PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Muscle Relaxants, Other Neuromuscular Blockers

    BOXED WARNING

    Cerebral palsy, children, distant spread of toxin effects

    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.

    DEA CLASS

    Rx

    DESCRIPTION

    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

    COMMON BRAND NAMES

    Myobloc

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia.
    Intramuscular dosage
    Adults

    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.

    For the treatment of chronic sialorrhea.
    Intraglandular dosage
    Adults

    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]

    MAXIMUM DOSAGE

    Adults

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

    Elderly

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

    Adolescents

    Safe and effective use has not been established.

    Children

    Safe and effective use has not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed.

    Renal Impairment

    No dosage adjustment needed.

    ADMINISTRATION

    Injectable Administration

    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]

    Intramuscular Administration

    Administer dose intramuscularly divided among affected muscles.[29875]

    Other Injectable Administration

    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]

    STORAGE

    Myobloc:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Previously sedentary patients who will resume activities after administration of rimabotulinumtoxinB should do so gradually.

    Dysphagia

    Patients with cervical dystonia should be informed of the possibility of experiencing dysphagia, which is typically mild to moderate, but could be severe. In the medical literature, there are reports of rare cases of dysphagia severe enough to warrant the insertion of a gastric feeding tube. Rare consequences of severe dysphagia include aspiration, dyspnea, pneumonia, and the need to reestablish an airway. There are also rare case reports where subsequent to the finding of dysphagia a patient developed aspiration pneumonia and died.

    Amyotrophic lateral sclerosis (ALS), autonomic neuropathy, myasthenia gravis, myopathy, neuromuscular disease

    Use rimabotulinumtoxinB cautiously in patients with myopathy associated with neuromuscular disease (e.g., amyotrophic lateral sclerosis (ALS), motor neuropathy (autonomic neuropathy), myasthenia gravis or Lambert-Eaton syndrome). These patients may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of rimabotulinumtoxinB. Published data report rare cases of extreme sensitivity to the systemic effects of typical clinical doses in patients with known or unrecognized neuromuscular disorders. In some cases, dysphagia lasted months and required placement of a gastric feeding tube. Caution should also be used when excessive muscle weakness or muscle atrophy is present in the target muscle(s).

    Infection, inflammation

    RimabotulinumtoxinB is contraindicated in the presence of infection at the proposed injection site(s), while cautious use is advised in the presence of inflammation at the proposed injection site(s).

    Albumin hypersensitivity

    RimabotulinumtoxinB is contraindicated in individuals with known hypersensitivity to any ingredient in the formulation. Commercial preparations contain albumin and should be used cautiously, if at all, in patients with albumin hypersensitivity.

    Cerebral palsy, children, distant spread of toxin effects

    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.

    Geriatric

    Geriatric patients in clinical studies of rimabotulinumtoxinB experienced the most frequently reported adverse reactions at similar rates as those in younger patients. Efficacy results did not suggest any large differences between elderly and younger patients. For patients >= 75 years, no conclusions regarding the safety and efficacy could be determined because very few patients in this age group were enrolled.

    Pregnancy

    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]

    Breast-feeding

    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]

    Viral infection

    RimabotulinumtoxinB products contain albumin, a derivative of human blood. As with other products derived from or purified with human blood components, the remote possibility of contamination or infection with hepatitis, Creutzfeldt-Jakob disease (CJD), and other bacterial or viral infections exists in patients receiving rimabotulinumtoxinB. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. Botulism toxin should be given only if a benefit is expected. All infections thought by a physician to have been possibly transmitted by this medication should be reported to the manufacturer. Prior to therapy initiation, discuss the risks and benefits of this product with the patient and/or the health care surrogate of the patient.

    Respiratory insufficiency

    Additional caution and monitoring may be needed in patients with respiratory insufficiency treated with rimabotulinumtoxinB. 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.

    Driving or operating machinery

    Caution all patients to avoid driving or operating machinery if they experience a loss of strength, muscle weakness, blurred vision, or drooping eyelids as a result of rimabotulinumtoxinB therapy.

    Surgery

    As with other botulinum toxin products, administer rimabotulinumtoxinB with caution in patients with a history of surgery in the treatment area as this may alter drug distribution within the injected muscles and thus alter the intended effect. Patients should be instructed to inform all health care professionals if there are plans to have surgery while receiving rimabotulinumtoxinB. 

    Requires an experienced clinician

    Use of rimabotulinumtoxinB requires an experienced clinician as safe and effective use depends upon proper product storage, dose selection, and administration technique, in addition to knowledge of the treated condition. Units of biological activity of various botulinum toxin products cannot be compared or converted to other such products. Physicians must understand the relevant neuromuscular anatomy of the area involved and know of any alterations to the anatomy due to prior surgical procedures. An understanding of standard electromyographic techniques may be useful for the treatment of cervical dystonia.

    ADVERSE REACTIONS

    Severe

    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

    Moderate

    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

    Mild

    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

    DRUG INTERACTIONS

    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; 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).
    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).
    Atropine; Edrophonium: (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).
    Bacitracin: (Minor) Botulinum Toxin Type B, which has skeletal muscle relaxant properties, should be used cautiously in patients receiving systemic bacitracin. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade.
    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 Alkaloids; Ergotamine; Phenobarbital: (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).
    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).
    Doxacurium: (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.
    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).
    Kanamycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission.
    Mepenzolate: (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.
    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.
    OnabotulinumtoxinA: (Major) The effect of administering botulinum toxin type A and type B neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
    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).
    Rapacuronium: (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.
    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.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants including botulinum toxins. When such combined therapy is contemplated, a dose reduction of one or both agents should be considered.
    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.
    Tubocurarine: (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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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]

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.

    Intramuscular Route

    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.