Dacomitinib

DAE Class; Rx

Common Brand Names; Vizimpro

• Antineoplastics, Tyrosine Kinase Inhibitors; 
• Antineoplastics, EGFR Inhibitors

Epidermal growth factor receptor (EGFR) kinase inhibitor
Used for the first-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 (L858R) substitution mutations
Monitor for diarrhea, dermatologic reactions, and symptoms of pneumonitis; an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary

Indicated for first-line treatment of patients with metastatic non-small lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test

None

>10% (All Grades)

Diarrhea (87%)

Rash (69%)

Paronychia (64%)

Stomatitis (45%)

Anemia (44%)

Hypoalbuminemia (44%)

Lymphopenia (42%)

Increased ALT (40%)

Hyperglycemia (36%)

Increased AST (35%)

Hypocalcemia (33%)

Decreased appetite (31%)

Dry skin (30%)

Hypokalemia (29%)

Decreased weight (26%)

Hyponatremia (26%)

Increased creatinine (24%)

Alopecia (23%)

Increased alkaline phosphatase (22%)

Hypomagnesemia (22%)

Pruritus (21%)

Cough (21%)

Nasal mucosal disorder (19%)

Conjunctivitis (19%)

Nausea (19%)

Hyperbilirubinemia (16%)

Palmar-plantar erythrodysesthesia syndrome (15%)

Pain in extremity (14%)

Dyspnea (13%)

Constipation (13%)

Asthenia (13%)

Mouth ulceration (12%)

Musculoskeletal pain (12%)

Upper respiratory tract infection (12%)

Dermatitis (11%)

Insomnia (11%)

1-10% (All Grades)

Chest pain (10%)

Fatigue (9%)

Vomiting (9%)

Skin fissures (9%)

Dysgeusia (7%)

Skin exfoliation/exfoliative skin reactions (3.5%)

Interstitial lung disease (2.6%)

Keratitis (1.8%)

Hypertrichosis (1.3%)

Dehydration (1.3%)

1-10% (Grade 3 or 4)

Hypokalemia (7%)

Lymphopenia (6%)

Decreased appetite (3.1%)

Hyponatremia (2.9%)

Decreased weight (2.2%)

Dyspnea (2.2%)

Asthenia (2.2%)

Upper respiratory tract infection (1.3%)

Dry skin (1.8%)

Dermatitis (1.8%)

Increased ALT (1.4%)

Hypocalcemia (1.4%)

Hyperglycemia (1%)

<1% (Grade 3 or 4)

Alopecia

Pruritus

Palmar-plantar erythrodysesthesia syndrome

Musculoskeletal pain

Insomnia

Anemia

Increased alkaline phosphatase

Hypomagnesemia

Hyperbilirubinemia

Increased AST

Severe and fatal ILD/pneumonitis occurred; monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold treatment and promptly investigate for ILD in patients who present with worsening of respiratory symptoms, which may be indicative of ILD (eg, dyspnea, cough, fever); permanently discontinue treatment if ILD is confirmed

Severe and fatal diarrhea occurred; promptly initiate antidiarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea

Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Dermatologic adverse reactions

• Rash and exfoliative skin reactions occurred; incidence and severity of rash and exfoliative skin reactions may increase with sun exposure
• At time of initiation of treatment, initiate use of moisturizers and appropriate measures to limit sun exposure
• Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids
• Initiate oral antibiotics for Grade ≥2 severe dermatologic adverse reactions

Drug interactions overview

• Dacomitinib inhibits UGT1A1, P-gp, BCRP, and organic cation transporter (OCT)1
• Dacomitinib is a P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) substrate

• Concomitant use of acid-reducing agents

  • Avoid use with proton pump inhibitors (PPIs)
  • As an alternative to PPIs, use locally acting antacids, or, if using a histamine 2 (H2)-receptor antagonist, administer dacomitinib at least 6 hr before or 10 hr after taking an H2-receptor antagonist
  • Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy

• Effect of dacomitinib on CYP2D6 substrates

  • Concomitant use of dacomitinib increases concentration of CYP2D6 substrates, which may increase the risk of toxicities of these drugs
  • Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities

Pregnancy

Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman

There are no available data on use in pregnant women

Lactation

There is no information regarding presence of dacomitinib or its metabolites in human milk or their effects on breastfed infants or on milk production

Adults

45 mg PO once daily.

Geriatric

45 mg PO once daily.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Dacomitinib