{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 408925000 | IUPAC_name = (5''R'',5a''R'',8a''R'',9''S'')-5,8,8a,9-Tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-9-({4,6-''O''-[(''R'')-2-thienylmethylene]-β-<small>D</small>-glucopyranosyl}oxy)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5a''H'')-one | image = Teniposide2DACS.svg | image_class = skin-invert-image <!--Clinical data--> | tradename = Vumon | Drugs.com = {{drugs.com|monograph|teniposide}} | MedlinePlus = a692045 | pregnancy_AU = D | pregnancy_US = D | legal_US = Rx-only | routes_of_administration = Intravenous <!--Pharmacokinetic data--> | bioavailability = N/A | protein_bound = >99% | metabolism = Hepatic (CYP2C19-mediated) | elimination_half-life = 5 hours | excretion = Renal and fecal <!--Identifiers--> | IUPHAR_ligand = 6843 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 29767-20-2 | ATC_prefix = L01 | ATC_suffix = CB02 | PubChem = 34698 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB00444 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 31930 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = 957E6438QA | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 75988 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D02698 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1200536 | synonyms = VM-26 <!--Chemical data--> | C=32 | H=32 | O=13 | S=1 | smiles = COc1cc(cc(c1O)OC)[C@@H]2c3cc4c(cc3[C@H]([C@@H]5[C@@H]2C(=O)OC5)O[C@H]6[C@@H]([C@H]([C@H]7[C@H](O6)COC(O7)c8cccs8)O)O)OCO4 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI=1S/C32H32O13S/c1-37-19-6-13(7-20(38-2)25(19)33)23-14-8-17-18(42-12-41-17)9-15(14)28(16-10-39-30(36)24(16)23)44-32-27(35)26(34)29-21(43-32)11-40-31(45-29)22-4-3-5-46-22/h3-9,16,21,23-24,26-29,31-35H,10-12H2,1-2H3/t16-,21+,23+,24-,26+,27+,28+,29+,31?,32-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = NRUKOCRGYNPUPR-PSZSYXFXSA-N }} '''Teniposide''' (trade name '''Vumon''') is a chemotherapeutic medication<ref>{{cite journal | vauthors = Cragg GM, Newman DJ | title = Plants as a source of anti-cancer agents | journal = Journal of Ethnopharmacology | volume = 100 | issue = 1–2 | pages = 72–79 | date = August 2005 | pmid = 16009521 | doi = 10.1016/j.jep.2005.05.011 | url = https://zenodo.org/record/1259111 }}</ref> used in the treatment of childhood acute lymphocytic leukemia (ALL), Hodgkin's lymphoma, certain brain tumours, and other types of cancer.<ref name="Austria-Codex">{{cite book|title=Austria-Codex| veditors = Jasek W|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=62nd|pages=8855–6|isbn=978-3-85200-181-4|language=German}}</ref> It is in a class of drugs known as podophyllotoxin derivatives and slows the growth of cancer cells in the body.<ref name="Drugs.com">Drugs.com: Teniposide {{drugs.com|monograph|teniposide}}.</ref>

==Medical uses== Teniposide is used for the treatment of a number of cancer types in children. In the US, it is approved for the second-line therapy of acute lymphocytic leukemia (ALL) in combination with other antineoplastic drugs.<ref name="Drugs.com" /> In Europe, it is also approved for the treatment of Hodgkin's lymphoma, generalized malignant lymphoma, reticulocyte sarcoma, acute leukaemia, primary brain tumours (glioblastoma, ependymoma, astrocytoma), bladder cancer, neuroblastoma and other solid tumours in children.<ref name="Austria-Codex" />

===Administration=== The medication is injected though a vein and burns if it leaks under the skin. It can be used in combination with other anticancer drugs.<ref name="Austria-Codex" />

==Contraindications== The drug is contraindicated during pregnancy and lactation, in patients with severe liver or kidney impairment or severely impaired haematopoiesis.<ref name="Austria-Codex" />

==Side effects== Teniposide, when used with other chemotherapeutic agents for the treatment of ALL, results in severe bone marrow suppression. Other common side effects include gastrointestinal toxicity, hypersensitivity reactions, and reversible alopecia.<ref name="Austria-Codex" />

== Interactions ==

No systematic interaction studies are available. The enzyme inducers phenobarbital and phenytoin have been found to lower its blood plasma concentrations.<ref name="Mutschler" /> Theoretically possible interactions include increased plasma concentrations when combined with sodium salicylate, sulfamethizole or tolbutamide, which displace teniposide from plasma protein binding, at least ''in vitro''.<ref name="Austria-Codex" /><ref name="Drugs.com" />

==Pharmacology==

===Mechanism of action=== Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA-protein cross-links.<ref name="Austria-Codex" /> The substance has been found to act as an inhibitor of topoisomerase II (an enzyme that aids in DNA unwinding),<ref name="Mutschler">{{Cite book | vauthors = Mutschler E, Schäfer-Korting M |title=Arzneimittelwirkungen |language=German |location=Stuttgart |publisher=Wissenschaftliche Verlagsgesellschaft |year=2001 |edition=8th |pages=894–5 |isbn=3-8047-1763-2 }}</ref><ref>{{cite journal | vauthors = de Jong S, Kooistra AJ, de Vries EG, Mulder NH, Zijlstra JG | title = Topoisomerase II as a target of VM-26 and 4'-(9-acridinylamino)methanesulfon-m-aniside in atypical multidrug resistant human small cell lung carcinoma cells | journal = Cancer Research | volume = 53 | issue = 5 | pages = 1064–1071 | date = March 1993 | pmid = 8382551 }}</ref> since it does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.{{citation needed|date=November 2015}}

==Chemistry== [[File:Podophyllum peltatum - Köhler–s Medizinal-Pflanzen-246.jpg|thumb|left|An illustration of the wild mandrake, showing part of the rhizome (at bottom)]] Teniposide is a semisynthetic derivative of podophyllotoxin<ref name="Austria-Codex" /> from the rhizome of the wild mandrake (''Podophyllum peltatum''). More specifically, it is a glycoside of podophyllotoxin with a <small>D</small>-glucose derivative. It is chemically similar to the anti-cancer drug etoposide, being distinguished only by a thienyl rest where etoposide has a methyl.<ref name="Mutschler" /> Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.<ref>{{cite book |title=Arzneistoff-Profile | veditors = Dinnendahl V, Fricke U |publisher=Govi Pharmazeutischer Verlag |location=Eschborn, Germany |date=2015 |edition=28th |volume=4 |isbn=978-3-7741-9846-3 |language=German }}</ref>

== References == {{Reflist|35em}}

{{Chemotherapeutic agents}}

Category:Topoisomerase inhibitors Category:IARC Group 2A carcinogens Category:Thiophenes Category:Phenol ethers Category:Furonaphthodioxoles Category:Phenols Category:Gamma-lactones Category:Methoxy compounds Category:CYP2C9 inhibitors