Frequently asked questions


Does the Prescribing Information for Tarceva contain any head-to-head comparisons between Tarceva and chemotherapy in advanced non-small cell lung cancer (NSCLC)?
The EURTAC trial evaluated the efficacy and safety of Tarceva versus standard chemotherapy in patients who had metastatic NSCLC with EGFR exon 19 deletions or exon 21 [L858R] substitution mutations.1
Learn more


What are the indications for Tarceva?

Advanced non-small cell lung cancer (NSCLC) indications
Tarceva is indicated for1:

  • The first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) activating mutations with exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
  • The maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy
  • The treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

Limitations of use:

  • Tarceva is not recommended for use in combination with platinum-based chemotherapy.
  • Safety and efficacy of Tarceva have not been evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.

Advanced pancreatic cancer indication
Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer.1


Are there any potential drug interactions with Tarceva?
CYP3A4 Inhibitors1

  • Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased erlotinib AUC by 67%. When Tarceva was co-administered with ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively. Dose modifications are recommended.

CYP3A4 Inducers1

  • Pre-treatment with the CYP3A4 inducer rifampicin for 7 to 11 days prior to Tarceva decreased erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs Affecting Gastric pH1

  • Co-administration of Tarceva with omeprazole decreased erlotinib AUC by 46% and co-administration of Tarceva with ranitidine 300 mg decreased erlotinib AUC by 33%. When Tarceva was administered with ranitidine 150-mg twice daily (at least 10 hours after the previous ranitidine evening dose and 2 hours before the ranitidine morning dose), erlotinib AUC decreased by 15%. Increasing the dose of Tarceva when co-administered with such agents is not likely to compensate for the loss of exposure. Scheduling modifications are recommended.

Anticoagulants1

  • 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 Tarceva. Regularly monitor prothrombin time or INR in patients taking coumarin-derived anticoagulants. Dose modifications of Tarceva are not recommended.

Please see additional Important Safety Information.


Does smoking affect the bioavailability of Tarceva?
Cigarette smoking reduces Tarceva exposure.1

  • Advise patients to stop smoking.
  • Advise patients that the dose of Tarceva may need to be adjusted if they smoke.
  • The exact dose to be recommended for patients who currently smoke is unknown.
  • For patients who currently smoke, increase Tarceva by 50-mg increments as tolerated at 2-week intervals to a maximum of 300 mg. Immediately reduce the dose of Tarceva to the recommended dose (150 mg for NSCLC or 100 mg for pancreatic cancer) upon cessation of smoking.
  • Cigarette smoking results in reductions in erlotinib AUC. Dose modifications are recommended.

Are there insurance information resources available for Tarceva?
Genentech BioOncology Access Solutions connects patients to their medicine. We are committed to helping all patients access their medicine, regardless of their ability to pay. Our dedicated Specialists can:

  • Help confirm benefits and coverage and resolve any related issues
  • Provide free medicine to qualified uninsured patients through the Genentech® Access to Care Foundation (GATCF)
  • Refer underinsured patients for co-pay assistance
  • Individualize services to meet the specific needs of your patients

Learn how to get started with Access Solutions

For more information on these programs, please call (888) 249-4918 or visit www.Genentech-Access.com/Tarceva.


How do I manage rash?

  • Given that skin reactions are anticipated when taking Tarceva, proactive intervention may include alcohol-free emollient cream and use of sunscreen or avoidance of sun exposure.1
  • Management of rash may include topical corticosteroids or antibiotics with anti-inflammatory properties. These approaches were used in the advanced NSCLC and advanced pancreatic pivotal clinical trials. Acne preparations with drying properties may aggravate the dry skin and erythema. Treatment of rash has not been formally studied and should be based on rash severity.1
  • Tarceva should be withheld for severe rash that is not responsive to medical treatment.1

For more information about rash in Tarceva trials, click here.


How do I manage diarrhea?
Diarrhea can usually be managed with loperamide.1
Tarceva should be withheld for persistent severe diarrhea not responsive to medical management.1

Please see additional Important Safety Information.


What if the dose of Tarceva needs to be discontinued, reduced, or interrupted?

