QuickView for Vincristine (compound)

Summary
General Info

PubChem

PubChem Compound 11957714

Name:	Vincristine
PubChem Compound ID:	11957714
Description:	Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)
Molecular formula:	C₄₆H₅₈N₄O₁₄S
Molecular weight:	923.037 g/mol
Synonyms:	EU-0101208

DrugBank

Identification

Name:	Vincristine
Name (isomeric):	DB00541
Drug Type:	small molecule
Description:	Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)
Synonyms:	Vincristina [DCIT]; Z-D-Val-Lys(Z)-OH; VCR; 22-Oxovincaleukoblastine; Vincristine Sulfate; Vincristinum [INN-Latin]; VIN; LCR; Leurocristine; Vincrystine. show more » Vincristina [DCIT]; Z-D-Val-Lys(Z)-OH; VCR; 22-Oxovincaleukoblastine; Vincristine Sulfate; Vincristinum [INN-Latin]; VIN; LCR; Leurocristine; Vincrystine; Vincrstine; Indole alkaloid show less «
Brand:	Onco TCS, Marqibo, Oncovin, Vincristine Sulfate PFS, Vincasar PFS, Vincrex, Vincasar, Vinkristin
Category:	Antineoplastic Agents, Tubulin Modulators, Antineoplastic Agents, Phytogenic
CAS number:	57-22-7

Pharmacology

Indication:	For treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, acute panmyelosis
Pharmacology:	Vincristine 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 sinc... show more » Vincristine 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. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific. show less «
Mechanism of Action:	The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca²⁺-transport ATPase activity, 3) cellular respir... show more » The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine 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. show less «
Protein binding:	~75%
Biotransformation:	Hepatic
Half Life:	19-155 hours
Toxicity:	IVN-RAT LD₅₀ 1300 mg/kg; IPR-MUS LD₅₀ 5.2 mg/kg
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Miconazole	Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Miconazole is initiated, discontinued or dose changed.
Saquinavir	Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Saquinavir is initiated, discontinued or dose changed.
Ritonavir	Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Aprepitant	Aprepitant may change levels of the chemotherapy agent, vincristine.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Voriconazole is initiated, discontinued or dose changed.

Miconazole	Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Miconazole is initiated, discontinued or dose changed.
Saquinavir	Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Saquinavir is initiated, discontinued or dose changed.
Ritonavir	Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Aprepitant	Aprepitant may change levels of the chemotherapy agent, vincristine.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Voriconazole is initiated, discontinued or dose changed.
Fosamprenavir	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Fosamprenavir is initiated, discontinued or dose changed.
Posaconazole	Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Posaconazole is initiated, discontinued or dose changed.
Conivaptan	Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Conivaptan is initiated, discontinued or dose changed.
Imatinib	Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Imatinib is initiated, discontinued or dose changed.
Nicardipine	Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nicardipine is initiated, discontinued or dose changed.
Quinidine	Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Quinidine is initiated, discontinued or dose changed.
Isoniazid	Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Isoniazid is initiated, discontinued or dose changed.
Erythromycin	Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Erythromycin is initiated, discontinued or dose changed.
Nefazodone	Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nefazodone 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.
Amprenavir	Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed.
Leflunomide	Vincristine 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 Vincristine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy.
Delavirdine	Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Delavirdine is initiated, discontinued or dose changed.
Quinupristin	This combination presents an increased risk of toxicity
Indinavir	Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Indinavir is initiated, discontinued or dose changed.
Itraconazole	Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Itraconazole is initiated, discontinued or dose changed.
Atazanavir	Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Atazanavir is initiated, discontinued or dose changed.
Lopinavir	Lopinavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Lopinavir is initiated, discontinued or dose changed.
Spiramycin	Spiramycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Spiramycin is initiated, discontinued or dose changed.
Darunavir	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Darunavir is initiated, discontinued or dose changed.
Ketoconazole	Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ketoconazole is initiated, discontinued or dose changed.
Natalizumab	Concomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Clarithromycin	Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Clarithromycin is initiated, discontinued or dose changed.
Nelfinavir	Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nelfinavir is initiated, discontinued or dose changed.
Telithromycin	Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Telithromycin is initiated, discontinued or dose changed.
Dirithromycin	Dirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Dirithromycin is initiated, discontinued or dose changed.
Digoxin	The antineoplasic agent decreases the effect of digoxin
Fluconazole	Increases the effect and toxicity of anticancer agent
Mitomycin	Potentially severe lung toxicity

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Targets

Tubulin beta chain

Tubulin alpha-1 chain

Enzymes

Cytochrome P450 3A5

Cytochrome P450 3A7

Cytochrome P450 3A4

Transporters

Multidrug resistance protein 1

Canalicular multispecific organic anion transporter 2

Solute carrier family 22 member 3

Multidrug resistance-associated protein 1

Multidrug resistance-associated protein 7

Canalicular multispecific organic anion transporter 1

Bile salt export pump

ATP-binding cassette sub-family G member 2