Dupilumab - Dupixent-@- (2017)- Dermatological
Drug Name:Dupilumab - Dupixent-@- (2017)- Dermatological
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:
DRUG INTERACTIONS
Live Vaccines: Avoid use of live vaccines with DUPIXENT.
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 11
Name of the Drug- Dupixent
Active Ingredient- Dupilumab Pharmacological Classification-
To treat adults with moderate-to-eczema (atopic dermatitis)
Date of Approval- 03-28-2017
(Ref- FDA approved List 2017) HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
DUPIXENT safely and effectively.
See full prescribing information for DUPIXENT.
DUPIXENT® (dupilumab) injection, for subcutaneous use
Initial U.S. Approval: 2017
NDICATIONS AND USAGE
DUPIXENT is an interleukin-4 receptor alpha antagonist indicated
for the treatment of adult patients with moderate-to-severe atopic
dermatitis whose disease is not adequately controlled with topical
prescription therapies or when those therapies are not advisable.
DUPIXENT can be used with or without topical corticosteroids.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (incidence .1%) are injection site reactions,
conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other
herpes simplex virus infection, and dry eye.
Contra-Indications:
CONTRAINDICATIONS
Known hypersensitivity to DUPIXENT or any of its excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity:
If a systemic hypersensitivity reaction occurs,discontinue DUPIXENT
immediately and initiate appropriate therapy.
Conjunctivitis and Keratitis:
Patients should report new onset or worsening eye symptoms to their
healthcare provider.
Comorbid Asthma:
Advise patients with comorbid asthma not to adjust or stop their asthma
treatment without consultation with their physicians.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
DUPIXENT is an interleukin-4 receptor alpha antagonist indicated
for the treatment of adult patients with moderate-to-severe atopic
dermatitis whose disease is not adequately controlled with topical
prescription therapies or when those therapies are not advisable.
DUPIXENT can be used with or without topical corticosteroids.
DOSAGE AND ADMINISTRATION
Administer by subcutaneous injection.
The recommended dose is an initial dose of 600 mg
(two 300 mg injections in different injection sites), followed by
300 mg given every other week.
DOSAGE FORMS AND STRENGTHS
Injection: 300 mg/2 mL solution in a single-dose pre-filled syringe
with needle shield.
Injection: 300 mg/2 mL solution in a single-dose pre-filled syringe
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patients and/or caregivers to read the FDA-approved patient labeling
(Patient Information and Instructions for Use) before the patient starts using
DUPIXENT and each time the prescription is renewed as there may be new
information they need to know.
Administration Instructions
Provide proper training to patients and/or caregivers on proper subcutaneous
injection technique, including aseptic technique, and the preparation and
administration of DUPIXENT prior to use. Advise patients to follow sharps
disposal recommendations.
Hypersensitivity
Advise patients to discontinue DUPIXENT and to seek immediate medical
attention if they experience any symptoms of systemic hypersensitivity reactions
Conjunctivitis and Keratitis
Advise patients to consult their healthcare provider if new onset or worsening
eye symptoms develop .
Comorbid Asthma
Advise patients with comorbid asthma not to adjust or stop their asthma
treatment without talking to their physicians..
Manufactured by:
Regeneron Pharmaceuticals, Inc.
Tarrytown, NY 10591
U.S. License No. 1760 Marketed by: sanofi-aventis U.S. LLC
(Bridgewater, NJ 08807) and Regeneron Pharmaceuticals, Inc
(Tarrytown, NY 10591)
DUPIXENT® is a registered trademark of Sanofi Biotechnology
© 201X Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC.
All rights reserved. Issue Date: March 2017
Initial U.S. Approval: 2017
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4)
and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rá subunit
shared by the IL-4 and IL-13 receptor complexes.
Dupilumab inhibits IL-4 signaling via the Type I receptor and both IL-4 and
IL-13 signaling through the Type II receptor.
Blocking IL-4Rá with dupilumab inhibits IL-4 and IL-13 cytokine-induced responses
including the release of proinflammatory cytokines, chemokines and IgE.
2. Pharmacodynamics
Consistent with receptor blockade, serum levels of IL-4 and IL-13 were increased
following dupilumab treatment. The relationship between the pharmacodynamic
activity and the mechanism(s) by which dupilumab exerts its clinical effects
is unknown.
3. Pharmacokinetics
Absorption
Following an initial subcutaneous (SC) dose of 600 mg, dupilumab reached
peak mean ±SD concentrations (Cmax) of 70.1±24.1 mcg/mL by approximately
1 week post dose.
