Dr. Ahmed Nucala Mepolizumab has been approved by the FDA since 2015 for the treatment of severe asthma who were non-responsive to conventional treatment. It has also been approved for the treatment of Churg-Strauss syndrome, also called Granulomatosis with polyangiitis.
Nucala (Mepolizumab), like Dupixent (Dupilumab), is a novel class of biological medicine that has been prepared by recombinant DNA technology.
It is a human monoclonal antibody of the IgG1 Kappa subtype that is directed at blocking the IL-5 receptor complex [Ref]
Nucala (Mepolizumab) Uses:
It is indicated in the treatment of adults and children above 6 years of age with eosinophilic asthma. It should not be used to treat the acute exacerbations of asthma.
Nucala has also been approved for the treatment of Churg-Strauss syndrome (Granulomatosis with polyangiitis).
It is also used to treat chronic rhinosinusitis with nasal polyps in patients who are at least 18 years of age.
Nucala has also been approved by the FDA for the treatment of hypereosinophilic syndrome that has been present for 6 months or more with any known cause [Ref]
Nucala Mepolizumab Dose and Dosage Strength:
Nucala Mepolizumab is available in a dose of 100 mg per injection or vial.
The drug is administered subcutaneously (into the skin).
Nucala Dose in Asthma:
Nucala (Mepolizumab) is administered every month (at four weeks intervals) in patients with severe asthma.
It may be administered in the anterior tummy (3 – 5 cm away from the navel), upper arms, or thighs.
Nucala Dose in Granulomatosis with Polyangiitis (Churg-Strauss syndrome):
The recommended dose in patients with Churg-Strauss syndrome (Granulomatosis with polyangiitis) is 300 mg monthly (at four weeks intervals).
Three injections should be separately administered at least 5 cm apart (as 3 prefilled autoinjections, vials, or syringes).
How to Administer Nucala?
Nucala should be administered by a healthcare provider who is experienced and can manage any untoward side effects or hypersensitivity reactions that might occur.
How to reconstitute Nucala in a vial?
Add 1.2 ml of sterile water to the vial using a 21 gauge needle and 2 to 3 ml syringe. The final solution will be equal to 100 mg/ml.
Inject the water straight into the vial and then swirl the vial for about 15 seconds. It may take five minutes or more for the powder to completely dissolve.
Avoid shaking the solution as this might result in foaming and precipitation of the medicine.
When using a swirler, do not exceed the 450 rpm speed and limit the time to 10 minutes at most. Swirling the vial at 1000 rpm for a maximum of 5 minutes is also acceptable.
After reconstitution, inspect the solution, it should be free of any particulate matter, may contain small bubbles, and should be clear white to slightly yellow.
Cloudy solutions or those that contain particulate matter should not be administered.
If there is a delay in administering the reconstituted solution, store it below 30 F but do not freeze it. Discard the solution if not used within 8 hours of reconstitution.
How to administer injection via syringe?
Use a 1 ml polypropylene syringe that is fitted with a 21 to 27 g (0.5 inch or 13 mm) needle.
Take one ml of the drug that is equivalent to 100 mg/ml and inject it into the skin of the abdomen, thighs, or upper arms.
Do not shake the vial before taking the one ml solution from the vial.
How to administer prefilled autoinjector or prefilled syringe?
Nucala autoinjector may be administered by the patient himself/ herself after proper training and education about the injection technique.
Before injecting it, keep the autoinjector pen for 30 minutes at room temperature. Do not warm using other methods.
The injection should not be administered after the expiry date, or if the content/ solution of the injection is cloudy or discolored.
If you drop the injection on a hard surface or if it is broken, avoid injecting it.
Inject Nucala (Mepolizumab) into the anterior aspect of the tummy 5 cm away from the navel or into the skin of the thighs. It may also be administered into the upper arms by a healthcare provider.
If more than 100 mg dose is administered, as in patients treated for Churg-Strauss syndrome (granulomatosis with polyangiitis), each 100 mg injection should be administered into three different skin areas placed at least 5 cm apart.
Avoid injecting into the skin that is red, tender, bruised, or infected. If a dose is missed, inject it as soon as possible. You can reschedule the dose based on your last dose administered.
Nucala Mepolizumab Dose in patients with kidney and liver diseases:
Since Nucala (Mepolizumab) is metabolized by proteolytic enzymatic degradation, there is no need to adjust the dose in patients with liver or renal impairment.
The manufacturer has not recommended any dosage adjustment in patients with hepatic or kidney impairment.
Nucala Mepolizumab Dose in Pregnancy and Breastfeeding:
Mepolizumab is a human IgG monoclonal antibody that can cross the placental barrier. Fetal exposure is likely, especially during the second and third trimesters.
Data regarding its use in human pregnancies is limited, however, in animal studies, no fetal adverse reactions were observed.
