Asfotase alfa- Strensiq- @- (Oct 2015) Metabolic Disorder
Drug Name:Asfotase alfa- Strensiq- @- (Oct 2015) Metabolic Disorder
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
STRENSIQ (asfotase alfa) injection, for subcutaneous use
Initial U.S. Approval: Pending
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.32
Drug Name - Asfotase Alfa
Active Ingredient- Strensiq
Date of approval - 10/23/2015
FDA-approved use - To treat perinatal, infantile and juvenile- onset
hyphosphatasia (HPP)
Approved by US FDA on 10/23/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
STRENSIQ is a tissue nonspecific alkaline phosphatase
indicated for the treatment of patients with perinatal/infantile-and
juvenile-onset hypophosphatasia (HPP).
Adverse Reaction:
Most common adverse reactions (. 10%) are injection site reactions,
lipodystrophy, ectopic calcifications and hypersensitivity reactions.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions: Monitor and if a severe reaction occurs,
discontinue treatment and initiate appropriate medical treatment.
.
Lipodystrophy: Localized reactions were reported after several months
of treatment; follow proper injection technique and rotate injection sites.
.
Ectopic Calcifications (eye and kidneys): Monitor using ophthalmologic
examinations and renal ultrasounds at baseline and periodically
during treatment.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
STRENSIQ is a tissue nonspecific alkaline phosphatase
indicated for the treatment of patients with perinatal/infantile-and
juvenile-onset hypophosphatasia (HPP).
DOSAGE AND ADMINISTRATION
Perinatal/Infantile-Onset HPP
Recommended dosage regimen is 2 mg/kg administered subcutaneously
three times per week, or 1 mg/kg administered six times per week.
Injection site reactions may limit the tolerability of the six times per week regimen.
The dose may be increased to 3 mg/kg three times per week for
insufficient efficacy. Juvenile-Onset HPP
.
Recommended dosage regimen is 2 mg/kg administered subcutaneously
three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.
.
The dose may be increased to 3 mg/kg three times per week for
insufficient efficacy. Juvenile-Onset HPP (2.2)
Injection site reactions may limit the tolerability of the six times per week regimen.
Preparation and Weight-Based Dosing
.
Caution: Do not use the 80 mg/0.8 mL vial in pediatric patients weighing
less than 40 kg because the systemic asfotase alfa exposure achieved
with the 80 mg/0.8 mL vial (higher concentration) is lower than that achieved
with the other strength vials (lower concentration).
A lower exposure may not be adequate for this subgroup of patients.
.
For subcutaneous injection only.
Rotate injection sites. Do not administer to areas that are reddened,
inflamed or swollen.
DOSAGE FORMS AND STRENGTHS
Injection: 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, or 80 mg/0.8 mL solution
in single-use vials.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling
Instructions for Use.
Advise patients or caregivers of the following:
Preparation
When preparing a volume for injection greater than 1 mL, split the volume
equally between two syringes, and administer two injections.
When administering the two injections, use two separate injection sites.
Inspect the solution in the vial(s) for particulate matter and discoloration.
Assemble injection supplies. Administer STRENSIQ using sterile disposable
syringes and injection needles. The syringes should be of small enough volume
that the prescribed dose can be withdrawn from the vial with reasonable
accuracy. Always use a new syringe and needle.
Remove vial cap, aseptically prepare the vial and insert the syringe into the vial
to withdraw the prescribed dose for administration.
Remove any air bubbles in the syringe and verify the correct dose. Administration
Administer STRENSIQ within 1 hour upon removal of the vial(s) from
refrigeration.
Rotate the injection site to reduce the risk of lipohypertrophy and injection
site atrophy.
Do NOT administer injections in areas that are reddened, inflamed, or swollen.
Inject STRENSIQ subcutaneously into the determined site and properly
dispose of the needle.
STRENSIQ vials are single use only. Discard any unused product.
Hypersensitivity Reactions
Reactions related to administration and injection may occur during and
after STRENSIQ treatment. Inform patients of the signs and symptoms
of hypersensitivity reactions, and have them seek immediate medical care
should signs and symptoms occur.
Lipodystrophy
Lipohypertrophy (enlargement or thickening of tissue) and localized atrophy
(depression in the skin) have been reported at injection sites after several
months. Follow proper injection technique and rotate injection sites.
Manufactured by: Baxter Oncology GmbH Halle/Westfalen Germany
Manufactured for: Janssen Products, LP Horsham, PA
© Janssen Products, LP. 2015
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
HPP is caused by a deficiency in TNSALP enzyme activity, which leads to elevations
in several TNSALP substrates, including inorganic pyrophosphate (PPi).
Elevated extracellular levels of PPi block hydroxyapatite crystal growth which
inhibits bone mineralization and causes an accumulation of unmineralized
bone matrix which manifests as rickets and bone deformation in infants and
children and as osteomalacia (softening of bones) once growth plates close,
along with muscle weakness. Replacement of the TNSALP enzyme upon
STRENSIQ treatment reduces the enzyme substrate levels.
2. Pharmacokinetics
Based on data in 38 HPP patients, the pharmacokinetics of asfotase alfa exhibit
dose proportionality across the dose range of 0.3 mg/kg to 3 mg/kg and appear
to be time-independent. Steady state exposure was achieved as early as three
weeks after the administration of the first dose.
The elimination half-life following subcutaneous administration was approximately 5 days.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
There are no available human data on STRENSIQ use in pregnant women to inform
a drug associated risk.
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 asfotase alfa in human milk, the effects on the
breastfed infant, or the effects on milk production. The developmental and health
benefits of breastfeeding should be considered along with the mother’s clinical
need for STRENSIQ and any potential adverse effects on the breastfed infant
from asfotase alfa or from the underlying maternal condition.
3. Pediatric Use
The safety and effectiveness of STRENSIQ have been established in pediatric
patients. Use of STRENSIQ is based on 4 prospective, open-label clinical trials
conducted in 99 adult and pediatric patients with perinatal/infantile-onset o
juvenile-onset HPP. The majority of patients were pediatric patients
1 day to 16 years of age (89/99 [90%])
4. Geriatric Use
No patients with perinatal/infantile-or juvenile-onset HPP aged 65 years were enrolled in clinical trials of STRENSIQ. Therefore, there is no information available to determine whether patients aged 65 years and over respond differently from younger patients.
