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Myobloc

Generic Name: RimabotulinumtoxinB
Class: Other Miscellaneous Therapeutic Agents
VA Class: MS900
Chemical Name: Botulin B
Molecular Formula: C6869H10545N1715O2036S34

Warning(s)

  • Distant Spread of Toxin Effects
  • Effects of any botulinum toxin may spread from local sites of injection, producing symptoms consistent with the mechanism of action of botulinum toxin.2 (See Distant Spread of Toxin Effects under Cautions.)

  • Symptoms reported hours to weeks following injection.2

  • Swallowing and breathing difficulties may be life-threatening; deaths reported.2

  • Children treated for limb spasticity probably at highest risk; however, such effects also can occur in adults, particularly those with underlying predisposing conditions.2 (See Pediatric Use under Cautions.)

  • In both labeled and unlabeled (e.g., spasticity in children) uses, symptoms consistent with the spread of toxin effect reported at doses comparable to or lower than those used in cervical dystonia.2

Introduction

Neurotoxin produced by Clostridium botulinum;1 2 3 5 31 37 70 79 disrupts neurotransmission by inhibiting release of acetylcholine from peripheral and ganglionic autonomic cholinergic nerve terminals.2 3 16 31 32 37 70 250 399

Uses for Myobloc

Currently, 3 botulinum toxin type A preparations (abobotulinumtoxinA [Dysport], incobotulinumtoxinA [Xeomin], and onabotulinumtoxinA [Botox, Botox Cosmetic]) and one botulinum toxin type B preparation (rimabotulinumtoxinB [Myobloc]) are commercially available in the US.1 2 5 403 408 409 These preparations are not interchangeable; assay methods used to determine potency of botulinum toxins are specific to each individual manufacturer and/or formulation.1 2 5 381 384 403 410

Cervical Dystonia

Management of cervical dystonia (spasmodic torticollis) to decrease severity of associated abnormal head position and neck pain;2 3 9 14 16 32 37 65 69 81 95 96 122 designated an orphan drug by FDA for this use.81

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Considered first-line therapy for cervical dystonia because of efficacy, relatively low incidence of adverse effects, and temporary dose-related therapeutic effects (compared with surgery).3 15 296 297

Also considered effective and safe in patients who are not responsive to type A botulinum toxins.3 14 15 16 17 32 60 65 79 354 355

Appears to be effective in patients who develop tolerance to type A botulinum toxins as well as in those who are responsive to type A botulinum toxins.2 14 17 69 297 345

Very limited experience in patients not previously treated with botulinum toxin type A (e.g., onabotulinumtoxinA).2 296 297 298

Hyperhidrosis

Has been used for symptomatic management of severe primary axillary hyperhidrosis157 160 261 and focal palmar hyperhidrosis;157 261 369 however, efficacy evidence and experience are limited.160 296 297

Cosmesis

Has been used for temporary improvement in appearance of vertical glabellar facial (“frown”) lines,156 301 302 337 lateral canthal lines (“crow’s feet”)152 156 310 337 338 and horizontal forehead lines156 338 in a limited number of individuals; efficacy evidence and experience are limited.152 156 310 337 338

Myobloc Dosage and Administration

General

  • Adjust dosage carefully according to response and particular condition treated.2 120

  • Generally, the effective IM dose depends on muscle mass; the larger the muscle, the higher the required dose.120

  • Optimal dosages for a number of conditions have not been fully elucidated.37 142 156 219 301 302 337 338

  • If a patient fails to respond, consider possibility of an inadequate drug dose, improperly stored drug solution, and/or misinjection.65 296

Controlling Injection Pain

  • Pretreatment with ice packs or topical or local anesthetics (e.g., lidocaine/prilocaine cream and an occlusive dressing, proparacaine ophthalmic solution) has been recommended.120 296

  • Some clinicians report that topical or local anesthetics are not useful to prevent injection pain since they do not penetrate underlying muscles and/or require additional injections.296 297

  • Dilution with 0.9% sodium chloride injection containing a preservative (benzyl alcohol) has been reported to reduce pain on injection;157 297 344 however, the manufacturer recommends use of 0.9% sodium chloride injection without preservative for dilution.1 2 5 298

  • Some clinicians suggest that injection pain (possibly due to acidity of the solution)152 157 286 may be decreased by adding a small amount of sodium bicarbonate to the injection solution.152 157 However, the compatibility and stability of such solutions remain to be fully elucidated.157 296 297

  • IV sedation or general anesthesia may be needed prior to injection in some patients (e.g., those in considerable pain).120 296 297

