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.

NUCALA (BLA-761122)

(MEPOLIZUMAB)

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

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08/06/2025 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Acute Symptoms of Asthma or Chronic Obstructive Pulmonary Disease or Acute Deteriorating Disease

Subsection title revised

Additions and/or revisions underlined:

NUCALA should not be used to treat acute symptoms or acute exacerbations of asthma or COPD. Do not use NUCALA to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma or COPD remains uncontrolled or worsens after initiation of treatment with NUCALA.

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

. . .

Chronic Obstructive Pulmonary Disease

The safety and effectiveness in pediatric patients aged younger than 18 years with COPD have not been established. COPD is largely a disease of adult patients.

. . .

8.5 Geriatric Use

Additions and/or revisions underlined:

Of the total number of patients treated with NUCALA (n = 4106) for severe asthma, HES, EGPA, CRSwNP, and COPD, 1073 (26%) were 65 years of age and older and 241 (6%) were 75 years of age and older [see Clinical Studies (14)]. No overall differences in safety and effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity in some older individuals cannot be ruled out.

. . .

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Hypersensitivity Reactions

Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after administration of NUCALA. Instruct patients to contact their healthcare provider if such reactions occur.

Not for Acute Symptoms or Deteriorating Disease

Inform patients that NUCALA does not treat acute asthma symptoms or acute exacerbations of asthma or COPD. Inform patients to seek medical advice if their asthma remains uncontrolled or COPD symptoms worsen after initiation of treatment with NUCALA.

. . .

PATIENT INFORMATION

Additions and/or revisions underlined:

. . .

NUCALA is a prescription medicine:

. . .

for add-on maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults whose disease is not controlled and who are at risk of flare-ups and increasing symptoms. NUCALA helps prevent flare-ups of COPD symptoms (exacerbations). NUCALA is not used to treat sudden breathing problems that can occur with COPD.

. . .

for the treatment of people 12 years of age and older with hypereosinophilic syndrome (HES) for 6 months or more. NUCALA helps reduce symptoms and prevent flares.

NUCALA works by targeting inflammation that plays a major role in severe asthma, CRSwNP, COPD, EGPA and HES. NUCALA reduces blood eosinophils. Eosinophils are a type of white blood cells that may contribute to your disease.
It is not known if NUCALA is safe and effective in:
children with severe asthma under 6 years of age.
children and adolescents with CRSwNP, COPD or EGPA under 18 years of age; or

. . .

The most common side effects of NUCALA include: headache, injection site reactions (pain, redness, swelling, itching, or a burning feeling at the injection site), back pain, and tiredness (fatigue). Mouth/throat pain and joint pain have been reported with CRSwNP. Diarrhea and cough have been reported with COPD.

. . .

07/29/2021 (SUPPL-6)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Clinical Trials Experience in Chronic Rhinosinusitis with Nasal Polyps

New subsection added

A total of 407 patients with CRSwNP were evaluated in 1 randomized, placebo-controlled, multicenter, 52-week treatment trial. Patients received NUCALA 100 mg or placebo subcutaneously once every 4 weeks. Patients had recurrent CRSwNP with a history of prior surgery and were on nasal corticosteroids for at least 8 weeks prior to screening [see Clinical Studies (14.2)]. Of the patients enrolled, 35% were female, 93% were White, and ages ranged from 18 to 82 years. Approximately 2% of patients receiving NUCALA 100 mg withdrew from study treatment due to adverse events compared with 2% of patients receiving placebo.

Table 2 summarizes adverse reactions that occurred in greater than or equal to 3% of NUCALA-treated patients and more frequently than in patients treated with placebo in the CRSwNP trial.

Please refer to label to view Table 2

Systemic Reactions, including Hypersensitivity Reactions

In the 52-week trial, the percentage of patients who experienced systemic (allergic [type I hypersensitivity] and other) reactions was <1% in the group receiving NUCALA 100 mg and

<1% in the placebo group. Systemic allergic (type I hypersensitivity) reactions were reported by

<1% of patients in the group receiving NUCALA 100 mg and no patients in the placebo group. The manifestations of systemic allergic (type I hypersensitivity) reactions included urticaria, erythema, and rash and 1 of the 3 reactions occurred on the day of dosing. Other systemic reactions were reported by no patients in the group receiving NUCALA 100 mg and <1% of patients in the placebo group.

Injection Site Reactions

Injection site reactions (e.g., erythema, pruritus) occurred at a rate of 2% in patients receiving NUCALA 100 mg compared with <1% in patients receiving placebo.

