What is Radotinib used for?

Radotinib is a second-generation tyrosine kinase inhibitor (TKI) primarily used in the treatment of chronic myeloid leukemia (CML), which is characterized by the presence of the Philadelphia chromosome. Known by its trade name Supect, Radotinib was developed by Ilyang Pharmaceutical Co., Ltd., a South Korean company. The drug selectively targets the BCR-ABL oncoprotein, a fusion protein that is the result of a chromosomal translocation and is responsible for the unchecked proliferation of leukemic cells. Since its development, Radotinib has been evaluated in various clinical trials to assess its efficacy and safety profile in patients who are either resistant or intolerant to first-generation TKIs like Imatinib.

Radotinib Mechanism of Action
Radotinib exerts its effects by selectively inhibiting the BCR-ABL tyrosine kinase. The BCR-ABL fusion protein possesses continuous tyrosine kinase activity, which leads to the activation of various pathways that promote cell proliferation and inhibit apoptosis. By binding to the ATP-binding site of the BCR-ABL protein, Radotinib effectively blocks its activity, thus halting the proliferation of leukemic cells and promoting their apoptosis. This action not only controls the progression of CML but also reduces the leukemic cell burden in the patient’s body. Additionally, Radotinib has shown efficacy against certain mutations in the BCR-ABL gene that render first-generation TKIs ineffective, providing a viable treatment option for patients with resistant forms of CML.

How to Use Radotinib
Radotinib is typically administered orally in the form of tablets. The standard dosage is 300 mg taken twice daily, approximately 12 hours apart. It is recommended that the drug be taken on an empty stomach, either at least two hours before or one hour after a meal, to enhance its absorption and efficacy. The onset of action for Radotinib varies among patients, but clinical trials have shown that a significant number of patients achieve a major cytogenetic response (MCyR) within the first three to six months of treatment.

Patients undergoing Radotinib treatment are usually monitored through regular blood tests to assess the drug’s efficacy and to check for potential side effects. In the case of missed doses, it is advised not to double up but to take the next dose at the scheduled time. Adjustments in dosage may be necessary based on the patient's response and tolerance to the medication, as well as any side effects they may experience.

What is Radotinib Side Effects
Like all medications, Radotinib is associated with a range of potential side effects. The most common adverse effects include hematological issues such as neutropenia, thrombocytopenia, and anemia. These conditions can lead to an increased risk of infections, bleeding, and fatigue, respectively. Non-hematological side effects may include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain. Some patients may also experience headaches, rash, and pruritus.

Severe side effects, though less common, can include hepatic dysfunction, manifesting as elevated liver enzymes, and cardiovascular events such as prolonged QT interval, which can lead to arrhythmias. It is crucial for patients to undergo regular monitoring to detect and manage these side effects promptly.

Contraindications for Radotinib use include hypersensitivity to the drug or any of its components. Additionally, caution is advised for patients with pre-existing liver or heart conditions, as they may be at a higher risk for severe complications. Pregnant or breastfeeding women are also advised against using Radotinib due to potential risks to the fetus or infant.

What Other Drugs Will Affect Radotinib
Certain medications and substances can interact with Radotinib, potentially altering its efficacy or increasing the risk of adverse effects. For instance, drugs that are strong inhibitors or inducers of the cytochrome P450 3A4 (CYP3A4) enzyme can significantly impact Radotinib’s metabolism. Inhibitors such as ketoconazole, itraconazole, and ritonavir can increase Radotinib levels in the blood, heightening the risk of toxic effects. Conversely, inducers like rifampin, phenytoin, and carbamazepine can reduce its plasma concentration, thereby diminishing its therapeutic effect.

Other drugs that may interact with Radotinib include those that prolong the QT interval, such as certain antiarrhythmics (e.g., amiodarone), antipsychotics (e.g., haloperidol), and antidepressants (e.g., citalopram). Co-administration of these drugs with Radotinib can exacerbate the risk of life-threatening arrhythmias.

Patients are also advised to avoid grapefruit and grapefruit juice while on Radotinib, as these can inhibit CYP3A4 and increase the drug’s plasma concentration, leading to potential toxicity. It is essential for patients to inform their healthcare provider about all the medications and supplements they are taking to manage potential interactions effectively.

In conclusion, Radotinib represents a significant advancement in the treatment of chronic myeloid leukemia, particularly for patients with resistance or intolerance to first-generation TKIs. Its selective inhibition of the BCR-ABL tyrosine kinase offers a targeted approach to managing CML. However, like all treatments, it comes with potential side effects and drug interactions that require careful monitoring and management by healthcare professionals. Through ongoing research and clinical monitoring, the therapeutic potential of Radotinib continues to be refined, offering hope to many patients battling this chronic leukemia.