Nucala

Nucala

mepolizumab

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Contents
Mepolizumab.
Description
Each vial contains 100 mg mepolizumab. After reconstitution, each ml of solution contains 100 mg mepolizumab.
Each 1 ml pre-filled pen contains 100 mg of mepolizumab.
Mepolizumab is a humanised monoclonal antibody produced in Chinese hamster ovary cells by recombinant DNA technology.
Excipients/Inactive Ingredients: Vial: Sucrose, Sodium phosphate dibasic heptahydrate, Polysorbate 80.
Pre-filled pen: Sucrose, Sodium phosphate dibasic heptahydrate, Citric acid monohydrate, Polysorbate 80, EDTA disodium dihydrate, Water for injections.
Action
Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for obstructive airway diseases. ATC code: R03DX09.
Pharmacology: Pharmacodynamics: Mechanism of action: Mepolizumab is a humanised monoclonal antibody (IgG1, kappa), which targets human interleukin-5 (IL-5) with high affinity and specificity. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation and survival of eosinophils. Mepolizumab inhibits the bioactivity of IL-5 with nanomolar potency by blocking the binding of IL-5 to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface, thereby inhibiting IL-5 signalling and reducing the production and survival of eosinophils.
Pharmacodynamic effects: In patients with severe refractory eosinophilic asthma (adults/adolescents), following a dose of 100 mg administered subcutaneously every 4 weeks for 32 weeks, blood eosinophils were reduced from a geometric mean count at baseline of 290 to 40 cells/μL at week 32 (n=182), a reduction of 84% compared to placebo. This magnitude of blood eosinophils reduction was maintained in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies. This magnitude of reduction was observed within 4 weeks of treatment.
Immunogenicity: Consistent with the potentially immunogenic properties of protein and peptide therapeutics, patients may develop antibodies to mepolizumab following treatment. In the placebo-controlled trials, 15/260 (6%) of adults and adolescents treated with 100 mg dose subcutaneously had detectable anti-mepolizumab antibodies after having received at least one dose of mepolizumab.
The immunogenicity profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to that observed in the placebo-controlled studies.
Neutralising antibodies were detected in one adult subject. Anti-mepolizumab antibodies did not discernibly impact the pharmacokinetics and pharmacodynamics of mepolizumab in the majority of patients and there was no evidence of a correlation between antibody titres and change in blood eosinophil level.
Clinical efficacy: The efficacy of mepolizumab in the treatment of a targeted group of patients with severe refractory eosinophilic asthma was evaluated in 3 randomised, double-blind, parallel-group clinical studies of between 24-52 weeks duration, in patients aged 12 years and older. These patients either remained uncontrolled (at least two severe exacerbations in the previous 12 months) on their current standard of care, including at least high doses of inhaled corticosteroids (ICS) plus an additional maintenance treatment(s), or were dependent on systemic corticosteroids. Additional maintenance treatments included long-acting beta2-adrenergic agonists (LABA), leukotriene modifiers, long-acting muscarinic antagonists (LAMA), theophylline, and oral corticosteroids (OCS).
The two exacerbations studies MEA112997 and MEA115588 enrolled a total of 1192 patients, 60% females, with a mean age of 49 years (range 12-82). The proportion of patients on maintenance OCS was 31% and 24%, respectively. Patients were required to have a history of two or more severe asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at baseline (pre-bronchodilator FEV1<80% in adults and <90% in adolescents). The mean number of exacerbations in the previous year was 3.6 and the mean predicted pre-bronchodilator FEV1 was 60%. Patients continued to receive their existing asthma medicine during the studies.
For the oral corticosteroid-sparing study MEA115575, a total of 135 patients were enrolled (55% were female; mean age of 50 years) who were being treated daily with OCS (5-35 mg per day), and high-dose ICS plus an additional maintenance medicine.
Dose-ranging efficacy MEA112997 (DREAM) study: In MEA112997, a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study of 52 weeks duration in 616 patients with severe refractory eosinophilic asthma, mepolizumab significantly reduced clinically significant asthma exacerbations (defined as worsening of asthma requiring use of oral/systemic corticosteroids and/or hospitalisation and/or emergency department visits) when administered in doses of 75 mg, 250 mg or 750 mg intravenously compared to placebo (see Table 1).

