Erlotinib

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to erlotinib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Tarceva^®

Erlotinib has been shown to cause maternal toxicity and fetal death in rabbits given high doses of erlotinib. Even though there are no well-controlled studies in pregnant women using erlotinib, women of childbearing age should be advised to avoid pregnancy while on erlotinib.

It is not known whether erlotinib is excreted in human milk. Because many medicines are excreted in human milk and because the effects of erlotinib on infants have not been studied, women should abstain from breastfeeding while receiving erlotinib.

Tablets: 25, 100, and 150 mg

Erlotinib should be stored at room temperature, 15 C - 30 C (59 F - 86 F).

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially those listed in the Tarceva Warnings section above, or any of the following:

• Angiogenesis inhibitors such as Avastin (bevacizumab)
• Antacids
• Biaxin (clarithromycin)
• Blood thinners such as Coumadin (warfarin)
• Certain antifungals such as Nizoral (ketoconazole), Sporanox (itraconazole) or Vfend (voriconazole)
• Cipro (ciprofloxacin)
• Dilantin (phenytoin)
• H2 blockers such as Axid (nizatidine), Pepcid (famotidine), Tagamet (cimetidine), or Zantac (ranitidine)
• HIV protease inhibitors such as Crixivan (indinavir), Fortovase and Invirase (saquinavir), Norvir (ritonavir), Reyataz (atazanavir), or Viracept (nelfinavir)
• Ketek (telithromycin)
• Luminal and Solfoton (phenobarbital)
• Medications for acne such as benzoyl peroxide (found in Epiduo, BenzaClin, Benzamycin, and others)
• Mycobutin (rifabutin)
• Nefazodone
• Non-steroidal anti-inflammatory drugs (NSAIDs) such as Advil and Motrin (ibuprofen) or Aleve and Naprosyn (naproxen)
• Oral steroids such as Decadron, Dexone (dexamethasone), Deltasone (prednisone), or Medrol (methylprednisolone)
• Proton pump inhibitors such as AcipHex (rabeprazole), Nexium (esomeprazole), Prevacid (lansoprazole), Prilosec (omeprazole), or Protonix (pantoprazole)
• Rifadin and Rimactane (rifampin)
• Rifapentine
• St. John's wort
• Taxane medications for cancer such as Taxotere (docetaxel) or Abraxane and Taxol (paclitaxel)
• Tegretol (carbamazepine)
• Troleandomycin (TAO)
• Versed (midazolam)

Tarceva and Grapefruit

Grapefruit and grapefruit juice may affect how Tarceva works in your body.

Avoid consuming grapefruit during your treatment.

Tarceva and Alcohol

Alcohol may increase the severity of certain side effects of Tarceva.

Avoid drinking alcohol while taking this medicine.

>10%

Rash (75-76%)

Anorexia (52-69%)

Diarrhea (54-55%)

Fatigue (52-79%)

Nausea (33-40%)

Infection (39%)

Vomiting (23-25%)

Dyspnea (24%)

Stomatitis (17-19%)

Cough (16%)

Pruritus (13%)

Conjunctivitis (12%)

Dry skin (12%)

Keratoconjunctivitis sicca (12%)

Abdominal pain (11%)

1-10%

Elevated LFT's (grade 2)

Acne

Paronychia

Weight loss

Pneumonitis pulmonary infiltrate

Pulmonary fibrosis

<1%

Interstitial lung disease-like events

Postmarketing Reports

Musculoskeletal and connective tissue disorders: Myopathy, including rhabdomyolysis, in combination with statin therapy

Eye disorders: Ocular inflammation including uveitis

Pregnancy

Based on animal data and its mechanism of action, erlotinib can cause fetal harm when administered to a pregnant woman

Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the last dose

Lactation

No data exist on the presence of erlotinib in human milk, or the effects of erlotinib on the breastfed infant or on milk production

Because of the potential for serious adverse reactions in breastfed infants, including interstitial lung disease, hepatotoxicity, bullous and exfoliative skin disorders, microangiopathic hemolytic anemia, with thrombocytopenia, ocular disorders, and diarrhea

Advise a lactating woman not to breastfeed during treatment and for 2 weeks after the final dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism Of Action

Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.

