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 [ see Description
].
Spread of Toxin Effect
Post-marketing safety data from DYSPORT™ and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and 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 related to spread of toxin effects. The risk of the symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.
Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia
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 effects occur, additional respiratory muscles may be involved [ see Warnings and Precautions
].
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.
Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been post-marketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients.
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 [ see Warnings and Precautions, Adverse Reactions, Clinical Pharmacology
].
Facial Anatomy in the Treatment of Glabellar Lines
Caution should be exercised when administering DYSPORT™ to patients with surgical alterations to the facial anatomy, excessive weakness or atrophy in the target muscle(s), marked facial asymmetry, inflammation at the injection site(s), ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin [ see Dosage and Administration (2.2.3)
] or the inability to substantially lessen glabellar lines by physically spreading them apart [ see Clinical Studies
].
Do not exceed the recommended dosage and frequency of administration of DYSPORT™. In clinical trials, subjects who received a higher dose of DYSPORT™ had an increased incidence of eyelid ptosis.
Pre-existing Neuromuscular Disorders
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g., 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™ [ see Adverse Reactions
].
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) is also 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.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C
DYSPORT™ produced embryo-fetal toxicity when given to pregnant rats at doses similar to or greater than the maximum recommended human dose (MRHD) of 1000 Units on a body weight (Units/kg) basis.
In an embryo-fetal development study in which pregnant rats received intramuscular injections daily (2.2, 6.6, or 22 Units/kg on gestation days 6 through 17) or intermittently (44 Units/kg on gestation days 6 and 12 only) during organogenesis, increased early embryonic death was observed with both dosing schedules. The no-effect dose for embryo-fetal developmental toxicity was 2.2 Units/kg (one-tenth the MRHD on a body weight basis). Maternal toxicity was seen at 22 and 44 Units/kg. In a pre-and post-natal development study in which female rats received 6 weekly intramuscular injections (4.4, 11.1, 22.2, or 44 Units/kg) beginning on day 6 of gestation and continuing through parturition to weaning, an increase in stillbirths was observed at the highest dose, which was maternally toxic. The no-effect dose for pre- and post-natal developmental toxicity was 22.2 Units/kg (approximately equal to the MRHD on a body weight basis).
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.
Nursing Mothers
It is not known whether DYSPORT™ is excreted in human milk.
Pediatric Use
Cervical Dystonia
Safety and effectiveness in pediatric patients have not been established [ see Warnings and Precautions
].
Glabellar Lines
DYSPORT™ is not recommended for use in pediatric patients less than 18 years of age.
Geriatric Use
Cervical Dystonia
There were insufficient numbers of patients aged 65 and over in the clinical studies to determine whether they respond differently than younger patients. 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 [ see Dosage and Administration (2.1.1)
].
Glabellar Lines
Of the total number of subjects in the placebo-controlled clinical studies of DYSPORT™, 8 (1%) were 65 and over. Efficacy was not observed in subjects 65 years and over [ see Clinical Studies
]. For the entire safety database of geriatric subjects, although there was no increase in the incidence of eyelid ptosis, geriatric subjects did have an increase in the number of ocular adverse events compared to younger subjects (11% vs. 5%) [ see Dosage and Administration
].
Ethnic Groups
Exploratory analyses in trials for glabellar lines in African-American subjects with Fitzpatrick skin types IV, V, or VI and in Hispanic subjects suggested that response rates at Day 30 were comparable to and no worse than the overall population.
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