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Botulinum Toxin Type B

Class: Other Miscellaneous Therapeutic Agents
VA Class: MS900
Brands: Myobloc

Warning(s)

Special Alerts:

[UPDATED 08/03/2009] FDA notified healthcare professionals of changes to the established drug names for botulinum toxin Type A (Botox/Botox Cosmetic, Dysport) and botulinum toxin Type B (Myobloc) to reinforce individual potencies and prevent medication errors, and provided recommendations for healthcare professionals to consider, plus information for patients, family members, and caregivers. For more information visit the FDA website at: and .

[Posted 04/30/2009] FDA notified healthcare professionals that after an ongoing safety review initiated in February 2008, the manufacturers of licensed botulinum toxin products [botulinum toxin Type A (Botox and Botox Cosmetic) and botulinum toxin Type B (Myobloc)] will be required by FDA to strengthen warnings in product labeling and add a boxed warning regarding the risk of adverse events when the effects of the toxin spread beyond the site where it was injected.

FDA will also require that manufacturers develop and implement a Risk Evaluation and Mitigation Strategy [REMS], including a communication plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The REMS would also include a Medication Guide that explains the risks to patients, their families, and caregivers. FDA is requiring the manufacturers to submit safety data after multiple administrations of the product in a specified number of children and adults with spasticity to assess the signal of serious risk regarding distant spread of toxin effects.

FDA’s evaluation of the data continues to support the recommendations made in the 2008 Early Communication. For more information visit the FDA website at: , and .

REMS:

FDA approved a REMS for rimabotulinumtoxinb (formerly botulinum toxin b) to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of rimabotulinumtoxinb (formerly botulinum toxin b) and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Neurotoxin produced by Clostridium botulinum;1 2 3 5 31 37 70 73 79 7 structurally similar but antigenically and serologically distinct botulinum toxin serotypes (A, B, C, D, E, F, and G) exist.2 3 31 32 37 70 73 75 79

Botulinum toxin disrupts neurotransmission by inhibiting release of acetylcholine at cholinergic nerve terminals of the peripheral nervous system and at ganglionic nerve terminals of the autonomic nervous system, inducing a chemical denervation and flaccid paralysis and inhibiting glandular secretion.2 3 31 32 37 43 72 73 75 194

Uses for Botulinum Toxin Type B

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Botulinum toxin type B (Myobloc) and type A (Botox, Botox Cosmetic) currently are the only botulinum toxin serotypes commercially available in the US;1 2 5 types C and F reportedly under clinical investigation in other countries.4

Cervical Dystonia

Management of cervical dystonia (also referred to as spasmodic torticollis) to decrease severity of associated abnormal head position and neck pain;2 3 4 9 14 16 29 30 32 35 37 40 54 65 69 81 85 95 96 122 123 designated an orphan drug by US 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 30 33 34 35 54 83 86 90 296 297

Also considered an effective and safe treatment for cervical dystonia in patients who are not responsive to therapy with botulinum toxin type A.3 14 15 16 17 32 35 41 42 60 64 65 79 137 348 350 354 355

Comparative safety and efficacy of botulinum toxin types A and B in cervical dystonia have not been established;14 69 botulinum toxin type B appears to be effective in patients who develop tolerance to type A as well as in those who are responsive to botulinum toxin type A.2 14 17 42 69 123 297 345

Very limited experience in patients not previously treated with botulinum toxin type A.2 296 297 298

Cosmesis

Has been used for temporary improvement in the appearance of facial wrinkles associated with hyperactivity of the orbiculus oculi muscle (lateral canthal wrinkles, also known as “crow’s feet”) in a limited number of individuals.152 156 310 337 338

Botulinum Toxin Type B Dosage and Administration

General

  • Adjust dosage carefully according to response and particular condition treated.4 120

  • Generally, the effective IM dose depends on muscle mass; the larger the muscle, the higher the required dose.4 120