Pharmacokinetics

Erlotinib is about 60% absorbed after oral administration. Peak plasma levels occur 4 hours after dosing.

Effect of Food

Food increased the bioavailability of erlotinib to approximately 100%.

Erlotinib is 93% protein bound to plasma albumin and alpha-1 acid glycoprotein (AAG).

Erlotinib has an apparent volume of distribution of 232 liters.

Erlotinib is eliminated with a median half-life of 36.2 hours in patients receiving the single-agent TARCEVA 2nd/3rd line regimen. Time to reach steady state plasma concentration would therefore be 7-8 days.

Metabolism

Erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1, in vitro.

Excretion

Following a 100 mg oral dose, 91% of the dose was recovered: 83% in feces (1% of the dose as intact parent) and 8% in urine (0.3% of the dose as intact parent).

Specific Populations

Neither age, body weight, nor gender had a clinically significant effect on the systemic exposure of erlotinib in NSCLC patients receiving single-agent TARCEVA for 2nd/3rd line treatment or for maintenance treatment, and in pancreatic cancer patients who received erlotinib plus gemcitabine. The pharmacokinetics of TARCEVA in patients with compromised renal function is unknown.

In vitro and in vivo evidence suggest that erlotinib is cleared primarily by the liver. However, erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh B) compared with patients with adequate hepatic function including patients with primary liver cancer or hepatic metastases.

In a single-dose pharmacokinetics trial in healthy volunteers, cigarette smoking (moderate CYP1A2 inducer) increased erlotinib clearance and decreased erlotinib AUC0-inf by 64% (95% CI, 46-76%) in current smokers compared with former/never smokers. In a NSCLC trial, current smokers achieved erlotinib steady-state trough plasma concentrations which were approximately 2-fold less than the former smokers or patients who had never smoked. This effect was accompanied by a 24% increase in apparent erlotinib plasma clearance. In another study which was conducted in NSCLC patients who were current smokers, pharmacokinetic analyses at steady-state indicated a dose-proportional increase in erlotinib exposure when the TARCEVA dose was increased from 150 mg to 300 mg. [see DOSAGE AND ADMINISTRATION, DRUG INTERACTIONS and PATIENT INFORMATION].

Drug Interaction Studies

Co-administration of gemcitabine had no effect on erlotinib plasma clearance.

Co-administration with a strong CYP3A4 inhibitor, ketoconazole, increased erlotinib AUC by 67%. Co-administration with a combined CYP3A4 and CYP1A2 inhibitor, ciprofloxacin, increased erlotinib exposure [AUC] by 39%, and increased erlotinib maximum concentration [Cmax] by 17%. [see Dose Modifications, DRUG INTERACTIONS].

Pre-treatment with the CYP3A4 inducer rifampicin, for 7-11 days prior to TARCEVA, decreased erlotinib AUC by 58% to 80% [see Dose Modifications, DRUG INTERACTIONS].

See Specific Populations Section [see Dose Modifications, DRUG INTERACTIONS].

Erlotinib solubility is pH dependent and decreases as pH increases. When a proton pump inhibitor (omeprazole) was co-administered with TARCEVA the erlotinib exposure [AUC] was decreased by 46% and the erlotinib maximum concentration [Cmax] was decreased by 61%. When TARCEVA was administered 2 hours following a 300 mg dose of an H-2 receptor antagonist (ranitidine), the erlotinib AUC was reduced by 33% and the erlotinib Cmax was reduced by 54%. When TARCEVA was administered with ranitidine 150 mg twice daily (at least 10 h after the previous ranitidine evening dose and 2 h before the ranitidine morning dose), the erlotinib AUC was decreased by 15% and the erlotinib Cmax was decreased by 17% [see Dose Modifications, DRUG INTERACTIONS].