6.5 Immunogenicity

Additions underlined

…

In patients with CRSwNP receiving NUCALA 100 mg, 6/196 (3%) had detectable anti-mepolizumab antibodies. No neutralizing antibodies were detected in any patients with CRSwNP.

…

8 Use in Specific Populations

8.4 Pediatric Use

Additions underlined

…

Chronic Rhinosinusitis with Nasal Polyps

The safety and effectiveness in patients aged younger than 18 years with CRSwNP have not been established.

8.5 Geriatric Use

Additions and/or revisions underlined

Clinical trials of NUCALA did not include sufficient numbers of patients aged 65 years and older that received NUCALA (n = 79) to determine whether they respond differently from younger patients.

…

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

PATIENT INFORMATION

Additions underlined

…

What is NUCALA?

…

for add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults whose disease is not controlled with nasal corticosteroids. NUCALA helps reduce symptoms (e.g., nasal congestion, nasal discharge, mucus in the throat, loss of smell). NUCALA helps reduce the size of your nasal polyps and the use of oral corticosteroid medicines. NUCALA helps prevent surgery for your nasal polyps.
…
The most common side effects of NUCALA include: headache, injection site reactions (pain, redness, swelling, itching, or a burning feeling at the injection site), back pain, and tiredness (fatigue). Mouth/throat pain and joint pain have been reported with CRSwNP.

09/25/2020 (SUPPL-5)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions underlined)

NUCALA is contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation [see Warnings and Precautions (5.1), Description (11)].

6 Adverse Reactions

6.3 Clinical Trials Experience in Hypereosinophilic Syndrome

(Newly added subsection)

A total of 108 adult and adolescent patients aged 12 years and older with HES were evaluated in a randomized, placebo-controlled, multicenter, 32-week treatment trial. Patients with non-hematologic secondary HES or FIP1L1-PDGFR? kinase-positive HES were excluded from the trial. Patients received 300 mg of NUCALA or placebo subcutaneously once every 4 weeks. Patients must have been on a stable dose of background HES therapy for the 4 weeks prior to randomization [see Clinical Studies (14.3)]. Of the patients enrolled, 53% were female, 93% were White, and ages ranged from 12 to 82 years. No additional adverse reactions were identified to those reported in the severe asthma trials.

Systemic Reactions, including Hypersensitivity Reactions

In the trial, no systemic allergic (type I hypersensitivity) reactions were reported. Other systemic reactions were reported by 1 (2%) patient in the group receiving 300 mg of NUCALA and no patients in the placebo group. The reported manifestation of other systemic reaction was multifocal skin reaction experienced on the day of dosing.

Injection Site Reactions

Injection site reactions (e.g., burning, itching) occurred at a rate of 7% in patients receiving 300 mg of NUCALA compared with 4% in patients receiving placebo.

6.4 Immunogenicity

(Additions and/or revisions underlined)

In adult and adolescent patients with severe asthma receiving NUCALA 100 mg, 15/260 (6%) had detectable anti-mepolizumab antibodies. Neutralizing antibodies were detected in 1 patient with asthma receiving NUCALA 100 mg. Anti-mepolizumab antibodies slightly increased (approximately 20%) the clearance of mepolizumab. There was no evidence of a correlation between anti-mepolizumab antibody titers and change in eosinophil level. The clinical relevance of the presence of anti-mepolizumab antibodies is not known. In the clinical trial of children aged 6 to 11 years with severe asthma receiving NUCALA 40 or 100 mg, 2/35 (6%) had detectable anti-mepolizumab antibodies during the initial short phase of the trial. No children had detectable anti-mepolizumab antibodies during the long phase of the trial.

In patients with EGPA receiving 300 mg of NUCALA, 1/68 (<2%) had detectable anti-mepolizumab antibodies. No neutralizing antibodies were detected in any patients with EGPA.

In adult and adolescent patients with HES receiving 300 mg of NUCALA, 1/53 (2%) had detectable anti-mepolizumab antibodies. No neutralizing antibodies were detected in any patients with HES.

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions underlined)

Eosinophilic Granulomatosis with Polyangiitis

The safety and efficacy in patients aged younger than 18 years with EGPA have not been established.

Hypereosinophilic Syndrome

The safety and effectiveness of NUCALA for HES have been established in adolescent patients aged 12 years and older. The safety and effectiveness in pediatric patients aged younger than 12 years with HES have not been established.

