Dacomitinib: Drug information

For additional information see "Dacomitinib: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Vizimpro

Brand Names: Canada

Vizimpro [DSC]

Pharmacologic Category

Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Note: Prior to treatment, confirm tumor epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. When beginning therapy with dacomitinib, initiate moisturizers and limit sun exposure to minimize dermatologic adverse events.

Non–small cell lung cancer, metastatic, first-line therapy

Non–small cell lung cancer, metastatic, first-line therapy (EGFR exon 19 deletion- or exon 21 L858R substitution mutation-positive): Oral: 45 mg once daily until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed or vomited, do not make up the missed/vomited dose; administer the next dose as scheduled.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment is necessary.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Liver Impairment: Adult

Mild, moderate, or severe (Child-Pugh A, B, or C) impairment: No dosage adjustment is necessary.

Dosing: Adjustment for Toxicity: Adult

**Recommended Dacomitinib Dose Reductions for Adverse Reactions**
Dose level	Dose
Initial/usual dose	45 mg once daily
First dose reduction	30 mg once daily
Second dose reduction	15 mg once daily

**Recommended Dose Modifications for Dacomitinib**
Adverse reaction	Severity	Dose modification
Interstitial lung disease	Worsening respiratory symptoms (eg, dyspnea, cough, and fever)	Withhold dacomitinib and promptly evaluate for interstitial lung disease.
Interstitial lung disease	Confirmed (any grade)	Permanently discontinue dacomitinib.
Diarrhea	Any	Promptly initiate antidiarrheal treatment (eg, loperamide or diphenoxylate and atropine).
	Grade 2	Withhold dacomitinib therapy until recovery to ≤ grade 1; resume therapy at the same dose. If grade 2 diarrhea recurs, withhold until recovery to ≤ grade 1; resume therapy at a reduced dose.
	Grade 3 or 4	Withhold dacomitinib therapy until recovery to ≤ grade 1; resume therapy at a reduced dose.
Dermatologic toxicity	Grade 1	Initiate topical antibiotics and topical steroids.
	Grade 2	Administer oral antibiotics. Withhold dacomitinib for persistent grade 2 reactions; upon recovery to ≤ grade 1, resume dacomitinib at the same dose. If grade 2 dermatologic toxicity recurs, withhold until recovery to ≤ grade 1; resume therapy at a reduced dose.
	Grade 3 or 4	Administer oral antibiotics. Withhold dacomitinib therapy until recovery to ≤ grade 1; resume therapy at a reduced dose.
Other toxicities	Grade 3 or 4 adverse reaction	Withhold dacomitinib therapy until recovery to ≤ grade 2; resume therapy at a reduced dose.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Alopecia (23%), dermatitis (11%), palmar-plantar erythrodysesthesia (15%), paronychia (64%), pruritus (21%), skin rash (69% to 78%), xeroderma (30%)

Endocrine & metabolic: Hyperglycemia (36%), hypoalbuminemia (44%), hypocalcemia (33%), hypokalemia (29%), hypomagnesemia (22%), hyponatremia (26%), weight loss (26%)

Gastrointestinal: Constipation (13%), decreased appetite (31%), diarrhea (87%; grades 3/4: 8% to 11%), nausea (19%; grades 3/4: 1%), oral mucosa ulcer (12%), stomatitis (45%; grades 3/4: 4%)

Hematologic & oncologic: Anemia (44%; grades 3/4: <1%), lymphocytopenia (42%; grades 3/4: 6%)

Hepatic: Hyperbilirubinemia (16%), increased serum alanine aminotransferase (40%), increased serum alkaline phosphatase (22%), increased serum aspartate aminotransferase (35%)

Nervous system: Asthenia (13%), insomnia (11%)

Neuromuscular & skeletal: Limb pain (14%), musculoskeletal pain (12%)

Ophthalmic: Conjunctivitis (19%)

Renal: Increased creatinine clearance (24%)

Respiratory: Cough (21%), dyspnea (13%), nasal signs and symptoms (19%; including epistaxis, nasal mucosa swelling, nasal mucosal ulcer, rhinitis), upper respiratory tract infection (12%)

1% to 10%:

Cardiovascular: Chest pain (10%)

Dermatologic: Exfoliation of skin (4% to 7%), hypertrichosis (1%), skin fissure (9%)

Endocrine & metabolic: Dehydration (1%)

Gastrointestinal: Dysgeusia (7%), vomiting (9%)

Nervous system: Fatigue (9%)

Ophthalmic: Keratitis (2%)

Respiratory: Interstitial lung disease (≤3%)

<1%: Respiratory: Pneumonitis

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to dacomitinib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Rash and exfoliative skin reactions have occurred with dacomitinib, including grade 3 or 4 events. Rash has been observed in over three-quarters of patients treated with dacomitinib. Sun exposure may increase the incidence and severity of dermatologic toxicity; limit sun exposure and utilize sunscreen when beginning dacomitinib treatment. Dry skin and nail disorders have been commonly reported with dacomitinib.

