Erlotinib
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Dosing in kidney impairment
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 [See Clinical Studies (14.1 , 14.2) ] .
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.
| 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 3-4 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 ठ| 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 2receptor 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 |
Dosing in liver impairment
Hepatic Impairment Hepatic failure and hepatorenal syndrome, including fatal cases, can occur with erlotinib treatment in patients with normal hepatic function; the risk of hepatic toxicity is increased in patients with baseline hepatic impairment [see Warnings and Precautions , Adverse Reactions (6.1 , 6.2) , and Dosage and Administration].
Monitor patients with hepatic impairment (total bilirubin greater than upper limit of normal (ULN) or Child-Pugh A, B and C) during therapy with erlotinib. Treatment with erlotinib should be used with increased monitoring in patients with total bilirubin greater than 3 x ULN [see Warnings and Precautions , Adverse Reactions (6.1 , 6.2) , and Dosage and Administration ].
| 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 3-4 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 ठ| 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 2receptor 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 |
Drug interactions
Check erlotinib against a medication listLabel text (6 paragraphs)
7 DRUG INTERACTIONS CYP3A4 Inhibitors Co-administration of erlotinib with a strong CYP3A4 inhibitor or a combined CYP3A4 and CYP1A2 inhibitor increased erlotinib exposure. Erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2. Increased erlotinib exposure may increase the risk of exposure-related toxicity [see Clinical Pharmacology (12.3) ].
Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin). Reduce the erlotinib dosage when co-administering with a strong CYP3A4 inhibitor or a combined CYP3A4 and CYP1A2 inhibitor if co-administration is unavoidable [see Dosage and Administration (2.4) ]. CYP3A4 Inducers Pre-treatment with a CYP3A4 inducer prior to erlotinib decreased erlotinib exposure [see Clinical Pharmacology (12.3) ].
Increase the erlotinib dosage if co-administration with CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital and St. John's wort) is unavoidable [see Dosage and Administration (2.4) ]. CYP1A2 Inducers and Cigarette Smoking Cigarette smoking decreased erlotinib exposure. Avoid smoking tobacco (CYP1A2 inducer) and avoid concomitant use of erlotinib with moderate CYP1A2 inducers (e.g., teriflunomide, rifampin, or phenytoin). Increase the erlotinib dosage in patients that smoke tobacco or when co-administration with moderate CYP1A2 inducers is unavoidable [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ].
Drugs the Increase Gastric pH Co-administration of erlotinib with proton pump inhibitors (e.g., omeprazole) and H-2 receptor antagonists (e.g., ranitidine) decreased erlotinib exposure [see Clinical Pharmacology (12.3) ]. For proton pump inhibitors, avoid concomitant use if possible. For H-2 receptor antagonists and antacids, modify the dosing schedule [see Dosage and Administration (2.4) ]. Increasing the dose of erlotinib when co-administered with gastric pH elevating agents is not likely to compensate for the loss of exposure.
Anticoagulants Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions, which in some cases were fatal, have been reported in patients receiving erlotinib. Regularly monitor prothrombin time or INR in patients taking coumarin-derived anticoagulants. Dose modifications of erlotinib are not recommended [see Warnings and Precautions (5.9) and Adverse Reactions (6.1) ]. • CYP3A4 inhibitors or a combined CYP3A4 and CYP1A2 inhibitor increase erlotinib plasma concentrations. Avoid concomitant use. If not possible, reduce erlotinib dose.
( 2.4 , 7 ) • CYP3A4 inducers decrease erlotinib plasma concentrations. Avoid concomitant use. If not possible, increase erlotinib dose. ( 2.4 , 7 ) • Cigarette smoking and CYP1A2 inducers decrease erlotinib plasma concentrations. Avoid concomitant use. If not possible, increase erlotinib dose. ( 2.4 , 7 ) • Drugs that increase gastric pH decrease erlotinib plasma concentrations. For proton pump inhibitors avoid concomitant use if possible. For H-2 receptor antagonists, take erlotinib 10 hours after H-2 receptor antagonist dosing. For use with antacids, separate dosing by several hours. ( 2.4 , 7 )
Contraindications
None. None.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action, erlotinib can cause fetal harm when administered to a pregnant woman. Limited available data on use of erlotinib in pregnant women are not sufficient to inform a risk of major birth defects or miscarriage. When given during organogenesis, erlotinib administration resulted in embryo-fetal lethality and abortion in rabbits at exposures approximately 3 times the exposure at the recommended human daily dose of 150 mg. Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Erlotinib has been shown to cause maternal toxicity resulting in embryo-fetal lethality and abortion in rabbits when given during the period of organogenesis at doses that result in plasma drug concentrations approximately 3 times those achieved at the recommended dose in humans (AUCs at 150 mg daily dose).
During the same period, there was no increase in the incidence of embryo-fetal lethality or abortion in rabbits or rats at doses resulting in exposures approximately equal to those in humans at the recommended daily dose. In an independent fertility study female rats treated with 30 mg/m 2 /day or 60 mg/m 2 /day (0.3 or 0.7 times the recommended daily dose, on a mg/m 2 basis) of erlotinib had an increase in early resorptions that resulted in a decrease in the number of live fetuses.
No teratogenic effects were observed in rabbits or rats dosed with erlotinib during organogenesis at doses up to 600 mg/m 2 /day in the rabbit (3 times the plasma drug concentration seen in humans at 150 mg/day) and up to 60 mg/m 2 /day in the rat (0.7 times the recommended dose of 150 mg/day on a mg/m 2 basis).
Lactation
8.3 Females and Males of Reproductive Potential Contraception Females Erlotinib can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with erlotinib and for one month after the last dose of erlotinib.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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