Administration

Administer by IM injection into affected muscles.2 3 120

Has been administered intradermally,60 79 157 160 intracutaneously,60 157 296 297 sub-Q,60 157 296 297 or directly into affected glands.320

IM Administration

Administer by IM injection into affected muscles.2 3 120

Dilution

Commercially available as a sterile solution containing 5000 units of rimabotulinumtoxinB per mL.2 Do not shake vial.2

Myobloc vials are overfilled to ensure delivery of the labeled volume of drug: the vial labeled as containing 2500 units in 0.5 mL actually contains approximately 4100 units in 0.82 mL, the vial labeled as containing 5000 units in 1 mL actually contains approximately 6800 units in 1.36 mL, and the vial labeled as containing 10,000 units in 2 mL actually contains approximately 12,650 units in 2.53 mL.2 156 297 338 Do not dilute drug solutions in the vial since this may result in a solution with a higher concentration than expected due to overfill.297 338

Allow stopper of the vial to dry thoroughly after cleansing with alcohol before entering vial with a needle to prevent toxin inactivation.142 296 297

May be diluted with 0.9% sodium chloride injection to obtain desired concentration; however, since the drug solution does not contain a preservative, use diluted solutions within 4 hours of preparation.2 296 297 Diluted solutions reportedly stable for at least 24 hours at 25°C.157 172

Vials are for single use only; discard any unused portions.2

Carefully dispose of all used vials, including expired vials and/or equipment used in preparation and administration, as medical waste.2

Injection Techniques/Precautions (General)

Targeting the injection to the appropriate muscle(s) may be facilitated by active electromyography (EMG), ultrasonography, palpation of muscle belly, and/or use of anatomic landmarks (e.g., evidence of muscular hypertrophy, stiffness, tenderness, visible abnormal muscular activity).120 229

EMG-guided injections often are recommended to ensure optimal placement of toxin, particularly in patients who have not responded adequately to previous injections, and to minimize adverse effects on nonaffected tissue.120 296 297

Injection into midbelly of larger muscles where motor end plates are located may enhance benefit.296

Injection Techniques/Precautions (Cervical Dystonia)

Clinicians who administer rimabotulinumtoxinB should be familiar with and experienced in the assessment and management of cervical dystonia.2

Total dose administered at each treatment session is given as several injections divided among affected muscles.2 65

Identify affected muscles by careful clinical evaluation, including physical examination (e.g., for areas of hypertrophy, pain) and palpation.9 65 Palpation of contracting muscles while patient’s head is placed in position most favored by dystonic pulling of neck muscles is reportedly helpful.9 65

EMG guidance may be useful in delineating involved muscles for injection, particularly in obese patients or for muscles difficult to identify by palpation.37 39 65

Injection Techniques/Precautions (Facial Cosmesis)

Some clinicians suggest that injection procedures be adapted to account for the relatively greater diffusion characteristics of rimabotulinumtoxinB compared with type A.142 157 296 297 301 302

Appears to have increased diffusion within the muscle (potentially reducing the number of injections and complications)142 157 301 302 353 354 and a somewhat faster onset of action (e.g., within 24–48 hours) than botulinum toxin type A;142 152 157 160 297 353 however, additional experience needed to establish the optimal dose, number of injection sites, and frequency of treatment for facial cosmesis.142 156 301 310 337

Minimize risk of ptosis by avoiding injections near levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.5 142 296 297

Do not treat entire forehead and glabellar lines during a single session; high risk of ptosis.157 296 297

Avoid eyelid ptosis by asking individual to remain upright (e.g., avoid naps in reclining position) for 4 hours following treatment, avoid rubbing or massaging treated area for 4 hours (to prevent excess diffusion and possible weakness of adjacent muscles), and frown and smile repeatedly for at least 1–4 hours296 297 following treatment.296 297

When injection sites are marked (e.g., with a ball-point pen) to ensure optimal targeting,296 297 avoid injecting directly into marked areas to prevent tattooing of skin.298

If concurrent cosmetic alteration of the eyebrow is planned,157 296 297 defer treatment of the lateral eyebrow until after treatment of lateral canthal lines (“crow’s feet”); increased diffusion may accomplish sufficient cosmetic alteration of the eyebrow to eliminate the need for further treatment.157 296 297

Dosage

Potency of rimabotulinumtoxinB expressed in units of biologic activity; each unit is equivalent to the median intraperitoneal lethal dose (LD50) in mice.2

Because of differences in assay methods, units of biologic activity of rimabotulinumtoxinB cannot be compared with or converted to units of any other botulinum toxin (e.g., abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA).1 2 5 381 384 403 410

Adults

Cervical Dystonia
IM

Titrate initial and subsequent dosage considering previous response, adverse reactions, and severity of dystonia based on head and neck position, localization of pain, mass of target muscles and their proximity to critical toxin-sensitive anatomic structures (e.g., larynx, pharynx), and muscular hypertrophy.296 297

Patients with a history of tolerating botulinum toxin treatment: Initially, total recommended dose per treatment session is 2500–5000 units divided among affected muscles.2 Total initial doses as high as 10,000 units per treatment session have been used.2 296 297

Toxin treatment-naive patients: Use a lower initial dose.2 296 297 (See Botulinum Toxin-naive Patients under Cautions.)

