8; Rash/Dermatitis acneiform2 90 16 11 0
Pruritus 21 0 1 0
Dry skin 31 0 2 0
Infections and infestations
Paronychia3 58 11 0 0
Cystitis 13 1 5 0
Metabolism and nutrition disorders
Decreased appetite 29 4 55 4
Respiratory, thoracic and mediastinal disorders
Epistaxis 17 0 2 1
Rhinorrhea 11 0 6 0
Investigations
Weight Investigations 17 1 14 1
General disorders and administration site conditions
Pyrexia 12 0 6 0
Eye disorders
Conjunctivitis 11 0 3 0
Table 2 Adverse Reactions of Laboratory Abnormalities from the Investigations SOC Reported in ≥5% of GILOTRIF-Treated Patients in Study 1 1Includes hypokalemia, blood potassium decreased
SOC=system organ class
GILOTRIF
n=229 Pemetrexed/Cisplatin
n=111
Adverse Reaction All Grades
(%) Grades 3-4
(%) All Grades
(%) Grades 3-4
(%)
Alanine aminotransferase increased 11 2 4 0
Hypokalemia1 11 4 5 4
Aspartate aminotransferase increased 8 2 2 1
7 DRUG INTERACTIONS
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers
Oral administration of a P-gp inhibitor (ritonavir at 200 mg twice daily) 1 hour before administration of GILOTRIF increased systemic exposure to afatinib by 48%. There was no change in afatinib exposure when ritonavir was administered simultaneously with or 6 hours after GILOTRIF. Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
Co-administration with oral dose of a P-gp inducer (rifampicin at 600 mg once daily for 7 days) decreased exposure to afatinib by 34%. Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s Wort) with GILOTRIF can decrease exposure to afatinib [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D
Risk Summary
Based on its mechanism of action, GILOTRIF can cause fetal harm when administered to a pregnant woman. Afatinib was embryotoxic and, in animals with maternal toxicity, led to abortions at late gestational stages in rabbits at doses of 5 mg/kg (approximately 0.2 times the exposure by AUC at the recommended human dose of 40 mg daily) or greater. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.6)].
Animal Data
Administration of afatinib to pregnant rabbits at doses of 5 mg/kg (approximately 0.2 times the exposure by AUC at the recommended human dose of 40 mg daily) or greater during the period of organogenesis caused in |
