VIZIMPRO® (dacomitinib) 6 ADVERSE REACTIONS

(dacomitinib)

Prescribing Information

6 ADVERSE REACTIONS

The following adverse drug reactions are described elsewhere in the labeling:

Interstitial Lung Disease [see Warnings and Precautions (5.1)]
Diarrhea [see Warnings and Precautions (5.2)]
Dermatologic Adverse Reactions [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in the Warnings and Precautions section reflect exposure to VIZIMPRO in 394 patients with first-line or previously treated NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations who received VIZIMPRO at the recommended dose of 45 mg once daily in 4 randomized, active-controlled trials [ARCHER 1050 (N=227), Study A7471009 (N=38), Study A7471011 (N=83), and Study A7471028 (N=16)] and one single-arm trial [Study A7471017 (N=30)]. The median duration of exposure to VIZIMPRO was 10.8 months (range 0.07–68) [see Warnings and Precautions (5)].

The data described below reflect exposure to VIZIMPRO in 227 patients with EGFR mutation-positive, metastatic NSCLC enrolled in a randomized, active-controlled trial (ARCHER 1050); 224 patients received gefitinib 250 mg orally once daily in the active control arm [see Clinical Studies (14)]. Patients were excluded if they had a history of ILD, interstitial pneumonitis, or brain metastases. The median duration of exposure to VIZIMPRO was 15 months (range 0.07–37).

The most common (>20%) adverse reactions in patients treated with VIZIMPRO were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%).

Serious adverse reactions occurred in 27% of patients treated with VIZIMPRO. The most common (≥1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%). Dose interruptions occurred in 57% of patients treated with VIZIMPRO. The most frequent (>5%) adverse reactions leading to dose interruptions were rash (23%), paronychia (13%), and diarrhea (10%). Dose reductions occurred in 66% of patients treated with VIZIMPRO. The most frequent (>5%) adverse reactions leading to dose reductions were rash (29%), paronychia (17%), and diarrhea (8%).

Adverse reactions leading to permanent discontinuation of VIZIMPRO occurred in 18% of patients. The most common (>0.5%) adverse reactions leading to permanent discontinuation of VIZIMPRO were: rash (2.6%), interstitial lung disease (1.8%), stomatitis (0.9%), and diarrhea (0.9%).

Tables 3 and 4 summarize the most common adverse reactions and laboratory abnormalities, respectively, in ARCHER 1050. ARCHER 1050 was not designed to demonstrate a statistically significant difference in adverse reaction rates for VIZIMPRO or for gefitinib for any adverse reaction or laboratory value listed in Table 3 or 4.

Table 3. Adverse Reactions Occurring in ≥10% of Patients Receiving VIZIMPRO in ARCHER 1050*
Adverse Reaction	VIZIMPRO (N=227)		Gefitinib (N=224)
	All Grades† %	Grades 3 and 4 %	All Grades %	Grades 3 and 4 %
* National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. † Grades 1 through 5 are included in All Grades. ‡ One Grade 5 (fatal) event in the VIZIMPRO arm. § Stomatitis includes mucosal inflammation and stomatitis. ¶ Rash includes dermatitis acneiform, rash, and rash maculo-papular. # Paronychia includes nail infection, nail toxicity, onychoclasis, onycholysis, onychomadesis, paronychia. Þ Dry skin includes dry skin, xerosis. ß Pruritus includes pruritus, pruritus generalized, rash pruritic. à Nasal mucosal disorder includes epistaxis, nasal inflammation, nasal mucosal disorder, nasal mucosal ulcer, rhinitis.
Gastrointestinal
Diarrhea‡	87	8	56	0.9
Stomatitis§	45	4.4	19	0.4
Nausea	19	1.3	22	0.4
Constipation	13	0	14	0
Mouth ulceration	12	0	6	0
Skin and Subcutaneous Tissue
Rash¶	69	23	47	0.4
Paronychia#	64	8	21	1.3
Dry skinÞ	30	1.8	19	0.4
Alopecia	23	0.4	13	0
Pruritusß	21	0.9	15	1.3
Palmar-plantar erythrodysesthesia syndrome	15	0.9	3.1	0
Dermatitis	11	1.8	4	0.4
Metabolism and Nutrition
Decreased appetite	31	3.1	25	0.4
Decreased weight	26	2.2	17	0.4
Respiratory
Cough	21	0	19	0.4
Nasal mucosal disorderà	19	0	4.9	0
Dyspnea	13	2.2	13	1.8
Upper respiratory tract infection	12	1.3	13	0
Chest pain	10	0	14	0
Eye
Conjunctivitis	19	0	4	0
Musculoskeletal
Pain in extremity	14	0	12	0
Musculoskeletal pain	12	0.9	13	0
General
Asthenia	13	2.2	13	1.3
Psychiatric
Insomnia	11	0.4	15	0

Additional adverse reactions (All Grades) that were reported in <10% of patients who received VIZIMPRO in ARCHER 1050 include:

General: fatigue 9%

Skin and subcutaneous tissue: skin fissures 9%, hypertrichosis 1.3%, skin exfoliation/exfoliative skin reactions 3.5%