Dose Modifications

Discontinue Tarceva for1:

  • Interstitial lung disease (ILD).
  • Severe hepatic toxicity that does not improve significantly or resolve within three weeks.
  • Gastrointestinal perforation.
  • Severe bullous, blistering, or exfoliating skin conditions.
  • Corneal perforation or severe corneal ulceration.

Withhold Tarceva1:

  • During diagnostic evaluation for possible ILD.
  • For severe (Common Terminology Criteria for Adverse Events [CTCAE] grade 3/4) renal toxicity, and consider discontinuation of Tarceva.
  • In patients without pre-existing hepatic impairment for total bilirubin levels >3 x the upper limit of normal (ULN), or transaminases >5 x ULN, and consider discontinuation of Tarceva.
  • In patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases values over baseline and consider discontinuation of Tarceva.
  • For persistent severe diarrhea not responsive to medical management (eg, loperamide).
  • For severe rash not responsive to medical management.
  • For keratitis of (National Cancer Institute Common Toxicity Criteria [NCI-CTC] version 4.0) grade 3/4 or for grade 2 lasting more than 2 weeks.
  • For acute/worsening ocular disorders such as eye pain, and consider discontinuation of Tarceva.

Reduce Tarceva by 50-mg decrements1:

  • If severe reactions occur with concomitant use of strong CYP3A4 inhibitors [such as atazasnavir, 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 (eg, ciprofloxacin). Avoid concomitant use if possible.
  • When restarting therapy following withholding treatment for a dose-limiting toxicity that has resolved to baseline or grade ≤1.

Increase Tarceva by 50-mg increments as tolerated for1:

  • Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John’s wort. Increase doses by 50-mg increments at 2-week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.
  • Concurrent cigarette smoking. Increase by 50-mg increments at 2-week intervals to a maximum of 300 mg. Immediately reduce the dose of Tarceva to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

Drugs affecting gastric pH1:

  • Avoid concomitant use of Tarceva with proton pump inhibitors if possible. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period.
  • If treatment with an H2-receptor antagonist such as ranitidine is required, Tarceva must be taken 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of the H2-receptor antagonist.
  • Although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the Tarceva dose should be separated by several hours, if an antacid is necessary.

What are the serious adverse reactions observed with Tarceva?
Adverse reactions, including fatalities, associated with Tarceva include1:

  • Interstitial lung disease (ILD)
  • Renal failure
  • Hepatotoxicity with or without hepatic impairment
  • Gastrointestinal perforation
  • Bullous and exfoliative skin disorders
  • Myocardial infarction/ischemia
  • Cerebrovascular accident
  • Microangiopathic hemolytic anemia with thrombocytopenia
  • Ocular disorders
  • Hemorrhage in patients taking warfarin
  • Embryo-fetal toxicity

What are the most common adverse reactions with Tarceva?

The most common adverse reactions in patients receiving Tarceva, rash and diarrhea, can usually be managed.

  • Withhold Tarceva for persistent severe diarrhea or severe rash not responsive to medical management.1
  • In the EURTAC trial for first-line therapy in patients who have metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations the most frequently reported adverse reactions leading to dose modification in Tarceva-treated patients were rash (13%), diarrhea (10%), and asthenia (3.6%).1
  • In the SATURN trial for maintenance therapy in patients with advanced NSCLC, rash and diarrhea led to study discontinuation in 1% and 0.5% of Tarceva-treated patients, respectively. Dose reduction or interruption was needed for rash and diarrhea in 5% and 3% of patients, respectively.1
  • In the BR.21 trial for second/third-line treatment in patients with advanced NSCLC, rash and diarrhea each led to study discontinuation in 1% of Tarceva-treated patients. Six-percent and 1% of patients needed dose reduction for rash and diarrhea, respectively.1
  • In the PA.3 trial for first-line treatment of patients with advanced pancreatic cancer rash and diarrhea each resulted in dose reductions in 2% of patients, and resulted in study discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.1

The most common adverse reactions were1:

  • Metastatic NSCLC – Most common (≥30%) in first-line treatment in patients with EGFR mutations: diarrhea, asthenia, rash, cough, dyspnea, and decreased appetite
  • Advanced NSCLC – Maintenance and second/third-line treatment: rash and diarrhea
  • Advanced Pancreatic Cancer – Tarceva plus gemcitabine: fatigue, rash, nausea, anorexia, and diarrhea

Please see section 17 of the full Prescribing Information.


