VIZIMPRO

Treatment with Vizimpro should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. 4). Posology The recommended dose of Vizimpro is 45 mg taken orally once daily, until disease progression or unacceptable toxicity occurs.

Patients should be encouraged to take their dose at approximately the same time each day. If the patient vomits or misses a dose, an additional dose should not be taken and the next prescribed dose should be taken at the usual time the next day.

Dose modifications Dose modifications may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose of Vizimpro should be reduced as described in Table 1. 8). Table 1. Recommended dose modifications for Vizimpro adverse reactions Dose level Dose (once daily) Recommended starting dose 45 mg First dose reduction 30 mg Second dose reduction 15 mg Table 2.

Dose modification and management for Vizimpro adverse reactions Adverse reactions Dose modification Interstitial lung disease (ILD/Pneumonitis) • Withhold dacomitinib during ILD/Pneumonitis diagnostic evaluation. • Permanently discontinue dacomitinib if ILD/Pneumonitis is confirmed.

Diarrhoea • For Grade 1 diarrhoea, no dose modification is required. , loperamide) at first onset of diarrhoea. Encourage adequate oral fluid intake during diarrhoea. , loperamide) and adequate oral fluid intake, withhold dacomitinib.

Upon recovery to Grade ≤ 1, resume dacomitinib at the same dose level or consider a reduction of 1 dose level. • For Grade ≥ 3 diarrhoea, withhold dacomitinib. , loperamide), and adequate oral fluid intake or intravenous fluids or electrolytes as appropriate.

Upon recovery to Grade ≤ 1, resume dacomitinib with a reduction of 1 dose level. Skin-related adverse reactions • For Grade 1 rash or erythematous skin conditions, no dose modification is required. , antibiotics, topical steroids, and emollients).

• For Grade 1 exfoliative skin conditions, no dose modification is required. , oral antibiotics and topical steroids). • For Grade 2 rash, erythematous or exfoliative skin conditions, no dose modification is required. , oral antibiotics and topical steroids).

• If Grade 2 rash, erythematous or exfoliative skin conditions persist for 72 hours despite treatment, withhold dacomitinib. Upon recovery to Grade ≤ 1, resume dacomitinib at the same dose level or consider a reduction of 1 dose level.

7 weeks. 4%). 7% of patients treated with dacomitinib. 2%). 2% of patients treated with dacomitinib. 5%). 7% of patients treated with dacomitinib. 8%). Tabulated list of adverse reactions Table 3 presents adverse reactions for Vizimpro. Adverse reactions are listed according to system organ class (SOC).

Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first, using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 3. Adverse reactions reported in dacomitinib clinical studies (N=255) System organ class Very common Common Metabolism and nutrition disorders Decreased appetite Hypokalaemiaa Dehydration Nervous system disorders Dysgeusia Eye disorders Conjunctivitisb Keratitis Respiratory, thoracic and mediastinal disorders Interstitial lung disease*c Gastrointestinal disorders Diarrhoea* Stomatitisd Vomiting Nausea Skin and subcutaneous tissue disorders Rashe Palmar-plantar erythrodysaesthesia syndrome Skin fissures Dry skinf Pruritusg Nail disorderh Alopecia Skin exfoliationi Hypertrichosis General disorders and administration site conditions Fatigue Asthenia Investigations Transaminases increasedj Weight decreased Data based on pool of 255 patients who received Vizimpro 45 mg once daily as starting dose for first-line treatment of NSCLC with EGFR-activating mutations across clinical studies.

* Fatal events were reported. a Hypokalaemia includes the following preferred terms (PTs): Blood potassium decreased, Hypokalaemia. b Conjunctivitis includes the following PTs: Blepharitis, Conjunctivitis, Dry eye, Noninfective conjunctivitis.

c Interstitial lung disease includes the following PTs: Interstitial lung disease, Pneumonitis. d Stomatitis includes the following PTs: Aphthous ulcer, Cheilitis, Dry mouth, Mucosal inflammation, Mouth ulceration, Oral pain, Oropharyngeal pain, Stomatitis.

Assessment of EGFR mutation status When assessing the EGFR mutation status of a patient, it is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations. 8). Patients with a history of ILD have not been studied.

, dyspnoea, cough, fever) should be performed to exclude ILD/pneumonitis. Treatment with dacomitinib should be withheld pending investigation of these symptoms. 2). 8). Diarrhoea may result in dehydration with or without renal impairment, which could be fatal if not adequately treated.

Proactive management of diarrhoea should start at the first sign of diarrhoea especially within the first 2 weeks of starting dacomitinib, including adequate hydration combined with anti-diarrhoeal medicinal products and continued until loose bowel movements cease for 12 hours.

, loperamide) should be used and, if necessary, escalated to the highest recommended approved dose. Patients may require dosing interruption and/or dose reduction of therapy with dacomitinib. 2). 8). For prevention of dry skin, initiate treatment with moisturizers, and upon development of rash, initiate treatment with topical antibiotics, emollients, and topical steroids.

Start oral antibiotics and topical steroids in patients who develop exfoliative skin conditions. Consider adding broad spectrum oral or intravenous antibiotics if any of these conditions worsen to greater than or equal to Grade 2 severity.

Rash, erythematous and exfoliative skin conditions may occur or worsen in areas exposed to the sun. Advise patients to use protective clothing and sunscreen before exposure to the sun. 2). 8). 6%) patients. Across the dacomitinib program, hepatic failure led to a fatal outcome in 1 patient.

Therefore, periodic liver function testing is recommended. 2). Medicinal products metabolised by cytochrome P450 (CYP)2D6 Vizimpro may increase exposure (or decrease exposure of active metabolites) of other medicinal products metabolised by CYP2D6.

1.