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Exacerbation reduction (MEA115588) MENSA study: MEA115588 was a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study which evaluated the efficacy and safety of mepolizumab as add-on therapy in 576 patients with severe refractory eosinophilic asthma defined as peripheral blood eosinophils greater than or equal to 150 cells/μL at initiation of treatment or greater than or equal to 300 cells/μL within the past 12 months.
Patients received mepolizumab 100 mg administered subcutaneously, mepolizumab 75 mg administered intravenously or placebo treatment once every 4 weeks over 32 weeks. The primary endpoint was the frequency of clinically significant exacerbations of asthma and the reductions for both mepolizumab treatment arms compared to placebo were statistically significant (p<0.001). Table 2 provides the results of the primary and secondary endpoints for patients treated with subcutaneous mepolizumab or placebo. (See Table 2.)

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Reduction of exacerbation rate by baseline blood eosinophil count: Table 3 shows the results of a combined analysis of the two exacerbation studies (MEA112997 and MEA115588) by baseline blood eosinophil count. The rate of exacerbations in the placebo arm increased with increasing baseline blood eosinophil count. The reduction rate with mepolizumab was greater in patients with higher blood eosinophil counts. (See Table 3.)

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Oral corticosteroid reduction study MEA115575 (SIRIUS): MEA115575 evaluated the effect of mepolizumab 100 mg administered subcutaneously on reducing the requirement for maintenance oral corticosteroids (OCS) while maintaining asthma control in subjects with severe refractory eosinophilic asthma. Patients had a blood eosinophil count of ≥150/μL at baseline or a blood eosinophil count of ≥300/μL in the 12 months prior to screening. Patients were administered mepolizumab or placebo treatment once every 4 weeks over the treatment period. Patients continued to receive their existing asthma medicine during the study with the exception of their OCS dose which was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained.
A total of 135 patients were enrolled: mean age was 50 years, 55% were female, and 48% had been receiving oral steroid therapy for at least 5 years. The baseline mean prednisone equivalent dose was approximately 13 mg per day.
The primary endpoint was the percent reduction in daily OCS dose (weeks 20-24), whilst maintaining asthma control by defined dose reduction categories (see Table 4). Predefined categories included percent reductions ranging from 90-100% reduction, to no decrease in the prednisone dose from the end of the optimisation phase. The comparison between mepolizumab and placebo was statistically significant (p=0.008). (See Table 4.)

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Open-label extension studies in severe refractory eosinophilic asthma MEA115666 (COLUMBA), MEA115661 (COSMOS) and 201312 (COSMEX): The long-term efficacy profile of Nucala in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies MEA115666, MEA115661 and 201312 was generally consistent with the 3 placebo-controlled studies.
Paediatric population: Vial: There were 25 adolescents 13 girls and 12 boys, 9 aged 12-14 years and 16 aged 15-17 years enrolled in study MEA115588. Of the total 25 subjects: 9 received placebo, 9 received mepolizumab 75 mg intravenously, and 7 received 100 mg subcutaneously. The same proportion of subjects (3/9) receiving placebo and mepolizumab intravenously reported clinically significant exacerbations; no exacerbations were reported in those receiving mepolizumab subcutaneously.
Paediatric population (12-17 years old): Pre-filled pen: Severe refractory eosinophilic asthma: In MEA115588 and in the double-blind placebo-controlled study 200862, there were 34 adolescents (12 to 17 years old). Of these 34 subjects: 12 received placebo, 9 received mepolizumab 75 mg intravenously, and 13 received 100 mg subcutaneously. In a combined analysis of these studies, a 40% reduction in clinically significant exacerbations was observed in adolescents following mepolizumab treatment compared to placebo (rate ratio 0.60; 95% CI: 0.17, 2.10).
Pharmacokinetics: Following subcutaneous dosing in patients with asthma, mepolizumab exhibited approximately dose-proportional pharmacokinetics over a dose range of 12.5 mg to 250 mg. Following administration of a single 100 mg subcutaneous dose in healthy subjects, mepolizumab systemic exposure was comparable between formulations.
Absorption: Following subcutaneous administration to healthy subjects or patients with asthma, mepolizumab was absorbed slowly with a median time to reach maximum plasma concentration (Tmax) ranging from 4 to 8 days.
Following a single subcutaneous administration in the abdomen, thigh or arm of healthy subjects, mepolizumab absolute bioavailability was 64%, 71% and 75%, respectively. In patients with asthma the absolute bioavailability of mepolizumab administered subcutaneously in the arm ranged from 74-80%. Following repeat subcutaneous administration every 4 weeks, there is approximately a two-fold accumulation at steady state.
