Dacomitinib: Drug information

(For additional information see "Dacomitinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (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: Hepatic 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%:

Cardiovascular: Chest pain (10%)

Central nervous system: Insomnia (11%)

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

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

Gastrointestinal: Diarrhea (87%), stomatitis (45%; grades 3/4: 4%), decreased appetite (31%), nausea (19%), constipation (13%), oral mucosa ulcer (12%)

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

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

Neuromuscular & skeletal: Limb pain (14%), asthenia (13%), musculoskeletal pain (12%)

Ophthalmic: Conjunctivitis (19%)

Renal: Increased creatinine clearance (24%)

Respiratory: Cough (21%), nasal signs and symptoms (19%), dyspnea (13%), upper respiratory tract infection (12%)

1% to 10%:

Central nervous system: Fatigue (9%)

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

Endocrine & metabolic: Dehydration (1%)

Gastrointestinal: Vomiting (9%), dysgeusia (7%)

Ophthalmic: Keratitis (2%)

Respiratory: Interstitial pulmonary disease (3%)

<1%, postmarketing, and/or case reports: 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): $641.17

30 mg (per each): $641.17

45 mg (per each): $641.17

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 (2016) 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 2016; 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:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

High-alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Amitriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

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

Amphetamines: CYP2D6 Inhibitors (Strong) may increase the 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 therapy

ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the 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

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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

Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the 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 serum concentrations of the active metabolite(s) of Benzhydrocodone. Risk C: Monitor therapy

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

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

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

ClomiPRAMINE: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Strong) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

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

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

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

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

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the serum concentration of Dextromethorphan. Risk C: Monitor therapy

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

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

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

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

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the 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 the 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 serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

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

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

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

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

Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy

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

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

Histamine H2 Receptor Antagonists: May decrease the 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 serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor therapy

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

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. 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 concentrations of the active metabolite(s) of Imipramine. The concentrations of desipramine may be increased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Imipramine. Risk C: Monitor therapy

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

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the 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 combination

Lofepramine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Pitolisant: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Risk D: Consider therapy modification

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy

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

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

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

RisperiDONE: CYP2D6 Inhibitors (Strong) may increase the 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 the 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

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) 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 the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the serum concentration of Thioridazine. Risk X: Avoid combination

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

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

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

TraMADol: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

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

Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the 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

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

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)

(AR) Argentina: Vizimpro;
(AT) Austria: Vizimpro;
(CH) Switzerland: Vizimpro;
(CN) China: Vizimpro;
(CO) Colombia: Vizimpro;
(DE) Germany: 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;
(SE) Sweden: Vizimpro;
(SK) Slovakia: Vizimpro;
(TR) Turkey: Vizimpro;
(TW) Taiwan: Vizimpro;
(ZA) South Africa: Vizimpro

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Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
Mok TS, Cheng Y, Zhou X, et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018;36(22):2244-2250. doi:10.1200/JCO.2018.78.7994 [PubMed 29864379]
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Vizimpro (dacomitinib) [prescribing information]. New York, NY: Pfizer Labs; December 2020.
Vizimpro (dacomitinib) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; July 2021.
Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomized, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. [PubMed 28958502]

Topic 119171 Version 88.0

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Dacomitinib: Drug information