Clinical Studies

Non-Small Cell Lung Cancer (NSCLC) - First-Line Treatment Of Patients With EGFR Mutations

The safety and efficacy of TARCEVA as monotherapy for the first-line treatment of patients with metastatic NSCLC containing EGFR exon 19 deletions or exon 21 (L858R) substitution mutations was demonstrated in Study 1, a randomized, open-label, clinical trial conducted in Europe. One hundred seventy-four (174) White patients were randomized 1:1 to receive erlotinib 150 mg once daily until disease progression (n = 86) or four cycles of a standard platinum-based doublet chemotherapy (n = 88); standard chemotherapy regimens were cisplatin plus gemcitabine, cisplatin plus docetaxel, carboplatin plus gemcitabine, and carboplatin plus docetaxel. The main efficacy outcome measure was progression-free survival (PFS) as assessed by the investigator. Randomization was stratified by EGFR mutation (exon 19 deletion or exon 21 (L858R) substitution) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs. 1 vs. 2). EGFR mutation status for screening and enrollment of patients was determined by a clinical trials assay (CTA). Tumor samples from 134 patients (69 patients from the erlotinib arm and 65 patients from the chemotherapy arm) were tested retrospectively by the FDA-approved companion diagnostic, cobas® EGFR Mutation Test.

Baseline demographics of the overall study population were: female (72%), White (99%), age ≥ 65 years (51%), ECOG PS 1 (53%), with ECOG PS 0 (33%), and ECOG PS 2 (14%), current smoker (11%), past-smoker (20%), and never smoker (69%). The disease characteristics were 93% Stage IV and 7% Stage IIIb with pleural effusion as classified by the American Joint Commission on Cancer (AJCC, 6th edition), 93% adenocarcinoma, 66% exon 19 mutation deletions and 34% exon 21 (L858R) point mutation by CTA.

A statistically significant improvement in investigator-determined PFS (based on RECIST 1.0 or clinical progression) was demonstrated for patients randomized to erlotinib compared to those randomized to chemotherapy (see Table 6 and Figure 1). Similar results for PFS (based on RECIST 1.0) were observed for the subgroup evaluated by an independent-review committee (approximately 75% of patients evaluated in Study 1) and in the subgroup of 134 patients (77% of Study 1 population) with EGFR mutations confirmed by the cobas® EGFR Mutation Test.

A protocol-specified analysis of overall survival (OS) conducted at the time of the final analysis of PFS showed no statistically significant difference between the TARCEVA and chemotherapy arms. At the time of the data cut-off, 84% of patients in the chemotherapy arm had received at least one subsequent treatment, of whom 97% received an EGFR-tyrosine kinase inhibitor. In the TARCEVA arm, 66% of patients had received at least one subsequent treatment.

Table 6: Efficacy Results (Study 1)

Figure 1: Kaplan-Meier Curves of Investigator-Assessed PFS in Study 1

In exploratory subgroup analyses based on EGFR mutation subtype, the hazard ratio (HR) for PFS was 0.27 (95% CI 0.17 to 0.43) in patients with exon 19 deletions and 0.52 (95% CI 0.29 to 0.95) in patients with exon 21 (L858R) substitution. The HR for OS was 0.94 (95% CI 0.57 to 1.54) in the exon 19 deletion subgroup and 0.99 (95% CI 0.56 to 1.76) in the exon 21 (L858R) substitution subgroup.

NSCLC -Lack Of Efficacy Of TARCEVA In Maintenance Treatment Of Patients Without EGFR Mutations

Lack of efficacy of TARCEVA for the maintenance treatment of patients with NSCLC without EGFR activating mutations was demonstrated in Study 2. Study 2 was a multicenter, placebo-controlled, randomized trial of 643 patients with advanced NSCLC without an EGFR exon 19 deletion or exon 21 L858R mutation who had not experienced disease progression after four cycles of platinum-based chemotherapy. Patients were randomized 1:1 to receive TARCEVA 150 mg or placebo orally once daily (322 TARCEVA, 321 placebo) until disease progression or unacceptable toxicity. Following progression on initial therapy, patients were eligible to enter an open-label phase. Baseline characteristics were as follows: median age 61 years (35% age ≥ 65 years), 75% male, 77% White, 21% Asian, 28% ECOG PS 0, 72% ECOG PS 1, 16% never smokers, 58% current smokers, 57% adenocarcinoma, 35% squamous cell carcinoma, 22% stage IIIB disease not amenable to combined modality treatment, and 78% stage IV disease. Fifty percent of patients randomized to TARCEVA entered the open-label phase and received chemotherapy, while 77% of patients randomized to placebo entered the open-label phase and received TARCEVA.