What is the Important Safety Information for Tarceva I should know?

CONTRAINDICATIONS

None

WARNINGS AND PRECAUTIONS

  • Interstitial Lung Disease (ILD): 
    • Cases of serious ILD, including fatal cases, can occur with Tarceva treatment. The overall incidence of ILD in approximately 32,000 Tarceva-treated patients in uncontrolled studies and studies with concurrent chemotherapy was approximately 1.1%. In patients with ILD, the onset of symptoms was between 5 days to more than 9 months (median 39 days) after initiating Tarceva therapy.
    • Withhold Tarceva for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue Tarceva.
  • Renal Failure: 
    • Hepatorenal syndrome, severe acute renal failure including fatal cases, and renal insufficiency can occur with Tarceva treatment. Renal failure may arise from exacerbation of underlying baseline hepatic impairment or severe dehydration.
    • The pooled incidence of severe renal impairment in the 3 monotherapy lung cancer studies was 0.5% in the Tarceva arms and 0.8% in the control arms. The incidence of renal impairment in the pancreatic cancer study was 1.4% in the Tarceva plus gemcitabine arm and 0.4% in the control arm.
    • Withhold Tarceva in patients developing severe renal impairment until renal toxicity is resolved. Perform periodic monitoring of renal function and serum electrolytes during Tarceva treatment.
  • Hepatotoxicity with or Without Hepatic Impairment:
    • Hepatic failure and hepatorenal syndrome, including fatal cases, can occur with Tarceva treatment in patients with normal hepatic function; the risk of hepatic toxicity is increased in patients with baseline hepatic impairment.
      • Hepatic Toxicity: One Tarceva-treated patient experienced fatal hepatic failure and four additional patients experienced grade 3-4 liver test abnormalities.
    • In clinical studies where patients with moderate to severe hepatic impairment were excluded, the pooled incidence of hepatic failure in the 3 monotherapy lung cancer studies was 0.4% in the Tarceva arms and 0% in the control arms. The incidence of hepatic failure in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0.4% in the control arm.
    • Perform periodic liver testing (transaminases, bilirubin, and alkaline phosphatase) during treatment with Tarceva. Increased frequency of monitoring of liver function is required for patients with pre-existing hepatic impairment or biliary obstruction.
    • Withhold Tarceva in patients without pre-existing hepatic impairment for total bilirubin >3 x ULN and/or transaminases >5 x ULN. Withhold Tarceva in patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases value over baseline.
    • Discontinue Tarceva in patients whose abnormal liver tests meeting the above criteria do not improve significantly or resolve within 3 weeks.
  • Gastrointestinal Perforation:
    • Gastrointestinal perforation, including fatal cases, can occur with Tarceva treatment. Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease may be at increased risk of perforation.
    • The pooled incidence of gastrointestinal perforation in the 3 monotherapy lung cancer studies was 0.2% in the Tarceva arms and 0.1% in the control arms. The incidence of gastrointestinal perforation in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
    • Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.
  • Bullous and Exfoliative Skin Disorders:
    • Bullous, blistering and exfoliative skin conditions, including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal, can occur with Tarceva treatment.
    • The pooled incidence of bullous and exfoliative skin disorders in the 3 monotherapy lung cancer studies was 1.2% in the Tarceva arms and 0% in the control arms. The incidence of bullous and exfoliative skin disorders in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
    • Discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.
  • Myocardial Infarction (MI)/Ischemia:
    • In the pancreatic carcinoma trial, 6 patients (incidence 2.1%) in the Tarceva plus gemcitabine group developed myocardial infarction/ischemia. One of these patients died due to myocardial infarction. In comparison, 3 patients in the placebo/gemcitabine group developed myocardial infarction (incidence 1.1%), and one died due to myocardial infarction. The pooled incidence of myocardial infarction/ischemia in the 3 monotherapy lung cancer studies was 0.2% in the Tarceva arms and 0.4% in the control arms.
  • Cerebrovascular Accident:
    • In the pancreatic carcinoma trial, 7 patients in the Tarceva plus gemcitabine group developed cerebrovascular accident (incidence 2.5%). One of these was hemorrhagic and was the only fatal event. In comparison, in the placebo/gemcitabine group there were no cerebrovascular accidents. The pooled incidence of cerebrovascular accident in the 3 monotherapy lung cancer studies was 0.6% in the Tarceva arms and 0.9% in the control arms.
  • Microangiopathic Hemolytic Anemia with Thrombocytopenia:
    • The pooled incidence of microangiopathic hemolytic anemia with thrombocytopenia in the 3 monotherapy lung cancer studies was 0% in the Tarceva arms and 0.1% in the control arms. The incidence of microangiopathic hemolytic anemia with thrombocytopenia in the pancreatic cancer study was 1.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
  • Ocular Disorders:
    • Decreased tear production, abnormal eyelash growth, keratoconjunctivitis sicca or keratitis can occur with Tarceva treatment and can lead to corneal perforation or ulceration. 
    • The pooled incidence of ocular disorders in the 3 monotherapy lung cancer studies was 17.8% in the Tarceva arms and 4% in the control arms. The incidence of ocular disorders in the pancreatic cancer study was 12.8% in the Tarceva plus gemcitabine arm and 11.4% in the control arm.
    • Interrupt or discontinue Tarceva therapy if patients present with acute or worsening ocular disorders such as eye pain.
  • Hemorrhage in Patients Taking Warfarin:
    • Severe and fatal hemorrhage associated with International Normalized Ratio (INR) elevations can occur when Tarceva and warfarin are administered concurrently.
    • Regularly monitor prothrombin time and INR during Tarceva treatment in patients taking warfarin or other coumarin-derivative anticoagulants.
  • Embryo-Fetal Toxicity:
    • Tarceva is pregnancy category D. Based on its mechanism of action, Tarceva can cause fetal harm when administered to a pregnant woman. If Tarceva is used during pregnancy, or if the patient becomes pregnant while taking Tarceva, the patient should be apprised of the potential hazard to a fetus.
    • Advise females of reproductive potential to use highly effective contraception during therapy and for at least 2 weeks after the last dose of Tarceva. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Tarceva.

