Mepolizumab

Indications

Mepolizumab is used for: Add-on treatment for severe refractory eosinophilic, asthma in adult patients.

Adult Dose

Asthma Indicated for add-on maintenance treatment of patients with severe asthma aged >12 year, and with an eosinophilic phenotype 100 mg SC once every 4 wk.

Child Dose

Asthma Indicated for add-on maintenance treatment of patients with severe asthma aged >12 year, and with an eosinophilic phenotype <12 years: Safety and efficacy not established >12 years: 100 mg SC q4wk

Renal Dose

Administration

SC Preparation Reconstitute each 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 Preparation of the 300-mg dose for treatment of EGPA requires the reconstitution of 3 separate 100-mg vials 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 SC into the upper arm, thigh, or abdomen 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

Contra Indications

Hypersensitivity.

Precautions

Should not be used to treat acute asthma exacerbations. Asthma-related adverse events or exacerbations may occur. Abrupt discontinuation of corticosteroid after initiation of Nucala therapy is not recommended. Acute & delayed systemic reactions, including hypersensitivity reactions. Patients w/ pre-existing helminth infections. Pregnancy & lactation.

Pregnancy-Lactation

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 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

Interactions

Side Effects

Side effects of Mepolizumab : >10% Headache (19%) Injection site reactions (8-15%) 1-10% Systemic allergic/nonallergic reactions (2-6%) Back pain (5%) Fatigue (5%) Systemic allergic/hypersensitivity reactions (1-4%) Influenza (3%) Urinary tract infection (3%) Upper abdominal pain (3%) Pruritus (3%) Eczema (3%) Muscle spasms (3%) Frequency Not Defined Abdominal pain Allergic rhinitis Asthenia Bronchitis Cystitis Dizziness Dyspnea Ear infection Gastroenteritis Lower respiratory tract infection Musculoskeletal pain Nasal congestion Nasopharyngitis Toothache Viral infection Viral respiratory tract infection

Mode 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