Steady-state concentrations were achieved by Week 16 following the
administration of 600 mg starting dose and 300 mg dose either weekly
(twice the recommended dosing frequency) or every other week.
Across clinical trials, the mean ±SD steady-state trough concentrations
ranged from 73.3±40.0 mcg/mL to 79.9±41.4 mcg/mL for 300 mg
administered every 2 weeks and from 173±75.9 mcg/mL to 193±77.0 mcg/mL
for 300 mg administered weekly.
The bioavailability of dupilumab following a SC dose is estimated to be 64%.
Distribution
The estimated total volume of distribution was approximately 4.8±1.3 L.
Elimination
The metabolic pathway of dupilumab has not been characterized.
As a human monoclonal IgG4 antibody, dupilumab is expected to be
degraded into small peptides and amino acids via catabolic pathways
in the same manner as endogenous IgG.
After the last steady-state dose of 300 mg Q2W or 300 mg QW dupilumab,
the median times to non-detectable concentration (<78 ng/mL) are
10 and 13 weeks, respectively.
Dose Linearity
Dupilumab exhibited nonlinear target-mediated pharmacokinetics with
exposures increasing in a greater than dose-proportional manner.
The systemic exposure increased by 30-fold when the dose increased
8-fold following a single dose of dupilumab from 75 mg to 600 mg
(i.e., 0.25times to 2-times the recommended dose).
Weight
Dupilumab trough concentrations were lower in subjects with higher body
weight.
Immunogenicity
Development of antibodies to dupilumab was associated with lower serum
dupilumab concentrations.
A few subjects who had high antibody titers also had no detectable serum
dupilumab concentrations.
Specific Populations
Geriatric Patients
In subjects who are 65 years and older, the mean ±SD steady-state trough
concentrations of dupilumab were 69.4±31.4 mcg/mL and 166±62.3 mcg/mL,
respectively, for 300 mg administered every 2 weeks and weekly.
No dose adjustment in this population is recommended.
Renal or Hepatic Impairment
No formal trial of the effect of hepatic or renal impairment on the
pharmacokinetics of dupilumab was conducted.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available data on DUPIXENT use in pregnant women
to inform any drug associated risk. Human IgG antibodies are known
to cross the placental barrier; therefore, DUPIXENT may be transmitted
from the mother to the developing fetus.
In an enhanced pre-and post-natal developmental study, no adverse
developmental effects were observed in offspring born to pregnant monkeys
after subcutaneous administration of a homologous antibody against
interleukin-4-receptor alpha (IL-4Rá) during organogenesis through parturition
at doses up to 10-times the maximum recommended human dose (MRHD).
The estimated background risk of major birth defects and miscarriage
for the indicated population is unknown. All pregnancies have a background
risk of birth defect, loss or other adverse outcomes.
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.
Data
Animal Data
In an enhanced pre-and post-natal development toxicity study, pregnant
cynomolgus monkeys were administered weekly subcutaneous doses of
homologous antibody against IL-4Rá up to 10 times the MRHD
(on a mg/kg basis of 100 mg/kg/week) from the beginning of
organogenesis to parturition.
No treatment-related adverse effects on embryofetal toxicity or malformations,
or on morphological, functional, or immunological development were observed
in the infants from birth through 6 months of age.
2. Lactation
Risk Summary
There are no data on the presence of dupilumab in human milk, the effects
on the breastfed infant, or the effects on milk production.
Human IgG is known to be present in human milk. The effects of local
gastrointestinal and limited systemic exposure to dupilumab on the
breastfed infant are unknown.
The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for DUPIXENT
and any potential adverse effects on the breastfed child from
DUPIXENT or from the underlying maternal condition.
3. Pediatric Use
Safety and efficacy in pediatric patients (<18 years of age) have not
been established.
4. Geriatric Use
Of the 1472 subjects with atopic dermatitis exposed to DUPIXENT
in a dose-ranging study and placebo-controlled trials, 67 subjects
were 65 years or older. Although no differences in safety or efficacy
were observed between older and younger subjects, the number of
subjects aged 65 and over is not sufficient to determine whether
they respond differently from younger subjects..
OVERDOSE
There is no specific treatment for DUPIXENT overdose.
In the event of overdosage, monitor the patient for any signs or symptoms
of adverse reactions and institute appropriate symptomatic treatment
immediately.
