ed adverse reactions of:
•NCI CTCAE* Grade 3 or higher
•Diarrhea of Grade 2 or higher persisting for 2 or more consecutive days while taking anti-diarrheal medication [see Warnings and Precautions (5.1)]
•Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable [see Warnings and Precautions (5.2)]
•Renal dysfunction of Grade 2 or higher
*National Cancer Institute Common Terminology Criteria for Adverse Events, v 3.0
Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1. Reinstitute Gilotrif at a reduced dose, i.e., 10 mg per day less than the dose at which the adverse reaction occurred.
Permanently discontinue Gilotrif for:
•Life-threatening bullous, blistering, or exfoliative skin lesions [see Warnings and Precautions (5.2)]
•Confirmed interstitial lung disease (ILD) [see Warnings and Precautions (5.3)]
•Severe drug-induced hepatic impairment [see Warnings and Precautions (5.4)]
•Persistent ulcerative keratitis [see Warnings and Precautions (5.5)]
•Symptomatic left ventricular dysfunction
•Severe or intolerable adverse reaction occurring at a dose of 20 mg per day
P-gp Inhibitors
For patients who require therapy with a P-glycoprotein (P-gp) inhibitor, reduce Gilotrif daily dose by 10 mg if not tolerated. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
P-gp Inducers
For patients who require chronic therapy with a P-gp inducer, increase Gilotrif daily dose by 10 mg as tolerated. Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
Gilotrif is available as:
40 mg tablets: light blue, film-coated, round, biconvex, bevel-edged tablets debossed with “T40” on one side and the Boehringer Ingelheim company symbol on the other side.
30 mg tablets: dark blue, film-coated, round, biconvex, bevel-edged tablets debossed with “T30” on one side and the Boehringer Ingelheim company symbol on the other side.
20 mg tablets: white to slightly yellowish, film-coated, round, biconvex, bevel-edged tablets debossed with “T20” on one side and the Boehringer Ingelheim company symbol on the other side.
4 CONTRAINDICATIONS
None
5 WARNINGS AND PRECAUTIONS
Diarrhea
Diarrhea has resulted in dehydration with or without renal impairment; some of these cases were fatal. In Study 1, diarrhea occurred in 96% of patients treated with Gilotrif (n=229), of which 15% was Grade 3 in severity and occurred within the first 6 weeks [see Adverse Reactions (6.1)]. Renal impairment as a consequence of diarrhea occurred in 6.1% of patients treated with Gilotrif, out of which 3 (1.3%) were Grade 3.
For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours or greater than or equal to Grade 3 diarrhea, withhold Gilotrif until diarrhea resolves to Grade 1 or less, and resume Gilotrif with appropriate dose reduction [see Dosage and Administration (2.3)]. Provide patients with an anti-diarrheal agent (e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal therapy until loose bowel movements cease for 12 hours |
