Dosing & Uses
Dosage Forms & Strengths
tablet
- 15mg
- 30mg
- 45mg
Non-small Cell Lung Cancer
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
45 mg PO qDay
Continue until disease progression or unacceptable toxicity occurs
Also see Administration
Dosage Modifications
First dose reduction: 30 mg qDay
Second dose reduction: 15 mg qDay
Interstitial lung disease (ILD)
- Any grade: Permanently discontinue treatment
Diarrhea
- Grade 2: Withhold treatment until recovery to Grade ≤1; then resume treatment at the same dose level
- For recurrent Grade 2 OR Grade ≥3: Withhold until recovery to Grade ≤1; then resume treatment at a reduced dose
Dermatologic adverse reactions
- Grade 2: Withhold treatment for persistent dermatologic adverse reactions; upon recovery to Grade ≤1, resume treatment at same dose level
- For recurrent persistent Grade 2 OR Grade ≥3 dermatologic adverse reactions, withhold until recovery to Grade ≤1; then resume treatment at a reduced dose
Other adverse reactions
- Grade 3 or 4: Withhold treatment until recovery to Grade ≤2; then resume treatment at a reduced dose
Renal impairment
- Mild or moderate (CrCl 30-89 mL/min estimated by Cockcroft-Gault equation): No dosage adjustment necessary
- Severe (CrCl <30 mL/min): Recommended dose not established
Hepatic impairment
- No dosage modification recommended in patients with mild, moderate or severe hepatic impairment (Child-Pugh A, B or C)
Dosing Considerations
Patient selection
- Select patients for treatment based on presence of an EGFR exon 19 deletion or exon 21 L858R substitution mutation in tumor specimens
- Information on FDA-approved tests for detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (64)
- amitriptyline
dacomitinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- amoxapine
dacomitinib will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- aripiprazole
dacomitinib will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- atomoxetine
dacomitinib will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- brexpiprazole
dacomitinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- captopril
dacomitinib will increase the level or effect of captopril by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- carvedilol
dacomitinib will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- chlordiazepoxide
dacomitinib will increase the level or effect of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- chloroquine
dacomitinib will increase the level or effect of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- chlorpromazine
dacomitinib will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- cinacalcet
dacomitinib will increase the level or effect of cinacalcet by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- citalopram
dacomitinib will increase the level or effect of citalopram by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- clomipramine
dacomitinib will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- codeine
dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- desipramine
dacomitinib will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- dexlansoprazole
dexlansoprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- doxepin
dacomitinib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- doxepin cream
dacomitinib will increase the level or effect of doxepin cream by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- doxorubicin
dacomitinib will increase the level or effect of doxorubicin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- doxorubicin liposomal
dacomitinib will increase the level or effect of doxorubicin liposomal by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- duloxetine
dacomitinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- eliglustat
dacomitinib will increase the level or effect of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- esomeprazole
esomeprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- flecainide
dacomitinib will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- fluoxetine
dacomitinib will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- fluphenazine
dacomitinib will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- fluvoxamine
fluvoxamine will increase the level or effect of dacomitinib by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP3D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities
- haloperidol
dacomitinib will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- iloperidone
dacomitinib will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- imipramine
dacomitinib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- lansoprazole
lansoprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- maprotiline
dacomitinib will increase the level or effect of maprotiline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- methamphetamine
dacomitinib will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- metoclopramide intranasal
dacomitinib will increase the level or effect of metoclopramide intranasal by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concurrent use of metoclopramide intranasal and strong CYP2D6 inhibitors is not recommended since the metoclopramide intranasal dose cannot be adjusted.
- metoprolol
dacomitinib will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- mirtazapine
dacomitinib will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- nebivolol
dacomitinib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- nortriptyline
dacomitinib will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- omeprazole
omeprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- palifermin
palifermin increases toxicity of dacomitinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pantoprazole
pantoprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- paroxetine
dacomitinib will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- perphenazine
dacomitinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- pimozide
dacomitinib will increase the level or effect of pimozide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- procainamide
dacomitinib will increase the level or effect of procainamide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- promethazine
dacomitinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- propafenone
dacomitinib will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- propranolol
dacomitinib will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- protriptyline
dacomitinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- rabeprazole
rabeprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.