The main efficacy outcome was overall survival (OS). Median OS was 9.7 months in the TARCEVA arm and 9.5 months in the placebo arm; the hazard ratio for OS was 1.02 (95% CI 0.85, 1.22). Median PFS was 3.0 months in the TARCEVA arm and 2.8 months in the placebo arm; the hazard ratio for PFS was 0.94 (95% CI 0.80, 1.11).

NSCLC - Maintenance Treatment Or Second/Third Line Treatment

Two randomized, double-blind, placebo-controlled trials, Studies 3 and 4, examined the efficacy and safety of TARCEVA administered to patients with metastatic NSCLC as maintenance therapy after initial treatment with chemotherapy (Study 3) or with disease progression following initial treatment with chemotherapy (Study 4). Determination of EGFR mutation status was not required for enrollment.

The efficacy and safety of TARCEVA as maintenance treatment of NSCLC were demonstrated in Study 3, a randomized, double-blind, placebo-controlled trial conducted in 26 countries, in 889 patients with metastatic NSCLC whose disease did not progress during first-line platinum-based chemotherapy. Patients were randomized 1:1 to receive TARCEVA 150 mg or placebo orally once daily (438 TARCEVA, 451 placebo) until disease progression or unacceptable toxicity. The primary objective of the study was to determine if the administration of TARCEVA after standard platinum-based chemotherapy in the treatment of NSCLC resulted in improved progression-free survival (PFS) when compared with placebo, in all patients or in patients with EGFR immunohistochemistry (IHC) positive tumors.

Baseline demographics of the overall study population were as follows: male (74%), age < 65 years (66%), ECOG PS 1 (69%), ECOG PS 0 (31%), white (84%), Asian (15%), current smoker (55%), past-smoker (27%), and never smoker (17%). Disease characteristics were as follows: Stage IV (75%), Stage IIIb with effusion (25%) as classified by AJCC (6th edition) with histologic subtypes of adenocarcinoma including bronchioalveolar (45%), squamous (40%) and large cell (5%); and EGFR IHC positive (70%), negative (14%), indeterminate (4%), and missing (12%).

Table 7: Efficacy Results (Study 3): (ITT Population)1

Figure 2 : depicts the Kaplan-Meier Curves for Overall Survival (ITT Population)

Figure 2: Kaplan-Meier Curves for Overall Survival (ITT Population)

The efficacy and safety of single-agent TARCEVA was assessed in Study 4, a randomized, double blind, placebo-controlled trial in 731 patients with locally advanced or metastatic NSCLC after failure of at least one chemotherapy regimen. Patients were randomized 2:1 to receive TARCEVA 150 mg or placebo (488 TARCEVA, 243 placebo) orally once daily until disease progression or unacceptable toxicity. Efficacy outcome measures included overall survival, response rate, and progression-free survival (PFS). Duration of response was also examined. The primary endpoint was survival. The study was conducted in 17 countries.

Baseline demographics of the overall study population were as follows: male (65%), White (78%), Asian (12%), Black (4%), age < 65 years (62%), ECOG PS 1 (53%), ECOG PS 0 (13%), ECOG PS 2 (25%), ECOG PS 3 (9%), current or ex-smoker (75%), never smoker (20%), and exposure to prior platinum therapy (93%). Tumor characteristics were as follows: adenocarcinoma (50%), squamous (30%), undifferentiated large cell (9%), and mixed non-small cell (2%).

The results of the study are shown in Table 8.

Table 8: Efficacy Results (Study 4)

Figure 3 depicts the Kaplan-Meier curves for overall survival.

