Cerliponase alfa- Brineura-@- (Apr 2017)- Neurological disorders
Drug Name:Cerliponase alfa- Brineura-@- (Apr 2017)- Neurological disorders
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 15
Name of the Drug- Brineura
Active Ingredient- Cerliponase Alfa Pharmacological Classification-
To treat specific form of Batten disease
Date of Approval- 04-27-2017
(Ref- FDA approved List 2017) HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
BRINEURA safely and effectively. See full prescribing information for
BRINEURA.
BRINEURA (cerliponase alfa) injection, for intraventricular use
Initial U.S. Approval: 2017
INDICATIONS AND USAGE
Brineura is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to
slow the loss of ambulation in symptomatic pediatric patients 3 years of age
and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also
known as tripeptidyl peptidase 1 (TPP1) deficiency.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (.8%) are: pyrexia, ECG abnormalities,
decreased CSF protein, vomiting, seizures, hypersensitivity, increased CSF
protein, hematoma, headache, irritability, pleocytosis, device-related infection,
bradycardia, feeling jittery, and hypotension.
Contra-Indications:
CONTRAINDICATIONS
Acute intraventricular access device-related complications (e.g., leakage,
device failure, or device-related infection).
Patients with ventriculoperitoneal shunts.
WARNINGS AND PRECAUTIONS
Intraventricular Access Device-Related Complications:
Inspect the scalp for skin integrity and for signs of intraventricular
access device leakage.
Do not administer if there are signs of device leakage or infection.
Routinely send CSF samples for testing to detect subclinical devicerelated
infections.
Cardiovascular Adverse Reactions:
Monitor vital signs before, during,and post-infusion.
Monitor Electrocardiogram (ECG) in patients with a history of bradycardia,
conduction disorder, or with structural heart disease, during the infusion.
In patients without cardiac abnormalities, perform regular 12-lead
ECG evaluations every 6 months.
Hypersensitivity Reactions:
Observe patients during and after the infusion.
If a severe hypersensitivity reaction occurs, immediately stop
the infusion and initiate appropriate treatment.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
Brineura is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to
slow the loss of ambulation in symptomatic pediatric patients 3 years of age
and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also
known as tripeptidyl peptidase 1 (TPP1) deficiency.
DOSAGE AND ADMINISTRATION
Aseptic technique must be strictly observed during preparation and
administration. Brineura should be administered by, or under the direction
of a physician knowledgeable in intraventricular administration.
Brineura is administered to the cerebrospinal fluid (CSF) by infusion
via a surgically implanted reservoir and catheter.
Pre-treatment of patients with antihistamines with or without antipyretics
or corticosteroids is recommended 30 to 60 minutes prior to the start of
infusion.
The recommended dosage is 300 mg administered once every other week
as an intraventricular infusion followed by infusion of Intraventricular
Electrolytes over approximately 4.5 hours.
For complete information on preparation, specific intraventricular access
device for use, and administration, see the full prescribing information.
DOSAGE FORMS AND STRENGTHS
Injection: Brineura 150 mg/5 mL (30 mg/mL) solution, two single-dose vials
per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a
single-dose vial.
Patient Information:
PATIENT COUNSELING INFORMATION
Intraventricular Access Device-Related Complications
Advise patients and caregivers of the risk of device-related infections.
If any signs of infection are present, instruct patients to immediately
contact their healthcare provider.
Cardiovascular Adverse Reactions
Advise patients and caregivers that hypotension and/or bradycardia
may occur during and following the infusion of Brineura.
Instruct patients immediately to contact their healthcare provider if these
reactions occur.
Hypersensitivity Reactions
Advise patients and caregivers that hypersensitivity reactions related
to Brineura treatment, including fever, vomiting, and irritability may occur.
Due to the potential for anaphylaxis, inform patients and caregivers
of the signs and symptoms of anaphylaxis, and instruct them to seek
immediate medical care should signs and symptoms occur.
Manufactured by:
BioMarin Pharmaceutical Inc.
Novato, CA 94949
US License Number 1649
1-866-906-6100 (phone)
:
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
CLN2 disease is a neurodegenerative disease caused by deficiency
of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1), which
catabolizes polypeptides in the CNS. TPP1 has no known substrate specificity.
Deficiency in TPP1 activity results in the accumulation of lysosomal storage
materials normally metabolized by this enzyme in the central nervous
system (CNS), leading to progressive decline in motor function.
2. Pharmacokinetics
The pharmacokinetics of cerliponase alfa were evaluated in patients with
CLN2 disease who received intraventricular infusions of 30 mg (0.1 times
the approved recommended dosage), 100 mg (approximately
0.3 times the approved recommended dosage), and 300 mg
over approximately 4.5 hours once every other week.
Cerliponase alfa CSF exposure following the initial single dose
administration of Brineura increased less than proportionally
across doses of 30 mg, 100 mg, and 300 mg.
There was no apparent accumulation of cerliponase alfa in CSF
or plasma when Brineura was administered at a dose of 300 mg
once every other week.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available data on Brineura use in pregnant women
to inform a drug-associated risk of pregnancy-related outcomes.
Animal reproduction studies have not been conducted using
cerliponase alfa
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.
2. Lactation
Risk Summary
There are no data on the presence of cerliponase alfa in human milk,
the effects on the breastfed child, or the effects on milk production.
The lack of clinical data during lactation precludes a clear determination
of the risk of Brineura to an infant during lactation; therefore,
the development and health benefits of breastfeeding should be considered
along with the mother’s clinical need for Brineura and any potential
adverse effects on the breastfed infant from Brineura or from the underlying
maternal condition.
3.Pediatric Use
Safety and effectiveness of Brineura have been established in pediatric
patients 3 years of age and older.
Pediatric use of Brineura to slow the loss of ambulation in symptomatic
pediatric patients 3 years of age and older with late infantile neuronal
ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl
peptidase 1 (TPP1) deficiency, is supported by a non-randomized
single-arm dose escalation clinical study with extension in patients
with CLN2 disease and compared to untreated patients with CLN2
disease from an independent natural history cohort.
Safety and effectiveness in patients less than 3 years of age have
not been established.
