Avapritinib

Avapritinib Brand Name– AYVAKIT

What is Avapritinib

Avapritinib is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor alpha (PDGFRA) and PDGFRA D842 mutations as well as multiple KIT exon 11, 11/17, and 17 mutations.

It is indicated for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

Central nervous system adverse reactions including cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations occur in more than half of patients treated with avapritinib and may require an interruption of therapy or dose reduction.

Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Indications

  • gastrointestinal stromal tumors (GIST)

For the treatment of gastrointestinal stromal tumors (GIST)

NOTE: The FDA has designated avapritinib as an orphan drug for this indication.

for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST) with platelet-derived growth factor-alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations

Side Effects

  1. abdominal pain
  2. agitation
  3. alopecia
  4. amnesia
  5. anemia
  6. anorexia
  7. anxiety
  8. asthenia
  9. confusion
  10. constipation
  11. dementia
  12. depression
  13. diarrhea
  14. dizziness
  15. dysarthria
  16. dysgeusia
  17. dyspepsia
  18. dysphoria
  19. dyspnea
  20. edema
  21. elevated hepatic enzymes
  22. encephalopathy
  23. fatigue
  24. fever
  25. GI bleeding
  26. hair discoloration
  27. hallucinations
  28. headache
  29. hyperbilirubinemia
  30. hypertension
  31. hyperthyroidism
  32. hypoalbuminemia
  33. hypokalemia
  34. hypomagnesemia
  35. hyponatremia
  36. hypophosphatemia
  37. hypothyroidism
  38. impaired cognition
  39. infection
  40. insomnia
  41. intracranial bleeding
  42. irritability
  43. lacrimation
  44. leukopenia
  45. maculopapular rash
  46. memory impairment
  47. nausea
  48. neutropenia
  49. palmar-plantar erythrodysesthesia (hand and foot syndrome)
  50. peripheral edema
  51. pleural effusion
  52. prolonged bleeding time
  53. rash
  54. renal failure (unspecified)
  55. stroke
  56. subdural hematoma
  57. testicular swelling
  58. thrombocytopenia
  59. vomiting
  60. weight loss

Monitoring Parameters

  • pregnancy testing

Contraindications

  • anxiety
  • breast-feeding
  • contraception requirements
  • dementia
  • depression
  • infertility
  • male-mediated teratogenicity
  • mental status changes
  • pregnancy
  • pregnancy testing
  • reproductive risk
  • stroke

Interactions

  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Amiodarone
  • Amobarbital
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Apalutamide
  • Aprepitant, Fosaprepitant
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Atazanavir
  • Atazanavir; Cobicistat
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Bexarotene
  • Bosentan
  • Brigatinib
  • Butabarbital
  • Carbamazepine
  • Cenobamate
  • Ceritinib
  • Chloramphenicol
  • Ciprofloxacin
  • Clarithromycin
  • Cobicistat
  • Conivaptan
  • Crizotinib
  • Cyclosporine
  • Dabrafenib
  • Danazol
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Delavirdine
  • Dexamethasone
  • Diltiazem
  • Dronedarone
  • Duvelisib
  • Efavirenz
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Elagolix
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Enzalutamide
  • Erythromycin
  • Erythromycin; Sulfisoxazole
  • Eslicarbazepine
  • Etravirine
  • Fedratinib
  • Fluconazole
  • Fluvoxamine
  • Fosamprenavir
  • Fosphenytoin
  • grapefruit juice
  • Idelalisib
  • Imatinib
  • Indinavir
  • Isavuconazonium
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Itraconazole
  • Ketoconazole
  • Lefamulin
  • Letermovir
  • Lopinavir; Ritonavir
  • Lorlatinib
  • Lumacaftor; Ivacaftor
  • Lumacaftor; Ivacaftor
  • Mephobarbital
  • Methohexital
  • Mifepristone
  • Mitotane
  • Modafinil
  • Nafcillin
  • Nefazodone
  • Nelfinavir
  • Netupitant, Fosnetupitant; Palonosetron
  • Nevirapine
  • Nilotinib
  • Ombitasvir; Paritaprevir; Ritonavir
  • Omeprazole; Amoxicillin; Rifabutin
  • Pentobarbital
  • Phenobarbital
  • Phenytoin
  • Posaconazole
  • Primidone
  • Ribociclib
  • Ribociclib; Letrozole
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Rifaximin
  • Ritonavir
  • Saquinavir
  • Secobarbital
  • St. John’s Wort, Hypericum perforatum
  • Telithromycin
  • Thiopental
  • Tipranavir
  • Trandolapril; Verapamil
  • Tucatinib
  • Verapamil
  • Voriconazole