mepolizumab (Rx)

>10%

Asthma

• Headache (19%)

EGPA

• Injection site reactions (15%)

1-10%

Asthma

• Injection site reactions (8%)
• Back pain (5%)
• Fatigue (5%)
• Influenza (3%)
• Urinary tract infection (3%)
• Upper abdominal pain (3%)
• Pruritus (3%)
• Eczema (3%)
• Muscle spasms (3%)
• Abdominal pain (≥3%)
• Allergic rhinitis (≥3%)
• Asthenia (≥3%)
• Bronchitis (≥3%)
• Cystitis (≥3%)
• Dizziness (≥3%)
• Dyspnea (≥3%)
• Ear infection (≥3%)
• Gastroenteritis (≥3%)
• Lower respiratory tract infection (≥3%)
• Musculoskeletal pain (≥3%)
• Nasal congestion (≥3%)
• Nasopharyngitis (≥3%)
• Toothache (≥3%)
• Viral infection (≥3%)
• Viral respiratory tract infection (≥3%)
• Systemic nonallergic reactions (2%)
• Systemic allergic/hypersensitivity reactions (1%)

CRSwNP

• Oropharyngeal pain (8%)
• Arthralgia (6%)
• Upper abdominal pain (3%)
• Diarrhea (3%)
• Nasal dryness (3%)
• Rash (3%)
• Injection site reactions (2%)

EGPA

• Systemic allergic/hypersensitivity reactions (4%)
• Systemic nonallergic reactions (1%)

HES

• Injection site reaction (7%)
• Other systemic reactions (ie, multifocal skin reaction) (2%)

<1%

CRSwNP

• Hypersensitivity reactions (<1%)

Postmarketing Reports

Hypersensitivity reactions, including anaphylaxis

Contraindications

Hypersensitivity

Cautions

Hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, urticaria, rash) reported; these reactions generally occur within hours of administration, but in some instances can have a delayed onset (ie, days); discontinue drug in the event of a hypersensitivity reaction

Not for treatment of acute asthma symptoms or acute exacerbations; do not use to treat acute bronchospasm or status asthmaticus; instruct patients to seek immediate medical advice if their asthma remains uncontrolled or worsens after initiating mepolizumab

In clinical trials, 2 serious adverse reactions of herpes zoster occurred during treatment compared with none in placebo; consider varicella vaccination if medically appropriate before initiating treatment

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation mepolizumab; reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician; reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy

Eosinophils may be involved in the immunological response to some helminth infections; patients with known parasitic infections were excluded from participation in clinical trials; treat patients with preexisting helminth infection before initiating mepolizumab; if helminth infection occurs while receiving mepolizumab that does not respond to treatment, discontinue mepolizumab until the infection resolves

Pregnancy

Data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk

Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters of pregnancy

Pregnancy exposure registry

• Healthcare providers can enroll patients or encourage patients to enroll themselves by 1-877-311-8972 or www.mothertobaby.org/asthma

Clinical considerations

• In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate
• Closely monitor the level of asthma control in pregnant women and treatment adjusted as necessary to maintain optimal control

Animal data

• In a prenatal and postnatal development study, pregnant cynomolgus monkeys received mepolizumab from gestation days 20 to 140 at doses that produced exposures up to ~9 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 100 mg/kg once every 4 weeks)
• Mepolizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 9 months after birth
• Examinations for internal or skeletal malformations were not performed
• Mepolizumab crossed the placenta in cynomolgus monkeys
• Concentrations of mepolizumab were ~2.4 times higher in infants than in mothers up to day 178 postpartum

Lactation

Unknown if distributed in human breast milk

However, mepolizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts

Present in the milk of cynomolgus monkeys postpartum following dosing during pregnancy; levels in milk were ≤0.5% of maternal serum concentration

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Humanized IgG1 kappa monoclonal antibody specific for IL-5; binds IL-5, and therefore stops IL-5 from binding to its receptor on the surface of eosinophils

Inhibiting IL-5 binding to eosinophils reduces blood, tissue, and sputum eosinophil levels

Absorption

Bioavailability: 80%

Following repeat SC administration once every 4 weeks, there was ~2-fold accumulation at steady-state

Distribution

Vd: 3.6 L (70-kg adult)

Metabolism

Degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue

Elimination

Half-life: 16-22 days

Systemic clearance: 0.28 L/day (70-kg adult)

SC Preparation

Lyophilized powder for reconstitution

• Reconstitute each vial with 1.2 mL sterile water for injection (SWI); final concentration of 100 mg/mL
• Do not mix with other medications
• Direct stream of SWI vertically onto the center of the lyophilized cake
• Gently swirl vial for 10 sec with a circular motion at 15-sec intervals until powder dissolves
• Reconstitution is typically complete within 5 min after the SWI has been added, but it may take additional time
• If a mechanical reconstitution device (swirler) is used, swirl at 450 rpm for ≤10 min; alternatively, may swirl at 1000 rpm for ≤5 min
• Visually inspect for particulate matter and clarity before use; solution should be clear to opalescent and colorless to pale yellow or pale brown; small air bubbles are expected and acceptable; discard if particulate matter remains in the solution or if solution appears cloudy or milky

Prefilled autoinjector or syringe

• Remove from refrigerator and allow to sit at room temperature for ~30 min before administration; do not warm in any other way
• Visually inspect window of autoinjector or syringe for particulate matter or discoloration
• Solution should be clear-to-opalescent, colorless-to-pale yellow or pale brown in color
• Do not use if solution appears discolored, cloudy, or has particulate matter
• Do not use if dropped on a hard surface

SC Administration

• Do NOT shake reconstituted solution; gently swirl to avoid foaming or precipitation
• For SC use only
• Administer SC into the upper arm, thigh, or abdomen
• Use each vial for a single patient; discard any remaining contents
• 40-mg dose: Remove 0.4 mL of reconstituted solution; administer 0.4 mL (equivalent to 40-mg dose)
• 40-mg/0.4-mL prefilled syringe is only for use in children aged 6-11 yr and must be administered by the healthcare provider or the patient caregiver
• 100-mg dose: Remove 1 mL of reconstituted solution; administer 1 mL (equivalent to 100-mg dose)
• 300-mg dose: Administer as 3 separate 100-mg injections; individual 100-mg injections should be administered at least 5-cm (~2-inches) apart if administered at the same site

Missed dose

• Administer as soon as possible; thereafter, resume dosing on usual day of administration; if next dose is due, then administer as scheduled

Storage

Lyophilized powder

• Store below 25ºC (77ºF)
• Do not freeze
• Store in the original package to protect from light

Reconstituted solution

• Store below 30ºC (86ºF)