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Vizimpro

Generic Name: Dacomitinib
Class: Antineoplastic Agents
Chemical Name: (E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide;hydrate
Molecular Formula: C24H27ClFN5O3
CAS Number: 1042385-75-0

Medically reviewed by Drugs.com. Last updated on Oct 22, 2018.

Introduction

See also: Alunbrig

Dacomitinib, a kinase inhibitor, is an antineoplastic agent.

Uses for Vizimpro

Dacomitinib has the following uses:

Dacomitinib is indicated for the first-line treatment of patients with metastatic non-small cell 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.1

Vizimpro Dosage and Administration

General

Dacomitinib is available in the following dosage form(s) and strength(s):

Tablets: 15 mg, 30 mg, and 45 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Recommended Dosage: 45 mg orally once daily with or without food.1

Cautions for Vizimpro

Contraindications

None.1

Warnings/Precautions

Interstitial Lung Disease (ILD)

Severe and fatal ILD/pneumonitis occurred in patients treated with dacomitinib and occurred in 0.5% of the 394 dacomitinib-treated patients; 0.3% of cases were fatal.1

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold dacomitinib and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue dacomitinib if ILD is confirmed.1

Diarrhea

Severe and fatal diarrhea occurred in patients treated with dacomitinib. Diarrhea occurred in 86% of the 394 dacomitinib-treated patients; Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal.1

Withhold dacomitinib for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity, then resume dacomitinib at the same or a reduced dose depending on the severity of diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea.1

Dermatologic Adverse Reactions

Rash and exfoliative skin reactions occurred in patients treated with dacomitinib. Rash occurred in 78% of the 394 dacomitinib-treated patients; Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients.1

Withhold dacomitinib for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity, then resume dacomitinib at the same or a reduced dose depending on the severity of the dermatologic adverse reaction. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of dacomitinib, 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 or more severe dermatologic adverse reactions.1

Embryo-fetal Toxicity

Based on findings from animal studies and its mechanism of action, dacomitinib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45 mg human dose. The absence of EGFR signaling has been shown to result in embryolethality as well as post-natal death in animals. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with dacomitinib and for at least 17 days after the final dose.1

Specific Populations

Pregnancy

Risk Summary: Based on findings from animal studies and its mechanism of action, dacomitinib can cause fetal harm when administered to a pregnant woman. There are no available data on dacomitinib use in pregnant women. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45 mg human dose. The absence of EGFR signaling has been shown to result in embryolethality as well as post-natal death in animals. Advise pregnant women of the potential risk to a fetus.1

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Animal Data: Daily oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss, maternal toxicity, and reduced fetal body weight at 5 mg/kg/day (approximately 1.2 times the exposure based on area under the curve [AUC] at the 45 mg human dose).1

Disruption or depletion of EGFR in mouse models has shown EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/post-natal survival and development. Reduction or elimination of embryo-fetal or maternal EGFR signaling in mice can prevent implantation, and can cause embryo-fetal loss during various stages of gestation (through effects on placental development), developmental anomalies, early death in surviving fetuses, and adverse developmental outcomes in multiple organs in embryos/neonates.1

Lactation

There is no information regarding the presence of dacomitinib or its metabolites in human milk or their effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from dacomitinib, advise women not to breastfeed during treatment with dacomitinib and for at least 17 days after the last dose.1

Females And Males Of Reproductive Potential

Verify the pregnancy status of females of reproductive potential prior to initiating dacomitinib.1

Dacomitinib can cause fetal harm when administered to a pregnant woman.1

Advise females of reproductive potential to use effective contraception during treatment with dacomitinib and for at least 17 days after the final dose.1

Pediatric Use

The safety and effectiveness of dacomitinib in pediatrics have not been established.1

Geriatric Use

Of the total number of patients (N=394) in five clinical studies with EGFR mutation-positive NSCLC who received dacomitinib at a dose of 45 mg orally once daily [ARCHER 1050 (N=227), Study A7471009 (N=38), Study A7471011 (N=83), Study A7471028 (N=16), and Study A7471017 (N=30)], 40% were 65 years of age and older.1

Exploratory analyses across this population suggest a higher incidence of Grade 3 and 4 adverse reactions (67% versus 56%, respectively), more frequent dose interruptions (53% versus 45%, respectively), and more frequent discontinuations (24% versus 10%, respectively) for adverse reactions in patients 65 years or older as compared to those younger than 65 years.1

Renal Impairment

No dose adjustment is recommended for patients with mild or moderate renal impairment (creatinine clearance [Clcr] 30 to 89 mL/min estimated by Cockcroft-Gault). The recommended dose of dacomitinib has not been established for patients with severe renal impairment (Clcr <30 mL/min).1

Hepatic Impairment

No dose adjustment is recommended in patients with mild (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN or total bilirubin > 1 to 1.5 × ULN with any AST) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment. The recommended dose of dacomitinib has not been established for patients with severe hepatic impairment (total bilirubin > 3 to 10 × ULN and any AST).1

Common Adverse Effects

Most common adverse reactions are (incidence >20%): diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Proton-pump Inhibitors (PPIs): Avoid use with dacomitinib; use locally acting antacids or H2-receptor antagonist, and administer dacomitinib at least 6 hours before or 10 hours after H2-receptor antagonist.1

  • CYP2D6 Substrates: Avoid concomitant use with dacomitinib where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.1

Actions

Mechanism Of Action

Dacomitinib is an irreversible inhibitor of the kinase activity 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). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.1

Dacomitinib demonstrated dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing subcutaneously implanted human tumor xenografts driven by HER family targets including mutated EGFR. Dacomitinib also exhibited antitumor activity in orally-dosed mice bearing intracranial human tumor xenografts driven by EGFR amplifications.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

Interstitial Lung Disease (ILD)

Advise patients of the risks of severe or fatal ILD, including pneumonitis. Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms.1

Diarrhea

Advise patients to contact their healthcare provider at the first signs of diarrhea. Advise patients that intravenous hydration and/or anti-diarrheal medication (e.g., loperamide) may be required to manage diarrhea.1

Dermatologic Adverse Reactions

Advise patients to initiate use of moisturizers and to minimize sun exposure with protective clothing and use of sunscreen at the time of initiation of dacomitinib. Advise patients to contact their healthcare provider immediately to report new or worsening rash, erythematous and exfoliative reactions.1

Drug Interactions

Advise patients to avoid use of PPIs while taking dacomitinib. Short-acting antacids or H2-receptor antagonists may be used if needed. Advise patients to take dacomitinib at least 6 hours before or 10 hours after taking an H2-receptor antagonist.1

Embryo-Fetal Toxicity

Advise females of reproductive potential that dacomitinib can result in fetal harm and to use effective contraception during treatment with dacomitinib and for 17 days after the last dose of dacomitinib. Advise females of reproductive potential to contact their healthcare provider with a known or suspected pregnancy.1

Lactation

Advise women not to breastfeed during treatment with dacomitinib and for 17 days after the last dose of dacomitinib.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dacomitinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Film Coated

15 mg

Vizimpro

Pfizer

30 mg

Vizimpro

Pfizer

45 mg

Vizimpro

Pfizer

AHFS Drug Information. © Copyright 2019, Selected Revisions October 22, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Pfizer. Vizimpro (dacomitinib) ORAL prescribing information. 2018 Sep. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ab27d2f-e385-4e9c-b324-fa69c10b855a

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