• Gastrointestinal toxicity: Severe and fatal diarrhea has occurred in patients treated with dacomitinib. Diarrhea was reported in the majority of patients; grade 3 or 4 events have been reported. Promptly initiate antidiarrheal treatment (eg, loperamide or diphenoxylate and atropine). Mucositis/stomatitis has been observed with dacomitinib.

• Pulmonary toxicity: Interstitial lung disease (ILD), including severe and fatal ILD/pneumonitis, has been reported with dacomitinib.

Special populations:

• Older adult: Patients ≥65 years of age may experience a higher incidence of grade 3 and 4 adverse events, more frequent dose interruptions, and more frequent treatment discontinuations.

Other warnings/precautions:

• Appropriate use: Confirm the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations in tumor specimen prior to therapy initiation. Information on diagnostic tests approved for detection of EGFR mutations may be found at www.fda.gov/companiondiagnostics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Vizimpro: 15 mg, 30 mg, 45 mg [contains fd&c blue #2 aluminum lake]

Generic Equivalent Available: US

Pricing: US

Tablets (Vizimpro Oral)

15 mg (per each): $660.40

30 mg (per each): $660.40

45 mg (per each): $660.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Vizimpro: 15 mg [DSC], 30 mg [DSC], 45 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]

Prescribing and Access Restrictions

Dacomitinib is available through specialty pharmacies and various specialty institutions/accounts. Examples from the manufacturer at may be found at https://vizimpro.pfizerpro.com/files/Specialty_Pharmacy_List.pdf.

Administration: Adult

Oral: Administer at the same time each day with or without food.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Dacomitinib may cause teratogenicity, reproductive toxicity, and has a structural or toxicity profile similar to existing hazardous agents.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Non–small cell lung cancer, metastatic: First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an approved test.

Medication Safety Issues

Sound-alike/look-alike issues:

Dacomitinib may be confused with afatinib, dabrafenib, dasatinib, erlotinib, gefitinib, osimertinib

High alert medication:

High alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of BCRP, CYP2D6 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Strong);

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Ajmaline. Risk C: Monitor

Amitriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amitriptyline. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor

Amoxapine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amoxapine. Risk C: Monitor

Amphetamines: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. Risk C: Monitor

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification

ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification

Atomoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider Therapy Modification

Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Benzhydrocodone. Risk C: Monitor

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder Risk D: Consider Therapy Modification

Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor

Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor

Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor

ClomiPRAMINE: CYP2D6 Inhibitors (Strong) may increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor

CloZAPine: CYP2D6 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor

Codeine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor

Dapoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk C: Monitor

Desipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Desipramine. Risk C: Monitor

Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification

Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dextromethorphan. Risk C: Monitor

Doxepin (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Doxepin (Systemic). Risk C: Monitor

Doxepin (Topical): CYP2D6 Inhibitors (Strong) may increase serum concentration of Doxepin (Topical). Risk C: Monitor

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DULoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of DULoxetine. Risk C: Monitor

Eliglustat: CYP2D6 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification

Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification

Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor

Flecainide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Flecainide. Risk C: Monitor

FLUoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FLUoxetine. Risk C: Monitor

FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor

FluvoxaMINE: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluvoxaMINE. Risk C: Monitor

Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor

Haloperidol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor

Histamine H2 Receptor Antagonists: May decrease serum concentration of Dacomitinib. Management: Administer dacomitinib at least 6 hours before or 10 hours after an histamine H2-receptor antagonist (H2RA). Risk D: Consider Therapy Modification

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor

Iboga: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iboga. Risk C: Monitor

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification

Imipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Imipramine. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Imipramine. The concentrations of desipramine may be increased. Risk C: Monitor

Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with PPIs and PCABs. Antacids may be used. Histamine H2-receptor antagonists (HR2A) may be used if dacomitinib is given at least 6 hours before or 10 hours after the H2RA. Risk X: Avoid

