Deferasirox Side Effects**

Like all medications, Deferasirox can have side effects, which vary in severity among different individuals. Common side effects include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain. Skin rashes and mild increases in serum creatinine, indicating changes in kidney function, are also frequently reported.

More serious but less common side effects include significant increases in liver enzymes, indicating potential liver injury, and severe hypersensitivity reactions such as anaphylaxis and severe skin reactions. There have also been reports of cytopenias, including leukopenia and thrombocytopenia, which necessitate careful monitoring during treatment.

Contraindications for Deferasirox include known hypersensitivity to the drug or any of its components, severe renal impairment (creatinine clearance below 40 mL/min), and high-risk myelodysplastic syndromes or advanced malignancies. Patients with these conditions should avoid using Deferasirox due to the heightened risk of adverse effects.

Patients on Deferasirox should undergo regular monitoring of their renal and hepatic functions, serum ferritin levels, and complete blood counts to detect any potential complications early and adjust treatment as necessary.

**What Other Drugs Will Affect Deferasirox**

Deferasirox has the potential to interact with various other medications, which can either diminish its effectiveness or exacerbate its side effects. One of the notable interactions is with aluminum-containing antacid preparations, which can interfere with the absorption of Deferasirox and should be avoided.

Co-administration with other potent UGT inducers, such as phenytoin, phenobarbital, and rifampicin, can reduce the plasma concentrations of Deferasirox, potentially lowering its efficacy. Conversely, inhibitors of UGT enzymes can increase Deferasirox levels in the blood, potentially increasing the risk of side effects.

Additionally, the concomitant use of nephrotoxic drugs, such as aminoglycoside antibiotics, amphotericin B, and NSAIDs, should be approached with caution due to the increased risk of renal impairment. Monitoring renal function closely in such cases is essential to prevent severe kidney damage.

It is also important to note that Deferasirox can affect the pharmacokinetics of other drugs, particularly those metabolized by CYP3A4 enzymes, such as certain statins and anticoagulants. Patients on these medications should be monitored for changes in drug levels and therapeutic effects to ensure optimal treatment outcomes.

In conclusion, Deferasirox is a vital medication for managing iron overload in patients requiring frequent blood transfusions. Understanding its mechanism of action, proper administration, potential side effects, and drug interactions is essential for optimizing treatment and ensuring patient safety. Regular monitoring and consultation with healthcare providers will help manage iron levels effectively and mitigate risks associated with Deferasirox therapy.