Distribution: Following a single intravenous administration to patients with asthma, mepolizumab distributes into a mean volume of distribution of 55 to 85 mL/kg.
Biotransformation: Mepolizumab is a humanized IgG1 monoclonal antibody degraded by proteolytic enzymes which are widely distributed in the body and not restricted to hepatic tissue.
Elimination: Following a single intravenous administration to patients with asthma, the mean systemic clearance (CL) ranged from 1.9 to 3.3 mL/day/kg, with a mean terminal half-life of approximately 20 days. Following subcutaneous administration of mepolizumab the mean terminal half-life (t1/2) ranged from 16 to 22 days. In the population pharmacokinetic analysis estimated mepolizumab systemic clearance was 3.1 mL/day/kg.
Paediatric population: Vial: There are limited pharmacokinetic data available in the paediatric population (59 subjects with eosinophilic esophagitis, 19 subjects with severe asthma). Intravenous mepolizumab pharmacokinetics was evaluated by population pharmacokinetic analysis in a paediatric study conducted in subjects aged 2-17 years old with eosinophilic esophagitis. Paediatric pharmacokinetics was largely predictable from adults, after taking into account bodyweight. Mepolizumab pharmacokinetics in adolescent subjects with severe eosinophilic asthma included in the phase 3 studies were consistent with adults (see Dosage & Administration).
Pre-filled pen: There are limited pharmacokinetic data available in the paediatric population (59 subjects with eosinophilic esophagitis, 55 subjects with severe refractory eosinophilic asthma). Intravenous mepolizumab pharmacokinetics was evaluated by population pharmacokinetic analysis in a paediatric study conducted in subjects aged 2-17 years old with eosinophilic esophagitis. Paediatric pharmacokinetics was largely predictable from adults, after taking into account bodyweight. Mepolizumab pharmacokinetics in adolescent subjects with severe refractory eosinophilic asthma included in the phase 3 studies were consistent with adults (see Dosage & Administration).
Special populations: Elderly patients (≥65 years old): There are limited pharmacokinetic data available in elderly patients (≥65 years old) across all clinical studies (N=90). However, in the population pharmacokinetic analysis, there were no indications of an effect of age on the pharmacokinetics of mepolizumab over the age range of 12 to 82 years.
Renal impairment: No formal studies have been conducted to investigate the effect of renal impairment on the pharmacokinetics of mepolizumab. Based on population pharmacokinetic analyses, no dose adjustment is required in patients with creatinine clearance values between 50-80 mL/min. There are limited data available in patients with creatinine clearance values <50 mL/min.
Hepatic impairment: No formal studies have been conducted to investigate the effect of hepatic impairment on the pharmacokinetics of mepolizumab. Since mepolizumab is degraded by widely distributed proteolytic enzymes, not restricted to hepatic tissue, changes in hepatic function are unlikely to have any effect on the elimination of mepolizumab.
Toxicology: Preclinical safety data: As mepolizumab is a monoclonal antibody, no genotoxicity or carcinogenicity studies have been conducted.
Animal toxicology and/or pharmacology: Non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology or repeated dose toxicity studies in monkeys. Intravenous and subcutaneous administration to monkeys was associated with reductions in peripheral and lung eosinophil counts, with no toxicological findings.
Eosinophils are thought to be associated with immune system responses to some parasitic infections. Studies conducted in mice treated with anti-IL-5 antibodies or genetically deficient in IL-5 or eosinophils have not shown impaired ability to clear parasitic infections. The relevance of these findings for humans is unknown.
Fertility: No impairment of fertility was observed in a fertility and general reproduction toxicity study in mice performed with an analogous antibody that inhibits IL-5 in mice. This study did not include a littering or functional offspring assessment.
Pregnancy: In monkeys, mepolizumab had no effect on pregnancy or on embryonic/fetal and postnatal development (including immune function) of the offspring. Examinations for internal or skeletal malformations were not performed. Data in cynomolgus monkeys demonstrate that mepolizumab crossed the placenta.
Concentrations of mepolizumab were about 1.2-2.4 times higher in infants than in mothers for several months post partum and did not affect the immune system of the infants.
Indications/Uses
Vial: Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adult patients (see Pharmacology: Pharmacodynamics under Actions).
