Dosing and uses of Nucala (mepolizumab)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 100mg/vial
Asthma
Indicated for add-on maintenance treatment of patients with severe asthma aged ≥12 yr, and with an eosinophilic phenotype
100 mg SC q4wk
Dosing Considerations
Not for treatment of other eosinophilic conditions
Not for relief of acute bronchospasm or status asthmaticus
Pediatric dosage forms and strengths
lyophilized powder for reconstitution
- 100mg/vial
Asthma
Indicated for add-on maintenance treatment of patients with severe asthma aged ≥12 yr, and with an eosinophilic phenotype
<12 years: Safety and efficacy not established
≥12 years: 100 mg SC q4wk
Dosing Considerations
Not for treatment of other eosinophilic conditions
Not for relief of acute bronchospasm or status asthmaticus
Nucala (mepolizumab) adverse (side) effects
>10%
Headache (19%)
1-10%
Systemic reactions, allergic and nonallergic (10%)
Injection site reaction (8%)
Back pain (5%)
Fatigue (5%)
Influenza (3%)
Urinary tract infection (3%)
Upper abdominal pain (3%)
Pruritus (3%)
Eczema (3%)
Muscle spasms (3%)
Systemic allergic/hypersensitivity reactions (1%)
Warnings
Contraindications
Hypersensitivity
Cautions
Hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, urticaria, rash) reported following administration; 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 controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred during mepolizumab 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
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 paitents or encourage patietns to enroll themselves by
- calling 1-877-311-8972 or
- visiting 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
- The level of asthma control should be closely monitored 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 approximately 30 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 approximately 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
Mepolizumab was present in the milk of cynomolgus monkeys postpartum following dosing during pregnancy; mepolizumab levels in milk were ≤0.5% of maternal serum concentration
Consider the 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.
Pharmacology of Nucala (mepolizumab)
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%
Distribution
Vd: 3.6 L
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
Administration
Preparation
Reconstitute vial with 1.2 mL sterile water for injection (SWI), preferably using a 2- or 3-mL syringe and a 21-G needle
Reconstituted solution yields a concentration of 100 mg/mL
Do not mix with other medications
Direct the stream of SWI 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 the reconstituted solution during the procedure as this may lead to product foaming or precipitation
Reconstitution is typically complete within 5 minutes 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 no longer than 10 minutes; alternatively, may swirl at 1000 rpm for no longer than 5 minutes
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
SC Administration
Do NOT shake solution; gently swirL
For subcutaneous (SC) use only
Use a 1-mL polypropylene syringe fitted with a disposable 21- to 27-G x 0.5-inch (13-mm) needle
Administer 100 mg (1 mL) by SC injection into the upper arm, thigh, or abdomen
Storage
Lyophilized powder
- Store below 25°C (77°F)
- Do not freeze
- Store in the original package to protect from light
Reconstituted solution
- Store below 30°C (86°F)
- Do not freeze
- Discard if not used within 8 hr of reconstitution
