Recommended Dose: General dosing considerations:
Select patients for the first-line treatment of metastatic non-small cell lung cancer based on the presence of EGFH exon 19 deletions or exon -21 (L858R) substitution mutations in tumour specimens. Information on FDA-approved tests. for the deletion of EGFR mutations is available at http://www.fda.gov/Companion Diagnostics. Dosage reduction may be required for patients with hepatic impairment (see Hepatic Function Impairment).
Adults: Non-small cell lung cancer:
150 mg daily.
100 mg daily, in combination with gemcitabine.
Hepatic function impairment:
Withhold erlotinib in patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin, or tripling of transaminases values over baseline. Discontinue therapy in patients whose abnormal liver tests do not improve significantly or resolve within 3 weeks. One guideline is shown in. the following table. Monitor patients with hepatic dysfunction closely, especially if total bilirubin is more than 3 times the upper limit of normal (ULN). (See Table 1.)
Click on icon to see table/diagram/image
When restarting, therapy following withholding treatment for a dose-limiting toxicity that has resolved to baseline or grade 1 or less, reduce the dose in 50 mg decrements.
Withhold erlotinib for severe rash not responsive to medical management. Discontinue erlotinib for severe bullous, blistering, or exfoliating skin conditions.
Withhold erlotinib for persistent severe diarrhoea not responsive to medical management (e.g., loperamide). Discontinue erlotinib for GI perforation.
Withhold erlotinib in patients without pre-existing hepatic impairment for total bilirubin levels greater than 3 times the ULN or transaminases greater than 5 times the ULN, and consider discontinuation. Discontinue erlotinib for severe hepatic toxicity that does not improve significantly or resolve within 3 weeks.
Withhold erlotinib for keratitis of grade 3 to 4 or for grade 2 lasting more than 2 weeks; Withhold erlotinib for acute/worsening ocular disorders, such as eye pain, and consider discontinuation. Discontinue erlotinib for corneal perforation or severe ulceration.
Withhold erlotinib during diagnostic evaluation for possible interstitial lung disease. Discontinue erlotinib for interstitial lung disease.
Withhold erlotinib for severe (grade 3 to 4) renal toxicity and consider discontinuation.
CYP3A4 inhibitors: Avoid concomitant use, if possible. Reduce the erlotinib dose by 50 mg decrements if severe reactions occur with concomitant use of strong cytochrome P450 (CYP-450) 3A4 inhibitors (e.g., atazanavir, clarithromycin, grapefruit juice, grapefruit, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole) or an inhibitor of CYP3A4 and CYP1A2 (eg, ciprofloxacin).
CYP3A4 inducers: Avoid concomitant use, if possible. Increase erlotinib by 50 mg increments at 2-week intervals to a maximum of 450 mg during concomitant use with CYP3A4 inducers (e.g., rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. Johns wort).
Drugs affecting gastric pH: Avoid concomitant use with proton pump inhibitors if possible. If treatment with an H2
-receptor antagonist (e.g., ranitidine) is required, give erlotinib 10 hours after the H2
-receptor antagonist dosing and at least 2 hours before the next dose of the H2
-receptor antagonist. If an antacid is necessary, separate the erlotinib dose and the antacid dose by several hours.
Increase erlotinib by 50 mg increments at 2-week intervals to a maximum of 300 mg during concurrent cigarette smoking. Immediately reduce the dose of erlotinib to the recommended dose upon cessation of smoking.
Duration of therapy:
Continue treatment until disease progression or unacceptable toxicity occurs. (27)
Mode of Administration: Preparation of administration:
Erlotinib is considered a cytotoxic agent. Follow safe handling procedures when preparing, administering, or dispensing erlotinib.
Administer on an empty stomach at least 1 hour before or 2 hours after food. Administration with food increases bioavailability to almost 100 %, when may cause increased toxicity.
For patients, unable to swallow tablets whole, place tablet in 100 mL of distilled water; do not crush tablet. Stir until dispersed, then have the patient drink the mixture immediately. To ensure that the entire dose is administered, rinse the inside of the container with another 40 mL of water and have the patient drink immediately. The suspension may also be administered via an enteral feeding tube.