Asthma, severe eosinophilic: Note: May consider as add-on therapy in patients with severe eosinophilic asthma inadequately controlled with standard therapies (eg, an inhaled glucocorticoid with a long-acting beta agonist) (GINA 2021). May consider use in patients with peripheral blood eosinophils ≥150 cells/mcL. The eosinophil threshold required for patients on systemic glucocorticoids is less clear (GINA 2021).
SUBQ: 100 mg once every 4 weeks. A minimum of 4 months of treatment is suggested to determine efficacy (GINA 2021).
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).
Hypereosinophilic syndrome: SUBQ: 300 mg once every 4 weeks.
Rhinosinusitis with nasal polyps: SUBQ: 100 mg once every 4 weeks.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on renal function is unlikely to be necessary as mepolizumab is not renally eliminated.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on hepatic function is unlikely to be necessary as mepolizumab is degraded by widely distributed proteolytic enzymes which are not restricted to hepatic tissue.
(For additional information see "Mepolizumab: Pediatric drug information")
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.
Hypereosinophilic syndrome (HES): Children ≥12 years and Adolescents: SubQ: 300 mg (divided into 3 separate 100 mg injections) once every 4 weeks. Note: Recommended patient population are those with ≥6 months duration of HES without an identifiable non-hematologic secondary cause; in clinical trials over a treatment period of 32 weeks, mepolizumab treatment group showed a 50% decrease in HES flare incidence.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on renal function is unlikely to be necessary as mepolizumab is not renally eliminated.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on hepatic function is unlikely to be necessary as mepolizumab is degraded by widely distributed proteolytic enzymes which are not restricted to hepatic tissue.
Refer to adult dosing.
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 (edta) disodium dihydrate, polysorbate 80]
Solution Reconstituted, Subcutaneous [preservative free]:
Nucala: 100 mg (1 ea) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous:
Nucala: 100 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Nucala: 100 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution Reconstituted, Subcutaneous:
Nucala: 100 mg (1 ea) [contains polysorbate 80]
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 5 cm [~2 inches] area surrounding the navel); 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 (~2 inches) apart if >1 injection administered at same site. Do not shake the reconstituted solution as this could lead to product foaming or precipitation.
SubQ:
Autoinjector, prefilled syringe: Allow device to reach room temperature ~30 minutes prior to administration. Administer via SubQ injection into the thigh or abdomen (avoid 5 cm [2 inches] area surrounding the navel); if a caregiver is administering, may also use upper arm; 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. See indication-specific dosing.
Vial (reconstituted solution for injection): Use a polypropylene syringe fitted with a 21- to 27-gauge 0.5-inch (13 mm) needle. Administer via SubQ injection into the upper arm, thigh, or abdomen; avoid skin that is tender, bruised, red, or hard. Do not shake the reconstituted solution as this could lead to product foaming or precipitation; if particulate matter is in the solution or if the solution appears cloudy or milky, discard the solution. See indication-specific dosing.
Asthma:
Children ≥6 years to 11 years: Administer 40 mg dose prepared from vial for injection SubQ into the upper arm, abdomen, or thigh; the autoinjector is not appropriate for partial doses.
Children ≥12 years and Adolescents: Administer 100 mg dose SubQ from either autoinjector or prepared from vial for injection into the upper arm, thigh, or abdomen (appropriate site dependent upon dosage form).
Hypereosinophilic syndrome: Children ≥12 years and Adolescents: Administer 300 mg dose as 3 separate 100 mg injections into the upper arm, thigh, or abdomen (appropriate site dependent upon dosage form). Injections should be administered at least 5 cm (2 inches) apart.
Asthma, severe eosinophilic: 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.
Hypereosinophilic syndrome: Treatment of adult and pediatric patients ≥12 years of age with hypereosinophilic syndrome for ≥6 months without an identifiable nonhematologic secondary cause.
Rhinosinusitis with nasal polyps: Add-on maintenance treatment of chronic rhinosinusitis with nasal polyps in adults with an inadequate response to nasal corticosteroids.
Eosinophilic granulomatosis with polyangiitis (relapsing or refractory)
After reconstitution, the concentration is 100 mg/mL, however, the entire vial contains 144 mg (which includes overfill). Ensure that the recommended 100 mg dose is drawn up as 1 mL with the overfill remaining in the vial. Dosing errors have been reported in cases where the entire contents of the vial have been withdrawn after reconstitution (ISMP 2018).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Local: Injection site reaction (≤15%; including burning sensation at injection site, erythema at injection site, itching at injection site, pain at injection site, swelling at injection site)
Nervous system: Headache (19%)
1% to 10%:
Dermatologic: Eczema (3%), pruritus (3%), skin rash (3%)
Gastrointestinal: Diarrhea (3%), upper abdominal pain (3%)
Genitourinary: Urinary tract infection (3%)
Hypersensitivity: Angioedema (1%), hypersensitivity reaction (≤6%; including type 1 and type IV hypersensitivity reaction)
Immunologic: Antibody development (≤6%; neutralizing: <1%)
Infection: Influenza (3%)
Nervous system: Fatigue (5%)
Neuromuscular & skeletal: Arthralgia (6%), back pain (5%), muscle spasm (3%)
Respiratory: Dry nose (3%), oropharyngeal pain (8%)
Miscellaneous: Fever (3%)
Frequency not defined: Infection: Herpes zoster infection
Postmarketing: Hypersensitivity: Anaphylaxis
Hypersensitivity to mepolizumab or any component of the formulation
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.
• 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.
None known.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Mepolizumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, 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 perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth and gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2019]; GINA 2020).
Use of monoclonal antibodies for the treatment of asthma in pregnancy may be considered when conventional therapies are insufficient; use of an agent other than mepolizumab may be preferred (ERS/TSANZ [Middleton 2019]).
Data collection to monitor pregnancy and infant outcomes following exposure to mepolizumab is ongoing. Health care providers are encouraged to enroll exposed pregnant females in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS) (877-311-8972 or http://mothertobaby.org). Patients may also enroll themselves.
It is not known if mepolizumab can be detected in breast milk; however, endogenous immune globulin is present in small amounts.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother. Use of monoclonal antibodies for the treatment of asthma in lactating women may be considered when conventional therapies are insufficient; use of an agent other than mepolizumab may be preferred (ERS/TSANZ [Middleton 2019]).
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.
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, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome). Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome has not been definitively established.
Distribution: Vd: ~3.6 L
Metabolism: Undergoes proteolytic degradation via enzymes that are widely distributed in the body and not restricted to hepatic tissue.
Bioavailability: ~80%
Half-life elimination: Terminal: 16 to 22 days
Excretion: Nonrenal
Solution (reconstituted) (Nucala Subcutaneous)
100 mg (per each): $3,857.39
Solution Auto-injector (Nucala Subcutaneous)
100 mg/mL (per mL): $3,990.41
Solution Prefilled Syringe (Nucala Subcutaneous)
100 mg/mL (per mL): $3,990.41
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
