Afatinib

Source: Wikipedia, the free encyclopedia.
Not to be confused with apatinib.

Afatinib
Clinical data
Trade namesGilotrif, Giotrif, Afanix
Other namesBIBW 2992
AHFS/Drugs.comMonograph
MedlinePlusa613044
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding95%
MetabolismCYP not involved
Elimination half-life37 hours
ExcretionFaeces (85%), urine (4%)
Identifiers
  • N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide
JSmol)
  • CN(C)C\C=C\C(=O)Nc3cc1c(Nc(cc2Cl)ccc2F)ncnc1cc3OC4COCC4
  • InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1 checkY
  • Key:ULXXDDBFHOBEHA-CWDCEQMOSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Afatinib, sold under the brand name Gilotrif among others, is a medication which is used to treat

non-small cell lung carcinoma (NSCLC).[2][3][4] It belongs to the tyrosine kinase inhibitor family of medications.[5] It is taken by mouth.[5][1]

It is mainly used to treating cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[6]

It is on the World Health Organization's List of Essential Medicines.[7]

Medical uses

It has received regulatory approval for use as a treatment for non-small cell lung cancer,[1][5][8][9] although there is emerging evidence to support its use in other cancers such as breast cancer.[10]

Adverse effects

Adverse effects by frequency include:[1][5][8][9][11]

Very common (>10% frequency)
  • Diarrhea (>90%)
  • Rash/dermatitis acneform
  • Stomatitis
  • Paronychia
  • Decreased appetite
  • Nose bleed
  • Itchiness
  • Dry skin
Common (1–10% frequency)
  • Dehydration
  • Taste changes
  • Dry eye
  • Cystitis
  • Cheilitis
  • Fever
  • Runny/stuffy nose
  • Low amount of potassium in the blood
  • Conjunctivitis
  • Increased ALT
  • Increased AST
  • Hand-foot syndrome
  • Muscle spasms
  • Kidney impairment and/or failure
Uncommon (0.1-1% frequency)

Mechanism of action

Like

tyrosine-kinase inhibitors (TKIs) like erlotinib or gefitinib, but also against less common mutations which are resistant to these drugs. However, it is not active against the T790M mutation which generally requires third generation drugs like osimertinib.[12] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.[3]

nM).[13]

Clinical trials

In March 2010, a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.[14] Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival.[15] In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.[16]

In January 2015, a Phase III trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type del 19-positive tumors, compared to cisplatin-based chemotherapy by a year (33 months vs. 21 months).[17] It also shows strong activity against exon 18 mutations (particularly G719) and is currently the preferred EGFR-TKI therapy for exon 18 mutations (particularly G719x).[18][verification needed]

Phase II results for breast cancer that over-expresses the protein

Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.[19]

Society and culture

Brand names

In Bangladesh under the trade name Afanix.

References

  1. ^ a b c d "Gilotrif (afatinib) tablet, film coated". DailyMed. Boehringer Ingelheim Pharmaceuticals, Inc. 18 October 2019. Retrieved 4 November 2020.
  2. ^ Spreitzer H (13 May 2008). "Neue Wirkstoffe – Tovok". Österreichische Apothekerzeitung (in German) (10/2008): 498.
  3. ^
    PMID 19037840
    .
  4. ^ "Gilotrif (afatinib)" (PDF). US Food and Drug Administration. Retrieved 11 March 2021.
  5. ^ a b c d "Giotrif Afatinib (as afatinib dimaleate)" (PDF). TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 7 November 2013. Retrieved 28 January 2014.
  6. PMID 29225480
    .
  7. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  8. ^ a b "Giotrif 20 mg film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Boehringer Ingelheim Limited. 20 January 2014. Retrieved 28 January 2014.
  9. ^ a b "Giotrif : EPAR -Product Information" (PDF). European Medicines Agency. Boehringer Ingelheim International GmbH. 16 October 2013. Retrieved 28 January 2014.
  10. ^
    PMID 22418700
    .
  11. ^ "Gilotrif (afatinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 28 January 2014.
  12. PMID 18408761
    .
  13. ^ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel Frühjahr 2013. (in German)
  14. ^ Clinical trial number NCT01085136 for "LUX-Lung 5: BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib" at ClinicalTrials.gov
  15. ^ "Afatinib (BIBW 2992*) Triples Progression Free Survival in Phase III Study in Lung Cancer Patients" (Press release). BusinessWire. 11 October 2010.
  16. PMID 22452896
    .
  17. PMID 25589191
    .
  18. PMID 26206867
    .
  19. PMID 22763464
    .

External links

Media related to Afatinib at Wikimedia Commons

  • "Afatinib". Drug Information Portal. U.S. National Library of Medicine.
  • "Afatinib dimaleate". Drug Information Portal. U.S. National Library of Medicine.
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