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.
AZACITIDINE (NDA-208216)
(AZACITIDINE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
12/19/2024 (SUPPL-7)
06/08/2023 (SUPPL-6)
07/13/2020 (SUPPL-5)
01/10/2018 (SUPPL-1)
5 Warnings and Precautions
5.2 Hepatic Toxicity in Patients with Severe Pre-existing Hepatic Impairment(additions underlined)
Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease. Patients with extensive tumor burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline albumin less than 30 g/L. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors. Monitor liver chemistries prior to initiation of therapy and with each cycle.
….
(additions underlined)
Renal toxicity ranging from elevated serum creatinine to renal failure and death have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for nonMDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to less than 20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium less than 3 mEq/L) developed in 5 patients with CML (an unapproved use) treated with azacitidine and etoposide. Monitor serum creatinine and electrolytes prior to initiation of therapy and with each cycle. If unexplained reductions in serum bicarbonate less than 20 mEq/L or elevations of BUN or serum creatinine occur, reduce or hold the dose.
…
(new subsection added)
Azacitidine for Injection may cause fatal or serious tumor lysis syndrome, including in patients with MDS. Tumor lysis syndrome may occur despite concomitant use of allopurinol. Assess baseline risk and monitor and treat as appropriate.
(additions underlined)
Based
on the mechanism of action and findings in animals, Azacitidine for Injection
can cause fetal harm when administered to a pregnant woman. In animal studies,
azacitidine caused adverse developmental outcomes when administered to
mice and rats at doses of 3 to 12 mg/m2 and 6 mg/m2 (approximately 4% to 16%
and 8%) of the recommended human daily dose of 75 mg/m2, respectively.
Advise pregnant women of the potential risk to the fetus.
Advise females of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 6 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 3 months following the final dose. Advise men to avoid fathering a child while receiving treatment with Azacitidine for Injection.
6 Adverse Reactions
(additions underlined)Myelosuppression
Hepatic Toxicity in Patients with Severe Pre-existing Hepatic Impairment
Renal Toxicity
Tumor Lysis Syndrome
Embryo-Fetal Toxicity
(additions underlined)
…
Most Commonly Occurring Adverse Reactions (Subcutaneous or Intravenous Route): nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia, ecchymosis. The most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia.
Adverse Reactions Most Frequently (Greater Than 2%) Resulting in Clinical Intervention (Subcutaneous or Intravenous Route):
Discontinuation: leukopenia, thrombocytopenia, neutropenia.
Dose Held: leukopenia, neutropenia, thrombocytopenia, pyrexia, pneumonia, febrile neutropenia.
Dose Reduced: leukopenia, neutropenia, thrombocytopenia.
8 Use in Specific Populations
8.1 Pregnancy(additions underlined)
Risk Summary
Based on its mechanism of action and findings in animals, Azacitidine for Injection can cause fetal harm when administered to a pregnant woman. There are no data on the use of azacitidine in pregnant women. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses lower than the recommended human daily dose (see Data). Advise pregnant women of the potential risk to the fetus.
The estimated background risk of major birth defects and miscarriage in the indicated populationis is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
…
(additions underlined)
Risk Summary
There is no information on the presence of azacitidine or its metabolites in human milk, the effects on a breast- fed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for azacitidine in animal studies and
the potential for serious adverse reactions in a nursing child from azacitidine, advise patients not to breastfeed during treatment with azacitidine and for 1 week after the final dose.
(additions underlined)
Based on its mechanism of action and findings in animals, Azacitidine for Injection can cause fetal harm when administered to a pregnant woman.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating Azacitidine for Injection.
Contraception
Females
Azacitidine for Injection can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 6 months after the final dose.
Males
Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 3 months after the final dose.
Infertility
Based on animal data, azacitidine could have an effect on male or female fertility.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(additions underlined)
Hepatic Toxicity in Patients with Severe Pre-Existing Hepatic Impairment Instruct patients to inform their physician about any underlying liver disease.
Renal Toxicity
Instruct patients to inform their physician about any underlying renal disease
Embryo-Fetal Toxicity
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to avoid pregnancy during treatment with Azacitidine for Injection. Advise females of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 6 months after the final dose.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Azacitidine for Injection and for 3 months after the final dose.
Lactation
Advise women not to breastfeed during treatment with Azacitidine for Injection and for 1 week after the final dose.
Infertility
Advise males and females of the potential for reduced fertility from Azacitidine for Injection.