The Food and Drug Administration (FDA) has approved ibrutinib (Imbruvica) to treat chronic lymphocytic leukemia (CLL) in patients who've already undergone other drug therapy at least once. Ibrutinib, a Bruton's tyrosine kinase inhibitor, was approved late last year to treat mantle cell lymphoma, a rare and aggressive blood cancer. Bruton's tyrosine kinase is an enzyme responsible for the signaling molecule of the B-lymphocyte (B-cell) antigen-receptor and cytokine-receptor pathways. Ibrutinib inhibits malignant B-cell proliferation and survival, as well as cell migration and substrate adhesion in vitro. Other tyrosine kinase inhibitors, such as imatinib (Gleevec) and gefitinib (Iressa) are used in the treatment of chronic myelogenous leukemia.
CLL is a type of cancer in which excessive numbers of abnormal and immature lymphocytes (those incapable of fighting infection) are produced by the bone marrow. Occurring primarily in adults, CLL is the second most common type of adult leukemia. The FDA approved ibrutinib through an accelerated approval process on the basis of a clinical trial of 48 treated patients, 58% of whom experienced a decrease in the number of cancerous lymphocytes. Whether there's an increase in survival or a decrease in disease-related symptoms in patients using ibrutinib hasn't yet been established.
Ibrutinib carries warnings that it may cause hemorrhage, infections, myelosuppression, renal toxicity (which can be serious or fatal), second primary malignancies (including skin cancers), and embryonic or fetal toxicity.
The most common adverse effects (occurring in 20% or more of patients) are thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever, constipation, peripheral edema, arthralgia, nausea, stomatitis, sinusitis, and dizziness.
Nurses prescribing or working with patients prescribed ibrutinib should instruct them to take the capsules once daily with a glass of water. Patients should be monitored for bleeding and signs of fever or infection. Patients should know the signs and symptoms of bleeding and early infection and report these immediately to the prescriber. Laboratory testing, including complete blood counts and renal function tests, should be performed regularly. The nurse should make sure patients keep hydrated to help minimize renal toxicity. The nurse should tell any woman of childbearing age that ibrutinib may cause fetal harm and that pregnancy should be avoided during drug therapy. Nurses should complete a thorough drug history because coadministration of drugs that are strong or moderate inhibitors of the cytochrome P-450 (CYP) enzyme system's CYP3A4 isoenzyme will increase the circulating level of ibrutinib and should be avoided. Strong CYP3A4 inducers should also be avoided because they will decrease the therapeutic effectiveness of ibrutinib. Patients should avoid grapefruit, grapefruit juice, and Seville oranges (often used in marmalades) while taking ibrutinib because they inhibit CYP3A4 and will significantly increase the amount of ibrutinib circulating in the blood.
Complete FDA prescribing information is available online at http://1.usa.gov/1f69Ef1.