Gastrointestinal: vomiting 9%

Nervous system: dysgeusia 7%

Respiratory: interstitial lung disease 2.6%

Ocular: keratitis 1.8%

Metabolism and nutrition: dehydration 1.3%

Table 4. Laboratory Abnormalities Worsening from Baseline in >20% of Patients in ARCHER 1050*
Laboratory Test Abnormality†	VIZIMPRO		Gefitinib
Laboratory Test Abnormality†	Change from Baseline All Grades (%)	Change from Baseline to Grade 3 or Grade 4 (%)	Change from Baseline All Grades (%)	Change from Baseline to Grade 3 or Grade 4 (%)
ALT=alanine aminotransferase; AST=aspartate aminotransferase.
* NCI CTCAE v4.03, except for increased creatinine which only includes patients with creatinine increase based on upper limit of normal definition. † Based on the number of patients with available baseline and at least one on-treatment laboratory test.
Hematology
Anemia	44	0.9	26	2.7
Lymphopenia	42	6	35	2.7
Chemistry
Hypoalbuminemia	44	0	34	0
Increased ALT	40	1.4	63	13
Hyperglycemia	36	1.0	38	2.5
Increased AST	35	0.5	57	8
Hypocalcemia	33	1.4	28	2.0
Hypokalemia	29	7	18	2.0
Hyponatremia	26	2.9	20	1.5
Increased creatinine	24	0	16	0.5
Increased alkaline phosphatase	22	0.5	21	2.0
Hypomagnesemia	22	0.5	9	0
Hyperbilirubinemia	16	0.5	22	0.5

Medication Guide

MEDICATION GUIDE

This Patient Information has been approved by the U.S. Food and Drug Administration.		Issued: September 2018
PATIENT INFORMATION VIZIMPRO® (vih-ZIM-pro) (dacomitinib) tablets
What is VIZIMPRO? VIZIMPRO is a prescription medicine used to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic): As your first treatment if your tumor has certain types of abnormal epidermal growth factor receptor (EGFR) gene(s). Your healthcare provider will perform a test to make sure that VIZIMPRO is right for you. It is not known if VIZIMPRO is safe and effective in children.
Before taking VIZIMPRO, tell your healthcare provider about all your medical conditions, including if you: have frequent diarrhea. have a history of lung or breathing problems other than lung cancer. are pregnant, or plan to become pregnant. VIZIMPRO can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with VIZIMPRO. You should use effective birth control (contraception) during treatment and for at least 17 days after your last dose of VIZIMPRO. Talk to your healthcare provider about birth control methods that may be right for you during this time. Tell your healthcare provider right away if you become pregnant during your treatment with VIZIMPRO. are breastfeeding or plan to breastfeed. It is not known if VIZIMPRO passes into your breast milk. Do not breastfeed during treatment and for at least 17 days after your last dose of VIZIMPRO. Talk to your healthcare provider about the best way to feed your baby during this time. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VIZIMPRO and other medicines or supplements may affect each other causing side effects.
How should I take VIZIMPRO? Take VIZIMPRO exactly as your healthcare provider tells you. Take your dose at approximately the same time each day. Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with VIZIMPRO if you have side effects. Take VIZIMPRO 1 time each day with or without food. If you take an antacid or H2 blocker medicine during treatment with VIZIMPRO, take your dose of VIZIMPRO at least 6 hours before or 10 hours after taking the antacid or H2 blocker medicine. Do not change your dose or stop taking VIZIMPRO unless your healthcare provider tells you. If you vomit or miss a dose of VIZIMPRO, do not take another dose or make up for the missed dose. Take your next dose at your regular time.
What should I avoid during treatment with VIZIMPRO? Minimize exposure to sunlight. VIZIMPRO can cause skin reactions. See "What are the possible side effects of VIZIMPRO?"
What are the possible side effects of VIZIMPRO? VIZIMPRO may cause serious side effects, including: Lung or breathing problems. VIZIMPRO may cause severe inflammation of the lung that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening lung symptoms, including trouble breathing or shortness of breath, cough, or fever. Diarrhea. Diarrhea is common during treatment with VIZIMPRO, and can be severe and lead to death. Diarrhea can cause you to lose too much body fluid (dehydration). Your healthcare provider may tell you to start drinking more fluids or start taking your anti-diarrheal medicines. Tell your healthcare provider right away, if you have any loose stools or have stools more often than is normal for you. Skin reactions. Skin reactions are common with VIZIMPRO and can be severe. These skin reactions may include: dry skin, redness, rash, acne, itching, and peeling or blistering of your skin. Use moisturizers every day when taking VIZIMPRO. Use sunscreen and wear protective clothing that covers your skin, while exposed to sunlight, while you are taking VIZIMPRO. Your healthcare provider may prescribe other medicines to help skin reactions. Tell your healthcare provider right away about any worsening skin reactions. The most common side effects of VIZIMPRO include:
rash diarrhea mouth pain and sores nail inflammation common cold	dry skin decreased appetite decreased weight dry, red, itchy eyes hair loss itching
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store VIZIMPRO? Store VIZIMPRO at 20 °C to 25 °C (68 °F to 77 °F). Keep VIZIMPRO and all medicines out of the reach of children.
General information about the safe and effective use of VIZIMPRO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VIZIMPRO for a condition for which it was not prescribed. Do not give VIZIMPRO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about VIZIMPRO that is written for health professionals.
What are the ingredients in VIZIMPRO? Active ingredient: dacomitinib Inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, and magnesium stearate. Film coating contains: Opadry II® Blue 85F30716 containing: Polyvinyl alcohol – partially hydrolyzed, Talc, Titanium dioxide, Macrogol/PEG 3350, and FD&C Blue #2/Indigo Carmine Aluminum Lake. LAB-1238-1.0 For more information, go to www.VIZIMPRO.com or call 1-800-438-1985.

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