RimabotulinumtoxinB

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intramuscular [preservative free]:

Myobloc: 2500 units/0.5 mL (0.5 mL); 5000 units/mL (1 mL); 10,000 units/2 mL (2 mL) [contains albumin human]

Pharmacology

Mechanism of Action

RimabotulinumtoxinB (previously known as botulinum toxin type B) is a neurotoxin produced by Clostridium botulinum, spore-forming anaerobic bacillus. It cleaves synaptic Vesicle Association Membrane Protein (VAMP; synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane. By blocking neurotransmitter release, rimabotulinumtoxinB paralyzes the muscle.

Pharmacokinetics/Pharmacodynamics

Absorption

Not expected to be present in peripheral blood at recommended doses

Duration of Action

12-16 weeks

Use: Labeled Indications

Cervical dystonia: Treatment of cervical dystonia (spasmodic torticollis)

Sialorrhea: Treatment of chronic sialorrhea in adults

Use: Off Label

Upper limb spasticityyes

Based on the American Academy of Neurology practice guidelines on the use of botulinum neurotoxin, rimabotulinumtoxinB may be considered as a treatment option for focal manifestations of adult upper limb spasticity.

Contraindications

Hypersensitivity to botulinum toxin or any component of the formulation; infection at the injection site(s)

Dosage and Administration

Dosing: Adult

Cervical dystonia: IM: Initial: 2,500 to 5,000 units divided among the affected muscles in patients previously treated with botulinum toxin; initial dose in previously untreated patients should be lower. Subsequent dosing should be optimized according to patient's response.

Sialorrhea (drooling): Intraglandular: 1,500 to 3,500 units divided among the parotid (500 to 1,500 units/gland) and submandibular (250 units/gland) glands. Subsequent dosing should be optimized according to patient’s response and should generally be repeated no sooner than every 12 weeks.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

May be diluted with normal saline. Do not shake.

Administration

IM: Cervical dystonia: Use an appropriately sized gauge needle to administer intramuscularly. Simultaneous electromyography (EMG) guided application may be helpful in locating active muscle not identified by physical examination alone (Chinnapongse 2010). Incidence of dysphagia may be reduced by administering sternocleidomastoid injections into the upper third of the muscle, increasing the concentration of the toxin, or by reducing the dose per muscle when administering bilateral sternocleidomastoid and hyoid muscle injections (Albanese 2015).

Intraglandular: Sialorrhea (drooling): Use a 30-gauge, 0.5 inch sterile needle. Locate salivary glands using ultrasound imaging or surface anatomical landmarks (refer to manufacturer's labeling).

Storage

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. Once diluted, use within 4 hours. Does not contain preservative. Single use vial. Do not freeze.

Drug Interactions

Aminoglycosides: May enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Monitor therapy

Anticholinergic Agents: Botulinum Toxin-Containing Products may enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of other Botulinum Toxin-Containing Products. Monitor therapy

Muscle Relaxants (Centrally Acting): May enhance the adverse/toxic effect of Botulinum Toxin-Containing Products. Specifically, the risk for increased muscle weakness may be enhanced. Monitor therapy

Neuromuscular-Blocking Agents: Botulinum Toxin-Containing Products may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (10% to 16%), pain (13%)

Gastrointestinal: Xerostomia (12% to 39%; severe: 6%), dysphagia (4% to 25%; severe: 3%)

Immunologic: Antibody development (20% to 50%; neutralizing: 10% to 18%)

Local: Pain at injection site (12% to 16%)

1% to 10%:

Cardiovascular: Chest pain (≥2%), edema (≥2%), vasodilation (≥2%)

Central nervous system: Dizziness (3% to 6%), anxiety (≥2%), chills (≥2%), hyperesthesia (≥2%), malaise (≥2%), migraine (≥2%), vertigo (≥2%)

Dermatologic: Pruritus (≥2%)

Gastrointestinal: Dyspepsia (10%), dental caries (5% to 7%), gastrointestinal disease (≥2%), hernia of abdominal cavity (≥2%)

