Myobloc

Muscle Relaxants, Other Neuromuscular Blockers

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Use each vial for 1 session and 1 patient only; discard any remaining solution.
If needed, the injection may be diluted with 0.9% Sodium Chloride Injection.
Once diluted or opened, use within 4 hours because the product does not contain a preservative.[29875]

Administer dose intramuscularly divided among affected muscles.[29875]

Intraglandular injection:
Locate the salivary glands using ultrasound imaging or surface anatomical landmarks.
Use a suitable sterile needle (e.g. 30-gauge, 0.5 inch).
Inject into the parotid and submandibular salivary glands on both sides.[29875]

torticollis / Delayed / 5.9-5.9
respiratory arrest / Rapid / Incidence not known
distant spread of toxin effects / Early / Incidence not known
angioedema / Rapid / Incidence not known
visual impairment / Early / Incidence not known

dysphagia / Delayed / 0-19.1
antibody formation / Delayed / 10.0-18.0
myasthenia / Delayed / 4.9-4.9
dyspnea / Early / 2.0
confusion / Early / 2.0
migraine / Early / 2.0
hyperesthesia / Delayed / 2.0
peripheral vasodilation / Rapid / 2.0
hypercholesterolemia / Delayed / 2.0
peripheral edema / Delayed / 2.0
edema / Delayed / 2.0
amblyopia / Delayed / 2.0
cystitis / Delayed / 2.0
chest pain (unspecified) / Early / 2.0
constipation / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
dysphonia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
urinary incontinence / Early / Incidence not known

xerostomia / Early / 14.0-39.0
infection / Delayed / 2.0-16.2
injection site reaction / Rapid / 14.2-14.2
musculoskeletal pain / Early / 5.4-14.2
headache / Early / 12.7-12.7
influenza / Delayed / 8.3-8.3
dental caries / Delayed / 0-7.0
dyspepsia / Early / 5.9-5.9
cough / Delayed / 5.9-5.9
back pain / Delayed / 5.4-5.4
dizziness / Early / 4.4-4.4
arthralgia / Delayed / 3.9-3.9
rhinitis / Early / 3.4-3.4
asthenia / Delayed / 3.4-3.4
weakness / Early / 3.4-3.4
drowsiness / Early / 2.0
vertigo / Early / 2.0
anxiety / Delayed / 2.0
tremor / Early / 2.0
pruritus / Rapid / 2.0
ecchymosis / Delayed / 2.0
tinnitus / Delayed / 2.0
dysgeusia / Early / 2.0
chills / Rapid / 2.0
fever / Early / 2.0
malaise / Early / 2.0
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
ptosis / Delayed / Incidence not known
diplopia / Early / Incidence not known
xerophthalmia / Early / Incidence not known

There have been postmarketing reports of the distant spread of toxin effects that have resulted in symptoms suggestive of systemic botulism (including asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, swallowing problems, dysphonia, dysarthria, urinary incontinence and breathing difficulties) after the use of botulinum toxins types A and B. These effects have been seen in patients who received the medication for a variety of conditions and a wide range of doses; however, the majority have occurred in children treated for cerebral palsy-associated limb spasticity. Several of these pediatric patients required the placement of feeding tubes and/or mechanical ventilation, and some cases were fatal. Adult cases have also been reported; however, none required mechanical ventilation or resulted in death. These adverse effects have occurred as early as one day and as late as several weeks after treatment. Patients and caregivers should be able to identify the signs and symptoms of systemic effects after receiving an injection of a botulinum toxin, and they should seek immediate medical attention if they have worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness. RimabotulinumtoxinB is not approved for dermatologic or cosmetic indications in the United States. The risk of distant spread of botulinum toxin after dermatologic use is not known. No definitive serious adverse events associated with dermatologic use have been identified.

Myobloc

Rx

Botulinum toxin used for treating cervical dystonia or chronic sialorrhea in adults
Found effective in patients with cervical dystonia who do and do not respond to onabotulinumtoxinA (botulinum toxin type A)
Distant spread of toxin effect from the injection site may occur which can cause swallowing or breathing difficulties

The recommended initial dose in patients with a prior history of tolerating botulinum toxin injections is 2500 to 5000 units divided among affected muscles. Those without prior history of tolerating botulinum toxin should receive a lower initial dose. The duration of effect observed in studies was between 12 and 16 weeks at doses of 5000 units or 10,000 units.

