Tarceva

Take the next dose at your regular time the next day. Do not take a double dose to make up for a missed one.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• diarrhea
• rash

Yes

Tarceva is part of the drug class:

• Protein kinase inhibitors

Tarceva comes as a tablet to take by mouth. It is usually taken on an empty stomach once a day, at least 1 hour before or 2 hours after eating a meal or snack. Take Tarceva at around the same time every day.

To prevent diarrhea that may be caused by Tarcev:

• drink small sips of a liquid such as a sugar-free sports drink often throughout the day
• eat mild foods such as crackers and toast
• avoid spicy foods

It is recommended that you should stop smoking if prescribed Tarceva. The dose may need to be adjusted if you smoke while taking Tarceva.

Erlotinib is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

Erlotinib is used to treat non-small cell lung cancer or pancreatic cancer that has spread to other parts of the body (metastatic).

Erlotinib is usually given after other cancer medicines have been tried without success.

Erlotinib may also be used for purposes not listed in this medication guide.

You should not take erlotinib if you are allergic to it.

To make sure erlotinib is safe for you, tell your doctor if you have:

• lung or breathing problems (other than lung cancer);

• kidney disease;

• liver disease;

• a history of stomach bleeding;

• eye problems;

• if you are dehydrated;

• if you smoke; or

• if you also take warfarin (Coumadin, Jantoven).

Do not take erlotinib if you are pregnant. It could harm the unborn baby. Use effective birth control while you are taking this medication and for at least 1 month after your last dose.

It is not known whether erlotinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking erlotinib.

Antineoplastic agent; a kinase inhibitor.1

Storage

Oral

25°C (may be exposed to 15–30°C).1

Medicines used to treat cancer are very strong and can have many side effects. Before using this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take this medicine on an empty stomach, at least 1 hour before or 2 hours after food.

If you take a stomach medicine for heartburn or ulcers (such as cimetidine, famotidine, ranitidine, Pepcid®, Tagamet®, Zantac®), take the heartburn medicine at least 10 hours before or 2 hours after you take this medicine.

If you take antacids (such as Gaviscon®, Maalox®, Mylanta®, Rolaids®), take the antacid several hours before or after you take this medicine.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine.

If there is a change in your tobacco smoking status, call your doctor. This could result in a change in dose.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For lung cancer:
    • Adults—150 milligrams (mg) once a day. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • For pancreas cancer:
    • Adults—100 milligrams (mg) once a day, taken with gemcitabine. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Itching.
• Pimples (acne).
• Skin irritation.
• Upset stomach.
• Loose stools (diarrhea).
• Not hungry.
• Mouth irritation or mouth sores.
• Headache.
• Back pain.
• Muscle or joint pain.
• Change in hair or nails.
• Dry skin.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

The following serious adverse reactions, which may include fatalities, are discussed in greater detail in other sections of the labeling:

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety evaluation of Tarceva is based on more than 1200 cancer patients who received Tarceva as monotherapy, more than 300 patients who received Tarceva 100 or 150 mg plus gemcitabine, and 1228 patients who received Tarceva concurrently with other chemotherapies. The most common adverse reactions with Tarceva are rash and diarrhea usually with onset during the first month of treatment. The incidences of rash and diarrhea from clinical studies of Tarceva for the treatment of NSCLC and pancreatic cancer were 70% for rash and 42% for diarrhea.

Non-Small Cell Lung Cancer

First-Line Treatment of Patients with EGFR Mutations

The most frequent (≥ 30%) adverse reactions in Tarceva-treated patients were diarrhea, asthenia, rash, cough, dyspnea, and decreased appetite. In Tarceva-treated patients the median time to onset of rash was 15 days and the median time to onset of diarrhea was 32 days.

The most frequent Grade 3-4 adverse reactions in Tarceva-treated patients were rash and diarrhea.

Dose interruptions or reductions due to adverse reactions occurred in 37% of Tarceva-treated patients, and 14.3% of Tarceva-treated patients discontinued therapy due to adverse reactions. In Tarceva-treated patients, the most frequently reported adverse reactions leading to dose modification were rash (13%), diarrhea (10%), and asthenia (3.6%).

