PHODACO(Dacomitinib)15mg

Brand Names: PHODACO(Dacomitinib)15mg

Generic name: Dacomitinib

Dosage form: 15mg* 30 tablets/bottle

Usual Adult Dose for:

Non-small Cell Lung Cancer

Indicated for first-line treatment of patients with metastatic non-small 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

45 mg PO qDay

Continue until disease progression or unacceptable toxicity occurs

Also see Administration

Dosage Modifications

First dose reduction: 30 mg qDay

Second dose reduction: 15 mg qDay

Interstitial lung disease (ILD)

• Any grade: Permanently discontinue treatment

Diarrhea

• Grade 2: Withhold treatment until recovery to Grade ≤1; then resume treatment at the same dose level
• For recurrent Grade 2 OR Grade ≥3: Withhold until recovery to Grade ≤1; then resume treatment at a reduced dose

Dermatologic adverse reactions

• Grade 2: Withhold treatment for persistent dermatologic adverse reactions; upon recovery to Grade ≤1, resume treatment at same dose level
• For recurrent persistent Grade 2 OR Grade ≥3 dermatologic adverse reactions, withhold until recovery to Grade ≤1; then resume treatment at a reduced dose

Other adverse reactions

• Grade 3 or 4: Withhold treatment until recovery to Grade ≤2; then resume treatment at a reduced dose

Renal impairment

• Mild or moderate (CrCl 30-89 mL/min estimated by Cockcroft-Gault equation): No dosage adjustment necessary
• Severe (CrCl <30 mL/min): Recommended dose not established

Hepatic impairment

• No dosage modification recommended in patients with mild, moderate or severe hepatic impairment (Child-Pugh A, B or C)

·Adverse Effects

·        >10% (All Grades)

• Diarrhea (87%)
• Rash (69%)
• Paronychia (64%)
• Stomatitis (45%)
• Anemia (44%)
• Hypoalbuminemia (44%)
• Lymphopenia (42%)
• Increased ALT (40%)
• Hyperglycemia (36%)
• Increased AST (35%)
• Hypocalcemia (33%)
• Decreased appetite (31%)
• Dry skin (30%)
• Hypokalemia (29%)
• Decreased weight (26%)
• Hyponatremia (26%)
• Increased creatinine (24%)
• Alopecia (23%)
• Increased alkaline phosphatase (22%)
• Hypomagnesemia (22%)
• Pruritus (21%)
• Cough (21%)
• Nasal mucosal disorder (19%)
• Conjunctivitis (19%)
• Nausea (19%)
• Hyperbilirubinemia (16%)
• Palmar-plantar erythrodysesthesia syndrome (15%)
• Pain in extremity (14%)
• Dyspnea (13%)
• Constipation (13%)
• Asthenia (13%)
• Mouth ulceration (12%)
• Musculoskeletal pain (12%)
• Upper respiratory tract infection (12%)
• Dermatitis (11%)
• Insomnia (11%)

·        1-10% (All Grades)

• Chest pain (10%)
• Fatigue (9%)
• Vomiting (9%)
• Skin fissures (9%)
• Dysgeusia (7%)
• Skin exfoliation/exfoliative skin reactions (3.5%)
• Interstitial lung disease (2.6%)
• Keratitis (1.8%)
• Hypertrichosis (1.3%)
• Dehydration (1.3%)

·        1-10% (Grade 3 or 4)

• Hypokalemia (7%)
• Lymphopenia (6%)
• Decreased appetite (3.1%)
• Hyponatremia (2.9%)
• Decreased weight (2.2%)
• Dyspnea (2.2%)
• Asthenia (2.2%)
• Upper respiratory tract infection (1.3%)
• Dry skin (1.8%)
• Dermatitis (1.8%)
• Increased ALT (1.4%)
• Hypocalcemia (1.4%)
• Hyperglycemia (1%)

·        <1% (Grade 3 or 4)

• Alopecia
• Pruritus
• Palmar-plantar erythrodysesthesia syndrome
• Musculoskeletal pain
• Insomnia
• Anemia
• Increased alkaline phosphatase
• Hypomagnesemia
• Hyperbilirubinemia
• Increased AST

Warnings

Contraindications

None

Cautions

Severe and fatal ILD/pneumonitis occurred; monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold treatment and promptly investigate for ILD in patients who present with worsening of respiratory symptoms, which may be indicative of ILD (eg, dyspnea, cough, fever); permanently discontinue treatment if ILD is confirmed

Severe and fatal diarrhea occurred; promptly initiate antidiarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea

Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Dermatologic adverse reactions

• Rash and exfoliative skin reactions occurred; incidence and severity of rash and exfoliative skin reactions may increase with sun exposure
• At time of initiation of treatment, 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 severe dermatologic adverse reactions

Drug interactions overview

• Dacomitinib inhibits UGT1A1, P-gp, BCRP, and organic cation transporter (OCT)1
• Dacomitinib is a P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) substrate
• Concomitant use of acid-reducing agents
  • Avoid use with proton pump inhibitors (PPIs)
  • As an alternative to PPIs, use locally acting antacids, or, if using a histamine 2 (H2)-receptor antagonist, administer dacomitinib at least 6 hr before or 10 hr after taking an H2-receptor antagonist
  • Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy
• Effect of dacomitinib on CYP2D6 substrates
  • Concomitant use of dacomitinib increases concentration of CYP2D6 substrates, which may increase the risk of toxicities of these drugs
  • Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities

Storage requirements:
-Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).

General:
-Concomitant use of proton pump inhibitors (PPIs) with this drug should be avoided.
-Treatment with this drug should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.