General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
dak-ohmi-ti-nib

Trade Name(s)

• Vizimpro

Ther. Class.

antineoplastics

Pharm. Class.

kinase inhibitors

Indications

  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.

Action

Irreversible EGFR tyrosine kinase inhibitor; blocks growth stimulation signals in cancer cells.

Therapeutic Effect(s):

Improved progression-free survival in NSCLC.

Pharmacokinetics

Absorption: 80% absorbed after oral administration.

Distribution: Widely distributed to tissues.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme to an active metabolite and to a lesser extent by the CYP3A4 isoenzyme. 79% excreted in feces (20% as unchanged drug), 3% in urine.

Half-life: 70 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:  Pregnancy;
• 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

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: hypoalbuminemia, weight loss

MS: pain

Neuro: fatigue, insomnia

Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE (ILD)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Proton pump inhibitors,  H₂  antagonists, or  antacids  may ↓ levels and effectiveness; 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.

Route/Dosage

PO (Adults): 45 mg once daily until disease progression or unacceptable toxicity.

Availability

Tablets: 15 mg, 30 mg, 45 mg

Assessment

• Monitor for signs and symptoms of ILD during therapy. If symptoms occur, hold dacomitinib and confirm diagnosis. If ILD 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, 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, ↑ ALT, AST, serum creatinine, alkaline phosphatase, and hyperbilirubinemia.
• May cause hyperglycemia, hypocalcemia, hypokalemia, hyponatremia, and hypomagnesemia.

Implementation

• 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.

Patient/Family Teaching

• 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 hr before or 10 hr after taking an H₂  antagonist.
• Advise patient to notify health care professional immediately if signs and symptoms of ILD 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 cause fetal harm. 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.

Evaluation/Desired Outcomes

Improved progression-free survival in NSCLC.