observed with use of vedolizumab alone. The safety and efficacy of vedolizumab in combination with antineoplastic agents have not been established. Also, vedolizumab should not be used in combination with immunosuppressants such as 6-mercaptopurine because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections.
Vorapaxar: Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Yellow Fever Vaccine, Live: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
PREGNANCY AND LACTATION
Pregnancy
Nelarabine is classified as FDA pregnancy risk category D and has been shown to produce toxic effects in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, nelarabine should be avoided during pregnancy, and women of childbearing potential should be instructed to avoid becoming pregnant during nelarabine therapy. If a women becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possibility of loss of pregnancy.
Adverse effects to the nursing infant are unknown. It also is unknown whether nelarabine or ARA-G are excreted into breast milk. According to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.
MECHANISM OF ACTION
Mechanism of Action: Nelarabine is as a prodrug for ARA-G (deoxyguanosine analogue 9-ß-Darabinofuranosylguanine), which acts as a cytotoxic agent and inhibits DNA synthesis. Upon administration, nelarabine, is rapidly demethylated by adenosine deaminase (ADA) to ARA-G. ARA-G is transported into cells by nucleoside transporters. Once inside the cell, ARA-G is mono-phosphorylated, and converted to the active 5'-triphosphate, ARA-GTP. Accumulation of ARA-GTP in leukemic blasts allows for incorporation into DNA. Incorporation into DNA halts DNA synthesis and causes cell death. Other mechanisms of action include inhibition of RNA synthesis and ribonucleotide reductase inhibition. ARA-G is thought to be more toxic to T-lymphoblasts than other blast cells due to enhanced accumulation of ARA-GTP in T-cells and increased elimination of ARA-GTP from B-cells. The clinical efficacy of nelarabine is associated with the intracellular concentrations of ARA-G.
PHARMACOKINETICS
Nelarabine is administered by intravenous infusion. Following intravenous administration nelarabine and ARA-G are extensively distributed throughout the body. For nelarabine, Vss values were 197 +/- 217 L/m2 and 213 +/- 358 L/m2 in adult and pediatric patients, respectively. For ARA-G, Vss/F values were 50 +/- 24 L/m2 and 33 +/- 9.3 L/m2 in adult and pediatric patients, re |
