Erlotinib: Package Insert and Label Information (Page 5 of 5)
14.4 NSCLC – Lack of Efficacy of Erlotinib Tablets 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 erlotinib tablets with platinum-based chemotherapy [carboplatin and paclitaxel (erlotinib tablets, N = 526) or gemcitabine and cisplatin (erlotinib tablets, N = 580)].
14.5 Pancreatic Cancer — Erlotinib Tablets Administered Concurrently with Gemcitabine
The efficacy and safety of erlotinib tablets 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 erlotinib tablets (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]). Erlotinib tablets 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 erlotinib tablets (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 erlotinib tablets 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.
| Efficacy Parameter | Erlotinib Tablets + Gemcitabine(N = 261) | Placebo + Gemcitabine(N = 260) |
|---|---|---|
| Overall Survival (OS) | ||
| Number of Deaths | 250 | 254 |
| Median OS in Months (95% CI) | 6.5 (6.0, 7.4) | 6.0 (5.1, 6.7) |
| Hazard Ratio (95% CI) * | 0.81 (0.68, 0.97) | |
| p-value (stratified log-rank test) † | 0.028 | |
| Progression-Free Survival (PFS) | ||
| Number of Progression or Deaths (%) | 225 | 232 |
| Median PFS in Months (95% CI) | 3.8 (3.6, 4.9) | 3.6 (3.3, 3.8) |
| Hazard Ratio (95% CI)* | 0.76 (0.64, 0.92) | |
| Objective Response | ||
| Objective Response Rate (95% CI) | 8.6% (5.4, 12.9) | 7.9% (4.8, 12.0) |
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
Note: HR is from Cox regression model with the following covariates: ECOG performance status and extent of disease. The p-value is from two-sided Log-Rank test stratified by ECOG performance status and extent of disease.
16. HOW SUPPLIED/STORAGE AND HANDLING
25 mg Tablets: Round, biconvex, white film-coated tablets debossed with “N 25” on one side and plain on the other side; supplied in:
Bottles of 30: NDC 51991-890-33
100 mg Tablets: Round, biconvex, white film-coated tablets debossed with “N 100” on one side and plain on the other side; supplied in:
Bottles of 30: NDC 51991-891-33
150 mg Tablets: Round, biconvex, white film-coated tablets debossed with “N 150” on one side and plain on the other side; supplied in:
Bottles of 30: NDC 51991-892-33
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature.
17. PATIENT COUNSELING INFORMATION
Skin rash, bullous and exfoliative skin disorders
- Advise patients that skin reactions can occur or worsen on sun-exposed areas while taking erlotinib tablets, and proactive intervention may include alcohol-free emollient cream and use of sunscreen or avoidance of sun exposure. Advise patients that hyperpigmentation or dry skin, with or without digital skin fissures, have been reported and in the majority of cases were associated with rash [see Adverse Reactions (6.1)].
- Advise patients that erlotinib tablets can increase the risk of bullous and exfoliative skin disorders and to seek immediately medical attention for severe skin reactions [see Warnings and Precautions (5.5)].
Diarrhea
Advise patients that diarrhea can usually be managed with loperamide and to contact their healthcare provider for severe or persistent diarrhea [see Adverse Reactions (6.1)].
Interstitial lung disease
Advise patients of the risk of severe or fatal ILD, including pneumonitis. Advise patients to contact their healthcare provider immediately to report new of worsening unexplained shortness of breath or coughing [see Dosage and Administration (2.4) and Warnings and Precautions (5.1)].
Renal failure
Advise patients of the risk of developing renal failure. Inform patients of the need for the healthcare provider to monitor kidney function and electrolytes [see Warnings and Precautions (5.2)].
Hepatotoxicity
Advise patients to immediately report signs or symptoms of hepatotoxicity [see Warnings and Precautions (5.3)].
Gastrointestinal perforations
Advise patients that erlotinib tablets can increase the risk of gastrointestinal perforation or fistula and to seek immediate medical attention for severe abdominal pain [see Dosage and Administration (2.4) and Warnings and Precautions (5.4)].
Cerebrovascular accident
Advise patients of the risk of cerebrovascular accident and see immediate medical attention [see Dosage and Administration (2.4) and Warnings and Precautions (5.6)].
Ocular disorders
Advise patients promptly to contact their healthcare provider if they develop eye signs or symptoms, lacrimation, light sensitivity, blurred vision, eye pain, red eye, or changes in vision [see Dosage and Administration (2.4) and Warnings and Precautions (5.8)].
Hemorrhage in patients taking warfarin
Advise patients who are receiving warfarin of the need to monitor INR or other coumarin-derivative anticoagulants [see Warnings and Precautions (5.9) and Drug Interactions (7)].
Hair and nail disorders
Advise patients that hair and nail disorders, including hirsutism and brittle and loose nails, have been reported [see Adverse Reactions (6.1)].
Embryo-fetal toxicity
- Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.10), Use in Specific Populations (8.1)].
- Advise females of reproductive potential to use effective contraception during treatment with erlotinib tablets, and for 1 month after the last dose [see Use in Specific Populations (8.3)].
Lactation
- Advise women not to breastfeed during treatment with erlotinib tablets and for 2 weeks after the final dose [see Use in Specific Populations (8.2)].
Smoking
- Advise patients to contact their health care provider for any changes in smoking status and that the dose of erlotinib tablets may need to be adjusted if they smoke [see Drug Interactions (7) and Clinical Pharmacology (12.3)]
- Advise patients to stop smoking [see Clinical Pharmacology (12.3)].
Manufactured by:
Natco Pharma Limited
Kothur-509228, India
Distributed by:
Breckenridge Pharmaceutical, Inc.
Berlin, CT 06037
Revised: 06/2019
PRINCIPAL DISPLAY PANEL — 25 mg Tablet Bottle Label
NDC 51991-890-33
Erlotinib Tablets
25 mg
Rx Only
30 Tablets
breckenridge
A TowaCompany
PRINCIPAL DISPLAY PANEL — 100 mg Tablet Bottle Label
NDC 51991-891-33
Erlotinib Tablets
100 mg
Rx Only
30 Tablets
breckenridge
A TowaCompany
PRINCIPAL DISPLAY PANEL — 150 mg Tablet Bottle Label
NDC 51991-892-33
Erlotinib Tablets
150 mg
Rx Only
30 Tablets
breckenridge
A TowaCompany
| ERLOTINIB erlotinib hydrochloride tablet, film coated | ||||||||||||||||||||
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| ERLOTINIB erlotinib hydrochloride tablet, film coated | ||||||||||||||||||||
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| ERLOTINIB erlotinib hydrochloride tablet, film coated | ||||||||||||||||||||
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| Labeler — Breckenridge Pharmaceutical, Inc. (150554335) |
| Registrant — Natco Pharma Limited (918588174) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Natco Pharma Limited | 918588174 | MANUFACTURE (51991-890), MANUFACTURE (51991-891), MANUFACTURE (51991-892) | |
Revised: 01/2023 Breckenridge Pharmaceutical, Inc.
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