Vandetanib
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| Systematic (IUPAC) name | |
| N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine | |
| Clinical data | |
| Trade names | Caprelsa |
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a611037 |
| Licence data | US FDA:link |
| Pregnancy cat. | D (US) |
| Legal status | ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Protein binding | 90–96% |
| Metabolism | CYP3A4, FMO1, FMO3 |
| Half-life | 19 days (mean) |
| Excretion | 44% faeces, 25% urine |
| Identifiers | |
| CAS number | 443913-73-3  |
| ATC code | L01XE12 |
| PubChem | CID 3081361 |
| DrugBank | DB08764 |
| ChemSpider | 2338979  |
| UNII | YO460OQ37K |
| ChEBI | CHEBI:49960 |
| ChEMBL | CHEMBL24828 |
| Synonyms | ZD6474 |
| Chemical data | |
| Formula | C22H24BrFN4O2 |
| Mol. mass | 475.354 g/mol |
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Vandetanib (INN, trade name Caprelsa) is an anti-cancer drug that is used for the treatment of certain tumours of the thyroid gland. It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET-tyrosine kinase.[1][2] The drug was developed by AstraZeneca.
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Approvals and indications [edit]
Vandetanib was the first drug to be approved by FDA (April 2011) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.[3] Vandetanib was first initially marketed without a trade name,[4] and is being marketed under the trade name Caprelsa since August 2011.[5]
Contraindications [edit]
Vandetanib is contraindicated in patients with congenital long QT syndrome.[2][6]
Adverse effects [edit]
Common side effects include abdominal pain and diarrhoea, rashes, prolonged QT interval, hypertension, headache, and fatigue.[2][6]
Interactions [edit]
Other drugs that prolong the QT interval can possibly add to this side effect of vandetanib. As the drug is partly metabolised via the liver enzyme CYP3A4, strong inducers of this enzyme can decrease its blood plasma concentrations. CYP3A4 inhibitors do not significantly increase vandetanib concentrations, presumably because it is also metabolised by flavin containing monooxygenase 1 (FMO1) and 3.[2][6]
Pharmacokinetics [edit]
Vandetanib is well absorbed from the gut, reaches peak blood plasma concentrations 4 to 10 hours after application, and has a half-life of 19 days on average. It has to be taken for about three months to achieve a steady-state concentration. In the blood, it is almost completely (90–96%) bound to plasma proteins such as albumin. It is metabolised to N-desmethylvandetanib via CYP3A4 and to vandetanib-N-oxide via FMO1 and 3. Both of these are active metabolites. Vandetanib is excreted via the faeces (44%) and the urine (25%) in form of the unchanged drug and the metabolites.[2][7][8]
Clinical trials [edit]
Non-small cell lung cancer [edit]
The drug underwent clinical trials as a potential targeted treatment for non-small-cell lung cancer. There have been some promising results from a phase III trial with docetaxel.[9] There have also been ambivalent results when used with pemetrexed.[10] Another trial with docetaxel was recruiting in July 2009.[11]
AstraZeneca withdrew EU regulatory submissions for vandetanib (under the proposed trade name Zactima) in October 2009 after trials showed no benefit when the drug was administered alongside chemotherapy.[12]
References [edit]
- ^ "Definition of vandetanib". NCI Drug Dictionary. National Cancer Institute.
- ^ a b c d e "Vandetanib Monograph". Drugs.com. Retrieved 29 August 2012.
- ^ "FDA approves new treatment for rare form of thyroid cancer". Retrieved 7 April 2011.
- ^ "FDA approves orphan drug vandetanib for advanced medullary thyroid cancer" (Press release). AstraZeneca. Retrieved 2011-08-17.
- ^ "AstraZeneca announces trade name CAPRELSA® for vandetanib" (Press release). AstraZeneca. Retrieved 2011-08-17.
- ^ a b c Haberfeld, H, ed. (2012). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- ^ Martin, P.; Oliver, S.; Kennedy, S. J.; Partridge, E.; Hutchison, M.; Clarke, D.; Giles, P. (2012). "Pharmacokinetics of Vandetanib: Three Phase I Studies in Healthy Subjects". Clinical Therapeutics 34 (1): 221–237. doi:10.1016/j.clinthera.2011.11.011. PMID 22206795.
- ^ a b "Clinical Pharmacology Review: Vandetanib". US Food and Drug Administration, Center for Drug Evaluation and Research. 20 August 2010. Retrieved 29 August 2012.
- ^ "Vandetanib Shows Clinical Benefit When Combined With Docetaxel For Lung Cancer". ScienceDaily. 3 June 2009.
- ^ "IASLC: Vandetanib Fails to Improve NSCLC Outcomes with Pemetrexed". Medpage today. 5 Aug 2009.
- ^ ClinicalTrials.gov NCT00687297 Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer
- ^ "Zactima". European Medicines Agency.
External links [edit]
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