Version November 2024
Asthma, severe (eosinophilic phenotype); maintenance therapy (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): Note: Recommended patient population are those with ≥6 months duration of HES without an identifiable nonhematologic secondary cause.
Children ≥12 years and Adolescents: SUBQ: 300 mg (divided into 3 separate 100 mg injections) 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: Drug information")
Asthma, severe eosinophilic: Note: May consider as add-on therapy in patients with severe eosinophilic asthma (peripheral blood eosinophils ≥150 cells/mcL) inadequately controlled with standard therapies (eg, an inhaled glucocorticoid with a long-acting beta agonist). The eosinophil threshold required for patients on systemic glucocorticoids is less clear (Ref).
SUBQ: 100 mg once every 4 weeks. A minimum of 3 to 6 months of treatment is suggested to determine efficacy (Ref).
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.
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 mepolizumab 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.
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: 40 mg/0.4 mL (0.4 mL); 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
Solution (reconstituted) (Nucala Subcutaneous)
100 mg (per each): $4,094.09
Solution Auto-injector (Nucala Subcutaneous)
100 mg/mL (per mL): $4,426.60
Solution Prefilled Syringe (Nucala Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $1,770.65
100 mg/mL (per mL): $4,426.60
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Auto-injector, Subcutaneous:
Nucala: 100 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Nucala: 40 mg/0.4 mL (0.4 mL); 100 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution Reconstituted, Subcutaneous:
Nucala: 100 mg ([DSC]) [contains polysorbate 80]
Parenteral: 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 health care provider or 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. The 40 mg prefilled syringe is intended for patients 6 to 11 years of age and may be administered by either a health care provider or the patient's caregiver (after adequate training). The 100 mg prefilled syringe or autoinjector is intended for patients ≥12 years of age and may be administered by the patient or patient's caregiver (after adequate training).
Vial (reconstituted solution for injection): The vial is intended for administration by health care provider. 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. Vial contains overfill.
SUBQ: 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. 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.
Autoinjector, prefilled syringe: Allow device to reach room temperature for 30 minutes prior to administration. Initial use is recommended under supervision of health care provider; self-injection may occur after proper training.
Vial (reconstituted solution for injection): The vial is intended for administration by health care provider. Use a polypropylene syringe fitted with a 21- to 27-gauge 0.5-inch (13 mm) needle. Do not shake the reconstituted solution as this could lead to product foaming or precipitation.
Prefilled autoinjector/syringe: Store at 2°C to 8°C (36°F to 46°F) in original container. Do not freeze; protect from light and heat. 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) in original container. 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.
Add-on maintenance treatment of severe asthma with an eosinophilic phenotype (FDA approved in ages ≥6 years and adults); treatment of hypereosinophilic syndrome (HES) with ≥6 months duration without an identifiable non-hematologic secondary cause (FDA approved in ages ≥12 years and adults); treatment of eosinophilic granulomatosis with polyangiitis (FDA approved in adults); maintenance treatment of chronic rhinosinusitis with nasal polyps with an inadequate response to nasal corticosteroids as add-on therapy (FDA approved in adults). Note: Not indicated for the relief of acute bronchospasm or status asthmaticus.
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).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Data related to the use of monoclonal antibodies for the treatment of asthma in pregnancy are limited. The long half-life of monoclonal antibodies should be considered when prescribing to patients planning to become pregnant (Pfaller 2021). An agent other than mepolizumab may be preferred (ERS/TSANZ [Middleton 2020]).
Mepolizumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Outcome data following maternal use of mepolizumab during pregnancy are limited (Shakuntulla 2022; Sitek 2023; Vittorakis 2022).
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 2020]; GINA 2022).
Data related to the use of monoclonal antibodies for the treatment of severe asthma during pregnancy are limited (GINA 2023). Use of monoclonal antibodies may be considered when conventional therapies are insufficient (ERS/TSANZ [Middleton 2020]). In general, monoclonal antibodies should not be initiated during pregnancy. The option to continue treatment in patients who become pregnant during therapy should be considered as part of a shared decision-making process (Dorscheid 2022, Pfaller 2021, Shakuntulla 2022).
Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant patients in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS) (1-877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.
Asthma: 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.
Hypereosinophilic syndrome: Absolute eosinophil count.
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
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