Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | 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.

VELCADE (NDA-021602)

(BORTEZOMIB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

10/25/2021 (SUPPL-45)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.11 Embryo-Fetal Toxicity

(Additions and/or revisions underlined)

Based on the mechanism of action and findings in animals, VELCADE can cause fetal harm when administered to a pregnant woman. Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused postimplantation loss and a decreased number of live fetuses [see Use in Specific Populations (8.1)].

Advise females of reproductive potential to use effective contraception during treatment with VELCADE and for seven months following treatment. Advise males with female partners of reproductive potential to use effective contraception during treatment with VELCADE and for four months following treatment. If VELCADE is used during pregnancy or if the patient becomes pregnant during VELCADE treatment, the patient should be apprised of the potential risk to the fetus [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified from the worldwide postmarketing experience with VELCADE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Cardiac Disorders: Cardiac tamponade

Ear and Labyrinth Disorders: Deafness bilateral

Eye Disorders: Optic neuropathy, blindness, chalazion/blepharitis

Gastrointestinal Disorders: Ischemic colitis

Infections and Infestations: Progressive multifocal leukoencephalopathy (PML), ophthalmic herpes, herpes meningoencephalitis

Nervous System Disorders: Posterior reversible encephalopathy syndrome (PRES, formerly RPLS), Guillain-Barré syndrome, demyelinating polyneuropathy

Respiratory, Thoracic and Mediastinal Disorders: Acute diffuse infiltrative pulmonary disease

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute febrile neutrophilic dermatosis (Sweet’s syndrome)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Discuss the following with patients prior to treatment with VELCADE:

Peripheral Neuropathy

Advise patients to report the development or worsening of sensory and motor peripheral neuropathy to their healthcare provider [see Warnings and Precautions (5.1)].

Hypotension

Advise patients to drink adequate fluids to avoid dehydration and to report symptoms of hypotension to their healthcare provider [see Warnings and Precautions (5.2)].

Instruct patients to seek medical advice if they experience symptoms of dizziness, light headedness or fainting spells, or muscle cramps.

Cardiac Toxicity

Advise patients to report signs or symptoms of heart failure to their healthcare provider [see Warnings and Precautions (5.3)].

Pulmonary Toxicity

Advise patients to report symptoms of ARDS, pulmonary hypertension, pneumonitis, and pneumonia immediately to their healthcare provider [see Warnings and Precautions (5.4)].

Posterior Reversible Encephalopathy Syndrome (PRES)

Advise patients to seek immediate medical attention for signs or symptoms of PRES [see Warnings and Precautions (5.5)].

Gastrointestinal Toxicity

Advise patients to report symptoms of gastrointestinal toxicity to their healthcare provider and to drink adequate fluids to avoid dehydration. Instruct patients to seek medical advice if they experience symptoms of dizziness, light headedness or fainting spells, or muscle cramps [see Warnings and Precautions (5.6)].

Thrombocytopenia/Neutropenia

Advise patients to report signs or symptoms of bleeding or infection immediately to their healthcare provider [see Warnings and Precautions (5.7)].

Tumor Lysis Syndrome

Advise patients of the risk of tumor lysis syndrome and to drink adequate fluids to avoid dehydration

[see Warnings and Precautions (5.8)].

Hepatic Toxicity

Advise patients to report signs or symptoms of hepatic toxicity to their healthcare provider [see Warnings and Precautions (5.9)].

Thrombotic Microangiopathy

Advise patients to seek immediate medical attention if any signs or symptoms of thrombotic microangiopathy occur [see Warnings and Precautions (5.10)].

Ability to Drive or Operate Machinery or Impairment of Mental Ability

VELCADE may cause fatigue, dizziness, syncope, orthostatic/postural hypotension. Advise patients not to drive or operate machinery if they experience any of these symptoms [see Warnings and Precautions (5.2, 5.5)].

Embryo-Fetal Toxicity

Advise females of the potential risk to the fetus and to use effective contraception during treatment with VELCADE and for seven months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VELCADE and for four months following the last dose. Instruct patients to report pregnancy to their physicians immediately if they or their female partner becomes pregnant during treatment or within seven months following last dose [see Warnings and Precautions (5.11)].

Lactation

Advise women not to breastfeed while receiving VELCADE and for two months after last dose [see Use in Specific Populations (8.2)].

Concomitant Medications

Advise patients to speak with their physicians about any other medication they are currently taking.

Diabetic Patients

Advise patients to check their blood sugar frequently if using an oral antidiabetic medication and to notify their physicians of any changes in blood sugar level.

Dermal

Advise patients to contact their physicians if they experience rash, severe injection site reactions [see Dosage and Administration (2.9)], or skin pain. Discuss with patients the option for antiviral prophylaxis for herpes virus infection [see Adverse Reactions (6.1)].

Other

Instruct patients to contact their physicians if they develop an increase in blood pressure, bleeding, fever, constipation, or decreased appetite.

04/25/2019 (SUPPL-44)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.2 Hypotension

… and patients who are dehydrated may be at increased risk of hypotension.

5.3 Cardiac Toxicity

Patients with risk factors for, or existing heart disease should be frequently monitored.

5.7 Thrombocytopenia/Neutropenia

Following Table 8, additions and/or revisions underlined:

The incidence of bleeding events (greater than or equal to Grade 3) was 1.7% in the VcR-CAP arm (four patients) and was 1.2% in the R-CHOP arm (three patients).

