Mepolizumab is a subcutaneous humanized interleukin-5 (IL-5) receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa). It is indicated for add-on maintenance treatment of severe asthma with an eosinophilic phenotype in patients 6 years and older, for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), which is also known as Churg-Strauss syndrome; for treatment of 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. Mepolizumab is directed against IL-5, which is known to play an important role in regulating the function of eosinophils, an inflammatory cell responsible for airway inflammation in some types of asthma and EGPA. Use of mepolizumab in patients with severe asthma (eosinophilic phenotype) led to fewer exacerbations requiring hospitalization and/or emergency department care and a longer time to the first exacerbation, compared to those who received placebo. Clinical trial data indicated that mepolizumab use may also lead to a decrease in dosage of oral maintenance corticosteroids, while maintaining asthma control, for these patients. Mepolizumab treatment did not result in a significant improvement in lung function, as measured by FEV1, in premarketing randomized trials. Among patients with relapsing or refractory EGPA and taking stable doses of prednisolone or prednisone, mepolizumab use resulted in more time in remission and a lower frequency of relapse compared to placebo, which allowed for a significantly lower oral glucocorticoid dose in the mepolizumab group. GINA recommends use in patients aged 6 years and older with severe eosinophilic asthma not controlled with usual therapies; GINA notes that their recommendations for ages 6 to 11 years were limited to data from one small uncontrolled study. The NAEPP includes add-on mepolizumab therapy as a consideration in adult and pediatric patients 12 years and older with severe persistent asthma after confirmatory phenotyping. However, the NAEPP has withheld specific recommendations for the use of newer biologics for patients with severe asthma (NAEPP steps 5 and 6) pending further clinical study assessments of the role of biologics in patients with specific phenotypes and/or endotypes.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-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.
Subcutaneous Administration
-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.
Among adult and adolescent patients aged 12 years and older with severe asthma, systemic reactions (allergic and non-allergic) occurred in 3% of patients receiving mepolizumab and 5% of those receiving placebo during clinical trials; the majority of these reactions were experienced on day of dosing. Serious adverse events that occurred in more than 1 subject treated with mepolizumab (n = 263) and at an incidence rate greater than placebo (n = 257) included herpes zoster (2 subjects vs. 0 subjects, respectively). Approximately 2% of mepolizumab-treated patients and 3% of placebo-treated patients with severe asthma withdrew from clinical trials due to adverse effects. The adverse reaction profile for patients aged 6 to 11 years was similar to that observed in patients aged 12 years and older. In the eosinophilic granulomatosis with polyangiitis (EGPA) clinical trial (n = 136), systemic reactions (allergic and non-allergic) occurred in 6% of patients receiving mepolizumab compared to 1% of those receiving placebo, with half of the reactions occurring on the day of dosing.
Overall, systemic non-allergic reactions were reported by 2% of mepolizumab-treated patients, compared to 3% of those receiving placebo in severe asthma clinical trials. The most commonly reported manifestations included rash, flushing, and myalgia. Fatigue (5% vs. 4%), back pain (5% vs. 4%), and muscle cramps/spasms (3% vs. less than 1%) occurred more frequently in patients receiving subcutaneous mepolizumab (n = 263) compared to placebo (n = 257), respectively, in the first 24 weeks of treatment in 2 confirmatory safety and efficacy trials. Fatigue, flushing, warm sensation in trunk and neck, and cold extremities were reported in the eosinophilic granulomatosis with polyangiitis (EGPA) clinical trial (n = 136). Asthenia and musculoskeletal pain were reported in 3% or more of patients receiving intravenous mepolizumab 75 mg (n = 153) during a 52-week dose-ranging and exacerbation-reduction trial; of note, mepolizumab is not indicated for intravenous use and should only be given by the subcutaneous route. Arthralgia (6%) was reported during adult trials for chronic rhinosinusitis with nasal polyps.
Headache was 1 of the most common adverse events reported during mepolizumab severe asthma clinical trials, occurring in 19% of patients receiving subcutaneous mepolizumab (n = 263) and 18% of those receiving placebo (n = 257) in the first 24 weeks of treatment in 2 confirmatory safety and efficacy trials. Dizziness (3% or more) was reported during a 52-week dose-ranging and exacerbation-reduction trial of intravenous mepolizumab 75 mg (n = 153); of note, mepolizumab is not indicated for intravenous use and should only be given by the subcutaneous route.