MOST COMMON ADVERSE REACTIONS

  • Metastatic NSCLC – First-Line Treatment of Patients With EGFR Mutations:
    • Most frequent (≥30%) adverse reactions were diarrhea, asthenia, rash, cough, dyspnea, and decreased appetite.
    • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (14%) and diarrhea (5%). In Tarceva-treated patients, the most frequently reported adverse reactions leading to dose modification were rash (13%), diarrhea (10%), and asthenia (3.6%). 
  • Advanced NSCLC – Maintenance Treatment:
    • Rash and diarrhea.
    • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (9%) and diarrhea (2%). Rash and diarrhea resulted in dose reductions or interruption (5% and 3%, respectively) and discontinuation (1% and 0.5%, respectively) of Tarceva-treated patients.
  • Advanced NSCLC – Second/Third-Line Treatment:
    • Rash and diarrhea.
    • Grade 3/4 (NCI-CTC Version 2.0) adverse reactions were rash (9%) and diarrhea (6%). Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients. 
  • Advanced Pancreatic Cancer – Tarceva Administered Concurrently with Gemcitabine:
    • Fatigue, rash, nausea, anorexia, and diarrhea. 
    • Grade 3/4 (NCI-CTC Version 2.0) adverse reactions were rash (5%) and diarrhea (5%). Rash and diarrhea each resulted in dose reductions in 2% of patients and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional Important Safety Information, please see full Prescribing Information.


What is the recommended dosing for Tarceva?

  • Dosing for advanced NSCLC1:
    • The recommended once-daily dose of Tarceva for the treatment of advanced NSCLC is 150 mg taken orally on an empty stomach.
  • Dosing for advanced pancreatic cancer1:
    • The recommended once-daily dose of Tarceva for the treatment of advanced pancreatic cancer is 100 mg in combination with gemcitabine taken orally on an empty stomach.
  • Treatment should continue until disease progression or unacceptable toxicity occurs.1
  • Patients should be instructed to take Tarceva on an empty stomach at least one hour before or two hours after the ingestion of food.1

For information about dose modification, please see the Important Safety Information and the FAQs about dose modifications included in this section.

