Tarceva Information
Tarceva (Erlotinib) . Indications And Usage
Tarceva (Erlotinib) 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 3 trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva (Erlotinib) with platinum-based chemotherapy [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting
Tarceva (Erlotinib) . Dosage And Administration
In patients who develop an acute onset of new or progressive pulmonary symptoms, such as dyspnea, cough or fever, treatment with Tarceva (Erlotinib) should be interrupted pending diagnostic evaluation. If Interstitial Lung Disease (ILD) is diagnosed, Tarceva (Erlotinib) should be discontinued and appropriate treatment instituted as necessary
Diarrhea can usually be managed with loperamide. Patients with severe diarrhea who are unresponsive to loperamide or who become dehydrated may require dose reduction or temporary interruption of therapy. Patients with severe skin reactions may also require dose reduction or temporary interruption of therapy.
When dose reduction is necessary, the Tarceva (Erlotinib) dose should be reduced in 50 mg decrements.
In patients who are taking Tarceva (Erlotinib) with a strong CYP3A4 inhibitor such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice, a dose reduction should be considered if severe adverse reactions occur. Similarly, in patients who are taking Tarceva (Erlotinib) with an inhibitor of both CYP3A4 and CYP1A2 like ciprofloxacin, a dose reduction of Tarceva (Erlotinib) should be considered if severe adverse reactions occur.
Pre-treatment with the CYP3A4 inducer rifampicin decreased erlotinib AUC by about 2/3 to 4/5. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, an increase in the dose of Tarceva (Erlotinib) should be considered as tolerated at two week intervals while monitoring the patient’s safety. The maximum dose of Tarceva (Erlotinib) studied in combination with rifampicin is 450 mg. If the Tarceva (Erlotinib) dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort. These too should be avoided if possible
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 (Erlotinib) , 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 (Erlotinib) dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking
Erlotinib is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh B), patients with hepatic impairment (total bilirubin > ULN or Child-Pugh A, B and C) should be closely monitored during therapy with Tarceva (Erlotinib) [ Treatment with Tarceva (Erlotinib) should be used with extra caution in patients with total bilirubin > 3 x ULN. Tarceva (Erlotinib) dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range. In the setting of worsening liver function tests, before they become severe, dose interruption and/or dose reduction with frequent liver function test monitoring should be considered. Tarceva (Erlotinib) dosing should be interrupted or discontinued if total bilirubin is >3 x ULN and/or transaminases are >5 x ULN in the setting of normal pretreatment values
Tarceva (Erlotinib) . Dosage Forms And Strengths
25 mg tablets
White film-coated tablets for daily oral administration. 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.
100 mg tablets
White film-coated tablets for daily oral administration. Round, biconvex face and straight sides, white film-coated, printed in gray with “T” and “100” on one side and plain on the other side.
150 mg tablets
White film-coated tablets for daily oral administration. Round, biconvex face and straight sides, white film-coated, printed in maroon with “T” and “150” on one side and plain on the other side.
Tarceva (Erlotinib) . Contraindications
Tarceva (Erlotinib) . Warnings And Precautions
There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva (Erlotinib) for treatment of NSCLC, pancreatic cancer or other advanced solid tumors. In the randomized single-agent NSCLC study, the incidence of ILD-like events (0.8%) was the same in both the placebo and Tarceva (Erlotinib) groups. In the pancreatic cancer study - in combination with gemcitabine – , the incidence of ILD-like events was 2.5% in the Tarceva (Erlotinib) plus gemcitabine group vs. 0.4% in the placebo plus gemcitabine group.
The overall incidence of ILD-like events in approximately 4900 Tarceva (Erlotinib) -treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) was approximately 0.7%. Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome and lung infiltration. Symptoms started from 5 days to more than 9 months (median 39 days) after initiating Tarceva (Erlotinib) therapy. In the lung cancer trials most of the cases were associated with confounding or contributing factors such as concomitant/prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections.
In the event of an acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever, Tarceva (Erlotinib) therapy should be interrupted pending diagnostic evaluation. If ILD is diagnosed, Tarceva (Erlotinib) should be discontinued and appropriate treatment instituted as needed
Pregnancy Category D
Women of childbearing potential should avoid becoming pregnant while being treated with Tarceva (Erlotinib) . Erlotinib administered to rabbits during organogenesis at doses that result in plasma drug concentrations of approximately 3 times those in humans (AUCs at 150 mg daily dose) was associated with embryo/fetal lethality and abortion. When erlotinib was administered to female rats prior to mating and through the first week of pregnancy, at doses 0.3 or 0.7 times the clinical dose of 150 mg, on a mg/m basis, there was an increase in early resorptions that resulted in a decrease in the number of live fetuses. [
Tarceva (Erlotinib) . Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reactions 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 (Erlotinib) is based on 856 cancer patients who received Tarceva (Erlotinib) as monotherapy, 308 patients who received Tarceva (Erlotinib) 100 or 150 mg plus gemcitabine, and 1228 patients who received Tarceva (Erlotinib) concurrently with other chemotherapies.