  • Individual susceptibility to the toxin varies;4 optimal dosages for a number of conditions have not been fully elucidated.37 133 138 142 156 218 219 238 243 301 302 313 321 337 338

  • Lower doses may be required in patients with preexisting weakness or when there is concern about weakness, in those with milder disease severity, and in women and patients with lower body weights.4

  • Patients with cervical dystonia who have not previously received botulinum toxin should receive a lower initial dose; very limited experience in patients who have not received prior therapy with botulinum toxin type A.2 296 297

  • If a patient fails to respond, consider possibility of an inadequate drug dose, improperly stored drug solution, and/or misinjection.65 296 348

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

Administration

Administer by IM injection into affected muscles.2 3 4 120

Has been administered intradermally30 35 60 67 79 85 123 157 158 160 170 259 , intracutaneously,60 157 163 164 165 296 297 sub-Q,60 157 163 164 165 296 297 or directly into affected glands.4 320

IM Administration

Administer by IM injection into affected muscles.2 3 4 120

Dilution

Commercially available as a sterile solution containing 5000 units of botulinum toxin type B per mL.2 Do not shake vial.2

Commercially available vials of botulinum toxin type B (Myobloc) 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 Drug solutions should not be diluted 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.121 142 296 297

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

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

IM Injection Techniques

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).4 120 147 229

EMG-guided injections often are recommended to ensure optimal placement of toxin for efficacy, particularly in patients who have not responded adequately to previous injections, and to minimize adverse effects on nonaffected tissue.120 140 143 147 296 297

EMG guidance may allow more accurate identification of the neural motor end plate, facilitating more precise injection and improving effectiveness of lower doses.240 360

Injection into midbelly of larger muscles where motor end plates are located may enhance benefit.240 296 360

Cervical Dystonia

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 33 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 also may be useful in delineating involved muscles for injection, particularly in obese patients or for muscles difficult to identify by palpation.35 37 39 56 65

Cosmesis of Lateral Canthal Wrinkles (“Crow’s Feet”)

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

Administration Precautions for Facial Cosmesis

Some clinicians suggest that injection procedures be adapted to account for the relatively greater diffusion characteristics of botulinum toxin type B 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.5 137 140 141 142 296 297

In older individuals, do not inject lower portion of brow (this muscle is used to raise eyebrows in order to see).143

Do not treat entire forehead and glabellar lines during a single session; high risk of ptosis.143 157 296 297

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 hours143 296 297 following treatment.140 141 143 296 297

Apply digital pressure at border of supraorbital ridge while injecting corrugator muscle to minimize potential for diffusion into levator muscle and resultant weakening.143

When injection sites are marked (e.g., with a ball-point pen) to ensure optimal targeting,140 296 297 avoid injecting directly into marked areas to prevent tattooing of skin.298

Before injection, instruct the individual to accentuate specific facial lines to be treated by squinting (for lateral canthal wrinkles).140

Controlling Injection Pain

Pretreatment with ice packs or topical or local anesthetics (e.g., lidocaine/prilocaine cream [EMLA] and an occlusive dressing, proparacaine hydrochloride ophthalmic drops) has been recommended prior to injection.120 140 275 296

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.270 296 297

Dilution with 0.9% sodium chloride injection containing a preservative (benzyl alcohol) has been reported to reduce pain on injection;62 64 138 157 297 344 however, the manufacturer recommends use of 0.9% sodium chloride injection without preservative for reconstitution and/or dilution.1 2 5 298

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

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Data on several different serotypes (e.g., botulinum toxin types A, B, C, F) and/or formulations of botulinum toxin have been reported;1 2 4 5 255 257 assay methods used to determine potency of these various toxins are specific to each individual manufacturer and/or formulation.1 2 4 5

Units of biologic activity for one serotype or formulation of botulinum toxin cannot be compared with or converted to units of other botulinum toxins.1 2 4 5

Unless otherwise noted, all botulinum toxin doses in this monograph refer to units of Myobloc.

