Included as part of the PRECAUTIONS section.
Spread Of Toxin Effect
Postmarketing safety data from
MYOBLOC 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 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.
Lack Of Interchangeability
Between Botulinum Toxin Products
The potency units of MYOBLOC
are specific to the preparation and biological activity assay method utilized.
Due to differences in the aspects of this assay such as the vehicle, dilution
scheme, and laboratory protocols for various potency assays, potency units are
not interchangeable with other preparations of botulinum toxin products and,
therefore, units of biological activity of MYOBLOC cannot be compared to or
converted into units of any other botulinum toxin products assessed with any
other specific assay method [see DESCRIPTION].
reactions have been reported with botulinum toxin products. Angioedema,
urticaria, and rash have occurred with MYOBLOC treatment [see ADVERSE
REACTIONS]. Hypersensitivity reactions can also include anaphylaxis, serum
sickness, soft tissue edema, and dyspnea. If serious and/or immediate
hypersensitivity reactions occur, discontinue further injection of MYOBLOC and
institute appropriate medical therapy immediately. The use of MYOBLOC in
patients with a known hypersensitivity to any botulinum neurotoxin or to any of
the excipients (human albumin, sucrose), could lead to a life-threatening
allergic reaction [see CONTRAINDICATIONS, ADVERSE REACTIONS].
Dysphagia And Breathing
Treatment with MYOBLOC 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.
Deaths as a complication of severe dysphagia have been
reported after treatment with botulinum toxin. Dysphagia may persist for
several months 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
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 postmarketing 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 ADVERSE
Individuals with peripheral motor neuropathic diseases,
amyotrophic lateral sclerosis, or neuromuscular junctional 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 MYOBLOC [see ADVERSE
Human Albumin And Transmission Of Viral Diseases
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 and
variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for
transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists,
the risk of transmission would be considered extremely remote. No cases of
transmission of viral diseases, CJD, or vCJD have ever been identified for
licensed albumin or albumin contained in other licensed products.
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide).
Swallowing, Speaking, Or Breathing
Difficulties Or Other Unusual Symptoms
Advise patients to inform their
healthcare provider if they develop any unusual symptoms, including difficulty
with swallowing, speaking or breathing, or if any existing symptom worsens [see
BOX WARNING and WARNINGS AND PRECAUTIONS]. Inform patients of the
risk of aspiration.
Ability To Operate Machinery Or
Counsel patients that if loss
of strength, muscle weakness, or impaired vision occur, they should avoid
driving a car or engaging in other potentially hazardous activities.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No long-term carcinogenicity studies in animals have been
No genetic toxicology studies have been conducted.
Impairment Of Fertility
Intramuscular administration of MYOBLOC (0, 300, 1000, or
3000 Units/kg/day) to male and female rats prior to and throughout the mating
period and continuing in females to gestation day 6 resulted in decreases in
implantation sites and viable fetuses at the high dose of 3000 Units/kg/day,
which was associated with maternal toxicity. The no-effect dose for
reproductive toxicity (1000 Units/kg/day) is 12 times the maximum recommended
human dose for cervical dystonia (5000 Units) on a body weight (Units/kg)
Use In Specific Populations
There are no adequate data on the developmental risks
associated with the use of MYOBLOC in pregnant women. No developmental toxicity
was observed in pregnant rats administered MYOBLOC by intramuscular injection
during gestation and lactation, at doses producing maternal toxicity.
In the U.S. general population, the 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.
When MYOBLOC was administered by intramuscular injection
to pregnant rats (0, 300, 1000, or 3000 Units/kg/day) or rabbits (0, 0.03, 0.1,
0.3, or 1.0 Units/kg/day) throughout gestation, no adverse effects on
embryofetal development were observed. The highest dose tested in rat, which
was associated with maternal toxicity, was 36 times the maximum recommended
human dose (MRHD) for cervical dystonia (5000 Units) on a body weight
The highest dose tested in rabbit was substantially less
than the MRHD for cervical dystonia on a Units/kg basis; maternal toxicity was
observed at all but the lowest dose tested.
There are no data on the presence of MYOBLOC 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 motherÃ¢â¬™s clinical need for MYOBLOC and any potential adverse
effects on the breastfed infant from MYOBLOC or from the underlying maternal
Safety and effectiveness in pediatric patients have not
In the controlled studies for MYOBLOC in patients with
cervical dystonia, 152 (75%) were under the age of 65, and 52 (26%) were 65
years of age or older [see Clinical Studies]. For these age groups, the
most frequently reported adverse reactions occurred at similar rates in both
age groups. Efficacy results did not suggest any large differences between
these age groups.
Very few patients age 75 or older were enrolled;
therefore, no conclusions regarding the safety and efficacy of MYOBLOC within
this age group can be determined.
Of the 166 MYOBLOC-treated patients in the
placebo-controlled studies for treatment of chronic sialorrhea [see Clinical
Studies], 105 (63%) were 65 years of age or older, and 43 (26%) were 75
years of age or older. No overall differences in safety or effectiveness were
observed between patients over 65 years of age and younger patients, but
greater sensitivity of some older patients cannot be ruled out.