Pre-filled pen: Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adults and adolescents aged 12 years and older (see Pharmacology: Pharmacodynamics under Actions).
Dosage/Direction for Use
Nucala should be prescribed by physicians experienced in the diagnosis and treatment of severe refractory eosinophilic asthma.
Posology: Adults and adolescents aged 12 years and over: The recommended dose of mepolizumab is 100 mg administered subcutaneously once every 4 weeks.
Nucala is intended for long-term treatment. The need for continued therapy should be considered at least on an annual basis as determined by physician assessment of the patient's disease severity and level of control of exacerbations.
Special populations: Elderly patients: No dose adjustment is required for elderly patients (see Pharmacology: Pharmacokinetics under Actions).
Renal and hepatic impairment: No dose adjustment is required in patients with renal or hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Vial: The safety and efficacy of Nucala in children and adolescents under 18 years of age has not yet been established. Very limited data are currently available in children 12 to 18 years old (see Adverse Reactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions) therefore no recommendations can be made.
Pre-filled pen: Children less than 12 years old: The safety and efficacy of mepolizumab in children less than 12 years old have not yet been established.
Method of administration: Nucala should be used for subcutaneous injection only.
Vial: Nucala should be administered by a healthcare professional. It may be injected into the upper arm, thigh, or abdomen.
The powder should be reconstituted prior to administration and the reconstituted solution should be used immediately. For instructions on the reconstitution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.
Pre-filled pen: Nucala may be self-administered by the patient or administered by a caregiver if their healthcare professional determines that it is appropriate, and the patient or caregiver are trained in injection techniques.
For self-administration the recommended injection sites are the abdomen or thigh. A caregiver can also inject Nucala into the upper arm.
Comprehensive instructions for subcutaneous administration of Nucala in a pre-filled pen is provided in the instructions for use under Cautions for Usage.
Overdosage
Single doses of up to 1,500 mg were administered intravenously in a clinical trial to patients with eosinophilic disease without evidence of dose-related toxicities.
There is no specific treatment for an overdose with mepolizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.
Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Description.
Special Precautions
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Asthma exacerbations: Nucala should not be used to treat acute asthma exacerbations.
Asthma-related adverse symptoms or exacerbations may occur during treatment. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment.
Corticosteroids: Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician.
Hypersensitivity and administration-related reactions: Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. anaphylaxis, urticaria, angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., typically within several days). These reactions may occur for the first time after a long duration of treatment (see Adverse Reactions).
Parasitic infections: Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections should be treated before starting therapy. If patients become infected whilst receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of therapy should be considered.
Effects on ability to drive and use machines: Nucala has no or negligible influence on the ability to drive and use machines.
Pre-filled pen: Excipients: This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e. essentially "sodium-free".
Use In Pregnancy & Lactation
Pregnancy: There is a limited amount of data (less than 300 pregnancy outcomes) from the use of mepolizumab in pregnant women.
Mepolizumab crosses the placental barrier in monkeys. Animal studies do not indicate reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). The potential for harm to a human fetus is unknown.
As a precautionary measure, it is preferable to avoid the use of Nucala during pregnancy. Administration of Nucala to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.
Breast-feeding: There are no data regarding the excretion of mepolizumab in human milk. However, mepolizumab was excreted into the milk of cynomolgous monkeys at concentrations of less than 0.5% of those detected in plasma.
A decision must be made whether to discontinue breast-feeding or to discontinue Nucala therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility: There are no fertility data in humans. Animal studies showed no adverse effects of anti-IL5 treatment on fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Adverse Reactions
Summary of the safety profile: Adults and adolescents: In clinical studies in subjects with severe refractory eosinophilic asthma, the most commonly reported adverse reactions during treatment were headache, injection site reactions and back pain.
Tabulated list of adverse reactions: A total of 896 adults and 19 adolescent subjects with severe refractory eosinophilic asthma received either a subcutaneous or an intravenous dose of mepolizumab during three placebo-controlled clinical studies of 24 to 52 weeks duration. The table as follows presents the adverse reactions from the two placebo controlled studies in patients receiving mepolizumab 100 mg subcutaneously (n=263).
The safety profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to that observed in the placebo-controlled studies.
The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 5.)