There have been reports of serious events, including fatalities, in patients receiving Tarceva (Erlotinib) for treatment of NSCLC, pancreatic cancer or other advanced solid tumors
Tarceva (Erlotinib) . Drug Interactions
Erlotinib is metabolized predominantly by CYP3A4, and inhibitors of CYP3A4 would be expected to increase exposure. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increases erlotinib AUC by 2/3. When Tarceva (Erlotinib) was co-administered with ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the erlotinib exposure [AUC] and maximum concentration [C] increased by 39% and 17% respectively. Caution should be used when administering or taking Tarceva (Erlotinib) with ketoconazole and other strong CYP3A4 inhibitors such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole and grapefruit or grapefruit juice. .
Pre-treatment with the CYP3A4 inducer rifampicin for 7 days prior to Tarceva (Erlotinib) decreased erlotinib AUC by about 2/3 to 4/5, which is equivalent to a dose of about 30 to 50 mg in NSCLC patients. In a separate study, treatment with rifampicin for 11 days, with co-administration of a single 450 mg dose of Tarceva (Erlotinib) on day 8 resulted in a mean erlotinib exposure (AUC) that was 57.6% of that observed following a single 150 mg Tarceva (Erlotinib) dose in the absence of rifampicin treatment . Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, adjusting the starting dose should be considered. If the Tarceva (Erlotinib) dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort
Cigarette smoking has been shown to reduce erlotinib AUC. Patients should be advised to stop smoking; however, if they continue to smoke, a cautious increase in the dose of Tarceva (Erlotinib) may be considered, while monitoring the patient’s safety. If the Tarceva (Erlotinib) dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking.
Pretreatment and co-administration of Tarceva (Erlotinib) decreased the AUC of CYP3A4 substrate, midazolam, by 24%. The mechanism is not clear.
In a study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.
Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. Co-administration of Tarceva (Erlotinib) with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%. Increasing the dose of Tarceva (Erlotinib) when co-administered with such agents is not likely to compensate for the loss of exposure. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with Tarceva (Erlotinib) should be avoided if possible. The use of antacids may be considered in place of histamine 2 receptor blockers (H blockers) or proton pump inhibitors in patients receiving Tarceva (Erlotinib) . However, no clinical study has been conducted to evaluate the effect of antacids on erlotinib pharmacokinetics. If an antacid is necessary, the antacid dose and the Tarceva (Erlotinib) dose should be separated by several hours [].
Tarceva (Erlotinib) . Use In Specific Populations
Pregnancy Category D [See ]
Erlotinib has been shown to cause maternal toxicity with associated embryo/fetal lethality and abortion in rabbits when given at doses that result in plasma drug concentrations of approximately 3 times those in humans (AUCs at 150 mg daily dose). When given during the period of organogenesis to achieve plasma drug concentrations approximately equal to those in humans, based on AUC, there was no increased incidence of embryo/fetal lethality or abortion in rabbits or rats. However, female rats treated with 30 mg/m/day or 60 mg/m/day (0.3 or 0.7 times the clinical dose, on a mg/m basis) of erlotinib prior to mating through the first week of pregnancy had an increase in early resorptions that resulted in a decrease in the number of live fetuses.
No teratogenic effects were observed in rabbits or rats dosed with erlotinib during organogenesis at doses up to 600 mg/m/day in the rabbit (3 times the plasma drug concentration seen in humans at 150 mg/day) and up to 60 mg/m/day in the rat (0.7 times the clinical dose of 150 mg/day on a mg/m basis).
There are no adequate and well-controlled studies in pregnant women using Tarceva (Erlotinib) . Women of childbearing potential should be advised to avoid pregnancy while on Tarceva (Erlotinib) . Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy. Treatment should only be continued in pregnant women if the potential benefit to the mother outweighs the risk to the fetus. If Tarceva (Erlotinib) is used during pregnancy, the patient should be apprised of the potential hazard to the fetus or potential risk for loss of the pregnancy
Of the total number of patients participating in the randomized NSCLC trial, 62% were less than 65 years of age, and 38% of patients were aged 65 years or older. The survival benefit was maintained across both age groups [HR = 0.75 (95% CI: 0.6, 0.9) in patients less than 65 years of age, and HR = 0.79 (95% CI: 0.6, 1.0) in patients who were 65 years or older]
In the pancreatic cancer study, 53% of patients were younger than 65 years of age and 47% were 65 years of age or older. There were no clinically relevant differences between the age groups [HR = 0.78 (95% CI: 0.6, 1.0) in patients less than 65 years of age, and HR = 0.94 (95% CI: 0.7, 1.2) in patients who were 65 years or older]. No meaningful differences in safety or pharmacokinetics were observed between younger and older patients in either study. Therefore, no dosage adjustments are recommended in elderly patients.
