NUCALA (mepolizumab)

NUCALA (mepolizumab)

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NUCALA (mepolizumab)

Mepolizumab is a humanized IL-5 antagonist monoclonal antibody. Mepolizumab is produced by recombinant DNA technology in Chinese hamster ovary cells. Mepolizumab has a molecular weight of approximately 149 kDa.

NUCALA (mepolizumab) for injection is a sterile, preservative-free, white to off-white, lyophilized powder in a single-dose vial for subcutaneous injection after reconstitution. Upon reconstitution with 1.2 mL of Sterile Water for Injection, USP, the resulting concentration is 100 mg/mL and delivers 1 mL. Each vial delivers 100 mg of mepolizumab, polysorbate 80 (0.67 mg), sodium phosphate dibasic heptahydrate (7.14 mg), and sucrose (160 mg), with a pH of 7.0.

The vial stopper is not made with natural rubber latex.

NUCALA injection is a sterile, preservative-free, clear to opalescent, colorless to pale yellow to pale brown solution for subcutaneous use. It is supplied in a single-dose, 1-mL, prefilled autoinjector with a fixed 29-gauge, half-inch needle or in a single-dose, 1-mL, prefilled syringe with a fixed 29-gauge, half-inch needle with a needle guard. Each 1 mL delivers 100 mg mepolizumab, citric acid monohydrate (0.95 mg), EDTA disodium dihydrate (0.019 mg), polysorbate 80 (0.20 mg), sodium phosphate dibasic heptahydrate (4.16 mg), and sucrose (120 mg), with a pH of 6.3.

The prefilled autoinjector and prefilled syringe are not made with natural rubber latex.

Mechanism of Action

Mepolizumab is an IL-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma, CRSwNP, EGPA, and HES. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma, CRSwNP, EGPA, and HES has not been definitively established.

Indications and usage

Maintenance Treatment of Severe Asthma: NUCALA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype.

Limitations of Use: NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus

Maintenance Treatment of Chronic Rhinosinusitis with Nasal Polyps: NUCALA is indicated for the add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids.

Eosinophilic Granulomatosis with Polyangiitis: NUCALA is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Hypereosinophilic Syndrome: NUCALA is indicated for the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause.

Dosage and administration

NUCALA is for subcutaneous use only.

Severe Asthma

Adults and Adolescents Aged 12 Years and Older: The recommended dosage of NUCALA in adults and adolescents aged 12 years and older is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.

Pediatric Patients Aged 6 to 11 Years: The recommended dosage of NUCALA for injection in pediatric patients aged 6 to 11 years is 40 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.

Chronic Rhinosinusitis with Nasal Polyps: The recommended dosage of NUCALA is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen.

Eosinophilic Granulomatosis with Polyangiitis: The recommended dosage of NUCALA is 300 mg administered once every 4 weeks by subcutaneous injection as 3 separate 100-mg injections into the upper arm, thigh, or abdomen. Administer individual 100-mg injections at least 5 cm (approximately 2 inches) apart.

Hypereosinophilic Syndrome: The recommended dosage of NUCALA is 300 mg administered once every 4 weeks by subcutaneous injection as 3 separate 100-mg injections into the upper arm, thigh, or abdomen. Administer individual 100-mg injections at least 5 cm (approximately 2 inches) apart.

Dosage forms and strengths

  • For injection: 100 mg white to off-white lyophilized powder in a single-dose vial for reconstitution.
  • Injection: 100 mg/mL as a clear to opalescent, colorless to pale yellow to pale brown solution in a single-dose prefilled autoinjector or a single-dose prefilled glass syringe.

Adverse reactions

Most common adverse reactions (incidence ≥5%):

  • Asthma: Headache, injection site reaction, back pain, and fatigue.
  • CRSwNP: Oropharyngeal pain and arthralgia.
  • EGPA and HES: Most common adverse reactions are similar to asthma.

Pharmacokinetics

Absorption: Following 100-mg subcutaneous administration in the upper arm of adult and adolescent subjects with asthma, the bioavailability of mepolizumab was estimated to be approximately 80%.

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Following repeat subcutaneous administration once every 4 weeks, there was approximately a 2-fold accumulation at steady state.

Distribution: The population central volume of distribution of mepolizumab in adult subjects with asthma is estimated to be 3.6 L for a 70-kg individual.

Elimination: Following subcutaneous administration of mepolizumab in adult subjects with asthma, the mean terminal half-life (t1/2) ranged from 16 to 22 days. The population apparent systemic clearance of mepolizumab in adult and adolescent subjects with asthma is estimated to be 0.28 L/day for a 70-kg individual.

Metabolism: Mepolizumab is a humanized IgG1 monoclonal antibody that is degraded by the proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.

Contraindications

NUCALA is contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation

Warning and precautions

Hypersensitivity Reactions: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred following administration of NUCALA. These reactions generally occur within hours of administration, but in some instances can have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, NUCALA should be discontinued.

Acute Asthma Symptoms or Deteriorating Disease: NUCALA should not be used to treat acute asthma symptoms or acute exacerbations. Do not use NUCALA to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with NUCALA

Opportunistic Infections: Herpes Zoster Herpes zoster has occurred in subjects receiving NUCALA 100 mg in controlled clinical trials. Consider vaccination if medically appropriate.

Reduction of Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with NUCALA. Reductions in corticosteroid dosage, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dosage may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection: Eosinophils may be involved in the immunological response to some helminth infections. Patients with known parasitic infections were excluded from participation in clinical trials. It is unknown if NUCALA will influence a patient’s response against parasitic infections. Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving treatment with NUCALA and do not respond to anti-helminth treatment, discontinue treatment with NUCALA until infection resolves.

Use in specific populations

Pregnancy: The data on pregnancy exposure 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 trimester of pregnancy.

Lactation: There is no information regarding the presence of mepolizumab in human milk, the effects on the breastfed infant, or the effects on milk production. However, mepolizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts.

Pediatric Use: The safety and effectiveness of NUCALA for severe asthma, and with an eosinophilic phenotype, have been established in pediatric patients aged 6 years and older.

The safety and effectiveness in patients aged younger than 18 years with CRSwNP have not been established.

The safety and effectiveness in patients aged younger than 18 years with EGPA have not been established.

The safety and effectiveness of NUCALA for HES have been established in adolescent patients aged 12 years and older. The safety and effectiveness in pediatric patients aged younger than 12 years with HES have not been established.

Overdosage

There is no specific treatment for an overdose with mepolizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.

Storage

NUCALA for Injection: Store vials below 77°F (25°C). Do not freeze. Store in the original carton to protect from light.

NUCALA Injection

Prior to Dispensing: Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Keep the product in the original carton to protect from light. Do not freeze. Do not shake. Avoid exposure to heat

Following Dispensing: Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Avoid exposure to heat.

If necessary, an unopened carton can be stored outside the refrigerator at up to 86°F (30°C) for up to 7 days. Discard if left out of the refrigerator for more than 7 days.

NUCALA injection must be administered within 8 hours after removal from the carton. Discard if not administered within 8 hours.

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