Drug Safety-related Labeling Changes (SrLC)
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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
NAVELBINE (NDA-020388)
(VINORELBINE TARTRATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
05/07/2019 (SUPPL-36)
5 Warnings and Precautions
5.1 Myelosuppression(Additions and/or revisions are underlined)
Myelosuppression, manifested by neutropenia, anemia and thrombocytopenia, occur in patients receiving NAVELBINE as a single agent and in combination with cisplatin. Neutropenia is the major dose-limiting toxicity with NAVELBINE…
(Additions and/or revisions are underlined)
Drug-induced liver injury manifest by elevated aspartate aminotransferase (AST) and bilirubin occur in patients receiving NAVELBINE as a single agent and in combination with cytotoxic agents. Assess hepatic function prior to initiation of NAVELBINE and periodically during treatment. Reduce the dose of NAVELBINE for patients who develop elevations in total bilirubin greater than or equal to 2 times upper limit of normal.
(Additions and/or revisions are underlined)
Severe and fatal paralytic ileus, constipation, intestinal obstruction, necrosis, and perforation occur in patients receiving NAVELBINE. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction and/or paralytic ileus, considering adequate dietary fiber intake, hydration and routine use of stool softeners.
(Additions and/or revisions are underlined)
Pulmonary toxicity, including severe acute bronchospasm, interstitial pneumonitis, acute respiratory distress syndrome (ARDS) occur in patients receiving NAVELBINE. Interstitial pneumonitis and ARDS included fatalities. The mean time to onset of interstitial pneumonitis and ARDS after vinorelbine administration was one week (range 3 to 8 days). Interrupt NAVELBINE in patients who develop unexplained dyspnea or have any evidence of pulmonary toxicity. Permanently discontinue NAVELBINE for confirmed interstitial pneumonitis or ARDS.
(Additions and/or revisions are underlined)
Based on findings from animal studies and its mechanism of action, NAVELBINE can cause fetal harm when administered to a pregnant woman. In animal reproduction studies in mice and rabbits, embryo and fetal toxicity were observed with administration of vinorelbine at doses approximately 0.33 and 0.18 times the human therapeutic dose, respectively.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with NAVELBINE and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with NAVELBINE and for 3 months after the final dose.
6 Adverse Reactions
(Additions and/or revisions are underlined)
The following clinically significant adverse reactions are described elsewhere in the labeling:
Hepatic Toxicity
Severe Constipation and Bowel Obstruction
Extravasation and Tissue Injury
Pulmonary Toxicity and Respiratory Failure
(Additions and/or revisions are underlined)
Single Agent
The data below reflect exposure to NAVELBINE as a single agent administered at a dose of 30 mg/m2 on a weekly basis to 365 patients enrolled in 3 controlled studies for metastatic NSCLC and advanced breast cancer. The population included 143 patients with previously untreated metastatic NSCLC (Study 3) who received a median of 8 doses of NAVELBINE. The patients were aged 32 to 79 (median 61 years), 71% were male, 91% White, 48% had adenocarcinoma histology. The data also reflect exposure to NAVELBINE in 222 patients with previously treated advanced breast cancer who received a median of 10 doses of NAVELBINE. NAVELBINE is not indicated for the treatment of breast cancer.
Selected adverse reactions reported in these studies are provided in Tables 1 and 2. The most common adverse reactions (greater than or equal to 20%) of single agent NAVELBINE were leukopenia, neutropenia, anemia, increased aspartate aminotransferase (AST), nausea, vomiting, constipation, asthenia, injection site reaction and peripheral neuropathy. The most common (greater than or equal to 5%) Grade 3 or 4 adverse reactions were neutropenia, leukopenia, anemia, increased total bilirubin, increased AST, injection site reaction and asthenia.
Approximately 49% of patients with NSCLC who were treated with NAVELBINE experienced at least one dose reduction due to an adverse reaction.
7 Drug Interactions
7.1 CYP3A Inhibitors(Additions and/or revisions are underlined)
Exercise caution in patients concurrently taking drugs known to inhibit CYP3A. Concurrent administration of NAVELBINE with a CYP3A inhibitor may cause an earlier onset and/or an increased severity of adverse reactions.
8 Use in Specific Populations
8.1 Pregnancy(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)
Risk Summary
Based on findings from animal studies and its mechanism of action, NAVELBINE can cause fetal harm when administered to a pregnant woman. Available human data are insufficient to inform the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies in mice and rabbits, embryo and fetal toxicity were observed with administration of vinorelbine at doses approximately 0.33 and 0.18 times the human therapeutic dose, respectively. Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.
(Newly Added Subsection)
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating NAVELBINE.
Contraception
Females
NAVELBINE can cause fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with NAVELBINE and for 6 months after the final dose.
Males
NAVELBINE may damage spermatozoa. Advise males with female sexual partners of reproductive potential to use effective contraception during treatment with NAVELBINE and for 3 months after the final dose.
Infertility
Males
Based on animal findings, NAVELBINE may impair fertility in males.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during treatment with NAVELBINE and for 6 months after the final dose.
Advise males with female partners of reproductive potential to use effective contraception during treatment with NAVELBINE and for 3 months after the final dose.
Lactation
Advise women not to breastfeed during treatment with NAVELBINE and for 9 days after the final dose.
Infertility
Advise males of reproductive potential that NAVELBINE may impair fertility.