Erlotinibdosage

NSCLC: 150 mg orally, on an empty stomach, once daily.

Pancreatic cancer: 100 mg orally, on an empty stomach, once daily.

2.1 Selection of

Patients with Metastatic NSCLC Select patients for the treatment of metastatic NSCLC with erlotinib tablets based on the presence of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in tumor or plasma specimens. If these mutations are not detected in a plasma specimen, test tumor tissue if available. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended

Dose – NSCLC The recommended daily dose of erlotinib tablets for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

2.3 Recommended

Dose – Pancreatic Cancer The recommended daily dose of erlotinib tablets for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take erlotinib tablets on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

2.4 Dose Modifications †

For additional information see Warnings and Precautions. * Reduce erlotinib tablets by 50 mg decrements when restarting therapy following withholding treatment for a dose-limiting toxicity that has resolved to baseline or grade ≤ 1. ‡ For additional information see Drug Interactions. § For additional information see Clinical Pharmacology. Adverse Reactions Pulmonary † Interstitial Lung Disease (ILD) Discontinue erlotinib tablets During diagnostic evaluation for possible ILD Withhold erlotinib tablets * Hepatic † Severe hepatic toxicity that does not improve significantly or resolve within three weeks Discontinue erlotinib tablets In patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases values over baseline Withhold erlotinib tablets * and consider discontinuation In patients without pre-existing hepatic impairment for total bilirubin levels greater than 3 times the upper limit of normal or transaminases greater than 5 times the upper limit of normal Withhold erlotinib tablets * and consider discontinuation Renal † For severe (CTCAE grade 3 to 4) renal toxicity Withhold erlotinib tablets * and consider discontinuation Gastrointestinal † Gastrointestinal perforation Discontinue erlotinib tablets For persistent severe diarrhea not responsive to medical management (e.g., loperamide) Withhold erlotinib tablets Skin † Severe bullous, blistering or exfoliating skin conditions Discontinue erlotinib tablets For severe rash not responsive to medical management Withhold erlotinib tablets * Ocular† Corneal perforation or severe ulceration Discontinue erlotinib tablets For keratitis of (NCI-CTC version 4.0) grade 3 to 4 or for grade 2 lasting more than 2 weeks Withhold erlotinib tablets * For acute/worsening ocular disorders such as eye pain Withhold erlotinib tablets* and consider discontinuation Drug Interactions CYP3A4 inhibitors ‡ If severe reactions occur with concomitant use of strong CYP3A4 inhibitors [such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., ciprofloxacin) Reduce erlotinib tablets by 50 mg decrements; avoid concomitant use if possible CYP3A4 inducers ‡ Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John’s Wort Increase erlotinib tablets by 50 mg increments at 2-week intervals to a maximum of 450 mg as tolerated. Avoid concomitant use if possible Concurrent Cigarette Smoking ‡§ Concurrent cigarette smoking Increase erlotinib tablets by 50 mg increments at 2-week intervals to a maximum of 300 mg. Immediately reduce the dose of erlotinib tablets to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking Proton Pump inhibitors Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period Avoid concomitant use if possible H 2 -receptor antagonists If treatment with an H 2 -receptor antagonist such as ranitidine is required, separate dosing. Erlotinib tablets must be taken 10 hours after the H 2 -receptor antagonist dosing and at least 2 hours before the next dose of the H 2- receptor antagonist Antacids The effect of antacids on erlotinib pharmacokinetics has not been evaluated. The antacid dose and the erlotinib tablets dose should be separated by several hours, if an antacid is necessary