Ipsen Biopharmaceuticals, Inc., is pleased to share some exciting news about Dysport® (abobotulinumtoxinA) for injection. On July 29, 2016, the FDA-approved Dysport® for the treatment of lower limb spasticity in pediatric patients 2 years of age and older.1 Dysport® is the first and only botulinum toxin (BoNT) that is approved for this condition.
Dysport®, and all botulinum toxin products, have a Boxed Warning that states the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Those symptoms include swallowing and breathing difficulties that can be life threatening. Please scroll down below for additional Important Safety Information.
The approval is based on a randomized, multicenter, double-blind, placebo-controlled, international Phase III pivotal study in 235 pediatric patients (158 received Dysport® and 77 received placebo; intent to treat population) aged 2 to 17 years with lower limb spasticity due to cerebral palsy causing dynamic equinus foot deformity.1 The trial included patients who were botulinum toxin naïve or previously treated with a botulinum toxin more than six months before study entry. Patients were randomized (1:1:1) to Dysport® 10 Units/kg/leg, Dysport®15 Units/kg/leg or placebo injected into the gastrocnemius-soleus muscle complex located in the calf.
Those treated with Dysport® showed statistically significant improvement in co-primary efficacy assessments: mean change from baseline in Modified Ashworth Scale (MAS) in ankle plantar flexor muscle tone and mean Physician’s Global Assessment (PGA) response to treatment score at Week 4 (primary endpoint) and at Week 12.1 The most common adverse reactions (≥10% of patients in any group and greater than placebo) in pediatric patients with lower limb spasticity for Dysport® 10 Units/kg, 15 Units/kg, 20 Units/kg, or 30 Units/kg; and placebo, respectively, were: nasopharyngitis (9%, 12%,16%, 10%, 5%), upper respiratory tract infection (9%, 20%, 5%, 10%, 13%), influenza (0%, 10%, 14%, 3%, 8%) and pharyngitis (5%, 0%,11%, 3%, 8%), cough (7%, 6%, 14%, 10%, 6%), and pyrexia (7%, 12%, 8%, 7%, 5%).
The Dysport® total dose per treatment session must not exceed 15 Units/kg for unilateral lower limb injections, 30 Units/kg for bilateral injections, or 1000 units, whichever is lower. Re-treatment, based on return of clinical symptoms, should not occur in intervals of less than 12 weeks.
The degree and pattern of muscle spasticity and overall clinical benefit at the time of re-injection may necessitate alterations in the dose of DYSPORT® and muscles to be injected.
Now, for the first time, pediatric patients 2 years of age and older with lower limb spasticity—and the parents who care for them—have an FDA-approved BoNT treatment option.1
To learn more about Dysport® go to www.dysport.com.
To register for Dysport® Faculty bureau-led injection training, visit http://www.dysport.com. The C.L.I.M.B.® program includes a full complement of dosing, dilution, and injection education:
- One-on-one, hands-on mentorship in your office
- The opportunity to observe faculty using Dysport® at another facility
- Live group training speaker programs with a simulator demonstration or live WebEx
- Dosing, reconstitution, and base injection simulator in-services
- Online education and simulator app
For additional support services for your office and your patients, visit www.IpsenCares.com.
For medical information support you may contact Ipsen Medical Information
at (855) 463-5127.
INDICATION
- Dysport® is indicated for the treatment of lower limb spasticity in pediatric patients 2 years of age and older.
The safety and effectiveness of Dysport® injected into upper limb muscles or proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established.
Safety and effectiveness in pediatric patients with lower limb spasticity below 2 years of age have not been evaluated.
Safety and effectiveness in pediatric patients with cervical dystonia or upper limb spasticity have not been established.
The safety and effectiveness of Dysport® in the treatment of lower limb spasticity in adult patients has not been demonstrated.
IMPORTANT SAFETY INFORMATION
Warning: Distant Spread of Toxin Effect
Postmarketing reports indicate that the effects of Dysport® and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including upper limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to lower than the maximum recommended total dose.
Contraindications
Dysport® is contraindicated in patients with known hypersensitivity to any botulinum toxin preparation or to any of the components; or in the presence of infection at the proposed injection site(s); or in patients known to be allergic to cow's milk protein.
Warnings and Precautions
Lack of Interchangeability between Botulinum Toxin Products.
The potency Units of Dysport® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products, and, therefore, units of biological activity of Dysport® cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method.
Dysphagia and Breathing Difficulties
Treatment with Dysport® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant side effects occur, additional respiratory muscles may be involved (see Boxed Warning). Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several weeks, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin.
Pre-existing Neuromuscular Disorders
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of Dysport®.
Human Albumin
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been reported for albumin.
Intradermal Immune Reaction
The possibility of an immune reaction when injected intradermally is unknown. The safety of Dysport® for the treatment of hyperhidrosis has not been established. Dysport® is approved only for intramuscular injection.
Adverse Reactions
Most common adverse reactions (≥10% in any group and greater than placebo) in pediatric patients with lower limb spasticity for Dysport® 10 Units/kg, 15 Units/kg, 20 Units/kg, or 30 Units/kg; and Placebo, respectively, were: upper respiratory tract infection (9%, 20%, 5%, 10%, 13%), nasopharyngitis (9%, 12%, 16%, 10%, 5%), influenza (0%, 10%, 14%, 3%, 8%), pharyngitis (5%, 0%, 11%, 3%, 8%), cough (7%, 6%, 14%, 10%, 6%), and pyrexia (7%, 12%, 8%, 7%, 5%).
Drug Interactions
Co-administration of Dysport® and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of botulinum toxin may be potentiated. Use of anticholinergic drugs after administration of Dysport® may potentiate systemic anticholinergic effects such as blurred vision. The effect of administering different botulinum neurotoxins at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by another administration of botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of Dysport®.
Use in Pregnancy
Based on animal data Dysport® may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Dysport® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pediatric Use
Based on animal data Dysport® may cause atrophy of injected and adjacent muscles; decreased bone growth, length, and mineral content; delayed sexual maturation; and decreased fertility.
Geriatric Use
In general, elderly patients should be observed to evaluate their tolerability of Dysport®, due to the greater frequency of concomitant disease and other drug therapy.
To report SUSPECTED ADVERSE REACTIONS or product complaints, contact Ipsen at 1-855-463-5127. You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Full Prescribing Information including Boxed WARNING regarding distant spread of toxin effect, also available at www.dysport.com.
References: 1. Dysport® (abobotulinumtoxinA). [Prescribing Information]. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc; July 2016. 2. McGuire JR. Epidemiology of spasticity in the adult and child. In: Brashear A, Elovic E, eds. Spasticity: Diagnosis and Management. New York, NY: Demos Medical Publishing; 2016:5-16.
Dysport® (abobotulinumtoxinA) for injection, for intramuscular use 300- and 500-unit vials.
Dysport® is a registered trademark of Ipsen Biopharm Limited.
©2016 Ipsen Biopharmaceuticals, Inc. October 2016. DYS-US-001274