Indications

Advanced Non-Small Cell Lung Cancer (NSCLC)

Tarceva is indicated for:

  • The first-line treatment of patients with metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
  • The maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
  • The treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Limitations of use:

  • Tarceva is not recommended for use in combination with platinum-based chemotherapy.
  • Safety and efficacy of Tarceva have not been evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.

Advanced Pancreatic Cancer

Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer.

Important Safety Information

CONTRAINDICATIONS

None

WARNINGS AND PRECAUTIONS

  • Interstitial Lung Disease (ILD): 
    • Cases of serious ILD, including fatal cases, can occur with Tarceva treatment. The overall incidence of ILD in approximately 32,000 Tarceva-treated patients in uncontrolled studies and studies with concurrent chemotherapy was approximately 1.1%. In patients with ILD, the onset of symptoms was between 5 days to more than 9 months (median 39 days) after initiating Tarceva therapy.
    • Withhold Tarceva for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue Tarceva.
  • Renal Failure: 
    • Hepatorenal syndrome, severe acute renal failure including fatal cases, and renal insufficiency can occur with Tarceva treatment. Renal failure may arise from exacerbation of underlying baseline hepatic impairment or severe dehydration.
    • The pooled incidence of severe renal impairment in the 3 monotherapy lung cancer studies was 0.5% in the Tarceva arms and 0.8% in the control arms. The incidence of renal impairment in the pancreatic cancer study was 1.4% in the Tarceva plus gemcitabine arm and 0.4% in the control arm.
    • Withhold Tarceva in patients developing severe renal impairment until renal toxicity is resolved. Perform periodic monitoring of renal function and serum electrolytes during Tarceva treatment.
  • Hepatotoxicity With or Without Hepatic Impairment:
    • Hepatic failure and hepatorenal syndrome, including fatal cases, can occur with Tarceva treatment in patients with normal hepatic function; the risk of hepatic toxicity is increased in patients with baseline hepatic impairment.
      • Hepatic Toxicity: One Tarceva-treated patient experienced fatal hepatic failure and four additional patients experienced grade 3-4 liver test abnormalities. 
    • In clinical studies where patients with moderate to severe hepatic impairment were excluded, the pooled incidence of hepatic failure in the 3 monotherapy lung cancer studies was 0.4% in the Tarceva arms and 0% in the control arms. The incidence of hepatic failure in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0.4% in the control arm.
    • Perform periodic liver testing (transaminases, bilirubin, and alkaline phosphatase) during treatment with Tarceva. Increased frequency of monitoring of liver function is required for patients with pre-existing hepatic impairment or biliary obstruction.
    • Withhold Tarceva in patients without pre-existing hepatic impairment for total bilirubin >3 x ULN and/or transaminases >5 x ULN. Withhold Tarceva in patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases value over baseline.
    • Discontinue Tarceva in patients whose abnormal liver tests meeting the above criteria do not improve significantly or resolve within 3 weeks.
  • Gastrointestinal Perforation:
    • Gastrointestinal perforation, including fatal cases, can occur with Tarceva treatment. Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease may be at increased risk of perforation.
    • The pooled incidence of gastrointestinal perforation in the 3 monotherapy lung cancer studies was 0.2% in the Tarceva arms and 0.1% in the control arms. The incidence of gastrointestinal perforation in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
    • Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.
  • Bullous and Exfoliative Skin Disorders:
    • Bullous, blistering and exfoliative skin conditions, including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal, can occur with Tarceva treatment.
    • The pooled incidence of bullous and exfoliative skin disorders in the 3 monotherapy lung cancer studies was 1.2% in the Tarceva arms and 0% in the control arms. The incidence of bullous and exfoliative skin disorders in the pancreatic cancer study was 0.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
    • Discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.
  • Myocardial Infarction (MI)/Ischemia:
    • In the pancreatic carcinoma trial, 6 patients (incidence 2.1%) in the Tarceva plus gemcitabine group developed myocardial infarction/ischemia. One of these patients died due to myocardial infarction. In comparison, 3 patients in the placebo/gemcitabine group developed myocardial infarction (incidence 1.1%), and one died due to myocardial infarction. The pooled incidence of myocardial infarction/ischemia in the 3 monotherapy lung cancer studies was 0.2% in the Tarceva arms and 0.4% in the control arms.
  • Cerebrovascular Accident:
    • In the pancreatic carcinoma trial, 7 patients in the Tarceva plus gemcitabine group developed cerebrovascular accident (incidence 2.5%). One of these was hemorrhagic and was the only fatal event. In comparison, in the placebo/gemcitabine group there were no cerebrovascular accidents. The pooled incidence of cerebrovascular accident in the 3 monotherapy lung cancer studies was 0.6% in the Tarceva arms and 0.9% in the control arms.
  • Microangiopathic Hemolytic Anemia With Thrombocytopenia:
    • The pooled incidence of microangiopathic hemolytic anemia with thrombocytopenia in the 3 monotherapy lung cancer studies was 0% in the Tarceva arms and 0.1% in the control arms. The incidence of microangiopathic hemolytic anemia with thrombocytopenia in the pancreatic cancer study was 1.4% in the Tarceva plus gemcitabine arm and 0% in the control arm.
  • Ocular Disorders:
    • Decreased tear production, abnormal eyelash growth, keratoconjunctivitis sicca or keratitis can occur with Tarceva treatment and can lead to corneal perforation or ulceration.
    • The pooled incidence of ocular disorders in the 3 monotherapy lung cancer studies was 17.8% in the Tarceva arms and 4% in the control arms. The incidence of ocular disorders in the pancreatic cancer study was 12.8% in the Tarceva plus gemcitabine arm and 11.4% in the control arm.
    • Interrupt or discontinue Tarceva therapy if patients present with acute or worsening ocular disorders such as eye pain.
  • Hemorrhage in Patients Taking Warfarin:
    • Severe and fatal hemorrhage associated with International Normalized Ratio (INR) elevations can occur when Tarceva and warfarin are administered concurrently.
    • Regularly monitor prothrombin time and INR during Tarceva treatment in patients taking warfarin or other coumarin-derivative anticoagulants.
  • Embryo-Fetal Toxicity:
    • Tarceva is pregnancy category D. Based on its mechanism of action, Tarceva can cause fetal harm when administered to a pregnant woman. If Tarceva is used during pregnancy, or if the patient becomes pregnant while taking Tarceva, the patient should be apprised of the potential hazard to a fetus.
    • Advise females of reproductive potential to use highly effective contraception during therapy and for at least 2 weeks after the last dose of Tarceva. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Tarceva.