Genitourinary: Cystitis (≥2%), urinary tract infection (≥2%)

Hematologic & oncologic: Bruise (≥2%)

Infection: Abscess (≥2%), viral infection (≥2%)

Neuromuscular & skeletal: Arthralgia (7%), back pain (4% to 7%), asthenia (6%)

Ophthalmic: Amblyopia (≥2%), visual disturbance (≥2%)

Respiratory: Flu-like symptoms (6% to 9%), increased cough (6% to 7%), dyspnea (≥2%), pneumonia (≥2%)

Miscellaneous: Cyst (≥2%)

Postmarketing: Angioedema, constipation, hypersensitivity reaction, respiratory failure, skin rash, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity (eg, serum sickness, urticaria, soft tissue edema, dyspnea) and anaphylactic reactions may occur; discontinue therapy immediately with signs/symptoms of hypersensitivity. Immediate medical treatment should be available.
• Antibody formation: Higher doses or more frequent administration may result in neutralizing antibody formation and loss of efficacy.
• Cardiovascular events: Rarely, arrhythmia and myocardial infarction have been reported with use of onabotulinumtoxinA (another botulinum toxin formulation), sometimes in patients with preexisting cardiovascular disease.
• Dysphagia: Common when used for cervical dystonia and may persist for several months after administration. In severe cases, patients may require alternative feeding methods. Risk factors include smaller neck muscle mass, bilateral injections into the sternocleidomastoid muscle, or injections into the levator scapulae.
• Systemic toxicity: [US Boxed Warning]: Distant spread of botulinum toxin beyond the site of injection has been reported; dysphagia and breathing difficulties have occurred and may be life threatening; other symptoms reported include blurred vision, diplopia, dysarthria, dysphonia, generalized muscle weakness, ptosis, and urinary incontinence which may develop within hours or weeks following injection. Risk likely greatest in children treated for the unapproved use of spasticity. Systemic effects have occurred following use in approved and unapproved uses, including low doses. Immediate medical attention required if respiratory, speech, or swallowing difficulties appear

Disease-related concerns:

• Neuromuscular disease: Use with caution in patients with neuromuscular diseases (eg, myasthenia gravis, Eaton-Lambert syndrome) and neuropathic disorders (eg, amyotrophic lateral sclerosis).
• Respiratory disease: Use extreme caution in patients with pre-existing respiratory disease; treatment of cervical dystonia using botulinum toxin may weaken accessory muscles that are necessary for these patients to maintain adequate ventilation. Risk of aspiration resulting from severe dysphagia is increased in patients with decreased respiratory function.

Concurrent drug therapy issues:

• Neuromuscular transmission: Use with extreme caution in patients receiving other agents that may interfere with neuromuscular transmission (eg, aminoglycosides, neuromuscular-blocking agents)

Dosage form specific issues:

• Albumin: Product contains albumin and may carry a remote risk of virus transmission and variant Creutzfeldt-Jakob disease (vCJD). There also is a theoretical risk for transmission of CJD.
• Product interchangeability: Botulinum products (abobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) are not interchangeable; potency units are specific to each preparation and cannot be compared or converted to any other botulinum product.

Other warnings/precautions:

• Appropriate use: Concurrent use of onabotulinumtoxinA (or abobotulinumtoxinA) or use within <4 months of rimabotulinumtoxinB is not recommended.
• Chronic therapy: Long-term effects of chronic therapy unknown.
• Injection site: Use with caution if there is inflammation, excessive weakness, or atrophy at the proposed injection site(s).

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

What is this drug used for?

• It is used to treat spasms of the neck.
• It is used to reduce drooling.
• It may be given to you for other reasons. Talk with doctor.

Frequently reported side effects of this drug

• Injection site pain
• Headache
• Dry mouth
• Nausea
• Flu-like signs
• Joint pain
• Back pain
• Dizziness
• Neck pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Blurred vision
• Change in voice
• Droopy eyelids
• Loss of strength and energy
• Trouble breathing
• Trouble swallowing
• Trouble speaking
• Muscle weakness
• Leaking of urine
• Double vision
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.