RimabotulinumtoxinB (formerly known as botulinum toxin type B) is a botulinum toxin produced from fermentation of Clostridium botulinum type B. RimabotulinumtoxinB is approved for treating cervical dystonia and chronic sialorrhea in adults. It decreases the severity of abnormal head position and neck pain in patients with cervical dystonia, and it has been found effective in patients with cervical dystonia who do and do not respond to type A. RimabotuliniumtoxinB significantly decreased salivary flow rate among patients with various neurologic disorders including Parkinson's disease, amyotrophic lateral sclerosis (ALS), and stroke. Spread of the toxin effect beyond the injection site may occur with use which can produce swallowing and breathing difficulties.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
Intramuscular Administration
-Administer dose intramuscularly divided among affected muscles.
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.
Dysphagia and xerostomia were the most frequently reported adverse digestive reactions to rimabotulinumtoxinB therapy across controlled studies in patients with cervical dystonia, occurring in 19.1% and 22.1% of patients. Most cases of dysphagia or xerostomia were reported as mild or moderate; however, they were the adverse reactions most frequently associated with discontinuation of therapy. The incidence of xerostomia appeared to be dose-related, occurring in 34% of patients who received a single 10,000 unit dose and 3% of those that received 2,500 units. The incidence of dysphagia increased with the administration of an increased dose in the sternocleidomastoid muscle. Severe dysphagia was reported by 3% of patients, none of these requiring medical intervention. Severe xerostomia was reported by 6% of patients. Across 2 placebo-controlled studies in adults with chronic sialorrhea during which patients received single treatments with 1,500 units, 2,500 units, or 3,500 units, xerostomia (14% to 39%), dental caries (0% to 7%), and dysphagia (0% to 9%) were reported. Dysphagia can result from spreading of the drug away from the area of injection to produce symptoms consistent with botulinum toxin effects. During clinical experience, death as a complication of dysphagia has been reported after treatment with botulinum toxin; dysphagia may persist for several months and require the use of a feeding tube to maintain nutrition. Aspiration may also occur. Dyspepsia (5.9%) was noted during controlled studies; unspecified GI disorders were reported in at least 2% of patients across all clinical studies. Constipation has been reported during postmarketing observation.
After using botulinum toxins, cases of distant spread of toxin effects, including respiratory difficulty leading to respiratory arrest and death, that are suggestive of systemic botulism have been reported. These effects have been seen in patients who received the medication for a variety of conditions and in a wide range of doses. The majority of adverse events in children have occurred after the treatment of cerebral palsy-associated limb spasticity. Several of these children required hospitalization and/or mechanical ventilation, and some cases were fatal. Adult cases have also been reported after use of botulinum toxin for the treatment of spasticity or cervical dystonia. In some cases, hospitalization was required with several patients requiring the placement of feeding tubes or mechanical ventilation. Several deaths were reported in adults; however, due to the nature of the patients' pre-existing conditions, the deaths can not be attributed to botulinum toxin. These adverse effects have been reported as early as one day and as late as several weeks after treatment. Other adverse respiratory effects associated with rimabotulinumtoxinB in at least 2% of patients during clinical studies include dyspnea, pneumonia, and unspecified lung disorders. Increases in cough were reported in 5.9% of patients during controlled studies, and rhinitis was reported in 3.4%.
Immunogenicity and neutralizing activity induced by treatment with rimabotulinumtoxinB was evaluated. Only patients with positive ELISA assay were subsequently tested for the presence of neutralizing activity against rimabotulinumtoxinB in the mouse neutralization assay (MNA). Approximately 12% of patients had positive ELISA assays at baseline. Antibody formation was detected after single treatment sessions. By six months after initiating treatment, ELISA positive rates were estimated at 20%, which continued to rise to 36% at one year and 50% positive ELISA status at 18 months. Serum neutralizing activity was primarily not seen in patients until after 6 months. Estimated rates of development were 10% at one year and 18% at 18 months in the overall group of patients, based on analysis of samples from ELISA positive individuals. The effect of conversion to ELISA or MNA positive status on efficacy was not evaluated and the clinical significance of antibody formation has not been determined.