Common adverse reactions in Study 1, occurring in at least 10% of patients who received Tarceva or chemotherapy and an increase in ≥ 5% in the Tarceva-treated group, are graded by National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0) Grade in Table 1. The median duration of Tarceva treatment was 9.6 months in Study 1.

Hepatic Toxicity: One Tarceva-treated patient experienced fatal hepatic failure and four additional patients experienced grade 3-4 liver test abnormalities in Study 1 [see Warnings and Precautions (5.3)].

Maintenance Treatment

Adverse reactions, regardless of causality, that occurred in at least 3% of patients treated with single-agent Tarceva at 150 mg and at least 3% more often than in the placebo group in the randomized maintenance trial (Study 3) are summarized by NCI-CTCAE v3.0 Grade in Table 2.

The most common adverse reactions in patients receiving single-agent Tarceva 150 mg were rash and diarrhea. Grade 3-4 rash and diarrhea occurred in 9% and 2%, respectively, in Tarceva-treated patients. Rash and diarrhea resulted in study discontinuation in 1% and 0.5% of Tarceva-treated patients, respectively. Dose reduction or interruption for rash and diarrhea was needed in 5% and 3% of patients, respectively. In Tarceva-treated patients the median time to onset of rash was 10 days, and the median time to onset of diarrhea was 15 days.

Liver test abnormalities including ALT elevations were observed at Grade 2 or greater severity in 3% of Tarceva-treated patients and 1% of placebo-treated patients. Grade 2 and above bilirubin elevations were observed in 5% of Tarceva-treated patients and in < 1% in the placebo group [see Dosage and Administration (2.4) and Warnings and Precautions (5.3)].

Second/Third Line Treatment

Adverse reactions, regardless of causality, that occurred in at least 10% of patients treated with single-agent Tarceva at 150 mg and at least 5% more often than in the placebo group in the randomized trial of patients with NSCLC are summarized by NCI-CTC v2.0 Grade in Table 3.

The most common adverse reactions in this patient population were rash and diarrhea. Grade 3-4 rash and diarrhea occurred in 9% and 6%, respectively, in Tarceva-treated patients. Rash and diarrhea each resulted in study discontinuation in 1% of Tarceva-treated patients. Six percent and 1% of patients needed dose reduction for rash and diarrhea, respectively. The median time to onset of rash was 8 days, and the median time to onset of diarrhea was 12 days.

Liver function test abnormalities [including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin] were observed in patients receiving single-agent Tarceva 150 mg. These elevations were mainly transient or associated with liver metastases. Grade 2 [> 2.5 – 5.0 x upper limit of normal (ULN)] ALT elevations occurred in 4% and < 1% of Tarceva and placebo treated patients, respectively. Grade 3 (> 5.0 – 20.0 x ULN) elevations were not observed in Tarceva-treated patients. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe [see Dosage and Administration (2.4)].

Pancreatic Cancer - Tarceva Administered Concurrently with Gemcitabine

This was a randomized, double-blind, placebo-controlled study of Tarceva (150 mg or 100 mg daily) or placebo plus gemcitabine (1000 mg/m2  by intravenous infusion) in patients with locally advanced, unresectable or metastatic pancreatic cancer (Study 5). The safety population comprised 282 patients in the erlotinib group (259 in the 100 mg cohort and 23 in the 150 mg cohort) and 280 patients in the placebo group (256 in the 100 mg cohort and 24 in the 150 mg cohort).

Adverse reactions that occurred in at least 10% of patients treated with Tarceva 100 mg plus gemcitabine in the randomized trial of patients with pancreatic cancer (Study 5) were graded according to NCI-CTC v2.0 in Table 4.

The most common adverse reactions in pancreatic cancer patients receiving Tarceva 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea. In the Tarceva plus gemcitabine arm, Grade 3-4 rash and diarrhea were each reported in 5% of patients. The median time to onset of rash and diarrhea was 10 days and 15 days, respectively. 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. Severe adverse reactions (≥ Grade 3 NCI-CTC) in the Tarceva plus gemcitabine group with incidences < 5% included syncope, arrhythmias, ileus, pancreatitis, hemolytic anemia including microangiopathic hemolytic anemia with thrombocytopenia, myocardial infarction/ischemia, cerebrovascular accidents including cerebral hemorrhage, and renal insufficiency [see Warnings and Precautions (5)].