Upper abdominal pain (3% vs. 2%) occurred more frequently in patients receiving subcutaneous mepolizumab (n = 263) compared to placebo (n = 257), respectively, in the first 24 weeks of treatment in 2 confirmatory safety and efficacy trials in severe asthma. Abdominal pain, gastroenteritis, dental pain (toothache), nausea, and vomiting were reported in 3% or more of patients receiving intravenous mepolizumab 75 mg (n = 153) during a 52-week dose-ranging and exacerbation-reduction trial; of note, mepolizumab is not indicated for intravenous use and should only be given by the subcutaneous route. Oropharyngeal pain (8%), upper abdominal pain (3%), and diarrhea (3%) were reported in adult trials for chronic rhinosinusitis.
Opportunistic herpes zoster infections have occurred in patients receiving mepolizumab; consider varicella vaccination prior to starting therapy if medically appropriate. In controlled trials in patients with severe asthma, 2 serious adverse reactions of herpes zoster occurred in patients receiving subcutaneous mepolizumab (n = 263) compared to none in patients receiving placebo (n = 257). In addition, 3 cases of herpes zoster occurred in patients treated with intravenous mepolizumab 75 mg (n = 153) during a 52-week dose-ranging and exacerbation-reduction trial, compared to 2 cases in those receiving placebo (n = 155); of note, mepolizumab is not indicated for intravenous use and should only be given by the subcutaneous route. Additional cases of herpes zoster have been reported in long-term open-label extension studies. Other infectious and/or respiratory events including influenza (3%), urinary tract infection (3%), fever (3%), and nasal dryness (3%) were reported during clinical trials. Allergic rhinitis, bronchitis, cystitis, dyspnea, ear infection, gastroenteritis, lower respiratory tract infection, nasal congestion, pharyngitis, nasopharyngitis, fever, viral infection, and viral respiratory tract infection were reported in 3% or more of patients receiving intravenous mepolizumab 75 mg (n = 153) during the 52-week dose-ranging trial (not an approved dosage or route). Dyspnea and stridor also were reported with use of mepolizumab in the eosinophilic granulomatosis with polyangiitis (EGPA) clinical trial (n = 136).
Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after mepolizumab administration. Such reactions generally occur within hours of administration, but may have a delayed onset (i.e., days). If a hypersensitivity reaction occurs, discontinue the drug and institute appropriate treatment. Overall, systemic allergic/hypersensitivity reactions were reported by 1% of mepolizumab-treated patients, compared to 2% of those receiving placebo during severe asthma clinical trials. The most commonly reported manifestations included rash (unspecified), pruritus, headache, and myalgia. Pruritus (3% vs. 2%) and eczema (3% vs. less than 1%) occurred more frequently in severe asthma patients receiving subcutaneous mepolizumab (n = 263) compared to placebo (n = 257), respectively, in the first 24 weeks of treatment in 2 confirmatory safety and efficacy trials. Rash (unspecified) was reported in 3% or more of patients receiving intravenous mepolizumab 75 mg (n = 153) during a 52-week dose-ranging trial; of note, mepolizumab is not indicated for intravenous use and should only be given by the subcutaneous route. Rash and pruritus also were reported during the eosinophilic granulomatosis with polyangiitis (EGPA) clinical trial (n = 136); in addition, angioedema was reported in 1 EGPA patient. Urticaria, erythema, flushing, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, and shortness of breath were reported as manifestations of hypersensitivity in clinical trials specific to adults. Multifocal skin reaction was also reported during clinical trials.
An injection site reaction (e.g., pain, erythema, swelling, itching, burning) occurred in 2% to 15% of patients receiving subcutaneous mepolizumab during clinical trials.
Antibody formation occurred in 6% or less of patients who received subcutaneous mepolizumab in clinical trials. Neutralizing antibodies were detected in 1 patient who had severe asthma and in no patients with eosinophilic granulomatosis with polyangiitis or hypereosinophilic syndrome. The clinical relevance of the presence of anti-mepolizumab antibodies is unknown. Antibodies increased the clearance of mepolizumab by about 20%. There was no evidence of a correlation between anti-mepolizumab antibody titers and change in eosinophil concentration.
