Mepolizumab

Mepolizumab® is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.

Limitations of Use

Mepolizumab (Mepolizumab) is a monoclonal antibody that affects the actions of the body's immune system. Mepolizumab works by reducing levels of a certain type of white blood cell that may contribute to the symptoms of asthma.

Mepolizumab is a subcutaneous injection given once a month that is used together with other medicines to help control severe asthma in adults and children who are at least 12 years old.

Mepolizumab may also be used for purposes not listed in this medication guide.

Recommended Dosage

Mepolizumab is for subcutaneous use only.

The recommended dose of Mepolizumab is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.

Preparation And Administration

Mepolizumab should be reconstituted and administered by a healthcare professional. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended.

Reconstitution Instructions

1. Reconstitute Mepolizumab in the vial with 1.2 mL Sterile Water for Injection, USP, preferably using a 2-or 3-mL syringe and a 21-G needle. The reconstituted solution will contain a concentration of 100 mg/mL Mepolizumab. Do not mix with other medications.
2. Direct the stream of Sterile Water for Injection vertically onto the center of the lyophilized cake. Gently swirl the vial for 10 seconds with a circular motion at 15-second intervals until the powder is dissolved.

   Note: Do not shake the reconstituted solution during the procedure as this may lead to product foaming or precipitation. Reconstitution is typically complete within 5 minutes after the Sterile Water for Injection has been added, but it may take additional time.

3. If a mechanical reconstitution device (swirler) is used to reconstitute Mepolizumab, swirl at 450 rpm for no longer than 10 minutes. Alternatively, swirling at 1,000 rpm for no longer than 5 minutes is acceptable.
4. Visually inspect the reconstituted solution for particulate matter and clarity before use. The solution should be clear to opalescent and colorless to pale yellow or pale brown, essentially particle free. Small air bubbles, however, are expected and acceptable. If particulate matter remains in the solution or if the solution appears cloudy or milky, discard the solution.
5. If the reconstituted solution is not used immediately:
   • store below 30°C (86°F),
   • do not freeze, and
   • discard if not used within 8 hours of reconstitution.

Administration

1. For subcutaneous administration, preferably using a 1-mL polypropylene syringe fitted with a disposable 21-to 27-G x 0.5-inch (13-mm) needle.
2. Just before administration, remove 1 mL of reconstituted Mepolizumab. Do not shake the reconstituted solution during the procedure as this could lead to product foaming or precipitation.
3. Administer the 1-mL injection (equivalent to 100 mg Mepolizumab) subcutaneously into the upper arm, thigh, or abdomen.

How supplied

Dosage Forms And Strengths

For injection: 100 mg of lyophilized powder in a single-dose vial for reconstitution.

Storage And Handling

Mepolizumab is supplied as a sterile, preservative-free, lyophilized powder for reconstitution and subcutaneous injection in cartons of 1 single-dose glass vial and a flip-off seal. The vial stopper is not made with natural rubber latex. Mepolizumab is available as:

100-mg single-dose vial (NDC 0173-0881-01).

Store below 25°C (77°F). Do not freeze. Store in the original package to protect from light.

Manufactured by: GlaxoSmithKline LLC, Philadelphia, PA 19112. Distributed by: GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: November 2015

See also:
What is the most important information I should know about Mepolizumab?

Mepolizumab should not be administered to patients with a history of hypersensitivity to Mepolizumab or excipients in the formulation.

Use: Labeled Indications

Asthma: Add-on maintenance treatment of severe asthma in adults and pediatric patients ≥6 years of age with an eosinophilic phenotype.

Limitations of use: Not indicated for the relief of acute bronchospasm or status asthmaticus.

Eosinophilic granulomatosis with polyangiitis: Treatment of adult patients with eosinophilic granulomatosis with polyangiitis.

Off Label Uses

Eosinophilic granulomatosis with polyangiitis (relapsing or refractory)

Data from a small randomized, double blind, placebo controlled trial supports the use of Mepolizumab in the treatment of relapsing or refractory eosinophilic granulomatosis with polyangiitis. Additional trials may be necessary to further define the role of Mepolizumab in this condition.

See also:
What other drugs will affect Mepolizumab?

Formal drug interaction trials have not been performed with Mepolizumab.

See also:
What are the possible side effects of Mepolizumab?