Adults

Cervical Dystonia
Patients With a History of Tolerating Botulinum Toxin Treatment
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.56 296 297

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 in patients with cervical dystonia.2 296 297

Toxin treatment-naive patients should receive 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

Cosmesis of Lateral Canthal Wrinkles (“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 by day 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

Prescribing Limits

Adults

Cervical Dystonia
IM

Do not exceed recommended dosage or frequency of administration; safety and efficacy of higher dosages have not been evaluated.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 Botulinum Toxin Type B

Contraindications

  • Hypersensitivity to botulinum toxin type B or any ingredient in the formulation.2

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adherence to Recommended Dosage

Do not exceed recommended dosage or frequency of administration; safety and efficacy of higher dosages have not been evaluated.2 296 Severe adverse effects, including a botulism-like syndrome, have been reported with use of higher than recommended dosages of botulinum toxins and/or unlicensed preparations of botulinum toxins.371 374 376 377 378 379

Comorbid Disorders

Increased risk of serious adverse systemic effects, including severe dysphagia, muscle weakness, and/or respiratory compromise, with recommended doses in patients with underlying conditions such as peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, motor neuropathy) or neuromuscular junction disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome); exercise caution when used in such patients.2 4 18 27 29 37 57 58 140 141 219 259 371 375 376 May be related to use of higher dosages in such patients.374 376

Rarely, extreme sensitivity to systemic effects of usual clinical 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 57 69

Some clinicians state that use for cosmetic treatment of neck wrinkles is contraindicated in patients with amyotrophic lateral sclerosis.141

Serious systemic effects related to distant spread of botulinum toxin reported, more often and with greater severity in children with cerebral palsy receiving such therapy; hospitalizations and deaths have occurred.371 372 373 374

Dysphagia

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Dysphagia is the most common serious adverse effect reported in patients with cervical dystonia;2 11 14 15 16 17 35 53 57 65 69 95 96 122 261 also can occur in patients receiving botulinum toxin type B for other indications (e.g., torticollis, muscle spasticity associated with cerebral palsy).371 375 376 Results from the diffusion of the toxin to tissues (e.g., posterior pharyngeal muscles) outside the injected muscles.29 30 33 57 58 60 65 83 371 Rarely, dysphagia may require placement of gastric feeding tube.2

Rarely, fatal aspiration pneumonia or other serious debilities may develop subsequent to dysphagia.2 9 53 64 68

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 35 57 86

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

Risk of Creutzfeldt-Jakob Disease

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

Major Toxicities

Systemic Toxicity (Botulism)

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Serious systemic toxicity, including respiratory compromise and death, reported during an ongoing FDA safety review of botulinum toxins type A and type B.371 372 373 374 More frequent and severe in children with limb spasticity associated with cerebral palsy.371 372 373 374 Causal relationship not established to date; FDA will review additional safety data from clinical studies, medical literature, and postmarketing adverse event reports to further evaluate risk of systemic toxicity.371 372 374

Botulism also possible after iatrogenic overdose or misinjection of botulinum toxin.1 2 5 51 58 59 60 65 70 87 377 378 Following IM injection of usual therapeutic doses, botulinum toxin type B generally not present in the peripheral blood and generally does not induce systemic effects (e.g., generalized or distant muscle weakness) in patients without predisposing neuromuscular dysfunction.2 14 However, systemic autonomic or anticholinergic effects (e.g., dry mouth, dyspepsia,296 swallowing difficulties, accommodation difficulty, corneal and conjunctival irritation, dryness of nasal mucosa, reduced sweating, and urinary voiding difficulties) reported.160 261 296 340 352

To date, botulism not reported after IM injections of botulinum toxin type B;2 however, generalized muscle weakness and a generalized botulism-like syndrome, including respiratory arrest, reported rarely after IM injections of therapeutic doses of another botulinum toxin serotype (type A).14 26 32 33 38 52 58 142 293

