Vinorelbine Tartrate

(BANM, USAN, rINNM)
Vinorelbine Tartrate Chemical formula
Synonyms: 5′-Nor-anhydrovinblastine Tartrate; Tartrato de vinorelbina; Vinorelbiinitartraatti; Vinorelbin Bitartrat; Vinorelbin-ditartarát; Vinorelbine Ditartrate; Vinorelbine, tartrate de; Vinorelbini Ditartras; Vinorelbini tartras; Vinorelbino tartratas; Vinorelbintartrat. 3′,4′-Didehydro-4′-deoxy-8′-norvincaleukoblastine ditartrate.
Cyrillic synonym: Винорелбина Тартрат.

💊 Chemical information

Chemical formula: C45H54N4O8,2C4H6O6 = 1079.1.
CAS — 71486-22-1 (vinorelbine); 125317-39-7 (vinorelbine tartrate).
ATC — L01C A04.
ATC Vet — QL01CA04.

Pharmacopoeias.

In Chin., Eur., and US.

Ph. Eur. 6.2

(Vinorelbine Tartrate). A white or almost white, hygroscopic powder. Freely soluble in water and in methyl alcohol; practically insoluble in hexane. A 1.4% solution in water has a pH of 3.3 to 3.8. Store under an inert gas at a temperature not exceeding −15°. Protect from light.

USP 31

(Vinorelbine Tartrate). A white to yellow or light brown amorphous powder. Freely soluble in water. pH of a 1% solution in water is between 3.3 and 3.8. Store at a temperature between −25° and −10° in airtight containers. Protect from light.

💊 Adverse Effects, Treatment, and Precautions

As for Vinblastine Sulfate. The main dose-limiting effect of vinorelbine is granulocytopenia. The nadir of the granulocyte count occurs 5 to 10 days after a dose, with recovery usually after a further 7 to 14 days. The drug should be stopped if moderate or severe neurotoxicity develops. Local pain and thrombophlebitis may be seen with repeated injection of vinorelbine. Gastrointestinal effects such as nausea and vomiting are common with the oral formulation.

Administration error.

Inadvertent intrathecal doses of vinca alkaloids result in ascending paralysis and death. For reference to the successful treatment of inadvertent intrathecal dosage of vincristine, and UK recommendations on dilution of vinca alkaloids to avoid intrathecal use.

Effects on the gastrointestinal tract.

For reference to a report of vinorelbine possibly exacerbating ischaemic colitis in patients receiving docetaxel.

💊 Interactions

💊 Pharmacokinetics

As with the other vinca alkaloids, vinorelbine exhibits triphasic pharmacokinetics after intravenous injection, and has a terminal half-life of between about 28 and 44 hours. It is rapidly absorbed from the gastrointestinal tract with peak plasma concentrations achieved between 1.5 and 3 hours after oral doses. It is metabolised in the liver; deacetylvinorelbine has antineoplastic activity. Vinorelbine and its metabolites are excreted primarily in faeces via the bile but also in urine.
1. Levêque D, Jehl F. Clinical pharmacokinetics of vinorelbine. Clin Pharmacokinet 1996; 31: 184–97
2. Marty M, et al. Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol 2001; 12: 1643–9
3. Bugat R, et al. The effects of food on the pharmacokinetic profile of oral vinorelbine. Cancer Chemother Pharmacol 2002; 50: 285–90
4. Variol P, et al. A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine. Eur J Clin Pharmacol 2002; 58: 467–76
5. Wong M, et al. Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer. J Clin Oncol 2006; 24: 2448–55.

