Daclizumab - Zinbryta -@-(May 2016)- Skeletal disorders
Drug Name:Daclizumab - Zinbryta -@-(May 2016)- Skeletal disorders
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
Hepatotoxic Drugs: Evaluate potential for increased risk of hepatotoxicity
with concomitant use
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
10. Zinbryta Daclizumab 5/27/2016 To treat multiple sclerosis Approved by FDA on 5/27/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
hese highlights do not include all the information needed to use
ZINBRYTA. safely and effectively.
See full prescribing information for ZINBRYTA.
ZINBRYTA (daclizumab) injection, for subcutaneous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
ZINBRYTA is an interleukin-2 receptor blocking antibody indicated for the
treatment of adult patients with relapsing forms of multiple sclerosis (MS).
Because of its safety profile, the use of ZINBRYTA should generally be
reserved for patients who have had an inadequate response to two or more
drugs indicated for the treatment of MS.
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions (incidence =5% and =2% higher
incidence than comparator) reported for ZINBRYTA were nasopharyngitis,
upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal
pain, bronchitis, eczema and lymphadenopathy compared with AVONEX; and
upper respiratory tract infection, depression, rash, pharyngitis, and increased
alanine aminotransferase (ALT) compared with placebo.
Contra-Indications:
CONTRAINDICATIONS
Pre-existing hepatic disease or hepatic impairment, including ALT or AST
at least 2 times the ULN.
History of autoimmune hepatitis or other autoimmune condition involving
the liver.
History of hypersensitivity to daclizumab or any other component of the
formulation.
WARNING:
HEPATIC INJURY INCLUDING AUTOIMMUNE
HEPATITIS and OTHER IMMUNE-MEDIATED DISORDERS
See full prescribing information for complete boxed warning.
Hepatic Injury Including Autoimmune Hepatitis
ZINBRYTA can cause severe liver injury including life-threatening events,
liver failure, and autoimmune hepatitis. Obtain transaminase and bilirubin
levels before initiation of ZINBRYTA.
Monitor and evaluate transaminase and bilirubin levels monthly and up
to 6 months after the last dose.
ZINBRYTA is contraindicated in patients with pre-existing hepatic disease
or hepatic impairment.
Other Immune-Mediated Disorders
Immune-mediated disorders including skin reactions, lymphadenopathy,
non-infectious colitis, and other immune-mediated disorders can occur
with ZINBRYTA .
These conditions may require treatment with systemic corticosteroids
or immunosuppressive medication.
ZINBRYTA is available only through a restricted distribution program
called the ZINBRYTA REMS Program .
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:
Risk of anaphylaxis and angioedema.
Discontinue and do not re-start ZINBRYTA if anaphylaxis or other allergic
reactions occur .
Infections: Increased risk of infections.
If serious infection develops, consider withholding ZINBRYTA until infection
resolves
Depression and Suicide:
Advise patients to immediately report symptoms of depression and/or
suicidal ideation to their health care provider.
Consider discontinuation if severe depression and/or suicidal ideation occur
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ZINBRYTA is an interleukin-2 receptor blocking antibody indicated for the
treatment of adult patients with relapsing forms of multiple sclerosis (MS).
Because of its safety profile, the use of ZINBRYTA should generally be
reserved for patients who have had an inadequate response to two or more
drugs indicated for the treatment of MS.
DOSAGE AND ADMINISTRATION
Recommended dosage: 150 milligrams once monthly
For subcutaneous use only .
Train patients in the proper technique for self-administration.
Conduct laboratory tests at baseline and at periodic intervals to monitor for
early signs of potentially serious adverse reactions..
DOSAGE FORMS AND STRENGTHS
Injection: 150 mg/mL solution in a single-dose prefilled syringe.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling
(Medication Guide and Instructions for Use).
Hepatic Injury
Inform the patient of the risk of severe hepatic injury associated with
ZINBRYTA.
Advise patients of the symptoms of hepatic dysfunction, and instruct
patients to report such symptoms to their health care provider immediately.
Discuss with the patient the importance of measuring hepatic laboratory
values and having them evaluated by the health care provider monthly
while taking ZINBRYTA and for up to 6 months after the last dose
of ZINBRYTA.
Discuss with the patient the risk of concomitant use of other hepatotoxic
medications, over the counter medications, herbal products,
or dietary supplements.
Inform the patient that they will be given a ZINBRYTA Patient Wallet Card
that they should carry with them at all times. This card describes symptoms
which, if experienced, should prompt the patient to immediately seek
medical evaluation.
Advise the patient to show the ZINBRYTA Patient Wallet Card to other
treating health care providers.
Immune-Mediated Disorders
Advise patients that ZINBRYTA can cause their immune system to attack
healthy cells in their body and that this can affect any organ system.
Skin Reactions
Advise patients that ZINBRYTA can cause dermatologic reactions
that can range from mild rashes to serious reactions that could require
treatment with other medications or result in hospitalization.
Instruct patients to seek immediate medical attention if dermatologic
reactions occur
Lymphadenopathy
Inform patients that ZINBRYTA may cause lymphadenopathy that can
range from mild events that can resolve on their own to serious
lymphadenopathy that may require invasive procedures for diagnosis.
