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Vinorelbine |
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indicationFor the treatment of non-small-cell lung carcinoma.pharmacologyVinorelbine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vinorelbine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.mechanism of actionThe antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Like other vinca alkaloids, vinorelbine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.half life27.7-43.6 hoursroute of eliminationVinorelbine undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans.drug interactionsAmprenavir: Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Amprenavir is initiated, discontinued or dose changed.Aprepitant: Aprepitant may change levels of the chemotherapy agent, vinorelbine. Atazanavir: Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Atazanavir is initiated, discontinued or dose changed. Atomoxetine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine Clarithromycin: Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Clarithromycin is initiated, discontinued or dose changed. Conivaptan: Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Conivaptan is initiated, discontinued or dose changed. Darunavir: Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Darunavir is initiated, discontinued or dose changed. Delavirdine: Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Delavirdine is initiated, discontinued or dose changed. Dirithromycin: Dirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Dirithromycin is initiated, discontinued or dose changed. Erythromycin: Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Erythromycin is initiated, discontinued or dose changed. Fosamprenavir: Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Fosamprenavir is initiated, discontinued or dose changed. Imatinib: Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Imatinib is initiated, discontinued or dose changed. Indinavir: Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Indinavir is initiated, discontinued or dose changed. Isoniazid: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Isoniazid is initiated, discontinued or dose changed. Itraconazole: Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Itraconazole is initiated, discontinued or dose changed. Ketoconazole: Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Ketoconazole is initiated, discontinued or dose changed. Leflunomide: Vinorelbine may increase the adverse/toxic effects of Leflunomide. This may increase the risk of hematologic toxicities such as pancytopenia, agranulocytosis and thrombocytopenia. In patients receiving Vinorelbine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy. Lopinavir: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Lopinavir is initiated, discontinued or dose changed. Miconazole: Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Miconazole is initiated, discontinued or dose changed. Natalizumab: Concomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided. Nefazodone: Nafazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nefazodone is initiated, discontinued or dose changed. Nelfinavir: Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nelfinavir is initiated, discontinued or dose changed. Nicardipine: Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nicardipine is initiated, discontinued or dose changed. Posaconazole: Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Posaconazole is initiated, discontinued or dose changed. Quinidine: Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Quinidine is initiated, discontinued or dose changed. Quinupristin: This combination presents an increased risk of toxicity Ritonavir: Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Ritonavir is initiated, discontinued or dose changed. Saquinavir: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Saquinavir is initiated, discontinued or dose changed. Telithromycin: Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Telithromycin is initiated, discontinued or dose changed. Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Voriconazole is initiated, discontinued or dose changed. |