Lofepramine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor

Lofexidine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Lofexidine. Risk C: Monitor

Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor

Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid

Methadone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Methadone. Risk C: Monitor

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider Therapy Modification

Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor

Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor

Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor

Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor

Nortriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nortriptyline. Risk C: Monitor

Oliceridine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor

Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor

Opipramol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Opipramol. Risk C: Monitor

OxyCODONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of OxyCODONE. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor

PARoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of PARoxetine. Risk C: Monitor

Perhexiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perhexiline. Risk C: Monitor

Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor

Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid

Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification

Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification

Propafenone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propafenone. Risk C: Monitor

Propranolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propranolol. Risk C: Monitor

Protriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Protriptyline. Risk C: Monitor

RisperiDONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification

Sertindole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider Therapy Modification

Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification

Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification

Thioridazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Thioridazine. Risk X: Avoid

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor

Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor

Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor

TraMADol: CYP2D6 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of TraMADol. Risk C: Monitor

Trimipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Trimipramine. Risk C: Monitor

Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification

Vortioxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level. Risk D: Consider Therapy Modification

Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor

Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Zuclopenthixol. Risk C: Monitor

Reproductive Considerations

Verify pregnancy status prior to initiating dacomitinib in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 17 days after the last dacomitinib dose.

Pregnancy Considerations

Based on data from animal reproduction studies and the mechanism of action, in utero exposure to dacomitinib may cause fetal harm.

Breastfeeding Considerations

It is not known if dacomitinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 17 days after the last dacomitinib dose.

Monitoring Parameters

Prior to treatment, confirm epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution mutation status. Verify pregnancy status prior to therapy initiation (in patients who could become pregnant). Monitor for signs/symptoms of interstitial lung disease/pneumonitis (eg, dyspnea, cough, fever), diarrhea, and dermatologic toxicity. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Mechanism of Action

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has activity against EGFR/HER1, HER2, and HER4, as well as some EGFR-activating mutations (exon 19 deletion or exon 21 L858R substitution mutation). Dacomitinib also has activity against DDR1, EPHA6, LCK, DDR2, and MNK1 (in vitro).

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_ss: 1,889 L

Protein binding: ~98%

Metabolism: Hepatic, primarily via oxidation and glutathione conjugation; CYP2D6 is involved in the formation of O-desmethyl dacomitinib (active), and CYP3A4 contributes to the formation of minor oxidative metabolites

Bioavailability: 80%

Half-life elimination: 70 hours

Time to peak: ~6 hours (range: 2 to 24 hours)

Excretion: Feces: 79% (20% as parent drug); Urine: 3% (<1% as parent drug)

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Vizimpro;
(AR) Argentina: Vizimpro;
(AT) Austria: Vizimpro;
(CH) Switzerland: Vizimpro;
(CN) China: Vizimpro;
(CO) Colombia: Vizimpro;
(DE) Germany: Vizimpro;
(EC) Ecuador: Vizimpro;
(EG) Egypt: Vizimpro;
(ES) Spain: Vizimpro;
(FI) Finland: Vizimpro;
(FR) France: Vizimpro;
(GB) United Kingdom: Vizimpro;
(ID) Indonesia: Davizim;
(IE) Ireland: Vizimpro;
(IN) India: Dacoplice;
(JP) Japan: Vizimpro;
(KR) Korea, Republic of: Vizimpro;
(KW) Kuwait: Vizimpro;
(LB) Lebanon: Vizimpro;
(MX) Mexico: Vizimpro;
(MY) Malaysia: Vizimpro;
(NL) Netherlands: Vizimpro;
(NO) Norway: Vizimpro;
(PE) Peru: Vizimpro;
(PL) Poland: Vizimpro;
(PR) Puerto Rico: Vizimpro;
(QA) Qatar: Vizimpro;
(SA) Saudi Arabia: Vizimpro;
(SE) Sweden: Vizimpro;
(SK) Slovakia: Vizimpro;
(TR) Turkey: Vizimpro;
(TW) Taiwan: Vizimpro;
(ZA) South Africa: Vizimpro

Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
Hodson L, Ovesen J, Couch J, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Managing hazardous drug exposures: information for healthcare settings, 2023. https://doi.org/10.26616/NIOSHPUB2023130. Updated April 2023. Accessed December 27, 2024.
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
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Topic 119171 Version 109.0

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Dacomitinib: Drug information