Figure 3: Kaplan-Meier Curves for Overall Survival of Patients by Treatment Group in Study 4

NSCLC - Lack Of Efficacy Of TARCEVA Administered Concurrently With Chemotherapy

Results from two, multicenter, placebo-controlled, randomized, trials in over 1000 patients conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of TARCEVA with platinum-based chemotherapy [carboplatin and paclitaxel (TARCEVA, N = 526) or gemcitabine and cisplatin (TARCEVA, N = 580)].

Pancreatic Cancer -TARCEVA Administered Concurrently With Gemcitabine

The efficacy and safety of TARCEVA in combination with gemcitabine as a first-line treatment was assessed in Study 5, a randomized, double-blind, placebo-controlled trial in 569 patients with locally advanced, unresectable or metastatic pancreatic cancer. Patients were randomized 1:1 to receive TARCEVA (100 mg or 150 mg) or placebo once daily on a continuous schedule plus gemcitabine by intravenous infusion (1000 mg/m², Cycle 1 -Days 1, 8, 15, 22, 29, 36 and 43 of an 8-week cycle; Cycle 2 and subsequent cycles -Days 1, 8 and 15 of a 4-week cycle [the approved dose and schedule for pancreatic cancer, see the gemcitabine package insert]). TARCEVA or placebo was taken orally once daily until disease progression or unacceptable toxicity. The primary endpoint was survival. Secondary endpoints included response rate, and progression-free survival (PFS). Duration of response was also examined. The study was conducted in 18 countries. A total of 285 patients were randomized to receive gemcitabine plus TARCEVA (261 patients in the 100 mg cohort and 24 patients in the 150 mg cohort) and 284 patients were randomized to receive gemcitabine plus placebo (260 patients in the 100 mg cohort and 24 patients in the 150 mg cohort). Too few patients were treated in the 150 mg cohort to draw conclusions.

In the 100 mg cohort, baseline demographics of the overall study population were as follows: male (52%), white (88%), Asian (7%), black (2%), age < 65 years (53%), ECOG PS 1 (51%), ECOG PS 0 (32%), and ECOG PS 2 (17%). There was a slightly larger proportion of females in the TARCEVA arm (51%) compared with the placebo arm (44%). The median time from initial diagnosis to randomization was approximately 1.0 month. The majority of the patients (76%) had distant metastases at baseline and 24% had locally advanced disease.

The results of the study are shown in Table 9.

Table 9: Efficacy Results: TARCEVA 100 mg Cohort (Study 5)

Survival was evaluated in the intent-to-treat population. Figure 4 depicts the Kaplan-Meier curves for overall survival in the 100 mg cohort. The primary survival and PFS analyses were two-sided log-rank tests stratified by ECOG performance status and extent of disease.

Figure 4: Kaplan-Meier Curves for Overall Survival: 100 mg Cohort in Study 5

Erlotinib is a prescription medication used to treat non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body in patients. It is used when other treatments have not succeeded. This medication is approved to treat patients whose tumors have specific epidermal growth factor receptor (EGFR) mutations.

Erlotinib is also used to treat pancreatic cancer that has spread to nearby tissues or to other parts of the body.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• angiogenesis inhibitors such as bevacizumab (Avastin)
• anticoagulants ('blood thinners') such as warfarin (Coumadin)
• certain antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend)
• carbamazepine (Tegretol)
• ciprofloxacin (Cipro, Proquin XR)
• clarithromycin (Biaxin)
• HIV protease inhibitors such as atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Fortovase, Invirase)
• H2 blockers such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac)
• medications for acne such as benzoyl peroxide (in Epiduo, in BenzaClin, in Benzamycin, others)
• midazolam (Versed)
• nefazodone
• nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn)
• oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone)
• phenobarbital (Luminal, Solfoton)
• phenytoin (Dilantin)
• proton pump inhibitors such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (AcipHex)
• rifabutin (Mycobutin)
• rifampin (Rifadin, Rimactane)
• rifapentine
• taxane medications for cancer such as docetaxel (Taxotere) and paclitaxel (Abraxane, Taxol
• telithromycin (Ketek)
• cigarette smoke
• St. John's wort

This is not a complete list of all drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D.  You should not become pregnant while you are taking erlotinib and for at least 2 weeks after your treatment. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking erlotinib, call your doctor immediately. Erlotinib may harm the fetus (unborn baby).