Precise risk of systemic autonomic or anticholinergic effects and/or generalized muscle weakness after treatment has not been fully elucidated.14 26 58 60 160 261 296 352

Maximum safe dose that does not produce toxicity is not known.37 Serious systemic toxicity has been reported during postmarketing experience with doses of 388–625 units/kg in children and doses of 10,000–20,000 units in adults.371

Manifestations of overdose (botulism) include diplopia, ptosis, blurred vision, photophobia, dry mouth, difficulty speaking and swallowing, autonomic dysfunction such as bowel stasis, and generalized muscle weakness that can progress to a symmetric, descending flaccid paralysis;70 87 89 250 manifestations not apparent immediately after the drug is injected.2

If accidental injection or ingestion occurs, closely monitor patient for up to several weeks for manifestations of systemic weakness or muscle paralysis.2 If botulism suspected, hospitalization may be required to monitor closely for systemic weakness, paralysis, and incipient respiratory failure.2 Recovery occurs through neurogenesis of axonal sprouts and motor end plates; can require weeks or months.32 37 79 70

In event of an overdose or misinjection (i.e., wrong muscle), contact manufacturer immediately for additional information and state health department to obtain botulinum antitoxin through CDC;2 if state health department is not available, contact CDC by telephone at 404-639-2206 or 404-639-2888 (after hours).70 Antitoxin will not reverse botulinum toxin-induced muscle weakness already evident at the time of antitoxin administration but may stabilize the deficits.2 265

Antitoxin to a given type of botulinum toxin does not neutralize other types (e.g., anti-A botulinum antitoxin does not neutralize botulinum toxin types B through G).2 31 32 37 70 73 75 79

For information about overdosage, contact Solstice Neurosciences at 888-461-2255.2 297 367

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Botulinum Toxin-naive Patients

Initiate treatment of botulinum toxin-naive patients with lower doses from the recommended dosage range.2

Clinical experience in patients who have not previously tolerated treatment with botulinum toxin type A is limited; to date, only a few such patients have been evaluated.2 296 297

Experience of Clinician

The manufacturer states that the drug should be administered to patients with cervical dystonia only by clinicians familiar with and experienced in the assessment and management of this condition.2

Thorough knowledge of diagnosis, management, and regional anatomy of the treated disorder, careful dose selection, and accomplished injection techniques are critical to obtaining therapeutic benefit and minimizing adverse effects.2 54 56 Some experts recommend limiting use to clinicians with specialized training.37 65 66 296 297

Working knowledge of EMG techniques useful for accurate injection of target muscles in patients with cervical dystonia,35 particularly when palpation is inadequate or adequate relief not obtained with conventional administration.9 35 83

Systemic Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Local spread of toxin may result in weakness to adjacent muscles.9 10 11 12 13 18 30 31 32 33 34 35 37 65 142 371 Systemic spread of botulinum toxin also is possible and can cause a botulism-like syndrome (e.g., dysphagia, muscle weakness, ptosis, respiratory failure).371 372 373 374 Condition treated determines muscles injected and therefore proximate muscles possibly affected by infiltration and resultant undesired weakness.29 37

Systemic autonomic or anticholinergic effects (e.g., dry mouth, dyspepsia,296 swallowing difficulties, accommodation difficulty, corneal and conjunctival irritation, dryness of nasal mucosa, reduced sweating, and urinary voiding difficulties) reported; incidence not fully elucidated.160 261 296 340 352 369

Incidence of autonomic effects (e.g., anticholinergic effects such as dry mouth, ptosis, accommodation difficulty) may be higher with botulinum toxin type B than with type A, possibly because of diffusion characteristics and systemic distribution of type B and/or different relative affinities of toxin serotypes for neuromuscular and autonomic nerve endings.142 160 261 296 320 340 345 352

