Drug Safety-related Labeling Changes (SrLC)

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OCREVUS (BLA-761053)

(OCRELIZUMAB)

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

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12/14/2020 (SUPPL-22)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

Adverse Reactions in Patients who Received 2-hour Infusions

Study 4 was designed to characterize the safety profile of OCREVUS infusions administered over 2 hours in patients with Relapsing-Remitting Multiple Sclerosis who did not experience a serious infusion reaction with any previous OCREVUS infusion. In this study, the incidence, intensity, and types of symptoms of infusion reactions were consistent with those of infusions administered over 3.5 hours [see Clinical Studies (14.3)].

The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of IgG and increased rates of serious infections. The type, severity, latency, duration, and outcome of serious infections observed during episodes of immunoglobulins below LLN were consistent with the overall serious infections observed in patients treated with OCREVUS.

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

MEDICATION GUIDE

(Extensive changes to table; please refer to label)

11/06/2020 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Infections

(Additions and/or revisions underlined)

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting.

5.3 Reduction in Immunoglobulins

(Newly added section)

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins [see Adverse Reactions (6.1)].

6 Adverse Reactions

(Newly added information)

  • Reduction in Immunoglobulins [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

Laboratory Abnormalities

Decreased Immunoglobulins

OCREVUS decreased total immunoglobulins with the greatest decline seen in IgM levels; however, a decrease in IgG levels was associated with an increased rate of serious infections.

The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of IgG and increased rates of serious infections. The type, severity, latency, duration, and outcome of SIs observed during episodes of immunoglobulins below LLN were consistent with the overall SIs observed in patients treated with OCREVUS.

8 Use in Specific Populations

8.1 Pregnancy

(Newly added information)

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to OCREVUS during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com.

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

Medication Guide

(Newly added information)

• Low Immunoglobulins: OCREVUS may cause a decrease in some types of antibodies. Your healthcare provider will do

blood tests to check your blood immunoglobulin levels.

Talk with your healthcare provider about what birth control method is right for you during this

time.

o If you become pregnant while taking OCREVUS, talk to your doctor about enrolling in the OCREVUS Pregnancy

Registry. You can enroll in this registry by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com. The

purpose of this registry is to monitor the health of you and your baby.

Patient Counseling Information

(Additions and/or revisions underlined)

Contraception

Females of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

Pregnancy Registry

Instruct patients that if they are pregnant or plan to become pregnant while taking OCREVUS they should inform their healthcare provider [see Use in Specific Populations (8.1)].

Encourage patients to enroll in the OCREVUS Pregnancy Registry if they become pregnant while taking OCREVUS [see Use in Specific Populations (8.1)].

05/15/2020 (SUPPL-24)

Approved Drug Label (PDF)

5 Warnings and Precautions

Infections

(Newly added information)

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life- threatening.

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered [see Patient Counseling Information (17)].

6 Adverse Reactions

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of OCREVUS. 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.

Serious herpes infections have been identified during postapproval use of OCREVUS [see Warnings and Precautions (5.2)].

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

Medication Guide

(Additions and/or revisions underlined)

Tell your healthcare provider if you have an infection or have any

of the following signs of infection including fever, chills, or a cough that does not go away. Signs of herpes infection include cold sores, shingles, genital sores and, if more serious, a severe or persistent headache, confusion, change in vision, eye redness, or eye pain.

PATIENT COUNSELING INFORMATION

(Newly added information)

Advise patients that herpes infections, including serious herpes infections affecting the central nervous system, skin, and eyes, have occurred during treatment with OCREVUS. Advise patients to promptly contact their healthcare provider if they experience any signs or symptoms of herpes infections including oral or genital symptoms, fever, skin rash, pain, itching, decreased visual acuity, eye redness, eye pain, headache, neck stiffness, or change in mental status [see  Warnings and Precautions (5.2)].

01/10/2020 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Infusion Reactions

Additions and/or reactions underlined:

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis.

5.2 Infections

Additions and/or reactions underlined:

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines.

OCREVUS may interfere with the effectiveness of non-live vaccines [see Drug Interactions (7.2)].

