Nucala

Immunotherapies for Reactive and Obstructive Airway Diseases
Interleukin-5 (IL-5) Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear to opalescent and colorless to pale yellow or pale brown.
Mepolizumab vials should be reconstituted and administered by a healthcare professional.
Monitoring of patients after administration of biologic agents is recommended.

Do not administer into areas where the skin is tender, bruised, red, or hard.
If a dose is missed, administer a dose as soon as possible. Thereafter, the patient can resume dosing on the usual day of administration. If the next dose is already due, then administer as planned.
 
Mepolizumab for Injection Vial
 
Reconstitution
Reconstitute mepolizumab in the vial with 1.2 mL Sterile Water for Injection, preferably using a 2- or 3-mL syringe and a 21-gauge needle. The final concentration will be 100 mg/mL (144 mg/vial). There will be overfill in the vial.
Direct the stream of diluent vertically into the center of the lyophilized powder. Gently swirl the vial for 10 seconds at 15-second intervals until the powder is dissolved. Do not shake the reconstituted solution, as this may lead to foaming or precipitation. Reconstitution is usually complete within 5 minutes but may take additional time.
If a mechanical reconstitution device (swirler) is used, swirl at 450 rpm for no longer than 10 minutes. Alternatively, swirling at 1,000 rpm for no longer than 5 minutes is acceptable.
The solution should be clear to opalescent and colorless to pale yellow or pale brown and essentially particle-free. Small air bubbles are expected and acceptable.
Do not mix with other medications.
Storage: If not used immediately, store below 30 degrees C (86 degrees F), but do not freeze. Discard if not used within 8 hours of reconstitution.
 
Subcutaneous Administration from the Vial
A 1-mL polypropylene syringe fitted with a disposable 21- to 27-gauge x 0.5-inch (13-mm) needle is preferred for subcutaneous administration.
For a 100 mg dose, remove 1 mL (100 mg) of the reconstituted solution from the vial.
For a 40 mg dose, remove 0.4 mL (40 mg) of the reconstituted solution from the vial.
Administer the dose into the upper arm, thigh, or abdomen.
Use each vial for a single patient and discard any remaining contents.
If multiple injections are needed, ensure injection sites are separated by at least 5 cm (2 inches).
 
Mepolizumab Injection Prefilled Autoinjector and Prefilled Syringe
Provide proper training in subcutaneous injection technique and on the preparation and administration of mepolizumab injection prior to use according to the "Instructions for Use".
The 100 mg/mL prefilled autoinjector and 100 mg/mL prefilled syringe are only for use in adults and adolescents 12 years and older.
The 40 mg/0.4 mL prefilled syringe is only for use in children 6 to 11 years. It must be administered by a healthcare provider or the patient caregiver, after the healthcare provider determines it is appropriate.
Do not use the prefilled autoinjector or prefilled syringe if it is dropped on a hard surface or if it looks damaged.
Remove the prefilled autoinjector or prefilled syringe from the refrigerator and allow it to sit at room temperature for approximately 30 minutes prior to injection. Do NOT warm mepolizumab in any other way.
Administer the subcutaneous injection into the thigh or abdomen, avoiding the 5 cm (2 inches) around the navel. The upper arm can also be used if a caregiver administers the subcutaneous injection. If multiple injections are needed, ensure injection sites are separated by at least 5 cm (2 inches).
Do not use the prefilled syringe or autoinjector more than 1 time. Throw away the autoinjector or prefilled syringe in an FDA-cleared sharps disposal container after injection.
Storage: Store unopened autoinjectors or prefilled syringes in the original carton in the refrigerator between 2 and 8 degrees C (36 and 46 degrees F); do not freeze. Protect from light. Do not shake. Keep away from heat. If needed, an unopened carton can be stored outside the refrigerator at up to 30 degrees C (86 degrees F) for up to 7 days. Dispose of the injection properly if it is left out of the refrigerator in the unopened carton for more than 7 days. The prefilled autoinjector must be used within 8 hours after it is removed from the carton. Discard properly if it is not used within 8 hours.

bronchospasm / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

antibody formation / Delayed / 0-6.0
dyspnea / Early / 3.0
cystitis / Delayed / 3.0
hypotension / Rapid / Incidence not known
erythema / Early / Incidence not known
hypertension / Early / Incidence not known

headache / Early / 19.0-19.0
injection site reaction / Rapid / 2.0-15.0
arthralgia / Delayed / 6.0-6.0
back pain / Delayed / 5.0-5.0
fatigue / Early / 5.0-5.0
muscle cramps / Delayed / 3.0-3.0
diarrhea / Early / 3.0-3.0
abdominal pain / Early / 3.0-3.0
influenza / Delayed / 3.0-3.0
nasal dryness / Early / 3.0-3.0
pruritus / Rapid / 3.0-3.0
asthenia / Delayed / 3.0
musculoskeletal pain / Early / 3.0
dizziness / Early / 3.0
dental pain / Delayed / 3.0
vomiting / Early / 3.0
nausea / Early / 3.0
pharyngitis / Delayed / 3.0
nasal congestion / Early / 3.0
infection / Delayed / 3.0
fever / Early / 3.0
rhinitis / Early / 3.0
rash / Early / 3.0
myalgia / Early / Incidence not known
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known

Nucala

Rx

Subcutaneous humanized monoclonal antibody directed against interleukin (IL)-5
Used for maintenance therapy in severe asthma (eosinophilic phenotype) in patients 6 years and older; adults with eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome; hypereosinophilic syndrome in patients 12 years and older; and as add-on maintenance for chronic rhinosinusitis with nasal polyps (CRSwNP) in adults 18 and older with inadequate response to nasal steroids
Reduces severe exacerbations of asthma and may allow more time in remission and lower frequency of relapse for EGPA, which may allow for oral corticosteroid dose reduction for both indications

100 mg subcutaneously every 4 weeks.

