Afatinib

Indications

Afatinib is used for: Non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma

Adult Dose

Oral Non-Small Cell Lung Cancer Metastatic Non-Small Cell Lung Cancer, Metastatic Squamous Non-Small Cell Lung Cancer Indicated for first-line treatment in metastatic non-small cell lung cancer (NSCLC) whose tumors have nonresistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test, Indicated for metastatic squamous NSCLC progressing after platinum-based chemotherapy 40 mg once daily, until disease progression or no longer tolerated by the patient, increased if tolerated to up to 50 mg once daily after 3 wk at initial dose.

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl 30-89 mL/min/1.73 m²): No dosage adjustment necessary Severe (CrCl 15-29 mL/min/1.73 m²): 30 mg PO qDay Severe (CrCl<15 mL/min/1.73 m²): Not studied

Administration

Oral Administration Take PO on an empty stomach, at least 1 hour before or 2 hours after a meal Should be taken on an empty stomach. Take at least 1 hr before or 3 hr after meals. Swallow whole. For patients with/ difficulty swallowing, tab may be dispersed in approximately 100 mL of plain, non-carbonated water. No other liqd should be used. Drop the tab in water & stir w/o crushing until it disperses (approx 15 min). Drink immediately. Rinse the glass with/ another 100 mL of water & drink. Dispersed liquid may also be administered via nasogastric tube.

Contra Indications

Hypersensitivity to afatinib. Dialysis patients. Severe hepatic (Child-Pugh class C) and renal (eGFR <15 mL/min/1.73m2) impairment. Lactation.

Precautions

Diarrhea: Diarrhea may result in dehydration and renal failure. Withhold Afatinib for severe and prolonged diarrhea not responsive to antidiarrheal agents. Bullous and exfoliative skin disorders: Severe bullous, blistering, and exfoliating lesions occurred in 0.2% of patients. Discontinue for life-threatening cutaneous reactions. Withhold Afatinib for severe and prolonged cutaneous reactions. Interstitial lung disease (ILD): Occurs in 1.6% of patients. Withhold Afatinib for acute onset or worsening of pulmonary symptoms. Discontinue Afatinib if ILD is diagnosed. Hepatic toxicity: Fatal hepatic impairment occurs in 0.2% of patients. Monitor with periodic liver testing. Withhold or discontinue Afatinib for severe or worsening liver tests. Gastrointestinal perforation: Occurs in 0.2% of patients. Permanently discontinue Afatinib in patients who develop gastrointestinal perforation. Keratitis: Occurs in 0.7% of patients. Withhold Afatinib for keratitis evaluation. Withhold or discontinue Afatinib for confirmed ulcerative keratitis. Embryo-fetal toxicity: This can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus and to use of effective contraception. Monitor with periodic liver testing.

Pregnancy-Lactation

Pregnancy Based on findings from animal studies and mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; there are no available data on use in pregnant women; administration to pregnant rabbits during organogenesis at exposures approximately 0.2 times exposure in humans at recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages; advise pregnant women of potential risk to a fetus Contraception Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose of afatinib Based on results from an animal fertility study, afatinib may reduce fertility in females and males of reproductive potential Unknown if the effects on fertility are reversible Lactation There are no data on presence of afatinib in human milk or effects on breastfed infant or on milk production; presence shown in milk of lactating rats; because of potential for serious adverse reactions in nursing infants, advise a lactating woman not to breastfeed during treatment and for 2 weeks after final dose

Interactions

P-glycoprotein (P-gp) Inhibitors: Co-administration of P-gp inhibitors can increase afatinib exposure. Reduce GILOTRIF by 10 mg per day if not tolerated. P-gp Inducers: Co-administration of chronic P-gp inducers orally can decrease afatinib exposure. Increase GILOTRIF by 10 mg per day as tolerated. Contraindicated (0) Serious - Use Alternative (60) aminolevulinic acid oral aminolevulinic acid topical amiodarone atorvastatin carbamazepine carvedilol clarithromycin cyclosporine darunavir dipyridamole dronedarone edoxaban erdafitinib erythromycin base erythromycin ethylsuccinate erythromycin lactobionate erythromycin stearate etravirine fosphenytoin grapefruit itraconazole ketoconazole lapatinib lasmiditan levoketoconazole lopinavir lovastatin mefloquine methyl aminolevulinate mifepristone nefazodone nelfinavir nifedipine nilotinib palifermin paliperidone phenobarbital phenytoin ponatinib posaconazole progesterone micronized propafenone propranolol quinidine quinine ranolazine rifampin riociguat ritonavir saquinavir simvastatin sotorasib St John's Wort sunitinib tacrolimus tamoxifen tepotinib tipranavir venetoclax verapamil

Adverse Effects

Side effects of Afatinib : >10% Diarrhea (75-96%) Rash/dermatitis acneiform (70-90%) Stomatitis (30-71%) Paronychia (11-58%) Increased ALT (10-54%) Decreased creatinine clearance (49%) Increase alkaline phosphate (34-51%) Increased AST (7-46%) Decreased lymphocytes (38%) Dry skin (31%) Decreased potassium (11-30%) Decreased appetite (25%) Pruritus (21%) Nausea (21%) Epistaxis (17%) Decreased weight (17%) Rash/dermatitis acneiform, Grade 3 or 4 (7-16%) Increased bilirubin (3-16%) Diarrhea, Grade 3 or 4 (11-15%) Vomiting (13%) Cystitis (13%) Decreased WBC (12%) Cheilitis (12%) Rhinorrhea (11%) Paronychia, Grade 3 or 4 (1-11%) 1-10% Stomatitis, Grade 3 or 4 (9%) Decreased lymphocytes, Grade 3 or 4 (9%) Decreased potassium, Grade 3 or 4 (1-8%) Stomatitis, Grade 3 or 4 (4%) Decreased appetite, Grade 3 or 4 (3%) Increased AST, Grade 3 or 4 (1-3%) Increase alkaline phosphate, Grade 3 or 4 (2-3%) Decreased creatinine clearance (2%) Nausea, Grade 3 or 4 (2%) Increased ALT, Grade 3 or 4 (1-2%) Decreased WBC, Grade 3 or 4 (1%) Vomiting, Grade 3 or 4 (1%) Cystitis, Grade 3 or 4 (1%) Decreased weight, Grade 3 or 4 (1%) Increased bilirubin, Grade 3 or 4 (1%) <1% Keratitis (0.8%)

Mechanism of Action

Afatinib is a selective 2nd generation tyrosine kinase inhibitor of the ErbB family, epidermal growth factor receptor (EGFR/ErbB1), and human epidermal growth factor receptor types 2 (HER2/ErbB2) and 4 (HER4/ErbB4), resulting in tumour growth inhibition and tumour regression.