The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B- cell repletion [see Clinical Pharmacology (12.2)].

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted [see Use in Specific Populations (8.1)].

7 Drug Interactions

Newly added subsection:

7.2 Vaccinations

A Phase 3b randomized, open-label study examined the concomitant use of OCREVUS and several non-live vaccines in adults 18-55 years of age with relapsing forms of MS (68 subjects undergoing treatment with OCREVUS at the time of vaccination and 34 subjects not undergoing treatment with OCREVUS at the time of vaccination). Concomitant exposure to OCREVUS attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide, pneumococcal conjugate vaccines, and seasonal inactivated influenza vaccines. The impact of the observed attenuation on vaccine effectiveness in this patient population is unknown. The safety and effectiveness of live or live-attenuated vaccines administered concomitantly with OCREVUS have not been assessed [see Warnings and Precautions (5.2)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:
Risk Summary

OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.  There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to OCREVUS have not been studied in clinical trials. The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown [see Warnings and Precautions (5.2)].

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

MEDICATION GUIDE

Additions and/or revisions underlined
What is OCREVUS?

OCREVUS is a prescription medicine used to treat:

  • Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
  • Primary progressive MS, in adults.

Before receiving OCREVUS, tell your healthcare provider about all of your medical conditions, including if you:

  • You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with OCREVUS

  • When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with OCREVUS. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with OCREVUS, talk to your healthcare provider.

  • If you are pregnant or planning to become pregnant talk to your doctor about vaccinations for your baby, as some precautions may be needed.

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Vaccination

Advise patients to complete any required live or live-attenuated vaccinations at least 4 weeks and, whenever possible, non-live vaccinations at least 2 weeks prior to initiation of OCREVUS …

07/16/2019 (SUPPL-18)

Approved Drug Label (PDF)

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

MEDICATION GUIDE

(additions underlined)

What is OCREVUS?

OCREVUS is a prescription medicine used to treat:

  • Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults

  • Primary progressive MS, in adults.

It is not known if OCREVUS is safe or effective in children.

11/12/2018 (SUPPL-12)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Infections

(additions underlined)

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines.

OCREVUS may interfere with the effectiveness of non-live vaccines.

The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B- cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

7 Drug Interactions

7.2 Vaccinations

(new subsection added)

A Phase 3b randomized, open-label study examined the concomitant use of OCREVUS and several non-live vaccines in adults 18-55 years of age with relapsing forms of MS (68 subjects undergoing treatment with OCREVUS at the time of vaccination and 34 subjects not undergoing treatment with OCREVUS at the time of vaccination). Concomitant exposure to OCREVUS attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide, pneumococcal conjugate vaccines, and seasonal inactivated influenza vaccines. The impact of the observed attenuation on vaccine effectiveness in this patient population is unknown. The safety and effectiveness of live or live-attenuated vaccines administered concomitantly with OCREVUS have not been assessed.

8 Use in Specific Populations

8.1 Pregnancy

(subsection revised, additions underlined)

Risk Summary

OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to OCREVUS have not been studied in clinical trials. The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown.

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

MEDICATION GUIDE

(additions underlined)

Before receiving OCREVUS, tell your healthcare provider about all of your medical conditions, including if you:

  • have had a recent vaccination or are scheduled to receive any vaccinations.

    • You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with OCREVUS. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with OCREVUS and until your healthcare provider tells you that your immune system is no longer weakened.

    • When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with OCREVUS. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with OCREVUS, talk to your healthcare provider.

PATIENT COUNSELING INFORMATION

(additions underlined)

Vaccination

Advise patients to complete any required live or live-attenuated vaccinations at least 4 weeks and, whenever possible, non-live vaccinations at least 2 weeks prior to initiation of OCREVUS. Administration of live-attenuated or live vaccines is not recommended during OCREVUS treatment and until B-cell recovery.

11/02/2017 (SUPPL-8)

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

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about OCREVUS? OCREVUS can cause serious side effects, including:

  • Infection

    • Progressive Multifocal Leukoencephalopathy (PML): Although no cases have been seen with OCREVUS treatment in clinical trials, PML may happen with OCREVUS.

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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