The following adverse reactions are described in greater detail in other sections:

• Hypersensitivity reactions
• Opportunistic infections: herpes zoster

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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 1,327 subjects with asthma were evaluated in 3 randomized, placebo-controlled, multicenter trials of 24 to 52 weeks' duration (Trials 1, 2, and 3). Of these, 1,192 had a history of 2 or more exacerbations in the year prior to enrollment despite regular use of high-dose inhaled corticosteroids plus an additional controller(s) (Trials 1 and 2), and 135 subjects required daily oral corticosteroids in addition to regular use of high-dose inhaled corticosteroids plus an additional controller(s) to maintain asthma control (Trial 3). All subjects had markers of eosinophilic airway inflammation. Of the subjects enrolled, 59% were female, 85% were white, and subjects ranged in age from 12 to 82 years. Mepolizumab was administered subcutaneously or intravenously once every 4 weeks; 263 subjects received Mepolizumab (Mepolizumab 100 mg subcutaneous [SC]) for at least 24 weeks. Serious adverse events that occurred in more than 1 subject and in a greater percentage of subjects treated with Mepolizumab (n = 263) than placebo (n = 257) included 1 event, herpes zoster (2 subjects vs. 0 subjects, respectively). Approximately 2% of subjects receiving Mepolizumab withdrew from clinical trials due to adverse events compared with 3% of subjects receiving placebo.

The incidence of adverse reactions in the first 24 weeks of treatment in the 2 confirmatory efficacy and safety trials (Trials 2 and 3) with Mepolizumab is shown in Table 1.

Table 1: Adverse Reactions with Mepolizumab with Greater than or Equal to 3% Incidence and More Common than Placebo in Subjects with Asthma (Trials 2 and 3)

52-Week Trial

Adverse reactions from Trial 1 with 52 weeks of treatment with Mepolizumab 75 mg intravenous (IV) (n = 153) or placebo (n = 155) and with greater than or equal to 3% incidence and more common than placebo and not shown in Table 1 were: abdominal pain, allergic rhinitis, asthenia, bronchitis, cystitis, dizziness, dyspnea, ear infection, gastroenteritis, lower respiratory tract infection, musculoskeletal pain, nasal congestion, nasopharyngitis, nausea, pharyngitis, pyrexia, rash, toothache, viral infection, viral respiratory tract infection, and vomiting. In addition, 3 cases of herpes zoster occurred in subjects treated with Mepolizumab 75 mg IV, compared with 2 subjects in the placebo group.

Systemic Reactions, including Hypersensitivity Reactions

In Trials 1, 2, and 3 described above, the percentage of subjects who experienced systemic (allergic and non-allergic) reactions was 7% in the placebo group and 10% in the group receiving Mepolizumab. Systemic allergic/hypersensitivity reactions were reported by 2% of subjects in the placebo group and 1% of subjects in the group receiving Mepolizumab. The most commonly reported manifestations of systemic allergic/hypersensitivity reactions reported in the group receiving Mepolizumab included rash, pruritus, headache, and myalgia. Systemic non-allergic reactions were reported by 2% of subjects in the group receiving Mepolizumab and 3% of subjects in the placebo group. The most commonly reported manifestations of systemic non-allergic reactions reported in the group receiving Mepolizumab included rash, flushing, and myalgia. A majority of the systemic reactions in subjects receiving Mepolizumab (5/7) were experienced on the day of dosing.

Injection Site Reactions

Injection site reactions (e.g., pain, erythema, swelling, itching, burning sensation) occurred at a rate of 8% in subjects treated with Mepolizumab compared with 3% in subjects treated with placebo.

Long-Term Safety

Nine hundred ninety-eight (998) subjects have received Mepolizumab in ongoing open-label extension studies, during which additional cases of herpes zoster have been reported. The overall adverse event profile was similar to the asthma trials described above.

Immunogenicity

Overall, 15/260 (6%) of subjects treated with Mepolizumab developed anti-Mepolizumab antibodies. The reported frequency may underestimate the actual frequency due to lower assay sensitivity in the presence of high drug concentration. Neutralizing antibodies were detected in 1 subject receiving Mepolizumab. 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.

The data reflect the percentage of patients whose test results were positive for antibodies to Mepolizumab in specific assays. The observed incidence of antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.