Idarucizumab - Praxbind -@- (Oct 2015) - Anticoagulant
Drug Name:Idarucizumab - Praxbind -@- (Oct 2015) - Anticoagulant
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
PRAXBIND® (idarucizumab) injection, for intravenous 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.29
Drug Name - Idarucizumab
Active Ingredient- Praxbind
Date of approval - 10/16/2015
FDA-approved use - For use in patient who are taking anticoagulant
Pradaxa ( Dabigatran) during emergency situations
when there is a need to reverse Pradaxas blood
thinning effects
Approved by US FDA on 10/16/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
In healthy volunteers, the most frequently reported adverse reactions in greater
than or equal to 5% of subjects treated with idarucizumab was headache.
In patients, the most frequently reported adverse reactions in greater than or
equal to 5% of patients treated with idarucizumab were hypokalemia,
delirium, constipation, pyrexia, and pneumonia.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Thromboembolic Risk: Reversing dabigatran therapy exposes patients
to the thrombotic risk of their underlying disease.
Resume anticoagulant therapy as soon as medically appropriate.
Re-elevation of Coagulation Parameters: In patients with elevated
coagulation parameters and reappearance of clinically relevant bleeding
or requiring a second emergency surgery/urgent procedure, an additional
5 g dose of PRAXBIND may be considered.
Hypersensitivity reactions: Discontinue administration and evaluate.
Risks of Serious Adverse Reactions in Patients with Hereditary Fructose
Intolerance due to Sorbitol Excipient: Patients with hereditary fructose
intolerance may be at risk of adverse reactions.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
PRAXBIND is a humanized monoclonal antibody fragment (Fab) indicated in
patients treated with Pradaxa® when reversal of the anticoagulant effects
of dabigatran is needeDdFor emergency surgery/urgent procedures
In life-threatening or uncontrolled bleeding
This indication is approved under accelerated approval based on a reduction
in unbound dabigatran and normalization of coagulation parameters in healthy
volunteers
Continued approval for this indication may be contingent upon the results of
an ongoing cohort case series study.
DOSAGE AND ADMINISTRATION
For intravenous use only.
The recommended dose of PRAXBIND is 5 g, provided as two separate vials
each containing 2.5 g/50 mL idarucizumab.
There is limited data to support administration of an additional 5 g of PRAXBIND.
DOSAGE FORMS AND STRENGTHS
Injection: 2.5 g/50 mL solution in a single-use vial
Patient Information:
PATIENT COUNSELING INFORMATION
Thromboembolic Risk Inform patients that reversing dabigatran therapy exposes
them to the thromboembolic risk of their underlying disease.
To reduce this risk, resumption of anticoagulant therapy should be considered
as soon as the patient is sufficiently stable
Recurrence of Bleeding
Inform patients to get immediate medical attention for any signs or symptoms of bleeding
Hypersensitivity Reactions
Inform patients of signs and symptoms of allergic hypersensitivity reactions such as
anaphylactoid reactions that may be experienced during or after injection of
PRAXBIND
Risk of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance
due to Sorbitol Excipient Inform patients with hereditary fructose intolerance (HFI)
that PRAXBIND contains sorbitol.
Parenteral administration of sorbitol in patients who have HFI has been associated
with reports of hypoglycemia, hypophosphatemia, metabolic acidosis, increase
in uric acid, acute liver failure with breakdown of excretory and synthetic function,
and death and may occur during or after injection of PR
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal
antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites
with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing
their anticoagulant effect.
2. Pharmacokinetics
There were no obvious differences in the idarucizumab plasma concentration time
profiles when idarucizumab was administered alone or after pretreatment with
dabigatran. A dose-dependent increase in the fraction of unchanged idarucizumab
excreted in urine was observed.
Distribution
Idarucizumab exhibited multiphasic disposition kinetics and limited extravascular
distribution. Following the intravenous infusion of a 5 g dose, the geometric mean
volume of distribution at steady state (Vss) was 8.9 L (geometric coefficient of
variation (gCV 24.8%)).
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no adequate and well-controlled studies of PRAXBIND in pregnant women
to inform on associated risks.
Animal reproductive and development studies have not been conducted with
idarucizumab. It is also not known whether PRAXBIND can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity.
PRAXBIND should be given to a pregnant woman only if clearly needed.
The background risk of major birth defects and miscarriage for the indicated population
is unknown. 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.
2. Lactation
Risk Summary
There are no data on the effects of PRAXBIND on the breastfed child or on milk production.
It is not known whether idarucizumab is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
PRAXBIND is administered to a nursing woman.
The developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for PRAXBIND and any potential adverse effects
on the breastfed child from PRAXBIND or from the underlying maternal condition.
3. Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
4. Geriatric Use
A total of 111 (90%) patients treated with idarucizumab in the case series trial were
65 years of age and older, and 74 (60%) were 75 years of age and older.
No overall differences in safety or effectiveness were observed between these
subjects and younger subjects, and other reported clinical experience has not
identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
Renal impairment did not impact the reversal effect of idarucizumab [see Clinical Pharmacology (12.3)]. No dose adjustment is required in renally impaired patients.
8.7 Hepatic Impairment
No formal studies o
