Mepolizumab- Nucala -@-(Nov 2015)- Respiratory
Drug Name:Mepolizumab- Nucala -@-(Nov 2015)- Respiratory
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Formal drug interaction trials have not been performed with NUCALA.
Indication:
NUCALA (mepolizumab) for injection, for subcutaneous use
Initial U.S. Approval: 2015
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.33
Drug Name - Mepolizumab
Active Ingredient- Nucala
Date of approval - 11/04/2015
FDA-approved use - For use with Asthma Medicines for the maintenance
treatment of asthma in patients age 12 years and older
Approved by US FDA on 11/04/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
NUCALA is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa)
indicated for add-on maintenance treatment of patients with severe asthma
aged 12 years and older, and with an eosinophilic phenotype.
Limitations of Use:
Not for treatment of other eosinophilic conditions.
Not for relief of acute bronchospasm or status asthmaticus.
Adverse Reaction:
Most common adverse reactions (incidence greater than or equal to 5%)
include headache, injection site reaction, back pain, and fatigue.
Contra-Indications:
CONTRAINDICATIONS
History of hypersensitivity to mepolizumab or excipients in the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension,
urticaria, rash) have occurred after administration of NUCALA.
Discontinue NUCALA in the event of a hypersensitivity reaction.
Do not use to treat acute bronchospasm or status asthmaticus.
Herpes zoster infections have occurred in patients receiving NUCALA.
Consider varicella vaccination if medically appropriate prior to starting
therapy with NUCALA.
Do not discontinue systemic or inhaled corticosteroids abruptly upon
initiation of therapy with NUCALA. Decrease corticosteroids gradually,
if appropriate.
Treat patients with pre-existing helminth infections before therapy with NUCALA.
If patients become infected while receiving treatment with NUCALA and
do not respond to anti-helminth treatment, discontinue NUCALA until
parasitic infection resolves.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
NUCALA is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa)
indicated for add-on maintenance treatment of patients with severe asthma
aged 12 years and older, and with an eosinophilic phenotype.
Limitations of Use:
Not for treatment of other eosinophilic conditions.
Not for relief of acute bronchospasm or status asthmaticus.
DOSAGE AND ADMINISTRATION
100mg administered subcutaneously once every 4 weeks.
See Full Prescribing Information for instructions on reconstitution
of lyophilized powder, and preparation and administration of the injection.
DOSAGE FORMS AND STRENGTHS
For injection: 100 mg of lyophilized powder in a single-dose vial for
reconstitution.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions
Inform patients that hypersensitivity reactions (e.g., angioedema, bronchospasm,
hypotension, urticaria, rash) have occurred after administration of NUCALA.
Instruct patients to contact their physicians if such reactions occur.
Not for Acute Symptoms or Deteriorating Disease
Inform patients that NUCALA does not treat acute asthma symptoms or acute
exacerbations. Inform patients to seek medical advice if their asthma remains
uncontrolled or worsens after initiation of treatment with NUCALA.
Opportunistic Infections: Herpes Zoster
Inform patients that herpes zoster infections have occurred in patients receiving
NUCALA and where medically appropriate, inform patients varicella vaccination
should be considered before starting treatment with NUCALA.
Reduction of Corticosteroid Dosage
Inform patients to not discontinue systemic or inhaled corticosteroids except
under the direct supervision of a physician. Inform patients that reduction in
corticosteroid dose may be associated with systemic withdrawal symptoms
and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Pregnancy Exposure Registry
Inform women there is a pregnancy exposure registry that monitors pregnancy
outcomes in women exposed to NUCALA during pregnancy and that they can
enroll in the Pregnancy Exposure Registry by calling 1-877-311-8972 or by
visiting www.mothertobaby.org/asthma
Manufactured by GlaxoSmithKline LLC Philadelphia, PA 19112
U.S. License Number 1727
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Mepolizumab is an interleukin-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.
2. Pharmacokinetics
Following SC dosing in subjects with asthma, mepolizumab exhibited approximately
dose-proportional pharmacokinetics over a dose range of 12.5 to 250 mg.
Absorption
Following 100-mg SC administration in the upper arm of subjects with asthma,
the bioavailability of mepolizumab was estimated to be approximately 80%.
Following repeat SC administration once every 4 weeks, there was approximately
a 2-fold accumulation at steady state.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women
exposed to NUCALA during pregnancy. Healthcare providers can enroll patients
or encourage patients to enroll themselves by calling 1-877-311-8972 or
visiting www.mothertobaby.org/asthma.
Risk Summary
The data on pregnancy exposure from the clinical trials 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;
2. Lactation
Risk Summary
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.
Mepolizumab was present in the milk of cynomolgus monkeys postpartum
following dosing during pregnancy
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for NUCALA and any potential adverse effects
on the breastfed infant from mepolizumab or from the underlying maternal condition.
3.Pediatric Use
The safety and efficacy in pediatric patients younger than 12 years have not been
established. A total of 28 adolescents aged 12 to 17 years with asthma were
enrolled in the phase 3 studies. Of these, 25 were enrolled in the 32-week
exacerbation trial and had a mean age of 14.8 years.
4 Geriatric Use
Clinical trials of NUCALA did not include sufficient numbers of subjects aged 65 years
and older that received NUCALA (n = 38) to determine whether they respond
differently from younger subjects.
Other reported clinical experience has not identified differences in responses
between the elderly and younger patients.
In general the dose selection of elderly,starts at the low end of the dosing range,
reflecting the greater frequency of decreased hepatic, renal, or cardiac function
and of concomitant disease or other drug therapy.
Based on available data, no adjustment of the dosage of NUCALA in geriatric
patients is necessary, but greater sensitivity in some older individuals
cannot be ruled out.
