Nusinersen - Spinraza- @- (Dec 2016) - Musculoskeletal
Drug Name:Nusinersen - Spinraza- @- (Dec 2016) - Musculoskeletal
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
SPINRAZA safely and effectively.
See full prescribing information for SPINRAZA.
SPINRAZA (nusinersen) injection, for intrathecal use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
SPINRAZA is a survival motor neuron-2 (SMN2)-directed antisense
oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA)
in pediatric and adult patients
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
22. Spinraza Nusinersen 12/23/2016
To treat children and adults with spiral muscular atrophy (SMA)
Press release
Drug Trials Snapshot
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions that occurred in at least 20%
of SPINRAZA-treated patients and occurred at least 5% more frequently
than in control patients were lower respiratory infection, upper respiratory
infection, and constipation
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Thrombocytopenia and Coagulation Abnormalities:
Increased risk for bleeding complications; testing required at baseline
and before each dose
Renal Toxicity:
Quantitative spot urine protein testing required at baseline and
prior to each dose
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
SPINRAZA is a survival motor neuron-2 (SMN2)-directed antisense
oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA)
in pediatric and adult patients
DOSAGE AND ADMINISTRATION
SPINRAZA is administered intrathecally
Dosing Information
The recommended dosage is 12 mg (5 mL) per administration
Initiate SPINRAZA treatment with 4 loading doses;
the first three loading doses should be administered at 14-day intervals;
the 4th loading dose should be administered 30 days after the 3rd dose;
a maintenance dose should be administered once every 4 months thereafter
Important
Preparation and Administration Instructions
Allow to warm to room temperature prior to administration
Administer within 4 hours of removal from vial
Prior to administration, remove 5 mL of cerebrospinal fluid
Administer as intrathecal bolus injection over 1 to 3 minutes
Laboratory Testing and Monitoring to Assess Safety
At baseline and prior to each dose, obtain a platelet count, coagulation
laboratory testing, and quantitative spot urine protein testing
DOSAGE FORMS AND STRENGTHS
Injection: 12 mg/5 mL (2.4 mg/mL) in a single-dose vial
Patient Information:
Storage and Handling
Store in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton
to protect from light. Do not freeze.
SPINRAZA should be protected from light and kept in the original carton
until time of use.If no refrigeration is available, SPINRAZA may be stored
in its original carton, protected from light at or below 30oC (86oF) for up to 14 days.
Prior to administration, unopened vials of SPINRAZA can be removed from
and returned to the refrigerator, if necessary. If removed from the original carton,
the total combined time out of refrigeration should not exceed 30 hours at a
temperature that does not exceed 25oC (77oF).
PATIENT COUNSELING INFORMATION
Thrombocytopenia and Coagulation Abnormalities Inform patients and
caregivers that SPINRAZA could increase the risk of bleeding.
Inform patients and caregivers of the importance of obtaining blood laboratory
testing at baseline and prior to each dose to monitor for signs of increased
potential for bleeding.
Instruct patients and caregivers to seek medical attention if unexpected bleeding
occurs
Renal Toxicity
Inform patients and caregivers that SPINRAZA could cause renal toxicity.
Inform patients and caregivers of the importance of obtaining urine testing
at baseline and prior to each dose to monitor for signs of potential
renal toxicity
Manufactured for:
Biogen Inc.
Cambridge, MA 02142
SPINRAZA is a trademark of Biogen.
© 2016 Biogen
Reference
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
SPINRAZA is an antisense oligonucleotide (ASO) designed to treat SMA caused
by mutations in chromosome 5q that lead to SMN protein deficiency
Using in vitro assays and studies in transgenic animal models of SMA,
SPINRAZA was shown to increase exon 7 inclusion in SMN2 messenger
ribonucleic acid (mRNA) transcripts and production of full-length SMN protein.
2. Pharmacokinetics
Absorption
Intrathecal injection of SPINRAZA into the cerebrospinal fluid (CSF) allows
nusinersen to be distributed from the CSF to the target central nervous system
(CNS) tissues. Following intrathecal administration, trough plasma concentrations
of nusinersen were relatively low, compared to the trough CSF concentration.
Median plasma Tmax values ranged from 1.7 to 6.0 hours.
Mean plasma Cmax and AUC values increased approximately dose-proportionally
up to a dose of 12 mg.
Metabolism
Nusinersen is metabolized via exonuclease (3’-and 5’)-mediated hydrolysis
and is not a substrate for, or inhibitor or inducer of CYP450 enzymes.
Excretion
The mean terminal elimination half-life is estimated to be 135 to 177 days in CSF,
and 63 to 87 days in plasma. The primary route of elimination is likely by urinary
excretion for nusinersen and its chain-shortened metabolites.
At 24 hours, only 0.5% of the administered dose was recovered in the urine.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the
use of SPINRAZA in pregnant women. No adverse effects on embryofetal
development were observed in animal studies in which nusinersen was
administered by subcutaneous injection to mice and rabbits during pregnancy
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.
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 nusinersen in human milk, the effects on
the breastfed infant, or the effects of the drug on milk production.
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for SPINRAZA and any potential adverse
effects on the breastfed infant from SPINRAZA or from the underlying
maternal condition.
3.Pediatric Use
The safety and effectiveness of SPINRAZA in pediatric patients from newborn
to 17 years have been established.
4. Geriatric Use
SMA is largely a disease of children and young adults; therefore, there is no
geriatric experience with SPINRAZA.