Duration of response to 5000–10,000 units is generally 12–16 weeks.2 14 16 17

Hyperhidrosis
Primary Axillary Hyperhidrosis
Intradermal

2000 units per axilla, distributed among 25 sites about 2 cm apart, suggested.157 160 296 297

Anhidrosis following rimabotulinumtoxinB injection may occur within 3–5 days, with peak effect in 1–2 weeks and duration 9–16 weeks; duration of response with 2000 or 4000 units per axilla does not appear dose related.160 296 297

Palmar Hyperhidrosis
Intradermal

7500–9000 units in each palm, distributed among 30–35 sites, suggested.157 261

Duration of muscle weakness (e.g., 2–3 weeks) following treatment with rimabotulinumtoxinB appears similar to that with onabotulinumtoxinA.157

Cosmesis
Glabellar Facial (“Frown”) Lines
IM

Total dose of 2400–3000 units divided among 6 injection sites used;301 total dose of 2000–3000 units divided among 3 injection sites also suggested.157 296 297 301 302

Injection procedure for rimabotulinumtoxinB may differ from that for onabotulinumtoxinA based on relatively greater diffusion of rimabotulinumtoxinB.142 157 296 297 298 301 302

Lateral Canthal Lines (“Crow’s Feet”)
IM

1500 units divided among 3 injection sites per side (total dosage 3000 units) has been used;310 wrinkle severity was reduced by day 30 and generally had returned to baseline between days 90 and 120.310

750 units divided among 3 injection sites per side also has been used (total dosage 1500 units if both sides treated); resolution of wrinkles occurred at 7 days.152

Horizontal Forehead Lines
IM

1000–2500 units on each side of forehead suggested.157 296 Some clinicians suggest that injections be placed slightly higher than the equator of the brow (no lower than 2.5–4 cm above the brow) to account for increased diffusion of rimabotulinumtoxinB.157 296 297

If planning to treat both glabellar and horizontal forehead lines, may treat glabellar facial lines first and reevaluate again in 2 weeks to determine if further treatment needed.157

Prescribing Limits

Adults

Cervical Dystonia
IM

Do not exceed recommended dosage or frequency of administration; safety and efficacy of higher dosages not established.2 296

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.296

Cautions for Myobloc

Contraindications

  • Hypersensitivity to rimabotulinumtoxinB or any ingredient in the formulation.2

    Infection at proposed injection site(s).2

Warnings/Precautions

Warnings

Distant Spread of Toxin Effects

Potential for systemic spread of toxin effects beyond local sites of injection; manifested as unintended muscular weakness in noncontiguous anatomic structures and other potentially life-threatening adverse effects.2 31 32 37 65 142 371 373 381 382 383 (See Boxed Warning.)

Monitor patients for possible systemic effects (e.g., dysphagia, dysphonia, respiratory compromise, generalized weakness) following administration.371

Weakness of adjacent muscles commonly reported with botulinum toxin administration.9 18 31 32 37 65 142 371

Adverse effects consistent with mechanism of botulinum toxin action (e.g., asthenia/unexpected loss of strength or generalized muscle weakness, blurred vision, breathing difficulties/respiratory impairment, diplopia, dysarthria, dysphagia, dysphonia, hoarseness, ptosis, urinary incontinence) reported2 70 250 in both children and adults receiving botulinum toxin for a variety of conditions in a wide range of dosages.1 5 371 372 373 381 382 403

Risk of toxin spread probably highest in children treated for spasticity (currently not an FDA-labeled use for rimabotulinumtoxinB).2 381 383 (See Pediatric Use under Cautions.)

In some cases, swallowing and breathing difficulties required hospitalization, mechanical ventilation, or feeding tubes and/or resulted in death.2 381 (See Dysphagia and Breathing Difficulties under Cautions.)