Inform patients of the symptoms and instruct patients to contact their health
care provider if they develop lymphadenopathy.
Non-Infectious Colitis
Inform patients that ZINBRYTA may cause gastrointestinal reactions that
may be serious and could require treatment. Advise patients of the symptoms
of colitis and instruct patients to promptly contact their healthcare provider
if they experience these symptoms.
.
ZINBRYTA REMS Program
ZINBRYTA is available only through a restricted program called the
ZINBRYTA REMS Program.
Inform the patient of the following notable requirements:
Patients must enroll in the program and comply with ongoing monitoring
requirements
ZINBRYTA is available only from certified pharmacies participating
in the program. Therefore,provide patients with the telephone number
and website for information on how to obtain the product.
Allergic Reactions and Anaphylaxis
Advise patients of the symptoms of allergic reactions and anaphylaxis,
and instruct patients to seek immediate medical attention if these symptoms
occur.
Risk of Infections
Inform patients that they may be more likely to get infections when taking
ZINBRYTA, and that they should contact their health care provider if they
develop symptoms of infection.
Depression and Suicide
Advise patients of the symptoms of depression and suicidal ideation as
they have occurred with the use of ZINBRYTA and instruct patients to
report symptoms of depression or thoughts of suicide to their health care
provider immediately.
Instructions for Self-Injection Technique and Procedures
Provide appropriate instruction for methods of self-injection, including
careful review of the ZINBRYTA Instructions for Use.
Instruct the patient in the use of aseptic technique when administering
ZINBRYTA.
Inform the patient that a health care provider should show them or their
caregiver how to inject ZINBRYTA before administering the first dose.
Tell the patient not to re-use needles or syringes, and instruct the patient
on safe disposal procedures.
Inform the patient to dispose of used needles and syringes in a
puncture-resistant container.
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
U.S. License # 1697
Distributed by:
AbbVie Inc.
North Chicago, IL 60064
ZINBRYTA is a trademark of Biogen.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
The precise mechanism by which daclizumab exerts therapeutic effects
in multiple sclerosis is unknown but is presumed to involve modulation
of IL-2 mediated activation of lymphocytes through binding to CD25,
a subunit of the high-affinity IL-2 receptor.
2. Pharmacokinetics
The pharmacokinetics of ZINBRYTA are similar for healthy volunteers
and patients with multiple sclerosis (MS).
Absorption
Following a single subcutaneous injection of ZINBRYTA, the maximum
concentration occurred between 5 and 7 days.
At steady state, daclizumab mean maximum serum concentration (Cmax)
was 30 µg/mL, minimum serum concentration (Cmin) was 15 µg/mL,
and area under the serum concentration-time curve over the dosing interval
(AUCtau) values were approximately 640 µg-days per mL.
The absolute bioavailability of 150 mg subcutaneous daclizumab was
approximately 90%.
After administration of ZINBRYTA 150 mg subcutaneously every 4 weeks,
serum daclizumab concentrations reached steady state by the fourth dose.
Daclizumab accumulated to a level approximately 2.5-fold compared
with a single dose.
The coefficient of variation between individual patients was approximately
35-40% for exposure (Cmax and AUC) and 27-51% for clearance
and volume of distribution.
Distribution
In multiple sclerosis patients taking 150 mg subcutaneous doses
of ZINBRYTA every 4 weeks,the estimated steady-state volume of
distribution of daclizumab was approximately 6.34 liters.
Metabolism and Elimination
Because it is a protein, daclizumab is expected to undergo catabolism
to peptides and amino acids in the same manner as endogenous IgG proteins
without renal elimination.
The estimated clearance of daclizumab is 0.212 liters per day with an
elimination half-life of 21 days.
Daclizumab clearance in patients who developed neutralizing antibodies
was 19% higher.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with use
of ZINBRYTA in pregnant women.
Administration of ZINBRYTA to monkeys during gestation resulted in
embryofetal death and reduced fetal growth at maternal exposures greater
than 30 times that expected clinically .
In the U.S. general population, the estimated background risk of major
birth defects and miscarriage in clinically recognized pregnancies
is 2-4% and 15-20%, respectively. The background risk of major birth
defects and miscarriage for the indicated population is unknown.
2. Lactation
Risk Summary
There are no data on the presence of daclizumab in human milk, the effects
on the breastfed child, or the effects of the drug on milk production.
Daclizumab was excreted in the milk of ZINBRYTA-treated monkeys.
The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for ZINBRYTA and any
potential adverse effects on the breastfed child from ZINBRYTA or from
the underlying maternal condition.
3. Pediatric Use
Safety and effectiveness of ZINBRYTA in patients less than 17 years old
have not been established. Use of ZINBRYTA is not recommended in
pediatric patients due to the risks of hepatic injury and immune-mediated
disorders.
4.Geriatric Use
Clinical studies of ZINBRYTA did not include a sufficient number of patients
aged 65 and over to determine whether they respond differently than
younger patients.
5. Hepatic Impairment
Clinical trials did not include patients with ALT or AST more than two times the
ULN. Patients with signs and symptoms of hepatic impairment may be at
increased risk for hepatotoxicity from ZINBRYTA.
