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Dacomitinib (Dacomitinib) instructions
Common name: Dacomitinib
Trade name: Vizimpro
All names: Dacomitinib, Dacomitinib, Dacomitinib, Dacomitinib, Vizimpro, DacoMitinib, Dacoplice, PF299804
Indications:
Intended for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R missense mutations
Usage and dosage:
The recommended dose is 45 mg orally daily until disease progression or unacceptable toxicity.
Can be taken with or without food.
Take Vizimpro at a fixed time every day. If the patient vomits or misses a dose, do not take additional or missed doses but continue with the next dose.
Adverse reactions:
>10%:
Cardiovascular: chest pain (10%)
Central nervous system: insomnia (11%)
Dermatology: rash (69%-78%), paronychia (64%), xeroderma (30%), alopecia (23%), pruritus (21%), palmar and plantar redness (15%), skin inflammation (11%)
Endocrine metabolism: hypoalbuminemia (44%), hyperglycemia (36%), hypocalcemia (33%), hypokalemia (29%), hyponatremia (26%), weight loss (26%), hypomagnesemia (22%)
Gastrointestinal tract: diarrhea (87%), stomatitis (45%; grade 3/4: 4%), decreased appetite (31%), nausea (22%) 19%), constipation (13%), oral mucosal ulcers (12%)
Hematology and tumors: anemia (44%; grade 3/4: <1%), lymphopenia (42%; grade 3/4: 6%)
Liver: elevated serum alanine aminotransferase (40%), elevated serum aspartate aminotransferase (35%), elevated serum alkaline phosphatase (22%), hyperbilirubinemia ( 16%)
Neuromuscular and skeletal: limb pain (14%), fatigue (13%), musculoskeletal pain (12%)
Ophthalmology: conjunctivitis (19%)
Renal: increased creatinine clearance (24%)
Respiratory system: cough (21%), nasal symptoms (19%), dyspnea (13%), upper respiratory tract infection (12%)
1% -10%:
Central nervous system: fatigue (9%)
Dermatology: chapped skin (9%), skin loss (4%-7%), hirsutism (1%)
Endocrine metabolism: dehydration (1%)
Gastrointestinal tract: vomiting (9%), Loss of appetite (7%)
Ophthalmology: Keratitis (2%)
Respiratory: Interstitial lung disease (3%)
<1%:
Postmarketing or case reports: Pneumonia
Contraindications:
None.
Notes:
Interstitial Lung Disease (ILD): Serious and fatal ILD/pneumonitis occurred in 0.5% of 394 patients treated with VIZIMPRO; 0.3% of cases died. Monitor patient's lungs for symptoms of ILD/pneumonitis. For patients who exhibit worsening of respiratory symptoms that may be ILD (e.g., dyspnea, cough, and fever), VIZIMPRO should be withheld and the presence of ILD investigated immediately. If ILD is confirmed, permanently discontinue VIZIMPRO.
Diarrhea: Serious and fatal diarrhea has occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of 394 patients treated with VIZIMPRO. Grade 3 or 4 diarrhea was reported in 11% of patients, and fatal cases occurred in 0.3%. For Grade 2 or higher diarrhea, VIZIMPRO should be discontinued until recovery to less than or equal to Grade 1 severity, then VIZIMPRO should be resumed at the same or reduced dose depending on the severity of the diarrhea. Promptly initiate antidiarrheal treatment (loperamide or phenethoxylate hydrochloride with atropine sulfate).
Adverse Skin Reactions: Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Among 394 patients treated with VIZIMPRO, the incidence of rash was 78%. Grade 3 or 4 rash occurred in 21% of patients. Exfoliative skin reactions occurred in 7% of patients and 1.8% of patients experienced grade 3 or 4 exfoliative skin reactions. For persistent Grade 2 or any Grade 3 or 4 dermatological adverse reaction, VIZIMPRO should be withheld until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or reduced dose based on the severity of the dermatological adverse reaction. The incidence and severity of rashes and exfoliative skin reactions may increase with sun exposure. When using VIZIMPRO, be careful to use moisturizer and take appropriate measures to protect against sun exposure. Once grade 1 rash occurs, treatment with topical antibiotics and topical steroids should be initiated. For grade 2 or more severe dermatological adverse reactions, oral antibiotics should be initiated.
Embryo-fetal toxicity: Based on the results of animal studies and its mechanism of action, VIZIMPRO can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during fetal organogenesis resulted in an increased incidence of postimplantation loss and decreased fetal weight. Lack of EGFR signaling has been shown to cause embryonic lethality and postnatal death in animals. Pregnant women are advised to be aware of potential risks to the fetus. Advise females of reproductive potential to use effective contraception whenever possible during treatment with VIZIMPRO and until at least 17 days after the last dose.
Storage:
Store at 20°C to 25°C (68°F to 77°F); excursions allowed between 15°C to 30°C (59°F to 86°F).
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 exon 21 L858R substitution mutation). Dacomitinib also inhibits the activities of DDR1, EPHA6, LCK, DDR2 and MNK1 in vitro at clinically relevant concentrations.
In mice carrying subcutaneously implanted human tumor xenografts driven by mutated HER family targets of the EGFR family, dacomitinib showed dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth. Dacomitinib also showed antitumor activity in mice orally administered intracranial human tumor xenografts driven by EGFR amplification.