Other Warnings/Precautions

Lack of Interchangeability Among Botulinum Toxin Preparations

The method used to determine potency of each botulinum toxin is specific to the individual manufacturer and/or preparation; therefore, units of biologic activity for rimabotulinumtoxinB cannot be compared with or converted to units of any other botulinum toxin.2 381 410

Dysphagia and Breathing Difficulties

Dysphagia is most common serious adverse effect reported in patients with cervical dystonia.2 14 15 16 17 65 69 95 96 122 261 Results from diffusion of the toxin to tissues (e.g., posterior pharyngeal muscles) outside the injected muscles.58 60 65 371 Rarely, dysphagia may require placement of gastric feeding tube.2 410

Rarely, fatal aspiration pneumonia or other serious debilities may develop subsequent to dysphagia.2 9

Risk increased in patients with cervical dystonia and smaller neck muscle mass (e.g., female) receiving bilateral injections and/or relatively high doses into the sternocleidomastoid muscle.2 9

Use lowest effective dose in such high-risk muscles.65 296

Immediate medical attention may be required if patients develop problems with swallowing, speech, or respiratory disorders.2

Preexisting Neuromuscular Disorders

Increased risk of serious adverse systemic effects (e.g., severe dysphagia, muscle weakness, respiratory compromise) with recommended doses in patients with neuromuscular disorders (e.g., peripheral motor neuropathic diseases [e.g., amyotrophic lateral sclerosis, motor neuropathy] or neuromuscular junction disorders [e.g., myasthenia gravis, Lambert-Eaton syndrome]); exercise caution in such patients.2 18 37 58 219 371 375 376 May be related to use of higher dosages in such patients.376

Rarely, extreme sensitivity to systemic effects of usual doses reported in patients with known or unrecognized neuromuscular disorders; some patients experienced several months of severe dysphagia and required a gastrostomy or nasogastric tube.2 9 69

Serious systemic effects related to distant spread of botulinum toxin reported more often and with greater severity in children with cerebral palsy.2 371 372 373 (See Pediatric Use under Cautions.)

Risk of Viral Disease Transmission

Formulation contains albumin derived from human blood.2 Remote risk of transmission of Creutzfeldt-Jakob disease (CJD) via albumin component; however, no cases identified to date.2

Botulinum Toxin-naive Patients

Clinical experience in patients who have not previously tolerated treatment with botulinum toxin type A is limited.2 296 297

Initiate treatment with lower doses than those recommended for patients with a history of tolerating such treatment.2

Injection-related Effects

Ecchymosis reported.2

Administer with caution to patients with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or those receiving anticoagulant therapy.296 297

Immunogenicity

Antibodies to the drug may develop in patients receiving repeated treatment; may have neutralizing activity.2 14 Such patients may still respond to the drug.14 31 79

Clinical importance not determined.2 Not known if patients with neutralizing antibodies to botulinum toxin type A are at increased risk of developing tolerance to botulinum toxin type B.345 351

Neutralizing antibodies generally not detected until after 6 months of treatment.2

Patients who develop tolerance to botulinum toxin type A may respond to botulinum toxin type B or other botulinum toxin serotypes (e.g., botulinum toxin type F);3 32 60 65 79 however, long-term response to other serotypes in such patients not fully elucidated.14 32

Reporting Adverse Effects or Overdosage

If the patient receives an overdose of rimabotulinumtoxinB or the drug is injected into the wrong muscle (i.e., misinjection), contact the local or state health department to process a request for botulism antitoxin through the CDC Drug Service.2 If a response is not received within 30 minutes, contact the CDC Emergency Operations Center directly at 770-488-7100.2 Information about the antitoxin is available at .

Botulism antitoxin will not reverse any botulinum toxin-induced muscle weakness evident at the time of antitoxin administration but may stabilize the deficits.2

Specific Populations

Pregnancy

Category C.2

Lactation

Not known whether distributed into human milk.2 Use with caution.2

Pediatric Use

Safety and efficacy not established in children <18 years of age with cervical dystonia.2 297

Serious systemic toxicity resembling botulism (e.g., dysphagia, respiratory failure) reported during postmarketing experience in children <16 years of age.371 Such effects observed with rimabotulinumtoxinB doses of 388–625 units/kg.371 Severe cases involving death or hospitalization or requiring use of gastric feeding tubes and/or mechanical ventilation have occurred, principally in children with cerebral palsy-associated limb spasticity.371 372 373 No deaths or serious complications requiring intubation or ventilatory support reported among such cases of botulism in adults.371

Geriatric Use

Safety and/or efficacy in those ≥65 years of age similar to that in younger adults.2

Safety and efficacy data in patients ≥75 years of age insufficient for any comparison to that in younger adults.2

Common Adverse Effects

Management of cervical dystonia: Dry mouth,2 14 15 16 17 261 dysphagia,2 14 15 16 17 95 96 122 261 dyspepsia, 2 261 injection-site pain.2 14 95 152 156 157 286

