"The U.S. Food and Drug Administration today approved Imbruvica (ibrutinib) to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of blood cancer.
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For Intravenous Use Only
Fatal if Given by Other Routes. Death has occurred with intrathecal use.
Extravasation Tissue Injury
Only administer through a secure and free-flowing venous access line. If extravasation is suspected, discontinue infusion immediately and consider local treatment measures.
Sensory and motor neuropathies are common and are cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, hyporeflexia, areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, burning sensation, arthralgia, myalgia, muscle spasm, or weakness, both before and during treatment. Orthostatic hypotension may occur. The risk of neurologic toxicity is greater if Marqibo is administered to patients with preexisting neuromuscular disorders or when other drugs with risk of neurologic toxicity are being given. In the studies of relapsed and/or refractory adult ALL patients, Grade ≥ 3 neuropathy events occurred in 32.5% of patients. Worsening neuropathy requires dose delay, reduction, or discontinuation of Marqibo [see DOSAGE AND ADMINISTRATION].
Monitor complete blood counts prior to each dose of Marqibo. If Grade 3 or 4 neutropenia, thrombocytopenia, or anemia develops, consider Marqibo dose modification or reduction as well as supportive care measures.
Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) may occur in patients with ALL receiving Marqibo. Anticipate, monitor for, and manage.
Constipation and Bowel Obstruction
Ileus, bowel obstruction, and colonic pseudo-obstruction have occurred. Marqibo can cause constipation [see ADVERSE REACTIONS]. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and/or paralytic ileus, considering adequate dietary fiber intake, hydration, and routine use of stool softeners, such as docusate. Additional treatments, such as senna, bisacodyl, milk of magnesia, magnesium citrate, and lactulose may be considered.
Marqibo can cause severe fatigue. Marqibo dose delay, reduction, or discontinuation may be necessary.
Fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred. Elevated levels of aspartate aminotransferase of Grade ≥ 3 occurred in 6-11% of patients in clinical trials. Monitor hepatic function tests. Reduce or interrupt Marqibo for hepatic toxicity.
Marqibo can cause fetal harm when administered to a pregnant woman. Vincristine sulfate liposome injection was teratogenic or caused embryo-fetal death in animals. Women of childbearing potential should avoid becoming pregnant while being treated with Marqibo. There are no adequate and well-controlled studies of Marqibo in pregnant women and there were no reports of pregnancy in any of the clinical studies in the Marqibo clinical development program. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use In Specific Populations].
Patient Counseling Information
Physicians are advised to discuss the following with patients prior to treatment with Marqibo:
Extravasation Tissue Injury: Advise patients to report immediately any burning or local irritation during or after the infusion [see WARNINGS AND PRECAUTIONS].
Ability to Drive or Operate Machinery or Impairment of Mental Ability: Marqibo may cause fatigue and symptoms of peripheral neuropathy. Advise patients not to drive or operate machinery if they experience any of these symptoms [see WARNINGS AND PRECAUTIONS].
Gastrointestinal/Constipation: Patients receiving Marqibo may experience constipation. Advise patients how to avoid constipation by a diet high in bulk fiber, fruits and vegetables, and adequate fluid intake as well as use of a stool softener, such as docusate. Instruct patients to seek medical advice if they experience symptoms of constipation such bowel movement infrequency, abdominal pain, bloating, diarrhea, nausea, or vomiting [see WARNINGS AND PRECAUTIONS].
Pregnancy/Nursing: Advise patients to use effective contraceptive measures to prevent pregnancy during treatment with Marqibo [see WARNINGS AND PRECAUTIONS]. Instruct patients to report pregnancy to their physicians immediately. Advise patients that they should not receive Marqibo while pregnant or breastfeeding. If a patient wishes to re-start breastfeeding after treatment, she should be advised to discuss the appropriate timing with her physician [see Use In Specific Populations].
Concomitant Medications: Advise patients to speak with their physicians about any other medication they are currently taking [see DRUG INTERACTIONS].
Peripheral Neuropathy: Advise patients to contact their physicians if they experience new or worsening symptoms of peripheral neuropathy such as tingling, numbness, pain, a burning feeling in the feet or hands, or weakness in the feet or hands [see WARNINGS AND PRECAUTIONS].
Other: Instruct patients to notify their physicians if they experience fever, productive cough, or decreased appetite [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity studies have been conducted with Marqibo or non-liposomal vincristine sulfate. Based on the mechanism of action and genotoxicity findings in nonclinical studies conducted with non-liposomal vincristine sulfate, Marqibo may be carcinogenic.
No genotoxicity studies have been conducted with Marqibo. Non-liposomal vincristine was genotoxic in some in vitro and in vivo studies.
The single- and repeat-dose animal toxicology study results indicate that Marqibo can impair male fertility, consistent with the literature on non-liposomal vincristine sulfate. Administration of vincristine liposome injection causes testicular degeneration and atrophy, and epididymal aspermia in rats.
Gonadal dysfunction has been reported in both male and female post-pubertal patients who received multi-agent chemotherapy including non-liposomal vincristine sulfate. The degree to which testicular or ovarian functions are affected is age-, dose-, and agent-dependent. Recovery may occur in some but not all patients.
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND PRECAUTIONS]
Based on its mechanism of action and findings from animal studies, Marqibo can cause fetal harm when administered to pregnant women.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. In an embryofetal developmental study, pregnant rats were administered vincristine sulfate liposome injection intravenously during the period of organogenesis at vincristine sulfate doses of 0.022 to 0.09 mg/kg/day. Drug-related adverse effects included fetal malformations (skeletal and visceral), decreases in fetal weights, increased numbers of early resorptions and post-implantation losses, and decreased maternal body weights Malformations were observed at doses ≥ 0.044 mg/kg/day in animals at systemic exposures approximately 20-40% of those reported in patients at the recommended dose.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.
The safety and effectiveness of Marqibo in pediatric patients have not been established.
Safety and effectiveness in elderly individuals have not been established. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
The influence of renal impairment on the safety, efficacy, and pharmacokinetics of Marqibo has not been evaluated.
Non-liposomal vincristine sulfate is excreted primarily by the liver. The influence of severe hepatic impairment on the safety and efficacy of Marqibo has not been evaluated.
The pharmacokinetics of Marqibo was evaluated in patients with moderate hepatic dysfunction (Child-Pugh B) secondary to melanoma liver metastases. The dose-adjusted maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) of Marqibo in patients with moderate hepatic impairment was comparable to the Cmax and AUC of patients with ALL who had otherwise normal hepatic function.
Last reviewed on RxList: 8/17/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Marqibo Information
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