Imatinib mesylate (Imatinib) is an oral tyrosine kinase inhibitor that initially received FDA approval for chronic myelogenous leukemia in 2001. Subsequently, it has received approval for the treatment of several other oncologic conditions. Currently, FDA approved indications include:
Imatinib mesylate is a 2-phenylamino-pyrimidine derivative protein tyrosine kinase inhibitor initially targeted to the platelet-derived growth factor receptor. Subsequently, it has also been found to inhibit other protein tyrosine kinases such as c-kit (gastrointestinal stromal tumors) and BCR-ABL fusion protein (Philadelphia chromosome chronic myelogenous leukemia). These protein tyrosine kinases as a whole phosphorylate specific amino acids on substrate proteins, which induce signal transduction resulting in changes to cell biology, including cell growth, differentiation, and death, constitutive activation of which, through mutation or other means, can lead to malignancy. Blocking of this constitutive action has been shown to induce downstream apoptosis without further differentiation. Imatinib, as a therapeutic, blocks constitutive action of protein tyrosine kinase by working as a competitive inhibitor of the ATP binding cleft of ABL inducing apoptosis of leukemic cells.
Imatinib is FDA-approved to be administered orally and is typically supplied in 100mg and 400mg tablet formulations. Imatinib was initially available under a branded name; however, after the expiration of several patents, there are no generic versions available. The recommended dosing for imatinib varies by indication:
800 mg doses should be administered as a 400 mg dose twice daily; all other doses should be given once daily. Patients should take imatinib with meals and a large glass of water to minimize gastrointestinal upset, and food does not impact bioavailability.
Clinically significant warnings and precautions include:
There are no contraindications for imatinib.
Imatinib gets metabolized through the enzyme cytochrome p450 3A4 (CYP3A4).
Imatinib is a powerful targeted therapeutic drug for several types of cancer. Despite showing a favorable risk/benefit tradeoff in several clinical trials, and being FDA approved for nearly two decades, it does require close monitoring for safety. In addition to the prescribing physician, pharmacists and nurses are responsible for educating the patient on the potential side effects of the drug. While most side effects occur in the first two years of use, many patients will be on chronic therapy for many years, so it is essential to stay vigilant in monitoring for side effects. Particularly severe side effects to carefully monitor for include Stevens-Johnson syndrome, gastrointestinal perforations/hemorrhage, fluid retention, organ (cardiac, renal and liver) failure, and hematologic toxicities. Additionally, imatinib does have several interactions with other medications that are also metabolized by CYP3A4. The pharmacist needs to monitor all medications that the patient is currently taking to make sure that there are no interactions. If concurrent medications are necessary, this requires proper dose adjustments due to potential drug-drug interactions. The physicians, nurses, and pharmacists should regularly check liver function, renal function, and complete blood counts to monitor for organ damage or immunosuppression and adjust imatinib dosing as necessary, while continually informing the ordering clinician. Nursing will notably have the optimal chance to see any issues that arise since they will have the first contact with the patient, so they must be familiar with the adverse event and interaction profile. This is where an oncology specialty nurse is invaluable. This collaborative paradigm exemplifies the type of interprofessional teamwork the healthcare team requires to administer imatinib effectively to achieve optimal patient outcomes while minimizing patient risks.
It was one of the first targeted therapeutics to reach the market and also now is generic. Imatinib presents interesting time-series data on the costs of precision medications. At approval in 2001, a one-month supply of the 400mg daily dose cost $2200 in the US. In 2010, this cost had ballooned to $5143 per month, and by 2018 it was $10620 per month. A generic form of imatinib was launched in the US in 2015 at a 30% discount to the branded price (which was substantially higher than the 82% discount at which the Canadian generic was launched). Therefore because of dysfunctional market maximizing forces, ironically, the price of imatinib generics was higher than the original branded version, and pricing relief remained elusive for years. However, during 2018, generic imatinib pricing finally dropped below its original launch price, yet it still cost several thousand dollars per annum despite being generic. With expensive therapies such as imatinib, the physicians, pharmacists, and other healthcare professionals (such as social workers or charity assistance programs) need to coordinate care and advocate for coverage to maximize access to life-saving medications.
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