Drug Safety-related Labeling Changes (SrLC)

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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.

MYOBLOC (BLA-103846)

(Botulinum Toxin Type B)

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

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03/10/2021 (SUPPL-5195)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

Additions underlined

The following adverse reactions have been reported during postmarketing use of MYOBLOC: angioedema, urticaria, rash, constipation, dry eye, and accommodation disorder. 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.

08/20/2019 (SUPPL-5190)

Approved Drug Label (PDF)

5 Warnings and Precautions

PLR conversion:

5.2 Lack of Interchangeability between Botulinum Toxin Products

Additions and/or revisions underlined:

The potency units of MYOBLOC are specific to the preparation and biological activity assay method utilized. Due to differences in the aspects of this assay such as the vehicle, dilution scheme, and laboratory protocols for various potency assays, potency units are not interchangeable

Newly added information:

5.3 Hypersensitivity Reactions

Serious hypersensitivity reactions have been reported with botulinum toxin products. Angioedema, urticaria, and rash have occurred with MYOBLOC treatment. Hypersensitivity reactions can also include anaphylaxis, serum sickness, soft tissue edema, and dyspnea. If serious and/or immediate hypersensitivity reactions occur, discontinue further injection of MYOBLOC and institute appropriate medical therapy immediately. The use of MYOBLOC in patients with a known hypersensitivity to any botulinum neurotoxin or to any of the excipients (human albumin, sucrose), could lead to a life-threatening allergic reaction.

Additions and/or revisions underlined:

5.5 Human Albumin and Transmission of Viral Diseases

… Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt- Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

6 Adverse Reactions

PLR conversion; additions and/or revisions underlined:

The following clinically significant adverse reactions to MYOBLOC are discussed in greater detail in other sections of the labeling:

Spread of Toxin Effect
Lack of Interchangeability Between Botulinum Toxin Products
Hypersensitivity Reactions
Dysphagia and Breathing Difficulties
Human Albumin and Transmission of Viral Diseases

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

Cervical Dystonia

In the treatment of cervical dystonia, MYOBLOC was studied in both placebo-controlled single treatment studies and open-label repeated treatment studies; most treatment sessions and patients were in the uncontrolled studies. The data described below reflect exposure to MYOBLOC at varying dosages in 570 subjects, including more than 300 patients with 4 or more treatment sessions. Most treatment sessions were at dosages of 12,500 Units or less.

Adverse reactions occurring in at least 5% of patients exposed to MYOBLOC treatment in pooled placebo-controlled clinical trials are shown in Table 2. The mean age of the population in these studies was 55 years, and approximately 66% were female. Most of the patients studied were Caucasian, and all had moderate to severe symptoms of cervical dystonia.

The most common adverse reactions (greater than 5% of MYOBLOC-treated patients at any dosage and at least 5% more common than placebo) in studies of cervical dystonia (Studies 1, 2, and 4) were dry mouth, dysphagia, injection site pain, and headache. Dry mouth and dysphagia were the adverse reactions most frequently … the splenius capitis, trapezius, and sternocleidomastoid muscles.

In the cervical dystonia program, only nine patients without a prior history of tolerating injections of type A botulinum toxin have been studied. Adverse reaction rates have not been adequately evaluated in these patients and may be higher than those described in Table 2.

Table 2: Adverse Reactions in at Least 5% of MYOBLOC-Treated Patients and Greater than Placebo, Following Single Treatment Session in Controlled Cervical Dystonia Studies (Studies 1, 2, and 4) Table has been reformatted; please refer to label for complete information.

In the overall clinical trial experience with MYOBLOC in cervical dystonia (570 patients, including the uncontrolled studies) … Dysphagia and dry mouth were the most frequent adverse reactions reported as a reason for discontinuation from repeated treatment studies. These adverse reactions led to discontinuation …

The following additional adverse events were reported in 2% or greater of patients participating in any of the clinical studies in cervical dystonia (by body system): Body as a Whole: chest pain, chills … Nervous System: migraine; anxiety, hyperesthesia …

Newly added information:

Chronic Sialorrhea

In the double-blind placebo-controlled studies (Study 1 and Study 2), 166 patients were treated with a single treatment of MYOBLOC (1,500 Units; 2,500 Units; or 3,500 Units) and 75 patients received placebo. The mean age of patients treated with MYOBLOC in these studies was 65 years; 83% of the patients were male; and 95% were White. Four MYOBLOC-treated patient and three patients on placebo discontinued because of an adverse event. One patient discontinued because of dry mouth (3,500 Unit dose). The adverse reactions that occurred in at least 5% of MYOBLOC-treated patients and were more frequent than placebo are shown in Table 3.

Table 3: Adverse Reactions in At Least 5% of MYOBLOC-Treated Patients and Greater than Placebo in Pooled Chronic Sialorrhea Studies (Studies 1 and 2) Table is newly added; please refer to label for complete information.

Newly added information:

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other rimabotulinumtoxinB products may be misleading.

Additions and/or revisions underlined:

Cervical Dystonia

A two-stage assay was used …

Chronic Sialorrhea

Immunogenicity potential was not further evaluated for MYOBLOC in the treatment of chronic sialorrhea.

Newly added information:

6.3 Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of MYOBLOC: angioedema, urticaria, rash, and constipation. 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.

7 Drug Interactions

PLR conversion; subsections as below. Please see label for complete information.

7.1 Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission

7.2 Anticholinergic Drugs

7.3 Other Botulinum Neurotoxin Products

7.4 Muscle Relaxants

8 Use in Specific Populations

PLR conversion as well at PLLR conversion to the following 2 subsections. Please refer to label for complete information:

8.1 Pregnancy

8.2 Lactation

Additions and/or revisions underlined:

8.5 Geriatric Use

Cervical Dystonia

In the controlled studies for MYOBLOC in patients with cervical dystonia, 152 (75%) were under the age of 65, and 52 (26%) were 65 years of age or older. For these age groups, the most frequently reported adverse reactions occurred at similar rates in both age groups. Efficacy results did not suggest any large differences between these age groups.

Very few patients age 75 or older were enrolled; therefore, no conclusions regarding the safety and efficacy of MYOBLOC within this age group can be determined.

Chronic Sialorrhea

Of the 166 MYOBLOC-treated patients in the placebo-controlled studies for treatment of chronic sialorrhea, 105 (63%) were 65 years of age or older, and 43 (26%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between patients over 65 years of age and younger patients, but greater sensitivity of some older patients cannot be ruled out.

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

MEDICATION GUIDE

PLR conversion; please refer to label for changes.

PATIENT COUNSELING INFORMATION

PLR conversion:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Swallowing, Speaking, or Breathing Difficulties or Other Unusual Symptoms

Advise patients to inform their healthcare provider if they develop any unusual symptoms, including difficulty with swallowing, speaking or breathing, or if any existing symptom worsens. Inform patients of the risk of aspiration.

Ability to Operate Machinery or Vehicles

Counsel patients that if loss of strength, muscle weakness, or impaired vision occur, they should avoid driving a car or engaging in other potentially hazardous activities.

Other

PLR conversion