Absorption

Bioavailability

Approximately 60% absorbed from the GI tract.1

Peak plasma concentrations occur at 4 hours following oral administration.1

Food

Presence of food in the GI tract increases oral bioavailability to almost 100%.1

Distribution

Plasma Protein Binding

Approximately 93% (mainly to albumin and α1-acid glycoprotein).1

Elimination

Metabolism

Extensively metabolized by CYP isoenzymes, principally CYP3A4 and, to a lesser extent, CYP1A1 and CYP1A2.1

Elimination Route

Excreted mainly as metabolites in feces (83%) via biliary excretion and in urine (8%).1

Half-life

Approximately 36 hours.1

Special Populations

Clearance rate is approximately 24% higher in smokers.1

Although erlotinib is eliminated mainly by the liver, systemic exposure was not substantially altered in patients with Child-Pugh class B hepatic impairment relative to those with adequate hepatic function (including individuals with primary liver cancer or hepatic metastases).1

• Antineoplastic agent; a kinase inhibitor.1

• Exact mechanism of antineoplastic activity not fully elucidated.1 Appears to inhibit intracellular phosphorylation of tyrosine kinase associated with epidermal growth factor receptor (EGFR), which is expressed on the surface of normal and cancer cells.1 Specificity with regard to other tyrosine kinase receptors not fully characterized.1

Use erlotinib as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Do not take cimetidine, famotidine, nizatidine, or ranitidine at the same time as erlotinib. Talk with your doctor.
• Do not take antacids at the same time as this medicine. Ask your doctor if you have a question about how to take antacids with erlotinib.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Reversibly inhibits overall epidermal growth factor receptor (HER1/EGFR) - tyrosine kinase activity. Intracellular phosphorylation is inhibited which prevents further downstream signaling, resulting in cell death. Erlotinib has higher binding affinity for EGFR exon 19 deletion or exon 21 L858R mutations than for the wild type receptor.

Absorption

Oral: ~60% on an empty stomach; food increases to ~100%

Distribution

232 L

Metabolism

Hepatic, via CYP3A4 (major), CYP1A1 (minor), CYP1A2 (minor), and CYP1C (minor)

Excretion

Primarily as metabolites: Feces (83%; 1% as unchanged drug); urine (8%; <1% as unchanged drug)

Time to Peak

Plasma: 4 hours

Half-Life Elimination

36.2 hours

Protein Binding

93% to albumin and alpha1-acid glycoprotein

Store at 25°C (77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F).

An oral suspension (10 mg/mL) prepared using erlotinib 150 mg tablets and Ora-Plus:Ora-Sweet (1:1 vehicle) is stable for at least 28 days at room temperature; do not refrigerate due to potential increased viscosity (Li 2016).

Adverse events were observed in animal reproduction studies. Erlotinib crosses the placenta (Ji 2015; Jovelet 2015). Information related to the use of erlotinib in pregnancy is limited (Ji 2015; Rivas 2012; Zambelli 2008). Based on the mechanism of action, erlotinib may cause fetal harm if administered in pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last erlotinib dose.

Severe renal dysfunction: Use is not recommended

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Use is not recommended in women who are pregnant or contemplating pregnancy. 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 a fetus. AU TGA pregnancy category: C US FDA pregnancy category: D Comments: Encourage use of adequate methods of contraception in females during therapy and for at least two weeks following the last dose.

Animal studies have shown maternal toxicity including embryo-fetal lethality and abortion during organogenesis at plasma levels higher than achieved at therapeutic doses. In animal studies where the drug was given prior to mating through the first week of pregnancy, an increase in early resorptions which resulted in a decrease in the number of live fetuses has been reported. Animal studies have shown no teratogenicity during organogenesis. There are no controlled data in human pregnancy. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.