- risperidone
dacomitinib will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- ritonavir
dacomitinib will increase the level or effect of ritonavir by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- sertraline
dacomitinib will increase the level or effect of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- tamoxifen
dacomitinib will increase the level or effect of tamoxifen by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- tamsulosin
dacomitinib will increase the level or effect of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- thioridazine
dacomitinib will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- timolol
dacomitinib will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- timolol ophthalmic
dacomitinib will increase the level or effect of timolol ophthalmic by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- tolterodine
dacomitinib will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- tramadol
dacomitinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- trimipramine
dacomitinib will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- valbenazine
dacomitinib will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- venlafaxine
dacomitinib will increase the level or effect of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- vortioxetine
dacomitinib will increase the level or effect of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
Monitor Closely (6)
- dengue vaccine
dacomitinib decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- deutetrabenazine
dacomitinib will increase the level or effect of deutetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Strong CYP2D6 inhibitors increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3-fold. Do not exceed 18 mg/dose and 36 mg/day of deutetrabenazine if coadministered with strong CYP2D6 inhibitors.
- dextroamphetamine transdermal
dacomitinib will increase the level or effect of dextroamphetamine transdermal by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and CYP2D6 inhibitor.
- oliceridine
dacomitinib will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
- pitolisant
dacomitinib will increase the level or effect of pitolisant by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. If coadministered with strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg/day and increase after 7 days to maximum of 17.8 mg/day. For patients currently taking pitolisant, reduce pitolisant dose by half upon initiating strong CYP2D6 inhibitors.
- siponimod
siponimod and dacomitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
Minor (0)
Adverse Effects
>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
Warnings
Contraindications
None
Cautions
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
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
Verify pregnancy status of females of reproductive potential prior to initiating treatment
Advise females of reproductive potential to use effective contraception during treatment and for at least 17 days after final dose
Animal data
- In animal reproduction studies, oral administration of dacomitinib to pregnant rats during organogenesis period resulted in an increased incidence of postimplantation loss and reduced fetal body weight at doses resulting in similar exposures seen at the 45-mg human dose
- Absence of EGFR signaling resulted in embryo lethality as well as postnatal death in animals
- Advise pregnant women of the potential risk to a fetus
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
Because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 17 days after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Irreversible kinase inhibitor of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR-activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation)
Also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 in vitro at clinically relevant concentrations
Demonstrates dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing SC implanted human tumor xenografts driven by HER family targets including mutated EGFR; also, exhibits antitumor activity in orally dosed mice bearing intracranial human tumor xenografts driven by EGFR amplifications
Absorption
Peak plasma concentration: 108 ng/mL
Peak plasma time (single 45-mg dose): 6 hr
AUC: 2213 ng·hr/mL
Time to steady-state: 14 days
Bioavailability: 80%
Effect of food
- Administration with a high-fat, high-calorie meal (~800-1000 calories with 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively) had no clinically meaningful effect on dacomitinib pharmacokinetics
Distribution
Vd (steady-state): 1889 L
Protein binding: 98%
Metabolism
Hepatic metabolism is main route of clearance, with oxidation and glutathione conjugation as the major pathways
Following oral administration of a single 45-mg dose of [14C] dacomitinib, the most abundant circulating metabolite was O-desmethyl dacomitinib, which had similar in vitro pharmacologic activity as dacomitinib
Elimination
Half-life (single 45-mg dose): 70 hr
Clearance (single 45-mg dose): 24.9 L/hr
Excretion: Feces 79% (20% unchanged); urine 3% (<1% unchanged)
Administration
Oral Administration
Administer with or without food at the same time each day
If patient vomits or misses a dose, do not take an additional dose or make up a missed dose but continue with next scheduled dose
Storage
Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
Images
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
