Vinorelbine

Vinorelbine

Systematic (IUPAC) name
4-(acetyloxy)- 6,7-didehydro- 15-((2R,6R,8S)-4-ethyl- 1,3,6,7,8,9-hexahydro- 8-(methoxycarbonyl)- 2,6-methano- 2H-azecino(4,3-b)indol-8-yl)- 3-hydroxy- 16-methoxy- 1-methyl- methyl ester,
Clinical data
Trade names	Navelbine
AHFS/Drugs.com	monograph
MedlinePlus	a695013
Pregnancy category	AU: D US: D (Evidence of risk)
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	intravenous, oral
Pharmacokinetic data
Bioavailability	43 ± 14% (oral)
Protein binding	79 to 91%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	27.7 to 43.6 hours
Excretion	Fecal (46%) and renal (18%)
Identifiers
CAS Number	71486-22-1 Y
ATC code	L01CA04 (WHO)
PubChem	CID: 5311497
DrugBank	DB00361 Y
ChemSpider	4470974 Y
UNII	Q6C979R91Y Y
KEGG	D08680 Y
ChEMBL	CHEMBL607994 N
Chemical data
Formula	C45H54N4O8
Molecular mass	778.932 g/mol
SMILES O=C(OC)[C@]4(c2nc1ccccc1c2CN3CC(=C/[C@H](C3)C4)\CC)c5c(OC)cc6c(c5)[C@@]89[C@@H](N6C)[C@@](O)(C(=O)OC)[C@H](OC(=O)C)[C@@]7(/C=C\CN([C@@H]78)CC9)CC
InChI InChI=1S/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1 Y Key:GBABOYUKABKIAF-IELIFDKJSA-N Y
NY (what is this?)  (verify)

Vinorelbine (NVB), sold under the trade name Navelbine, is a chemotherapy medication that is used to treat a number of types of cancer, including breast cancer and non-small cell lung cancer.

It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system. The wholesale price as of 2014 is between 8.60 and 42.80 USD a vial.

Medical uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer. It is used off-label for other cancers such as metastatic breast cancer. It is also active in rhabdomyosarcoma.

Side effects

Vinorelbine has a number of side-effects that can limit its use:

Chemotherapy-induced peripheral neuropathy (a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs), lowered resistance to infection, bruising or bleeding, anaemia, constipation, diarrhea, nausea, tiredness and a general feeling of weakness (asthenia), inflammation of the vein into which it was injected (phlebitis). Seldom severe hyponatremia is seen.

Less common effects are hair loss and allergic reaction.

Pharmacology

The antitumor activity is due to inhibition of mitosis through interaction with tubulin. Vinorelbine is the first 5´NOR semi-synthetic vinca alkaloid. It is obtained by semi-synthesis from alkaloids extracted from the rosy periwinkle, Catharanthus roseus. It is marketed in India by Abbott Healthcare under the brand name Navelbine.

History

Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France in the 1980s and was licensed to the oncology department of the Pierre Fabre Group. It is a semi-synthetic vinca alkaloid. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small cell lung cancer. It gained approval to treat metastatic breast cancer in 1991. Vinorelbine received approval by the United States Food and Drug Administration (FDA) in December 1994 sponsored by Burroughs Wellcome Company. Pierre Fabre Group now markets Navelbine in the U.S., where the drug went generic in February 2003.

In most European countries, vinorelbine is approved to treat non-small cell lung cancer and breast cancer. In the United States it is approved only for non-small cell lung cancer.

Oral formulation

An oral formulation has been marketed and registered in most European countries. It has similar efficacy as the intravenous formulation, but it avoids venous toxicities of an infusion and is easier to take. The oral form is not approved in the United States or Australia.