Hypertension was reported during the eosinophilic granulomatosis with polyangiitis (EGPA) clinical trial (n = 136).
Mepolizumab is contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation. Use with caution in patients with hamster protein hypersensitivity, as the drug is produced in Chinese hamster ovary cells. Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after mepolizumab administration. Such reactions generally occur within hours of administration, but may have a delayed onset (i.e., days). If a hypersensitivity reaction occurs, discontinue the drug and institute appropriate treatment.
Mepolizumab should not be used to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after mepolizumab initiation. Short-acting beta-agonists, such as albuterol, should be available for rescue therapy.
Do not discontinue systemic or inhaled corticosteroid therapy abruptly upon mepolizumab initiation. Corticosteroid withdrawal and dosage reduction, if appropriate, should be done gradually under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
In pre-marketing clinical trials, 2 cases of serious herpes infection (herpes zoster) occurred in patients who received mepolizumab compared to none in the placebo group. Nine hundred ninety-eight (998) subjects have received mepolizumab in ongoing open-label extension studies, during which additional cases of herpes zoster have been reported. If medically appropriate, consider varicella vaccination prior to treatment initiation.
Treat patients with a pre-existing helminth infection prior to initiating therapy with mepolizumab. If a patient becomes infected while receiving mepolizumab therapy and does not respond to anti-helminth treatment, discontinue mepolizumab therapy until the infection resolves. Mepolizumab reduces the production and survival of eosinophils, which may be involved in the immunological response to some helminth infections. Although it is not known whether if mepolizumab will influence the body's response against parasitic infections, caution is warranted. Patients with known parasitic infections were excluded from clinical trials.
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.
For asthma maintenance treatment as add-on therapy in persons with severe asthma (eosinophilic phenotype):
Subcutaneous dosage:
Adults: 100 mg subcutaneously every 4 weeks.
Children and Adolescents 12 to 17 years: 100 mg subcutaneously every 4 weeks.
Children 6 to 11 years: 40 mg subcutaneously every 4 weeks.
For the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome):
Subcutaneous dosage:
Adults: 300 mg subcutaneously every 4 weeks; administer as 3 separate 100-mg injections at least 5 cm (approximately 2 inches) apart.
For the treatment of hypereosinophilic syndrome (HES) present for at least 6 months without an identifiable non-hematologic secondary cause:
NOTE: Mepolizumab has been designated by the FDA as an orphan drug for the first-line treatment of HES.
Subcutaneous dosage:
Adults: 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.
Adolescents and Children 12 years and older: 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.
For add-on maintenance treatment of inadequately controlled chronic rhinosinusitis with nasal polyps (CRwNP):
Subcutaneous dosage:
Adults: 100 mg subcutaneously every 4 weeks.
Maximum Dosage Limits:
-Adults
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.
-Geriatric
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.
-Adolescents
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.
-Children
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.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure 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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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 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
-Route-Specific Pharmacokinetics
Subcutaneous Route
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.
-Special Populations
Hepatic Impairment
Mepolizumab is degraded by widely distributed proteolytic enzymes, not restricted to hepatic tissue. Changes in hepatic function are not expected to affect elimination; however, no clinical trials have been conducted to investigate the effect of hepatic impairment on mepolizumab pharmacokinetics.
Renal Impairment
Mepolizumab is not cleared renally. Based on population pharmacokinetic analyses, mepolizumab clearance was comparable between patients with a CrCl 50 to 80 mL/minute and those with normal renal function. There is limited data in patients with a CrCl less than 50 mL/minute; however, changes in renal function are not expected to affect mepolizumab pharmacokinetics.
Pediatrics
There is no significant effect of age on mepolizumab clearance in patients 12 years and older. In a pharmacokinetic study in patients aged 6 to 11 years with severe asthma, simulation of a 40 mg subcutaneous dose every 4 weeks in children aged 6 to 11 years, irrespective of body weight, resulted in predicted exposures similar to that observed in adults and adolescents.
Geriatric
There is no significant effect of age on mepolizumab clearance in patients 12 to 82 years of age.
Gender Differences
There is no significant effect of gender on mepolizumab clearance.
Ethnic Differences
There is no significant effect of race on mepolizumab clearance.