100 mg subcutaneously every 4 weeks.

40 mg subcutaneously every 4 weeks.

300 mg subcutaneously every 4 weeks; administer as 3 separate 100-mg injections at least 5 cm (approximately 2 inches) apart.

300 mg subcutaneously every 4 weeks; administer as 3 separate 100-mg injections at least 5 cm (approximately 2 inches) apart. Significantly fewer patients who received mepolizumab experienced a HES flare during the 32-week treatment period compared with placebo (28% vs. 56%; odds ratio = 0.28; 95% CI, 0.12 to 0.64; p = 0.002) in a randomized, double-blind trial (n = 108). Patients were 12 years of age or older (mean age, 46 years), had HES for at least 6 months (mean duration, 5.55 years), and were on stable HES therapy (e.g., oral corticosteroids or immunosuppressive or cytotoxic therapy) for the 4 weeks prior to randomization. Patients with non-hematologic secondary HES (e.g., drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy) or FIP1L1-PDGFR alpha kinase-positive HES were excluded from the trial.

300 mg subcutaneously every 4 weeks; administer as 3 separate 100-mg injections at least 5 cm (approximately 2 inches) apart. Significantly fewer patients who received mepolizumab experienced a HES flare during the 32-week treatment period compared with placebo (28% vs. 56%; odds ratio = 0.28; 95% CI, 0.12 to 0.64; p = 0.002) in a randomized, double-blind trial (n = 108). Patients were 12 years of age or older (mean age, 46 years), had HES for at least 6 months (mean duration, 5.55 years), and were on stable HES therapy (e.g., oral corticosteroids or immunosuppressive or cytotoxic therapy) for the 4 weeks prior to randomization. Patients with non-hematologic secondary HES (e.g., drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy) or FIP1L1-PDGFR alpha kinase-positive HES were excluded from the trial.

100 mg subcutaneously every 4 weeks.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.

Mepolizumab/Nucala Subcutaneous Inj Sol: 0.4mL, 1mL, 40mg, 100mg
Nucala Subcutaneous Inj Pwd F/Sol: 100mg

100 mg subcutaneously every 4 weeks for severe asthma and chronic rhinosinusitis with nasal polyps (CRwNP); 300 mg subcutaneously every 4 weeks for eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.

100 mg subcutaneously every 4 weeks for severe asthma and chronic rhinosinusitis with nasal polyps (CRwNP); 300 mg subcutaneously every 4 weeks for eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.

100 mg subcutaneously every 4 weeks for severe asthma; 300 mg subcutaneously every 4 weeks for hypereosinophilic syndrome; safety and efficacy have not been established for eosinophilic granulomatosis with polyangiitis.

1 to 5 years: Safety and efficacy have not been established.6 to 11 years: 40 mg subcutaneously every 4 weeks for asthma; safety and efficacy for other indications have not been established.12 years: 100 mg subcutaneously every 4 weeks for asthma; 300 mg subcutaneously every 4 weeks for hypereosinophilic syndrome; safety and efficacy have not been established for eosinophilic granulomatosis with polyangiitis.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mepolizumab is a fully-humanized monoclonal antibody (IgG1 kappa) that targets human interleukin (IL)-5. Inflammation is a major component in the pathogenesis of asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome; many cell types (e.g., eosinophils) and mediators (e.g., cytokines) are involved in inflammation. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab selectively binds to IL-5, blocking it from binding to the alpha chain of the IL-5 receptor complex located on the eosinophil cell surface. This, in turn, inhibits IL-5 signaling and reduces the production and survival of eosinophils. Other undefined mechanisms of action may also play a role.

Mepolizumab is administered by subcutaneous injection. The central volume of distribution (Vd) of mepolizumab in adult patients with asthma is approximately 3.6 L for a 70-kg individual. Mepolizumab is a humanized IgG1 monoclonal antibody, and degradation occurs via proteolytic enzymes that are widely distributed throughout the body and not restricted to hepatic tissue. Apparent systemic clearance in adult and adolescent patients is estimated to be 0.28 L/day for a 70-kg individual. Mean terminal half-life in adult patients ranges from 16 to 22 days.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

After subcutaneous administration in the upper arm, the bioavailability of mepolizumab in adult and adolescent patients with asthma was approximately 80%. After repeated subcutaneous administration once every 4 weeks, there was approximately a 2-fold accumulation at steady state.

Pregnancy exposure data is 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 fetal effects are likely to be greater during the second and third trimesters. In a development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV mepolizumab administration throughout pregnancy at drug exposures approximately 30 times the exposure at the maximum recommended human dose (100 mg subcutaneously). In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Asthma control should be closely monitored during pregnancy and treatment adjusted to maintain optimal control.

There is no information regarding the presence of mepolizumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Mepolizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts. The FDA-approved product label recommends considering the developmental and health benefits of breast-feeding, the mother's need for mepolizumab therapy, and potential adverse effects of the drug or inadequately treated asthma on the breast-fed infant. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.