Newly added subsection:

5.10 Thrombotic Microangiopathy

Cases, sometimes fatal, of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in the postmarketing setting in patients who received VELCADE. Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop VELCADE and evaluate. If the diagnosis of TTP/HUS is excluded, consider restarting VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing TTP/HUS is not known.

5.11 Embryo-fetal Toxicity

Additions and/or revisions underlined:

Advise females of reproductive potential that they must use contraception during treatment with VELCADE and for seven months following treatment. Advise males with female sexual partners of reproductive potential that they must use contraception during treatment with VELCADE and for four months following treatment.

6 Adverse Reactions

Additions and/or revisions underlined:

ADVERSE REACTIONS

Addition of the term ‘clinically significant’ prior to adverse reactions are also discussed and of Thrombotic Microangiopathy to the bulleted line listing:

6.1 Clinical Trials Experience

Following Table 12, additions and/or revisions underlined:

The incidences of Grade greater than or equal to 3 bleeding events were similar between the two arms (four patients in the VcR-CAP arm and three patients in the R-CHOP arm).

6.2 Postmarketing Experience

Additions and/or revisions underlined:

Eye Disorders: Optic neuropathy, blindness, chalazion/blepharitis

7 Drug Interactions

This section has been revised. Subsections now read as:

7.1 Effects of Other Drugs on VELCADE

7.2 Drugs Without Clinically Significant Interactions with VELCADE

Please refer to label for complete information on above subsections.

8 Use in Specific Populations

Additions and/or revisions underlined:

8.3 Females and Males of Reproductive Potential

Pregnancy Testing

Conduct pregnancy testing in females of reproductive potential prior to initiating VELCADE treatment.

Contraception

Females

Advise females of reproductive potential to avoid pregnancy and use effective contraception during treatment with VELCADE and for at least seven months after the last dose.

Males

Males with female sexual partners of reproductive potential should use effective contraception during treatment with VELCADE and for at least four months after the last dose.

8.6 Renal Impairment

No starting dosage adjustment of VELCADE is recommended for patients with renal impairment. In patients requiring dialysis, VELCADE should be administered after the dialysis procedure

8.7 Hepatic Impairment

No starting dosage adjustment of VELCADE is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to 1x ULN and AST > ULN, or total bilirubin >1 to 1.5x ULN and any AST). The exposure of bortezomib is increased in patients with moderate (total bilirubin greater than or equal to 1.5 to 3x ULN and any AST) and severe (total bilirubin >3x ULN and any AST) hepatic impairment. Reduce the starting dose in patients with moderate or severe hepatic impairment.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Extensive changes; please refer to label for complete information.

06/09/2017 (SUPPL-43)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Embryo-fetal Toxicity

(Additions and/or revisions are underlined)

Based on the mechanism of action and findings in animals, VELCADE can cause fetal harm when administered to a pregnant woman…

Females of reproductive potential should avoid becoming pregnant while being treated with VELCADE. Advise females and males of reproductive potential that they must use contraception during treatment with VELCADE and for 2 months following treatment. If VELCADE is used during pregnancy or if the patient becomes pregnant during VELCADE treatment, the patient should be apprised of the potential risk to the fetus.

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

Cardiac disorders: Cardiac tamponade

Ear and labyrinth disorders: Deafness bilateral Eye disorders: Optic neuropathy, blindness Gastrointestinal disorders: Ischemic colitis

Infections and infestations: Progressive multifocal leukoencephalopathy (PML), ophthalmic herpes, herpes meningoencephalitis

Nervous system disorders: Posterior reversible encephalopathy syndrome (PRES, formerly RPLS)

Respiratory, thoracic and mediastinal disorders: Acute diffuse infiltrative pulmonary disease

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute febrile neutrophilic dermatosis (Sweet’s syndrome)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions are underlined)

Risk Summary

Based on its mechanism of action and findings in animals, VELCADE can cause fetal harm when administered to a pregnant woman. There are no studies with the use of VELCADE in pregnant women to inform drug-associated risks. Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose. Advise pregnant women of the potential risk to the fetus.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Data

Animal Data

…Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area)…

8.2 Lactation

(Revised subsection title; additions and/or revisions are underlined)

Risk Summary

There are no data on the presence of bortezomib or its metabolites in human milk, the effects of the drug on the breast fed infant, or the effects of the drug on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in breastfed infants from VELCADE is unknown, advise nursing women not to breastfeed during treatment with VELCADE and for 2 months after treatment.

8.3 Females and Males of Reproductive Potential

(Newly added subsection)

Based on its mechanism of action and findings in animals, VELCADE can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating VELCADE treatment.

Contraception

Advise patients of reproductive potential to use effective contraception during treatment with VELCADE and for at least 2 months after treatment.

Infertility

Based on the mechanism of action and findings in animals, VELCADE may have an effect on either male or female fertility.

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 females of the potential risk to the fetus and to avoid pregnancy during treatment with VELCADE. Advise patients to use effective contraceptive measures to prevent pregnancy during treatment with VELCADE and for 2 months following treatment. Instruct patients to report pregnancy to their physicians immediately if they or their female partner becomes pregnant during treatment or within 2 months following treatment.

Lactation: Advise patients to avoid breastfeeding while receiving VELCADE and for 2 months after treatment.