Asthma exacerbations may be associated with adverse fetal outcomes. Optimizing treatment during and before a planned pregnancy is recommended.
Nucala Mepolizumab is also excreted in human breast milk. Its effects on neonates and nursing children are not known.
The manufacturer recommends weighing the clinical benefits and possible risks associated with Nucala treatment before recommending it to lactating women.
Use in extremes of ages:
Mepolizumab has not been studied in children who were younger than 12 years of age and adults older than 65 years of age.
It should not be advised to children who are younger than 12 years of age. In aged people, it should be advised with caution.
Nucala Mepolizumab Contraindications and Warnings:
Nucala is not indicated in patients who are allergic to the drug or any component of its formulations. Allergic reactions may occur in the form of mild skin rashes to severe life-threatening anaphylaxis.
It may occur within hours of injecting it, but occasionally may be delayed and occur after days of administering the drug.
Warnings and Precautions:
Acute severe asthma:
Nucala should not be used to treat the acute symptoms of asthma. It is not indicated for acute severe asthma or asthma exacerbations.
Patients who have worsened symptoms while on Nucala Mepoilzumab treatment must consult their healthcare providers.
Herpes Zoster:
The risk of herpes zoster infection is increased with Nucala use. Patients may need to be vaccinated before starting the treatment.
Reducing Corticosteroid Dose:
Sometimes patients tend to reduce their oral and inhaled corticosteroid dosage abruptly. This may lead to acute severe asthma exacerbation.
This may also unmask the symptoms of an underlying other autoimmune disorder that could coexist with asthma such as eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome) or ABPA (allergic bronchopulmonary aspergillosis)
Worms infestation (helminthic infections):
Eosinophils are important cells that are involved in clearing worms and helminthic infections from our bodies.
Since Nucala depletes eosinophils, the immune response against helminthic infections is impaired.
It is recommended to treat any underlying helminthic infection before starting the patient on Nucala treatment.
In addition, patients on Mepolizumab treatment who develop a helminthic infection that is resistant to treatment should temporarily discontinue Mepolizumab treatment.
Nucala Mepolizumab Side effects:
Injection site reactions are common. These may manifest as redness, swelling, pain, induration, and itching at the site of the infection.
The following side effects were commonly observed:
Side effects of Nucala | Nucala (100 mg S/C) | Placebo |
| Headache | 19% | 18% |
| Injection Site reaction | 8% | 3% |
| Back pain | 5% | 4% |
| Fatigue | 5% | 4% |
| Influenza | 3% | 2% |
| Urinary Tract Infection | 3% | 2% |
| Abdominal Pain | 3% | 2% |
| Pruritis | 3% | 2% |
| Eczema | 3% | <1% |
| Muscle spasm | 3% | <1% |
Less common side effects include:
- Abdominal pain
- Allergic rhinitis, nasal congestion, nasopharyngitis, and
- Asthenia, fatigue, and lethargy
- bronchitis
- dizziness
- cystitis
- Shortness of breath
- Ear infection
- Gastroenteritis
- Body aches and pains especially myalgias or muscle pain
- Fever
- Toothache
- Viral infections
- nausea and vomiting
Long-term side effects of Nucala Mepolizumab:
Herpes Zoster was observed later months after the administration of the drug.
Nucala Mepolizumab Monitoring Parameters:
Patients treated with Mepolizumab should be monitored for improvement in their asthma symptoms and if the requirement for short-acting reliever medicine has increased or decreased.
The FEV1 should be monitored along with the side effects of the drug (mentioned above).
Mechanism of action (MOA) of Mepolizumab:
Mepolizumab blocks the action of IL-5. It blocks the binding of IL-5 to the alpha chain of the IL-5 receptor complex that is expressed on the surface of Eosinophils.
Blocking the binding of IL-5 and IL-5 receptor complex reduces the production and survival of Eosinophils.
Eosinophils play an important role in the pathogenesis of asthma and allergic conditions, Mepolizumab is one kind of effective treatment in patients who have moderate to severe eosinophilic asthma.
By blocking IL-5, Mepolizumab inhibits the growth, differentiation, recruitment, and survival of eosinophils.
Absorption:
When administered subcutaneously, it has a bioavailability of about 80%.
Terminal Half-life:
The mean terminal half-life of Mepolizumab is about 16 to 22 hours.
Metabolism:
It is metabolized by proteolytic degradation into amino acids.
Brands and cost of Mepolizumab Injections:
A single dose pre-filled autoinjector or a single-dose prefilled glass syringe costs $ 3239 USD to $ 3394 USD.
The cost amounts to $ 19,434 – $ 20,364 for a total of six months. One year of Nucala will cost double this price.
With the Medicare Insurance plan, the cost is cut by 80%. Hence you can get a one-year supply @ about $ 7773 USD or less.