Of the total number of patients participating in the randomized NSCLC trial, 65% were males and 35% females. There were no clinically relevant differences in safety and efficacy based on gender [HR = 0.76 (95% CI: 0.6, 0.9) in males and HR = 0.80 (95% CI: 0.6, 1.1) in females].
In the pancreatic cancer study, 52% of patients were males and 48% females. There were no clinically relevant differences in safety and efficacy based on gender [HR = 0.74 (95% CI: 0.6, 0.9) in males and HR = 1.0 (95% CI: 0.8, 1.3) in females].
In the randomized NSCLC trial, 78% of all patients were Caucasian and 12% were Asian. There were no clinically relevant differences in safety and efficacy based on race [HR = 0.79 (95% CI: 0.6, 1.0) in Caucasians and HR = 0.61 (95% CI: 0.4, 1.0) in Asians].
In the pancreatic cancer study, 88% of all patients were Caucasian and 7% were Asian. There were no clinically relevant differences in safety and efficacy based on race [HR = 0.88 (95% CI: 0.7, 1.1) in Caucasians and HR = 0.61 (95% CI: 0.3, 1.3) in Asians].
Patients with hepatic impairment (total bilirubin > ULN or Child Pugh A, B and C) should be closely monitored during therapy with Tarceva (Erlotinib) . Treatment with Tarceva (Erlotinib) should be used with extra caution in patients with total bilirubin > 3 x ULN [.
Tarceva (Erlotinib) . Overdosage
Single oral doses of Tarceva (Erlotinib) up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Tarceva (Erlotinib) in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse events, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose In case of suspected overdose, Tarceva (Erlotinib) should be withheld and symptomatic treatment instituted.
Tarceva (Erlotinib) . Description
Tarceva (Erlotinib) (erlotinib), a kinase inhibitor, is a quinazolinamine with the chemical name N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine. Tarceva (Erlotinib) contains erlotinib as the hydrochloride salt that has the following structural formula:
Erlotinib hydrochloride has the molecular formula CHNO.HCl and a molecular weight of 429.90. The molecule has a pK of 5.42 at 25C. Erlotinib hydrochloride is very slightly soluble in water, slightly soluble in methanol and practically insoluble in acetonitrile, acetone, ethyl acetate and hexane.
Aqueous solubility of erlotinib hydrochloride is dependent on pH with increased solubility at a pH of less than 5 due to protonation of the secondary amine. Over the pH range of 1.4 to 9.6, maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2.
Tarceva (Erlotinib) tablets for oral administration are available in three dosage strengths containing erlotinib hydrochloride (27.3 mg, 109.3 mg and 163.9 mg) equivalent to 25 mg, 100 mg and 150 mg erlotinib and the following inactive ingredients: lactose monohydrate, hypromellose, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate and titanium dioxide. The tablets also contain trace amounts of color additives, including FD&C Yellow #6 (25 mg only) for product identification.
Tarceva (Erlotinib) . Clinical Pharmacology
Absorption and Distribution:
Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Erlotinib solubility decreases as pH increases. Co-administration of Tarceva (Erlotinib) with omeprazole, a proton pump inhibitor, decreased the erlotinib exposure [AUC] and maximum concentration [C] by 46% and 61% respectively .
Following absorption, erlotinib is approximately 93% protein bound to plasma albumin and alpha-1 acid glycoprotein (AAG). Erlotinib has an apparent volume of distribution of 232 liters.
Metabolism and Excretion:
A population pharmacokinetic analysis in 591 patients receiving single-agent Tarceva (Erlotinib) showed a median half-life of 36.2 hours. Time to reach steady state plasma concentration would therefore be 7 – 8 days. No significant relationships of clearance to covariates of patient age, body weight or gender were observed. Smokers had a 24% higher rate of erlotinib clearance.
A second population pharmacokinetic analysis was conducted that incorporated erlotinib data from 204 pancreatic cancer patients who received erlotinib plus gemcitabine. This analysis demonstrated that covariates affecting erlotinib clearance in patients from the pancreatic study were very similar to those seen in the prior single-agent pharmacokinetic analysis. No new covariate effects were identified. Co-administration of gemcitabine had no effect on erlotinib plasma clearance.