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Description of selected adverse reaction: Local injection site reactions: In 2 placebo-controlled studies the incidence of local injection site reactions with mepolizumab 100 mg subcutaneous and placebo was 8% and 3%, respectively. These events were all non-serious, mild to moderate in intensity and the majority resolved within a few days. Local injection site reactions occurred mainly at the start of treatment and within the first 3 injections with fewer reports on subsequent injections. The most common manifestations reported with these events included pain, erythema, swelling, itching, and burning sensation.
Paediatric population: Vial: The clinical trial data currently available in paediatric patients is too limited to characterise the safety profile of mepolizumab in this population (see Pharmacology: Pharmacodynamics under Actions). However, the frequency, type and severity of adverse reactions in the paediatric population are expected to be similar to those seen in adults.
Pre-filled pen: Paediatric population (12-17 years old): Thirty-seven adolescents (aged 12-17) were enrolled in four placebo-controlled studies (25 mepolizumab treated intravenously or subcutaneously) of 24 to 52 weeks duration. The safety profile was similar to that seen in adults. No additional adverse reactions were identified.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
Drug Interactions
No interaction studies have been performed.
Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of mepolizumab. Increased levels of pro-inflammatory cytokines (e.g. IL-6), via interaction with their cognate receptors on hepatocytes, have been shown to suppress the formation of CYP450 enzymes and drug transporters, however, elevation of systemic pro-inflammatory markers in severe refractory eosinophilic asthma is minimal and there is no evidence of IL-5 receptor alpha expression on hepatocytes. The potential for interactions with mepolizumab is therefore considered low.
Caution For Usage
Special precautions for disposal and other handling: Vial: Nucala does not contain a preservative therefore reconstitution should be carried out under aseptic conditions.
Instructions for reconstitution: 1. Reconstitute the contents of the vial with 1.2 mL of sterile water for injection preferably using a 2 to 3 mL syringe and a 21 gauge needle. The stream of sterile water should be directed vertically, onto the centre of the lyophilised cake. Allow the vial to sit at room temperature during reconstitution, gently swirling the vial for 10 seconds with circular motion at 15-second intervals until the powder is dissolved.
Note: The reconstituted solution must not be shaken during the procedure as this may lead to product foaming or precipitation. Reconstitution is typically complete within 5 minutes after the sterile water has been added, but it may take additional time.
2. If a mechanical reconstitution device (swirler) is used to reconstitute Nucala, reconstitution can be accomplished by swirling at 450 rpm for no longer than 10 minutes. Alternatively, swirling at 1000 rpm for no longer than 5 minutes is acceptable.
3. Following reconstitution, Nucala should be visually inspected for particulate matter and clarity prior to use. The solution should be clear to opalescent, and colourless to pale yellow or pale brown, free of visible particles. Small air bubbles, however, are expected and acceptable. If particulate matter remains in the solution or if the solution appears cloudy or milky, the solution must not be used.
4. The reconstituted solution, if not used immediately must be: Protected from sunlight; Stored below 30°C, not frozen; Discarded if not used within 8 hours of reconstitution.
Instructions for administration: 1. For subcutaneous administration a 1 mL polypropylene syringe fitted with a disposable needle 21 gauge to 27 gauge x 0.5 inch (13 mm) should preferably be used.
2. Just prior to administration, remove 1 mL of reconstituted Nucala. Do not shake the reconstituted solution during the procedure as this could lead to product foaming or precipitation.
3. Administer the 1 mL injection (equivalent to 100 mg mepolizumab) subcutaneously into the upper arm, thigh, or abdomen.
Pre-filled pen: Before administration, the solution should be inspected visually. The liquid should be clear to opalescent, colourless to pale yellow to pale brown. If the solution is cloudy, discoloured or contains particles, the solution should not be used.
After removing the pre-filled pen from the refrigerator, allow the pen to reach room temperature for at least 30 minutes before injecting Nucala.
Comprehensive instructions for subcutaneous administration of Nucala in a pre-filled pen is provided as follows.
Step by step instructions for using the pre-filled pen: Administer once every four weeks.
Follow these instructions on how to use the pre-filled pen. Failure to follow these instructions may affect proper function of the pre-filled pen. Training on how to use the pre-filled pen should be obtained. Nucala pre-filled pen is for use under the skin only (subcutaneous).
Before using Nucala: The pre-filled pen should be used only once and then discarded.
Do not share Nucala pre-filled pen with another person.
Do not shake the pen.
Do not use the pen if dropped onto a hard surface.