Various musculoskeletal adverse reactions to rimabotulinumtoxinB have been reported. During controlled studies, musculoskeletal pain occurred in up to 14.2% of patients. Back pain occurred in 5.4% of patients, while neck pain or generalized pain that may have been related to cervical dystonia or torticollis occurred in 14.2% and 6.4% of patients, respectively. Torticollis was observed in 5.9% of patients, myasthenia in 4.9%, and arthralgia in 3.9%. Generalized muscle weakness may result from spreading of the drug away from the area of injection to produce symptoms consistent with botulinum toxin effects. Reactions occurring in a least 2% of patients included arthritis and other unspecified joint disorders. Systemic reactions to rimabotulinumtoxinB during controlled studies included asthenia or generalized weakness (3.4%). In some patients, generalized weakness can represent spread of the toxin outside of the local area. Injection site reaction, specifically injection site pain, was noted in 14.2% of patients.
Headache was the most frequently reported adverse neurologic reaction to rimabotulinumtoxinB during controlled studies, occurring in 12.7% of patients. Headache may be related to the injection itself. Migraine has been observed in >= 2% of patients, and dizziness in 4.4%. Dysphonia and dysarthria may occur with use; these reactions are consistent with the spread of botulinum toxin effects beyond the initial site of injection. Other reactions reported in at least 2% of patients during clinical studies include anxiety, tremor, hyperesthesia, somnolence or drowsiness, confusion, vertigo, and peripheral vasodilation.
Edema, peripheral edema, and hypercholesterolemia have been reported in at least 2% of patients during clinical studies of rimabotulinumtoxinB.
Hypersensitivity reactions to rimabotulinumtoxinB include angioedema, urticaria, rash, and pruritus. Hypersensitivity reactions may include anaphylaxis, serum sickness, soft-tissue edema, and dyspnea. Pruritus and ecchymosis were reported in 2% or more of patients during clinical studies. If serious hypersensitivity reactions occur, discontinue further injection of rimabotulinumtoxinB and treat symptoms as clinically appropriate.
RimabotulinumtoxinB may cause visual impairment such as amblyopia, which occurred in at least 2% of patients during clinical studies. Blurred vision, diplopia, ptosis, xerophthalmia, and accommodation disorder may result from spreading of the drug away from the area of injection; these reactions have been observed with botulinum toxin use during postmarketing experience. Tinnitus, otitis media, and taste perversion (dysgeusia) occurred in 2% or more of patients across all clinical studies.
Genitourinary adverse reactions reported in at least 2% of patients during clinical studies of rimabotulinumtoxinB include urinary tract infections such as cystitis, as well as vaginal moniliasis. Post-marketing safety data suggest that urinary incontinence may occur from the spreading of the drug away from the area of injection to produce symptoms consistent with botulinum toxin effects.
Systemic reactions to rimabotulinumtoxinB during controlled studies included pain, reported in 9.8% of patients, as well as infection (16.2%), and influenza (8.3%). Viral infections were observed in at least 2% of patients across all clinical studies. Other reactions that occurred in at least 2% of patients include chills, fever, malaise, chest pain (unspecified), hernia, abscess, cyst, and neoplasm.
Previously sedentary patients who will resume activities after administration of rimabotulinumtoxinB should do so gradually.
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.
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).
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).
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
General dosing information:
-RimabotulinumtoxinB is not interchangeable with other preparations of botulinum toxin products.
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: 500 to 1,500 units intraglandular in each parotid gland and 250 units intraglandular in each submandibular gland. May repeat treatment based on clinical response, but generally no sooner than every 12 weeks.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
*non-FDA-approved indication
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; 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.
Colistimethate, Colistin, Polymyxin E: (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.
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).
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.
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.
-Route-Specific Pharmacokinetics
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.