The 150 mg cohort was associated with a higher rate of certain class-specific adverse reactions including rash and required more frequent dose reduction or interruption.

Ten patients (4%) in the Tarceva/gemcitabine group and three patients (1%) in the placebo/gemcitabine group developed deep venous thrombosis. The overall incidence of grade 3 or 4 thrombotic events, including deep venous thrombosis was 11% for Tarceva plus gemcitabine and 9% for placebo plus gemcitabine.

The incidences of liver test abnormalities (≥ Grade 2) in Study 5 are provided in Table 5 [see Dosage and Administration (2.4) and Warnings and Precautions (5.3)].

NSCLC and Pancreatic Indications: Selected Low Frequency Adverse Reactions

Gastrointestinal Disorders

Cases of gastrointestinal bleeding (including fatalities) have been reported, some associated with concomitant warfarin or NSAID administration [see Warnings and Precautions (5.9) and Drug Interactions (7)]. These adverse reactions were reported as peptic ulcer bleeding (gastritis, gastroduodenal ulcers), hematemesis, hematochezia, melena and hemorrhage from possible colitis.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of Tarceva. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis, in combination with statin therapy

Eye Disorders: ocular inflammation including uveitis

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

Absorption

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%.

Distribution:

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

Erlotinib has an apparent volume of distribution of 232 liters.

Elimination

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.

Patients with Hepatic Impairment

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.

Patients That Smoke Tobacco Cigarettes

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 (2.4), Drug Interactions (7) and Patient Counseling Information (17)].

Drug Interaction Studies

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

CYP3A4 Inhibitors

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 (2.4), Drug Interactions (7)].

CYP3A4 Inducers

Pre-treatment with the CYP3A4 inducer rifampicin, for 7-11 days prior to Tarceva, decreased erlotinib AUC by 58% to 80% [see Dose Modifications (2.4), Drug Interactions (7)].

CYP1A2 Inducers or Smoking Tobacco

See Specific Populations Section [see Dose Modifications (2.4), Drug Interactions (7)].

Drugs that Increase Gastric pH

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 (2.4), Drug Interactions (7)].

Tarceva (erlotinib) is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

Tarceva is used to treat non-small cell lung cancer or pancreatic cancer that has spread to other parts of the body (metastatic).

Tarceva is usually given after other cancer medicines have been tried without success.

Usual Adult Dose for Non-Small Cell Lung Cancer:

150 mg orally once a day

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:
-There is no evidence that treatment beyond disease progression is beneficial.

Uses:
-First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.
-Maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
-Treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Usual Adult Dose for Pancreatic Cancer:

100 mg orally once a day

Duration of therapy: Until disease progression or unacceptable toxicity

Use: First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine.

Tarceva is used to treat non-small cell lung cancer (NSCLC) that has spread and has certain types of genetic mutations. Tarceva is also used to treat pancreatic cancer.

This drug comes in the form of a tablet you take by mouth.

Tarceva is a brand name for the drug erlotinib. It’s not available as a generic drug.

The more common side effects of this drug can include rash, tiredness, shortness of breath, or cough. They can also include loss of appetite, diarrhea, nausea, or vomiting.

In some cases, Tarceva can cause serious side effects. These can include lung disease, kidney failure, liver problems, tears in the stomach or intestines, skin problems, or eye problems.

• Interstitial lung disease (ILD) See Details

• Kidney problems See Details

• Liver problems See Details

• Skin problems See Details

What is Tarceva?

This drug is a prescription drug. It comes in the form of a tablet you take by mouth.

Tarceva is a brand name for the drug erlotinib. It’s not available as a generic drug.

If you’re using this drug to treat pancreatic cancer, you’ll use this drug as part of a combination therapy. This means you need to take it with another drug called gemcitabine.

If you’re using this drug to treat non-small cell lung cancer, you will not use it with other medications to treat your condition.

Why it's used

This drug is used to treat two types of cancer: non-small cell lung cancer (NSCLC) and pancreatic cancer.

More Details

How it works

This drug belongs to a class of drugs called epidermal growth factor receptor inhibitors.

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