DRUG INTERACTIONS-

Formal drug interaction trials have not been performed with NUCALA.

33/15 PRODUCT DETAILS 

Name of the drug-      NUCALA

Active ingriendents-   Mepolizumab

FDA approved use-    For use with other asthma medicines for the maintenance of                                           asthma in patients age 12 years and older                                                                                                    

 Date of Approval         11/4/2015

HIGHLIGHTS OF PRESCRIBING INFORMATION -

WARNINGS AND PRECAUTIONS -

 These highlights do not include all the information needed to use NUCALA® safely and effectively. See full prescribing information for NUCALA. NUCALA (mepolizumab) for injection, for subcutaneous use

Initial U.S. Approval: 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

. (1) Limitations of Use: • Not for treatment of other eosinophilic conditions. (1) • Not for relief of acute bronchospasm or status asthmaticus

CONTRA-INDICATIONS-

 History of hypersensitivity to mepolizumab or excipients in the formulation. (4)

ADVERSE REACTIONS-

 Most common adverse reactions (incidence greater than or equal to 5%) include headache, injection site reaction, back pain, and fatigue.

CONTRA-INDICATIONS-

 History of hypersensitivity to mepolizumab or excipients in the formulation.sEN

Sensitivity  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.

DOSAGE AND ADMINISTRATION -

 100 mg administered subcutaneously once every 4 weeks. (2) • 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 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 orby visiting www.mothertobaby.org/asthma 

NUCALA is a registered trademark of the GSK group of companies

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.

2. Pharmacodynamics-                                                                                                      The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in subjects with asthma and blood eosinophil levels greater than 200 cells/mcL

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.

Distribution-                                                                                                                   The population central volume of distribution of mepolizumab in patients with asthma is estimated to be 3.6 L for a 70-kg individual.

Metabolism -                                                                                                          Mepolizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.

Elimination -                                                                                                                  Following SC administration of mepolizumab, the mean terminal half-life (t1/2) ranged from 16 to 22 days. The population apparent systemic clearance of mepolizumab in patients with asthma is estimated to be 0.28 L/day for a 70-kg individual.

Specific Populations Race and Gender:                                                                           A population pharmacokinetics analysis indicated there was no significant effect of race and gender on mepolizumab clearance.

Age: A population pharmacokinetics analysis of subjects ranging in age from 12 to 82 years indicated there was no significant effect of age on mepolizumab clearance.

Renal Impairment:                                                                                                              No clinical trials have been conducted to investigate the effect of renal impairment on the pharmacokinetics of mepolizumab. Based on population pharmacokinetic analyses, mepolizumab clearance was comparable between subjects with creatinine clearance values between 50 and 80 mL/min and patients with normal renal function.

Drug-Drug Interactions:                                                                                                    No formal drug interaction studies have been conducted with NUCALA. In the population pharmacokinetics analyses of the phase 3 studies, there was no evidence of an effect of commonly coadministered small molecule drugs on mepolizumab exposure. 

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.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-                                                                                  Associated Maternal and/or Embryo-Fetal Risk: In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.

The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

Data Animal Data:                                                                                                             In a prenatal and postnatal development study, pregnant cynomolgus monkeys received mepolizumab from gestation days 20 to 140 at doses that produced exposures up to approximately 30 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 100 mg/kg once every 4 weeks).

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 [see Use in Specific Populations (8.1)].

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 (Trial 2) 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.

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.

 OVERDOSAGE-                                                                                                          Single doses of up to 1,500 mg have been administered intravenously to subjects in a clinical trial 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.