Do not use the pen if it appears damaged.
Do not remove the needle cap until just before the injection.
Prepare: 1. Get ready what to be needed: Find a comfortable, well-lit and clean surface. Make sure to have the following within reach: Nucala pre-filled pen, Alcohol wipe (not included), Gauze pad or cotton wool ball (not included).
Do not perform the injection if all these are not available.
2. Take out the pre-filled pen: Take the carton out of the refrigerator.
Remove the tray from the carton.
Peel back the film cover from the tray.
Holding the middle of the pen, carefully take it out of the tray.
Place the pen on a clean, flat surface, at room temperature, away from direct sunlight and out of the reach of children.
Do not remove the needle cap at this stage.
3. Inspect and wait 30 minutes before use: Check the expiry date on the label of the pen.
Look in the inspection window to check that the liquid is clear (free from cloudiness or particles) and colourless to pale yellow to pale brown.
It is normal to see one or more air bubbles.
Wait 30 minutes (and no more than 8 hours) before use.
Do not warm the pen in a microwave, hot water, or direct sunlight.
Do not inject if the solution looks cloudy or discoloured, or has particles.
Do not use the pen if left out of the carton for more than 8 hours.
Do not remove the needle cap during this step.
4. Choose injection site: Nucala can be injected into the thighs or abdomen.
If someone else gives the patient the injection, they can also use the upper arm.
Do not inject where the skin is bruised, tender, red or hard.
Do not inject within 5 cm of the navel (belly button).
5. Clean the injection site: Wash hands with soap and water.
Clean the injection site by wiping the skin with an alcohol wipe and allowing the skin to air dry.
Do not touch the injection site again until finished with the injection.
Inject: 6. Remove the clear needle cap: Remove the clear needle cap from the pen by firmly pulling it straight off.
Do not worry if a drop of liquid is seen at the end of the needle. This is normal.
Inject straight after removing the needle cap, and always within 5 minutes.
Do not touch the yellow needle guard with fingers. This could activate the pen too soon and may cause a needle injury.
After removal, do not put the needle cap back onto the pen, as it may accidentally start the injection.
7. Start the injection: Hold the pen with its inspection window facing towards the patient, so it can be seen, and with the yellow needle guard facing down.
Place the pen straight onto the injection site with the yellow needle guard flat against the surface of the skin.
To start the injection, push the pen down all the way and keep it held down against the skin. The yellow needle guard will slide up into the pen.
The 1st "click" should be heard to tell that the injection has started.
The yellow indicator will move down through the inspection window as dose is being received.
Do not lift the pen from the skin at this stage, as that may mean the full dose of medicine is not received. The injection may take up to 15 seconds to complete.
Do not use the pen if the yellow needle guard doesn't slide up as described. Dispose of it, and start again with a new pen.
8. Hold the pen in place to complete the injection: Continue to hold the pen down until the 2nd "click" is heard, and the stopper and yellow indicator have stopped moving and fill the inspection window.
Continue to hold the pen in place while counting to 5. Then lift the pen away from the skin.
If the 2nd "click" is not heard: Check that the inspection window is filled with the yellow indicator.
If not sure, hold the pen down for another 15 seconds to make sure the injection is complete.
Do not lift the pen until complete injection is assured.
A small drop of blood at the injection site may be noticed. This is normal. Press a cotton wool ball or gauze on the area for a few moments if necessary. Do not rub the injection site.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Vial: Do not freeze.
Keep the vial in the outer carton in order to protect from light.
Pre-filled pen: If necessary, the Nucala pre-filled pen can be removed from the refrigerator and kept in the unopened pack for up to 7 days at room temperature (up to 30°C), when protected from light. The pack should be discarded if left out of the refrigerator for more than 7 days.
The pre-filled pen must be administered within 8 hours once the pack is opened. The pack should be discarded if not administered within 8 hours.
Shelf life: Vial: After reconstitution: Chemical and physical stability of the reconstituted medicinal product have been demonstrated for 8 hours when stored below 30°C.
From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of user.
ATC Classification
R03DX09 - mepolizumab ; Belongs to the class of other systemic drugs used in the treatment of obstructive airway diseases.
Presentation/Packing
Powd for soln for inj (vial) 100 mg (lyophilised white powder) x 1's. Soln for inj (pre-filled pen) 100 mg/mL (clear to opalescent, colourless to pale yellow to pale brown solution) x 1's.
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