Gefitinib

Gefitinib Brand Name– Iressa

What is Gefitinib

Gefitinib is an oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).

EGRF is expressed, overexpressed, or dysregulated in many cancers including breast, ovarian, non-small cell (NSCLC), mesothelioma, colorectal, and head and neck cancers.

Clinically, EGFR expression has been associated with poor prognosis, development of metastasis, and resistance to chemotherapy, hormonal therapy, and radiation therapy.

Gefitinib was originally approved by the FDA in 2002 for the third-line treatment of advanced NSCLC.

However, in 2005 the indication was modified to only include patients who benefited from either current or past gefitinib treatment, due to a large clinical trial in patients with refractory NSCLC showing no survival benefit, as well as the early termination of another clinical trial after an interim analysis due to a lack of survival at in advanced NSCLC following chemotherapy and radiation.

Of note, the impact of EGFR status on efficacy was unknown at that time. In 2015, the FDA approved gefitinib for the first-line treatment of metastatic NSCLC in patients with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations based on a small, single-arm, open-label study.

Serious adverse reactions include interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, bullous and exfoliative skin disorders, and ocular disorders; the most common side effects are diarrhea and skin reactions. Periodically monitor liver function tests during therapy.

Indications

  • head and neck cancer
  • non-small cell lung cancer (NSCLC)

For the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test

Side Effects

  1. acne vulgaris
  2. acneiform rash
  3. acute respiratory distress syndrome (ARDS)
  4. alopecia
  5. angioedema
  6. anorexia
  7. anorexia
  8. asthenia
  9. bleeding
  10. blepharitis
  11. bullous rash
  12. cheilitis
  13. conjunctivitis
  14. corneal erosion
  15. cough
  16. cystitis
  17. dehydration
  18. diarrhea
  19. diarrhea
  20. dyspnea
  21. elevated hepatic enzymes
  22. elevated hepatic enzymes
  23. epistaxis
  24. erythema
  25. erythema multiforme
  26. exfoliative dermatitis
  27. fever
  28. folliculitis
  29. GI perforation
  30. hematuria
  31. hemorrhagic cystitis
  32. hepatotoxicity
  33. hyperbilirubinemia
  34. hyperbilirubinemia
  35. keratitis
  36. maculopapular rash
  37. nausea
  38. ocular inflammation
  39. ocular irritation
  40. ocular pruritus
  41. onycholysis
  42. oral ulceration
  43. pancreatitis
  44. pneumonitis
  45. pneumonitis
  46. proteinuria
  47. proteinuria
  48. pruritus
  49. pulmonary embolism
  50. pulmonary fibrosis
  51. rash
  52. Stevens-Johnson syndrome
  53. stomatitis
  54. stomatitis
  55. toxic epidermal necrolysis
  56. urticaria
  57. vasculitis
  58. vesicular rash
  59. visual impairment
  60. vomiting
  61. vomiting
  62. xerophthalmia
  63. xerosis
  64. xerostomia

Monitoring Parameters

  • LFTs

Contraindications

  • breast-feeding
  • chronic lung disease (CLD)
  • contraception requirements
  • diarrhea
  • GI perforation
  • hepatic disease
  • infertility
  • keratitis
  • ocular disease
  • pneumonitis
  • pregnancy
  • pulmonary disease
  • pulmonary fibrosis
  • reproductive risk
  • serious rash

Interactions

  • Abiraterone
  • Acetaminophen; Oxycodone
  • Aluminum Hydroxide
  • Aluminum Hydroxide; Magnesium Carbonate
  • Aluminum Hydroxide; Magnesium Hydroxide
  • Aluminum Hydroxide; Magnesium Hydroxide; Simethicone
  • Aluminum Hydroxide; Magnesium Trisilicate
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Antacids
  • Apalutamide
  • Aripiprazole
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Atazanavir
  • Atazanavir; Cobicistat
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Bupropion
  • Bupropion; Naltrexone
  • Calcium Carbonate
  • Calcium Carbonate; Magnesium Hydroxide
  • Calcium Carbonate; Risedronate
  • Calcium Carbonate; Simethicone
  • Carbamazepine
  • Ceritinib
  • Chloramphenicol
  • Cimetidine
  • Cinacalcet
  • Clarithromycin
  • Cobicistat
  • Conivaptan
  • Dacomitinib
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Delavirdine
  • Dexamethasone
  • Dexlansoprazole
  • Dextromethorphan; Quinidine
  • Dronedarone
  • Duloxetine
  • Eliglustat
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Enzalutamide
  • Escitalopram
  • Esomeprazole
  • Esomeprazole; Naproxen
  • Famotidine
  • Famotidine; Ibuprofen
  • Fedratinib
  • Fluoxetine
  • Fluoxetine; Olanzapine
  • Fosamprenavir
  • Fosphenytoin
  • grapefruit juice
  • Halofantrine
  • Ibuprofen; Oxycodone
  • Idelalisib
  • Indinavir
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Itraconazole
  • Ketoconazole
  • Lansoprazole
  • Lansoprazole; Naproxen
  • Letermovir
  • Lopinavir; Ritonavir
  • Lumacaftor; Ivacaftor
  • Lumacaftor; Ivacaftor
  • Magnesium Hydroxide
  • Mephobarbital
  • Mifepristone
  • Mirabegron
  • Mitotane
  • Nefazodone
  • Nelfinavir
  • Nizatidine
  • Ombitasvir; Paritaprevir; Ritonavir
  • Omeprazole
  • Omeprazole; Amoxicillin; Rifabutin
  • Omeprazole; Sodium Bicarbonate
  • Oxycodone
  • Panobinostat
  • Pantoprazole
  • Paroxetine
  • Pentosan
  • Phenobarbital
  • Phentermine; Topiramate
  • Phenytoin
  • Pimozide
  • Posaconazole
  • Primidone
  • Propafenone
  • Quinidine
  • Quinine
  • Rabeprazole
  • Ranitidine
  • Ranolazine
  • Ribociclib
  • Ribociclib; Letrozole
  • Rifampin
  • Ritonavir
  • Rolapitant
  • Saquinavir
  • Sodium Bicarbonate
  • St. John’s Wort, Hypericum perforatum
  • Telithromycin
  • Terbinafine
  • Thioridazine
  • Tipranavir
  • Topiramate
  • Tucatinib
  • Voriconazole
  • Warfarin