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.
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)
|PO||unknown||6 hr||24 hr|
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Severe renal impairment
- Rep: Women of reproductive potential;
- Pedi: Safety and effectiveness not established in children;
- Geri: ↑ risk of adverse reactions in older adults.
Adverse Reactions/Side Effects
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
F and E: hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia
GI: DIARRHEA, constipation, ↓ appetite, hyperbilirubinemia, ↑ liver enzymes, nausea, stomatitis, metallic taste, vomiting
GU: ↑ serum creatinine
Hemat: anemia, lymphopenia
Metabolic: hypoalbuminemia, ↓ weight
Neuro: fatigue, insomnia
Resp: INTERSTITIAL LUNG DISEASE, cough, dyspnea
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- ↓ levels with proton pump inhibitors, H2 antagonists, or antacids ; avoid concurrent use with proton pump inhibitor; take ≥6 hr before or ≥10 hr after H2 antagonist.
- May ↑ levels and risk of toxicity of CYP2D6 substrates ; avoid concurrent use with narrow-therapeutic index CYP2D6 substrates.
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.
- Monitor for rash and exfoliative skin reactions during therapy. Effects may increase with sun exposure. Start use of moisturizers when starting therapy. If Grade 2 reactions occur, hold dacomitinib for persistent reactions, upon recovery to ≤Grade 1 and resume at same dose. For recurrent persistent Grade 2 reactions, hold dacomitinib until recovery to ≤Grade 1 and resume at reduced dose. If Grade 3 or 4 reactions occur, 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.
- Verify negative pregnancy test before starting dacomitinib.
- May cause anemia and lymphopenia.
- May cause hypoalbuminemia, increased ALT, AST, creatinine, alkaline phosphatase, and hyperbilirubinemia.
- May cause hyperglycemia, hypocalcemia, hypokalemia, hyponatremia, and hypomagnesemia.
- Dose reduction recommendations: 1st dose reduction, 30 mg 2nd dose reduction, 15 mg.
- PO Administer once daily at the same time each day without regard to food.
- Avoid taking proton pump inhibitors during therapy; locally acting antacids may be used. If H2 antagonists are used administer dacomitinib 6 hr before or 10 hr after H2 antagonist.
- Instruct patient to take dacomitinib at the same time each day as directed. If vomiting occurs after dose or dose is missed, skip dose and resume the next day as scheduled; do not take an additional dose or make up a missed dose. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
- Advise patient to avoid use of proton pump inhibitors. Antacids or H2 antagonists may be used. Instruct patient to take dacomitinib at least 6 hrs before or 10 hrs after taking an H2 antagonist.
- Advise patient to notify health care professional immediately if signs and symptoms of interstitial lung disease or diarrhea occur.
- Advise patient to use sunscreen and wear protective clothing to prevent skin reactions. Instruct patient use moisturizers and to notify health care professional if new or worsening rash, redness or exfoliative reactions occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May be teratogenic. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during and for at least 17 days after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.
Improved progression-free survival in NSCLC.