The recommended initial dosage is 1,500 to 3,500 units divided among the parotid and submandibular glands. Between 500 to 1,500 units per parotid gland and 250 units per submandibular gland may be given. The typical duration of effect of each treatment is up to 3 months. Frequency of treatment should be guided by clinical response but should generally be no more frequent than every 12 weeks.[29875]

No dosage adjustment needed.

No dosage adjustment needed.

Amikacin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Anticholinergics: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Aspirin, ASA; Carisoprodol: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Atracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Atropine; Difenoxin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Baclofen: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Belladonna; Opium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Benztropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Capreomycin: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
Capsaicin; Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Carisoprodol: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Chlordiazepoxide; Clidinium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Chlorzoxazone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Cisatracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Colistin: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Cyclobenzaprine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Dantrolene: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Dicyclomine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Diphenoxylate; Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Flavoxate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Gentamicin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Homatropine; Hydrocodone: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Indacaterol; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Methscopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Mivacurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Neomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, neomycin oral and topical products are not well absorbed systemically; interactions are not expected.
Neostigmine; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Neuromuscular blockers: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Oxybutynin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Pancuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Paromomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, paromomycin is not well absorbed following oral administration; interactions are not expected.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Propantheline: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Rocuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Skeletal Muscle Relaxants: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Solifenacin: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins.
Streptomycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Succinylcholine: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
Tobramycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
Trihexyphenidyl: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Trospium: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins.
Vecuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.

Myobloc Intramuscular Inj Sol: 1mL, 5000U
Myobloc Intramuscular Sol: 0.5mL, 1mL, 2500U, 5000U

Maximum dosage is not well defined; dosage is dependent upon treatment effect and indication.

Maximum dosage is not well defined; dosage is dependent upon treatment effect and indication.

Safe and effective use has not been established.

Safe and effective use has not been established.

RimabotulinumtoxinB blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering nerve terminals, and inhibiting the release of acetylcholine. Specifically, the process involves 3 stages: 1) heavy chain mediated neurospecific binding of the toxin, 2) internalization of the toxin by receptor-mediated endocytosis, and 3) ATP and pH dependent translocation of the light chain to the neuronal cytosol where it acts as a zinc-dependent endoprotease cleaving polypeptides essential for neurotransmitter release. RimabotulinumtoxinB has been shown to specifically cleave synaptic vesical associated membrane protein (VAMP, also known as synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane, a key step to neurotransmitter release.

RimabotulinumtoxinB is administered by local intramuscular injection. Patients who respond to therapy should notice an effect within 4 weeks. The duration of effect observed in studies was between 12 and 16 weeks at doses of 5000 Units or 10,000 Units.

Measurable concentrations of the toxin are not expected to be present in the peripheral blood following IM injection at the recommended doses. The recommended quantities of neurotoxin administered at each treatment session are not expected to result in systemic, overt distant clinical effects (e.g., muscle weakness) in patients without other neuromuscular dysfunction. However, sub-clinical systemic effects have been shown by single-fiber electromyography after IM doses of botulinum toxins appropriate to produce clinically observable local muscle weakness.

There are no adequate data on the developmental risk associated with rimabotulinumtoxinB use during human pregnancy. No developmental toxicity was observed in the offspring of pregnant rats given rimabotulinumtoxinB during gestation and lactation at doses that produced maternal toxicity. The highest dose tested in rats that was associated with maternal toxicity was 36 times the maximum recommended human dose (MRHD) for cervical dystonia (5,000 units) on a body weight (units/kg) basis. In rabbits, maternal toxicity occurred at doses less than the MRHD for cervical dystonia on a body weight basis.[29875]

There are no data on the presence of rimabotulinumtoxinB in human milk, the effects on the breast-fed infant, or the effects on milk production. RimabotulinumtoxinB is not detectable systemically after intramuscular use, thus excretion into breast milk is considered unlikely. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.[29875]