MOST COMMON ADVERSE REACTIONS

  • Metastatic NSCLC – First-Line Treatment of Patients With EGFR Mutations:
    • Most frequent (≥30%) adverse reactions were diarrhea, asthenia, rash, cough, dyspnea, and decreased appetite.
    • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (14%) and diarrhea (5%). In Tarceva-treated patients, the most frequently reported adverse reactions leading to dose modification were rash (13%), diarrhea (10%), and asthenia (3.6%). 
  • Advanced NSCLC – Maintenance Treatment:
    • Rash and diarrhea.
    • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (9%) and diarrhea (2%). Rash and diarrhea resulted in dose reductions or interruption (5% and 3%, respectively) and discontinuation (1% and 0.5%, respectively) of Tarceva-treated patients.
  • Advanced NSCLC – Second/Third-Line Treatment:
    • Rash and diarrhea.
    • Grade 3/4 (NCI-CTC Version 2.0) adverse reactions were rash (9%) and diarrhea (6%). Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients. 
  • Advanced Pancreatic Cancer – Tarceva Administered Concurrently with Gemcitabine:
    • Fatigue, rash, nausea, anorexia, and diarrhea. 
    • Grade 3/4 (NCI-CTC Version 2.0) adverse reactions were rash (5%) and diarrhea (5%). Rash and diarrhea each resulted in dose reductions in 2% of patients and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the Tarceva full Prescribing Information for additional Important Safety Information.

Reference

  1. Tarceva [package insert]. Northbrook, IL: OSI Pharmaceuticals, LLC, an affiliate of Astellas Pharma US, Inc.; 2015.