💊 Uses and Administration

Vinorelbine is a semisynthetic derivative of vinblastine with similar general properties. It is used in the treatment of advanced breast cancer and non-small cell lung cancers, and has been tried in other malignancies including lymphomas and tumours of ovary and prostate. Vinorelbine is given as the tartrate but doses are calculated in terms of vinorelbine: vinorelbine tartrate 1.385 mg is equivalent to about 1 mg of vinorelbine. It may be given by intravenous injection over 5 to 10 minutes, as a solution containing the equivalent of vinorelbine 1.5 to 3 mg/mL in glucose 5% or sodium chloride 0.9% injection, directly or into a freely-running intravenous infusion. However, UK guidelines recommend that for patients over the age of 10 years, solutions of vinorelbine should generally be diluted to a volume of at least 20 mL to avoid inadvertent intrathecal use; higher concentrations can be used for children under 10 years of age. It may also be given by intravenous infusion over 20 to 30 minutes after dilution in 125 mL of glucose 5% or sodium chloride 0.9%. The usual initial intravenous dose in the treatment of breast cancer or non-small cell lung cancer is the equivalent of vinorelbine 25 to 30 mg/m 2 weekly. In the UK, the manufacturers recommend that if the neutrophil count falls below 2000 cells/mm 3 subsequent doses should be delayed until recovery. In the USA it is suggested that subsequent doses should be halved if granulocyte counts fall to between 1000 and 1500 cells/mm 3 ; treatment should be interrupted if counts are below 1000 cells/mm 3 and stopped if granulocytopenia persists for more than 2 weeks. Doses should also be reduced in hepatic impairment and in patients with massive liver metastases (but see also below). In the treatment of non-small cell lung cancer, vinorelbine is also given orally at a dose of 60 mg/m 2 once weekly for 3 weeks. Subsequent doses may be increased to 80 mg/m 2 , unless the neutrophil count falls below 500 cells/mm 3 , or to between 500 and 1000 cells/mm 3 on two separate occasions, in which case the dose is kept at 60 mg/m 2 for the next 3 doses.
1. Gregory RK, Smith IE. Vinorelbine—a clinical review. Br J Cancer 2000; 82: 1907–13
2. Sarris AH, et al. Infusional vinorelbine in relapsed or refractory lymphomas. Leuk Lymphoma 2000; 39: 291–9
3. Sorensen P, et al. Phase II study of vinorelbine in the treatment of platinum-resistant ovarian carcinoma. Gynecol Oncol 2001; 81: 58–62
4. Oudard S, et al. Phase II study of vinorelbine in patients with androgen-independent prostate cancer. Ann Oncol 2001; 12: 847–52
5. Domenech GH, Vogel CL. A review of vinorelbine in the treatment of breast cancer. Clin Breast Cancer 2001; 2: 113–28
6. Aapro MS, et al. Developments in cytotoxic chemotherapy: advances in treatment utilising vinorelbine. Crit Rev Oncol Hematol 2001; 40: 251–63
7. Gridelli C, De Vivo R. Vinorelbine in the treatment of non-small cell lung cancer. Curr Med Chem 2002; 9: 879–91
8. Freyer G, et al. Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 2003; 21: 35–40
9. Gebbia V, Puozzo C. Oral versus intravenous vinorelbine: clinical safety profile. Expert Opin Drug Saf 2005; 4: 915–28
10. Aapro MS, et al. Oral vinorelbine: role in the management of metastatic breast cancer. Drugs 2007; 67: 657–67
11. Gralla RJ, et al. Oral vinorelbine in the treatment of non-small cell lung cancer: rationale and implications for patient management. Drugs 2007; 67: 1403–10.

Administration in hepatic impairment.

Clearance of vinorelbine was markedly reduced in patients with diffuse liver metastases and hence severely altered hepatic function: a 50% dose reduction was probably appropriate in such patients even if hyperbilirubinaemia was not marked.1 However, reduced doses were not necessary in patients with moderate liver involvement in whom liver function, as measured by lidocaine metabolism, was not markedly reduced. Licensed product information in the UK suggests that the intravenous dose be reduced by one-third in patients with massive liver metastases (more than 75% of liver volume replaced by tumour cells). In the USA, licensed information recommends that the intravenous dose of vinorelbine be reduced by 50% in patients with bilirubin values of 2.1 to 3 mg per 100 mL and by 75% in those with bilirubin greater than 3 mg per 100 mL.
1. Robieux I, et al. Pharmacokinetics of vinorelbine in patients with liver metastases. Clin Pharmacol Ther 1996; 59: 32–40.

💊 Preparations

USP 31: Vinorelbine Injection.

Proprietary Preparations

Arg.: Filcrin; Navelbine; Neocitec; Sulcoline; Vilbine†; Vilne; Vinarine; Vinkebir; Vinorel; Vinorgen; Austral.: Navelbine; Austria: Navelbine; Belg.: Navelbine; Braz.: Navelbine; Neocitec; Norelbin; Canad.: Navelbine; Chile: Navelbine; Cz.: Navelbine; Navirel; Nibrevin; Denm.: Navelbine; Navirel; Fin.: Navelbine; Fr.: Navelbine; Ger.: Navelbine; Gr.: Navelbine; Hong Kong: Navelbine; Hung.: Navelbin; India: Vinelbine; Israel: Navelbine; Ital.: Navelbine; Jpn: Navelbine; Malaysia: Navelbine; Mex.: Navelbine; Viessia; Vinilex; Neth.: Navelbine; Norw.: Navelbine; NZ: Navelbine; Philipp.: Navelbine; Vinotel; Pol.: Navelbine; Navirel; Port.: Navelbine; Vinorel; Rus.: Maverex (Маверекс); Navelbine (Навельбин); S.Afr.: Navelbine; Singapore: Navelbine; Spain: Navelbine; Swed.: Navelbine; Switz.: Navelbine; Thai.: Navelbine; Vinelbine; Turk.: Navelbine; UK: Navelbine; USA: Navelbine.
Published April 11, 2019.