Interactions for Myobloc

Specific Drugs

Drug

Interaction

Comments

Anticholinesterases

Potential for prolonged paralytic effect of toxin296

Use concomitantly with caution79 219 296

Anti-infective agents interfering with neuromuscular transmission (aminoglycosides, lincosamides, polymyxins)

Potential for prolonged paralytic effect of toxin2 296 297

Use concomitantly with caution2 79 219 296 297

Botulinum toxin treatment, concurrent or sequential

Possible increased paralytic effect with concurrent or sequential use within several months of administration of rimabotulinumtoxinB2 297

Data on concurrent or sequential use of botulinum toxins lacking2 297

Magnesium salts (magnesium sulfate)

Potential for prolonged paralytic effect of toxin296

Use concomitantly with caution79 219 296

Neuromuscular blocking agents (e.g., atracurium, succinylcholine)

Potential for prolonged paralytic effect of toxin2 296 297

Use concomitantly with caution2 79 219 296 297

Quinidine

Potential for prolonged paralytic effect of toxin296

Use concomitantly with caution79 219 296

Myobloc Pharmacokinetics

Absorption

Bioavailability

No formal pharmacokinetic studies; manufacturer states that drug is not expected to be present in peripheral circulation in measurable concentrations following IM or intradermal injection of recommended doses.2 14

Duration

Duration of response to 5000–10,000 units in cervical dystonia is generally 12–16 weeks.2 14 16 17

Stability

Storage

Parenteral

Injection

Stable for up to 48 months at 2–8°C when stored in unopened vials;14 39 142 157 297 do not freeze or shake.2 Do not use after the expiration date marked on the vial.2

Reportedly stable for up to 9 months when stored in unopened vials at 15–30ºC.14 39 142 157 297

Use solutions diluted with 0.9% sodium chloride injection without preservatives within 4 hours of preparation.2 296 297

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Drug Compatibility

Buffering agents (e.g., sodium bicarbonate) reportedly may destabilize the toxin and/or alter its diffusion characteristics.157 296

Actions

  • Induces chemical denervation and flaccid paralysis by disruption of neurotransmission; inhibits release of acetylcholine at presynaptic cholinergic nerve terminals of the peripheral nervous system and at ganglionic nerve terminals of the autonomic nervous system.2 3 16 31 32 37

  • Inhibits sweat production by blocking release of acetylcholine, which mediates sympathetic neurotransmission in eccrine glands.3 79 157 160 296 297

  • Induces neuromuscular blockade via a zinc-dependent endopeptidase, which blocks vesicles containing acetylcholine from fusing with the terminal membrane of the motor neuron.16 31 37 70 79

  • Without acetylcholine release, the muscle is unable to contract31 37 70 79 and flaccid paralysis ensues.1 3 5 16 31 32 37

  • At therapeutic doses, muscular paralysis limited to injected muscle; however, weakness or paralysis of adjacent muscles may occur as a result of local diffusion.31

  • Selective chemodenervation is reversible; although muscular atrophy occurs, regeneration of extrajunctional receptors and terminals limits the duration of activity to a few months.3 5 31

  • Recovery of neuromuscular activity occurs through neurogenesis of axonal sprouts and motor end plates.32 37 79

  • Functional recovery develops in 3–6 months, but sprouting and remodeling may continue for as long as 3 years.37 79

  • Response in autonomic disorders involving excessive glandular secretion (e.g., hyperhidrosis) may be longer than in conditions involving overactivity of striated or smooth muscle;296 297 additional study needed to elucidate mechanism in glandular and non-muscle tissue.

Advice to Patients

  • Inform patients with cervical dystonia of possibility of dysphagia (typically mild to moderate);9 14 69 402 rarely, severe dysphagia occurs, sometimes associated with aspiration, dyspnea, pneumonia, and need to reestablish an airway.2 402

  • Inform patients of possible systemic effects (e.g., weakness, shortness of breath, respiratory complications, swallowing difficulties) following local injection.2 371 402

  • Advise patients and/or caregivers to seek immediate medical attention if unexpected muscle weakness or swallowing, speech, or respiratory disorders occur.2 371 402 Advise patients to avoid driving a car or engaging in other potentially hazardous activities if they have such symptoms.2 402

  • Advise previously sedentary patients to resume activity gradually following treatment.296 297

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., neuromuscular disorders).2 402

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.2 402

  • Importance of informing patients of other important precautionary information.2 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

RimabotulinumtoxinB

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

5000 units/mL

Myobloc

Solstice Neurosciences

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions April 27, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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