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Mepolizumab

Generic name: mepolizumab systemic

Brand names: Nucala

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous [preservative free]:

Nucala: 100 mg/mL (1 mL) [contains disodium edta, polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Nucala: 100 mg/mL (1 mL) [contains edetate disodium dihydrate, polysorbate 80]

Solution Reconstituted, Subcutaneous [preservative free]:

Nucala: 100 mg (1 ea) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Mepolizumab is an interleukin-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils (a cell type associated with inflammation and an important component of the pathogenesis of asthma). Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma has not been definitively established.

Pharmacokinetics/Pharmacodynamics

Distribution

Vd: ~3.6 L

Metabolism

Undergoes proteolytic degradation via enzymes that are widely distributed in the body and not restricted to hepatic tissue.

Excretion

Nonrenal

Half-Life Elimination

Terminal: 16 to 22 days

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.

Use: Off Label

Eosinophilic granulomatosis with polyangiitis (relapsing or refractory)b

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 Wechsler 2017. Additional trials may be necessary to further define the role of mepolizumab in this condition.

Contraindications

Hypersensitivity to mepolizumab or any component of the formulation

Dosage and Administration

Dosing: Adult

Asthma: SubQ: 100 mg once every 4 weeks

Eosinophilic granulomatosis with polyangiitis (treatment): SubQ: 300 mg once every 4 weeks

Eosinophilic granulomatosis with polyangiitis (relapsing or refractory) (off label use): SubQ: 300 mg once every 4 weeks (in combination with corticosteroids with or without immunosuppressive therapy) (Wechsler 2017)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Asthma, severe (eosinophilic phenotype); maintenance (add-on therapy):

Children ≥6 years to 11 years: SubQ: 40 mg once every 4 weeks.

Children ≥12 years and Adolescents: SubQ: 100 mg once every 4 weeks.

Reconstitution

Vial: Reconstitute by adding 1.2 mL SWFI to the vial using a 2 or 3 mL syringe and a 21-gauge needle. Direct the stream of SWFI 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; do not shake. Manual reconstitution is typically complete within 5 minutes. If a mechanical reconstitution device (eg, swirler) is used, swirl at 450 rpm for no longer than 10 minutes or 1,000 rpm for no longer than 5 minutes. After reconstitution, the final concentration is 100 mg/mL (Note: vial contains 144 mg including overfill). The solution should be clear to opalescent, colorless to pale yellow or pale brown, and essentially particle free. If particulate matter remains in the solution or if the solution appears cloudy or milky, discard the solution. Do not mix with other medications.

Administration

SubQ: If using vials, use a polypropylene syringe fitted with a 21- to 27-gauge, 0.5-inch (13 mm) needle. If using prefilled autoinjector/syringe, allow to sit at room temperature for 30 minutes prior to administration. Administer via SubQ injection into the upper arm, thigh, or abdomen; avoid skin that is tender, bruised, red, or hard. Initial use is recommended under supervision of health care provider; self-injection of prefilled autoinjector/syringe may occur after proper training. For the 300 mg dose, administer as 3 separate 100 mg injections into the upper arm, thigh, or abdomen ≥5 cm apart if >1 injection administered at same site. Do not shake the reconstituted solution as this could lead to product foaming or precipitation.

Storage

Prefilled autoinjector/syringe: Store at 2°C to 8°C (36°F to 46°F). Do not freeze; protect from light. Do not shake. An unopened carton may be stored at ≤30°C (86°F) for ≤7 days; discard if kept at room temperature for >7 days. Once autoinjector/syringe is removed from carton must administer within 8 hours; otherwise discard.

Vial: Store intact vials at <25°C (77°F). Do not freeze; protect from light. Following reconstitution, use immediately. Alternatively, reconstituted solutions may be stored at <30°C (86°F) for up to 8 hours; do not freeze. Discard if not used within 8 hours of reconstitution.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

As reported in patients with severe asthma, unless otherwise noted.

>10%:

Central nervous system: Headache (19%)

Local: Injection site reaction (eosinophilic granulomatosis: 15%; asthma: 8%)

1% to 10%:

Central nervous system: Fatigue (5%)

Dermatologic: Eczema (3%), pruritus (3%)

Gastrointestinal: Upper abdominal pain (3%)

Genitourinary: Urinary tract infection (3%)

Hypersensitivity: Hypersensitivity reaction (≤4%), angioedema (eosinophilic granulomatosis: 1%)

Immunologic: Antibody development (asthma: 6%, eosinophilic granulomatosis: <2%; neutralizing: <1%)

Infection: Influenza (3%)

Neuromuscular & skeletal: Back pain (5%), muscle spasm (3%)

Frequency not defined:

Hypersensitivity: Type IV hypersensitivity reaction

Infection: Herpes zoster infection

Postmarketing: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

  • Hypersensitivity reactions: Hypersensitivity reactions (eg, angioedema, anaphylaxis, bronchospasm, hypotension, urticarial, rash) may occur, typically within hours of administration. Delayed hypersensitivity reactions, occurring days after administration, have also been reported. Discontinue use in patients who experience a hypersensitivity reaction.
  • Infection: Use may result in an opportunistic infection of herpes zoster; consider herpes zoster vaccination prior to initiation of therapy with mepolizumab.

Disease-related concerns:

  • Asthma: Not indicated for the treatment of acute asthma symptoms (eg, acute bronchospasm) or acute exacerbations, including status asthmaticus. Appropriate rescue medication should be available. Patients who experience continued uncontrolled asthma or worsening of symptoms following treatment initiation with mepolizumab should seek medical attention.
  • Helminth infections: It is unknown if administration of mepolizumab will influence a patient's response against parasitic infections. Therefore, patients with preexisting helminth infections should undergo treatment of the infection prior to initiation of mepolizumab therapy. Patients who become infected during treatment and do not respond to anti-helminth therapy should discontinue mepolizumab until the infection resolves.

Concurrent drug therapy issues:

  • Corticosteroids: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of mepolizumab. Reductions in corticosteroid dose should be gradual, if appropriate. Clinicians should note that a reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Dosage form specific issues:

  • Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

  • Limitation of use: Mepolizumab is not indicated for the treatment of other eosinophilic conditions.

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests. Monitor for increased use of short-acting beta2-agonist inhalers; may be a marker of a deteriorating asthma condition.

Pregnancy

Pregnancy Considerations

Mepolizumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of preeclampsia, preterm birth, low birth weight infants). Asthma should be closely monitored in pregnant women.

Patients or health care providers are encouraged to enroll women exposed to mepolizumab during pregnancy in an asthma pregnancy registry (1-877-311-8972 or http://www.mothertobaby.org/asthma).

Patient Education

What is this drug used for?

  • It is used to treat asthma.
  • It is used to treat eosinophilic granulomatosis with polyangiitis (EGPA).

For asthma:

  • Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.

Frequently reported side effects of this drug

  • Back pain
  • Loss of strength and energy
  • Injection site pain, burning, swelling, redness, or irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Severe headache
  • Flushing
  • Sensation of warmth
  • Sensation of cold
  • Shortness of breath
  • Dizziness
  • Passing out
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated January 3, 2020.