Dosing and Administration Guidelines for Advanced NSCLC

Supported by clinical guidelines

Tarceva (erlotinib) is one of only three agents supported by the NCCN for use in second-line NSCLC.⁴

Indication and Usage

Tarceva monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

Results from two, multicenter, placebo-controlled, randomized, Phase III trials 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 or gemcitabine and cisplatin] and its use is not recommended in that setting.

Recommended dosing

• The recommended once-daily dose of Tarceva monotherapy for the treatment of advanced NSCLC is 150 mg taken orally.¹

Do not take with food

• Patients should be instructed to take Tarceva at least one hour before or two hours after the ingestion of food, since food substantially alters the bioavailability of erlotinib and may increase the risk of adverse reactions.^{1, 2, 5} Tarceva tablets should be taken on an empty stomach to help ensure that patients obtain consistent plasma levels of the drug.^{1, 2}
• If a dose is missed, Tarceva can be taken at any time during the same day between meals. If the daily dose is missed entirely, the regularly prescribed dose should be taken the next day, one hour before or two hours after a meal.^{1, 2}
• Caution your patients not to double the daily prescribed dose of Tarceva. Administering Tarceva above the recommended daily dose may result in an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation.¹

Treatment should continue until disease progression or unacceptable toxicity occurs; there is no evidence that treatment beyond disease progression is beneficial.

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Dose adjustment

• If patients experience intolerable adverse reactions, such as intolerable skin reactions, intolerable diarrhea that is unresponsive to loperamide or that causes dehydration, or severe liver function test abnormalities, consider dose reduction or interruption of Tarceva.¹ When dose reduction is necessary, the Tarceva dose should be reduced in 50 mg decrements.
  • six percent and 1% of NSCLC patients required dose reduction for rash and diarrhea, respectively, in the single-agent Phase III trial
  • Cigarette smoking has been shown to reduce erlotinib exposure. Patients should be advised to stop smoking. If a patient continues to smoke, a cautious increase in the dose of TARCEVA, not exceeding 300 mg may be considered, while monitoring the patient's safety. However, efficacy and long-term safety (> 14 days) of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes. If the TARCEVA dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking.

Multiple tablet strengths allow for dose adjustment when appropriate

• To allow for reduction when appropriate, Tarceva is available in 100-mg and 25-mg strengths.¹
• When dose reduction is necessary, the Tarceva dose should be reduced by 50-mg decrements.¹
• Dose reduction is not appropriate if Interstitial Lung Disease (ILD), hepatic failure, or gastrointestinal perforations is diagnosed- Tarceva therapy should be discontinued. Interrupt or discontinue Tarceva in patients with dehydration who are at risk for renal failure, in patients with severe bullous, blistering or exfoliative skin conditions, or in patients with acute/worsening ocular disorders.

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Most common adverse reactions in patients taking Tarceva

• The most common side effects in patients with NSCLC receiving Tarceva monotherapy 150 mg were mild to moderate rash and diarrhea. Severe rash and diarrhea (9% & 6% NCI-CTC Grades 3–4, respectively) were reported. Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients during the single-agent Phase III trial.

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How Supplied

Tarceva is available in 150-mg, 100-mg and 25-mg strengths. Tarceva is supplied as white film-coated tablets for daily oral administration.

Tarceva® (erlotinib) Tablets, 150 mg Round, biconvex face and straight sides, white film-coated, printed in maroon with a "T" and "150" on one side and plain on the other side. Supplied in bottles of 30 tablets (NDC 50242-064-01).	Not actual size
Tarceva® (erlotinib) Tablets, 100 mg Round, biconvex face and straight sides, white film-coated, printed in gray with a "T" and "100" on one side and plain on the other side. Supplied in bottles of 30 tablets (NDC 50242-063-01).	Not actual size
Tarceva® (erlotinib) Tablets, 25 mg Round, biconvex face and straight sides, white film-coated, printed in orange with a "T" and "25" on one side and plain on the other side. Supplied in bottles of 30 tablets (NDC 50242-062-01).	Not actual size

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Storage

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F). See USP Controlled Room Temperature.

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Overdosage

• Single oral doses of Tarceva up to 1,000 mg in healthy subjects and up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of single-agent Tarceva 200 mg in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, severe adverse reactions, such as diarrhea, rash, and possibly liver transaminase elevations, may occur above the recommended dose. In case of suspected overdose, Tarceva should be withheld and symptomatic treatment instituted.

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Concomitant use with CYP3A4 inhibitors and inducers

• The potent CYP3A4 inhibitor ketoconazole has been shown to increase erlotinib AUC; thus, caution should be used during co-treatment with Tarceva and ketoconazole or other CYP3A4 inhibitors such as, but not limited to: atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO) and voriconazole, and grapefruit or grapefruit juice.
• The CYP3A4 inducer rifampicin has been shown to decrease erlotinib AUC, thus, alternate treatments lacking CYP3A4 inducing activity are strongly recommended. In the absence of an alternative treatment, Tarceva dose modification should be considered. If the Tarceva dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other CYP3A4 inducers. The maximum dose of Tarceva studied in combination with rifampicin is 450mg. Other CYP3A4 inducers include: rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort.

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Important Safety Information:

There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva for treatment of NSCLC, pancreatic cancer or other advanced solid tumors. In the event of an acute onset of new or progressive, unexplained pulmonary symptoms such as dyspnea, cough and fever, Tarceva therapy should be interrupted pending diagnostic evaluation. If ILD is diagnosed, Tarceva should be discontinued and appropriate treatment instituted as needed.

Cases of hepatic failure, hepatorenal syndrome, acute renal failure (all including fatalities), and renal insufficiency have been reported during use of Tarceva. Treatment with Tarceva should be used with extra caution in patients with total bilirubin > 3 x ULN. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe. Patients should be closely monitored during therapy with Tarceva.

Gastrointestinal perforation (including fatalities) has been reported in patients receiving Tarceva. Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.

Bullous, blistering and exfoliative skin conditions have been reported including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal. Interrupt or discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.

Corneal perforation and ulceration have been reported during use of Tarceva. Interrupt or discontinue Tarceva therapy if patients present with acute/worsening ocular disorders such as eye pain.

When receiving Tarceva therapy, women should be advised against becoming pregnant or breastfeeding. Tarceva is pregnancy category D.

The most common adverse reactions in patients with NSCLC receiving Tarceva monotherapy 150 mg were mild to moderate rash and diarrhea. Severe rash and diarrhea (9% & 6% NCI-CTC Grades 3-4, respectively) were reported. Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients during the single-agent Phase III trial.

• Please see the Tarceva full prescribing information for complete safety information.

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• 1. Tarceva® (erlotinib) full prescribing information,OSI Pharmaceuticals,Inc., 2009.
• 2. Data on file, OSI Pharmaceuticals, Inc.
• 4. National Comprehensive Cancer Network. NCCN® Clinical Practice Guidelines in Oncology - v.2.2005: non-small-cell lung cancer. National Comprehensive Cancer Network. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf. Accessed July 28, 2005.
• 5. Hidalgo M, Siu LL, Nemunaitis J, et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol. 2001;19:3267-3279.