In vitro
Cigarette smoking reduces erlotinib exposure. In the Phase 3 NSCLC trial, current smokers achieved erlotinib steady-state trough plasma concentrations which was 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 a separate study which evaluated the single-dose pharmacokinetics of erlotinib in healthy volunteers, current smokers cleared the drug faster than former smokers or volunteers who had never smoked. The AUC in smokers was about 1/3 to 1/2 of that in never/former smokers. In another study which was conducted in NSCLC patients (N=35) who were current smokers, pharmacokinetic analyses at steady-state indicated a dose-proportional increase in erlotinib exposure when the Tarceva (Erlotinib) dose was increased from 150 mg to 300 mg. However, the exact dose to be recommended for patients who currently smoke is unknown
Special Populations:
Patients with Hepatic Impairment
Patients with hepatic impairment (total bilirubin > ULN or Child Pugh A, B and C) should be closely monitored during therapy with Tarceva (Erlotinib) . Treatment with Tarceva (Erlotinib) should be used with extra caution in patients with total bilirubin > 3 x ULN .
Patients with Renal Impairment
Less than 9% of a single dose is excreted in the urine. No clinical studies have been conducted in patients with compromised renal function.
Tarceva (Erlotinib) . Clinical Studies
The efficacy and safety of single-agent Tarceva (Erlotinib) was assessed in 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 (Erlotinib) 150 mg or placebo (488 Tarceva (Erlotinib) , 243 placebo) orally once daily until disease progression or unacceptable toxicity. Study endpoints 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.
Table 4 summarizes the demographic and disease characteristics of the study population. Demographic characteristics were well balanced between the two treatment groups. About two-thirds of the patients were male. Approximately one-fourth had a baseline ECOG performance status (PS) of 2, and 9% had a baseline ECOG PS of 3. Fifty percent of the patients had received only one prior regimen of chemotherapy. About three quarters of these patients were known to have smoked at some time.
The results of the study are shown in Table 5.
Survival was evaluated in the intent-to-treat population. Figure 1 depicts the Kaplan-Meier curves for overall survival. The primary survival and PFS analyses were two-sided Log-Rank tests stratified by ECOG performance status, number of prior regimens, prior platinum, best response to prior chemotherapy.
Note:
The efficacy and safety of Tarceva (Erlotinib) in combination with gemcitabine as a first-line treatment was assessed in 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 (Erlotinib) (100 mg or 150 mg) or placebo once daily on a continuous schedule plus gemcitabine IV (1000 mg/m, 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 (Erlotinib) 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 (Erlotinib) (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.
Table 6 summarizes the demographic and disease characteristics of the study population that was randomized to receive 100 mg of Tarceva (Erlotinib) plus gemcitabine or placebo plus gemcitabine. Baseline demographic and disease characteristics of the patients were similar between the 2 treatment groups, except for a slightly larger proportion of females in the Tarceva (Erlotinib) arm (51%) compared with the placebo arm (44%). The median time from initial diagnosis to randomization was approximately 1.0 month. Most patients presented with metastatic disease at study entry as the initial manifestation of pancreatic cancer.
The results of the study are shown in Table 7.
Survival was evaluated in the intent-to-treat population. Figure 2 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.
Note:
Tarceva (Erlotinib) . How Supplied/storage And Handling
25 mg Tablets
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:NDC 50242-062-01
100 mg Tablets
Round, biconvex face and straight sides, white film-coated, printed in gray with “T” and “100” on one side and plain on the other side; supplied in:
Bottles of 30:NDC 50242-063-01
150 mg Tablets
Round, biconvex face and straight sides, white film-coated, printed in maroon with “T” and “150” on one side and plain on the other side; supplied in:
Bottles of 30:NDC 50242-064-01
Store at 25°C (77°F); excursions permitted to 15° – 30°C (59° – 86°F). See USP Controlled Room Temperature.
Tarceva (Erlotinib) . Patient Counseling Information
If the following signs or symptoms occur, patients should be advised to seek medical advice promptly
Given that skin reactions are anticipated when taking Tarceva (Erlotinib) , proactive intervention may include alcohol-free emollient cream and sunscreen and the management of rash should be discussed with the patient. This may include topical corticosteroids or antibiotics with anti-inflammatory properties. These approaches were used in the NSCLC and 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.
Women of childbearing potential should be advised to avoid becoming pregnant while taking Tarceva (Erlotinib)
Smokers should be advised to stop smoking while taking Tarceva (Erlotinib) as plasma concentrations of erlotinib are reduced due to the effect of cigarette smoking
OSI Pharmaceuticals Inc., Melville, NY 11747
Schwarz Pharma Manufacturing, Seymour, IN 47274
Genentech USA, Inc., 1 DNA Way, South San Francisco, CA 94080-4990
Tarceva (Erlotinib)