Use of NUCALA for this indication is supported by evidence from an adequate and well-controlled study (NCT #02836496) in adults and adolescents and an open-label extension study (NCT #03306043). One adolescent received NUCALA during the controlled study and this patient and an additional three adolescents received NUCALA during the open-label extension study [see Clinical Studies (14.3)]. The one adolescent treated with NUCALA in the 32-week trial did not have a HES flare or an adverse event reported. All adolescents received 300 mg of NUCALA for 20 weeks in the open-label extension.

09/12/2019 (SUPPL-3)

Approved Drug Label (PDF)

6 Adverse Reactions

Clinical Trials Experience in Severe Asthma

Additions and/or revisions underlined:

Adult and Adolescent Subjects Aged 12 Years and Older

A total of 1,327 subjects with severe asthma were evaluated in 3 randomized, placebo-controlled, multicenter trials of 24 to 52 weeks’ duration (Trial 1, NCT #01000506; Trial 2, NCT #01691521; and Trial 3, NCT #01691508).

Change in title of table 1 underlined:

Adverse Reactions with NUCALA with ?3% Incidence and More Common than Placebo in Subjects with Severe Asthma (Trials 2 and 3)

Immunogenicity

Additions and/or revisions underlined:

In adult and adolescent subjects with severe asthma receiving NUCALA 100 mg, 15/260 (6%) had detectable anti-mepolizumab antibodies. Neutralizing antibodies were detected in 1 subject with asthma receiving NUCALA 100 mg. Anti-mepolizumab antibodies slightly increased (approximately 20%) the clearance of mepolizumab. There was no evidence of a correlation between anti-mepolizumab antibody titers and change in eosinophil level. The clinical relevance of the presence of anti-mepolizumab antibodies is not known. In the clinical trial of children aged 6 to 11 years with severe asthma receiving NUCALA 40 or 100 mg, 2/35 (6%) had detectable anti-mepolizumab antibodies during the initial short phase of the trial. No children had detectable anti-mepolizumab antibodies during the long phase of the trial.

8 Use in Specific Populations

Pediatric Use

Additions and/or revisions underlined:

Severe Asthma

The safety and efficacy of NUCALA for severe asthma, and with an eosinophilic phenotype, have been established in pediatric patients aged 6 years and older.

Use of NUCALA in adolescents aged 12 to 17 years is supported by evidence from adequate and well-controlled trials in adults and adolescents. A total of 28 adolescents aged 12 to 17 years with severe asthma were enrolled in the Phase 3 asthma trials. Of these, 25 were enrolled in the 32-week exacerbation trial (Trial 2, NCT #01691521) and had a mean age of 14.8 years. Subjects had a history of 2 or more exacerbations in the previous year despite regular use of medium- or high-dose ICS plus additional controller(s) with or without OCS and had blood eosinophils of ?150 cells/mcL at screening or ?300 cells/mcL within 12 months prior to enrollment. Subjects had a reduction in the rate of exacerbations that trended in favor of mepolizumab. Of the 19 adolescents who received mepolizumab, 9 received 100 mg and the mean apparent clearance in these subjects was 35% less than that of adults. The safety profile observed in adolescents was generally similar to that of the overall population in the Phase 3 studies.

Use of NUCALA in children aged 6 to 11 years with severe asthma, and with an eosinophilic phenotype, is supported by evidence from adequate and well-controlled trials in adults and adolescents with additional pharmacokinetic, pharmacodynamic, and safety data in children aged 6 to 11 years. A single, open-label clinical trial (NCT #02377427) was conducted in 36 children aged 6 to 11 years (mean age: 8.6 years, 31% female) with severe asthma. Enrollment criteria were the same as for adolescents in the 32-week exacerbation trial (Trial 2). Based upon the pharmacokinetic data from this trial, a dose of 40 mg SC every 4 weeks was determined to have similar exposure to adults and adolescents administered a dose of 100 mg SC.

The efficacy of NUCALA in children aged 6 to 11 years is extrapolated from efficacy in adults and adolescents with support from pharmacokinetic analyses showing similar drug exposure levels for 40 mg administered subcutaneously every 4 weeks in children aged 6 to 11 years compared with adults and adolescents. The safety profile and pharmacodynamic response observed in this trial for children aged 6 to 11 years were similar to that seen in adults and adolescents.

The safety and efficacy in pediatric patients aged younger than 6 years with severe asthma have not been established.

New subsection:

Eosinophilic Granulomatosis with Polyangiitis

The safety and efficacy in patients aged younger than 18 years with EGPA have not been established.