Genetic Implications:
Pronunciation:
dak-ohmi-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patient with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations.
Irreversible EGFR tyrosine kinase inhibitor; blocks growth stimulation signals in cancer cells.
Therapeutic Effect(s):
Improved progression-free survival in NSCLC.
Absorption: 80% absorbed after oral administration.
Distribution: Widely distributed to tissues.
Metabolism and Excretion: Primarily metabolized by the liver via CYP2D6 to an active metabolite; CYP3A4 also involved in metabolism (minor pathway). 79% excreted in feces (20% as unchanged drug), 3% in urine.
Half-life: 70 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 6 hr | 24 hr |
Contraindicated in:
Use Cautiously in:
Derm: alopecia, dermatitis, dry skin, nail infection, palmar-plantar erythrodysesthesia syndrome, pruritus, rash
EENT: conjunctivitis, epistaxis, nasal inflammation, nasal mucosal ulcer, rhinitis, keratitis, skin fissures
Endo: hyperglycemia
F and E: hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia
GI: ↓ appetite, ↑ liver enzymes, constipation, DIARRHEA, hyperbilirubinemia, nausea, stomatitis, metallic taste, vomiting
GU: ↑ serum creatinine
Hemat: anemia, lymphopenia
Metabolic: ↓ weight, hypoalbuminemia
MS: pain
Neuro: fatigue, insomnia
Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
PO (Adults): 45 mg once daily until disease progression or unacceptable toxicity.
Tablets: 15 mg, 30 mg, 45 mg
Monitor for signs and symptoms of interstitial lung disease during therapy. If symptoms occur, hold dacomitinib and confirm diagnosis. If interstitial lung disease is confirmed discontinue dacomitinib permanently.
Monitor for diarrhea. Promptly treat with loperamide or diphenoxylate/atropine. May require IV hydration. May be fatal. If Grade 2 diarrhea occurs, hold dacomitinib until recovery to ≤Grade 1 and resume at same dose. For recurrent Grade 2 diarrhea, hold dacomitinib until recovery to ≤Grade 1 and resume at reduced dose. If Grade 3 or 4 diarrhea occurs, hold dacomitinib until recovery to ≤Grade 1 and resume at reduced dose.
Lab Test Considerations:
Patient selection is based on the presence of an EGFR exon 19 deletion or exon 21 L858R substitution mutation in tumor specimens. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
Advise patient to notify health care professional immediately if signs and symptoms of interstitial lung disease or diarrhea occur.
Improved progression-free survival in NSCLC.