Anticholinergic effects (e.g., dry mouth) appear to be dose related; reported more frequently with doses >10,000 units.243 261 340

Incidence of dry mouth appears dose-related in cervical dystonia after injections in the splenius capitis, trapezius, and sternocleidomastoid muscles.2

Monitor patients for possible systemic effects including dysphagia, dysphonia, respiratory compromise, and generalized weakness following administration of botulinum toxin type B.371

Injection-related Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Ecchymosis reported.2

Administer with caution to patients with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or those receiving anticoagulant therapy.53 296 297

Antibody Formation and Tolerance

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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 has not been determined.2 It is not known if patients with neutralizing antibodies to botulinum toxin type A are at increased risk of developing tolerance to the type B toxin.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 35 41 42 60 64 65 79 137 348 350 however, long-term response to other serotypes in such patients has not been fully elucidated.14 32 33 41 359

Dosing Precautions

Ensure accuracy of dosing information; units of biologic activity for different serotypes or formulations of botulinum toxin cannot be compared with or converted to units of other botulinum toxins.2 4

Dosing errors reported;32 76 77 157 173 296 297 use care in evaluating medical literature on different toxin serotypes (e.g., botulinum toxin types A, B, C, F) since assay methods used to determine potency of different serotypes are specific to each individual manufacturer and/or formulation.1 2 4 5 255 257

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 were observed with botulinum toxin type B 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.371 372 373 374 No deaths or serious complications requiring intubation or ventilatory support reported among such cases of botulism in adults.371 374

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

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

Interactions for Botulinum Toxin Type B

Specific Drugs

Drug

Interaction

Comments

Anticholinesterases

Potential for prolonged paralytic effect of toxin297

Use concomitantly with caution8 33 59 61 79 140 219 296 297

Other botulinum toxin serotypes

Possible increased paralytic effect with concurrent or sequential use within several months of administration of type B2

Concurrent or sequential use has not been evaluated2

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

Potential for prolonged paralytic effect of toxin2 297

Use concomitantly with caution2 8 33 59 61 79 140 219 296 297

Magnesium salts (magnesium sulfate)

Potential for prolonged paralytic effect of toxin297

Use concomitantly with caution8 33 59 61 79 140 219 296 297

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

Potential for prolonged paralytic effect of toxin2 297

Use concomitantly with caution2 8 33 59 61 79 140 219 296 297

Quinidine

Potential for prolonged paralytic effect of toxin297

Use concomitantly with caution8 33 59 61 79 140 219 296 297

Botulinum Toxin Type B Pharmacokinetics

Absorption

Bioavailability

Formal pharmacokinetic studies with botulinum toxin type B have not been performed; the manufacturer states that the drug is not expected to be present in peripheral circulation in measurable concentrations following IM or intradermal injection of recommended doses.2

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 (unopened vials);14 39 142 157 297 do not freeze or shake.2 Do not use after the expiration date marked on the single-use vial.2

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

May be diluted with 0.9% sodium chloride injection without preservatives to obtain desired concentration; use solutions within 4 hours of preparation.2 296 297

Compatibility

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

Parenteral

Solution Compatibility

Some clinicians suggest that the addition of a small amount of sodium bicarbonate to the botulinum toxin type B solution may decrease pain on injection;152 157 however, use of such buffering agents reportedly may destabilize the toxin and/or alter its diffusion characteristics.157 296 297

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 72 73 75 194

  • Inhibits sweat production by blocking release of acetylcholine, which mediates sympathetic neurotransmission in eccrine glands.3 4 30 35 45 49 50 67 79 85 123 137 138 143 157 160 168 237 259 296 297

  • Induces neuromuscular blockade via a zinc-dependent endopeptidase, which blocks vesicles containing acetylcholine from fusing with the terminal membrane of the motor neuron.16 30 31 37 70 71 74 75 79

  • Without acetylcholine release, the muscle is unable to contract31 37 70 79 and flaccid paralysis ensues.1 3 5 16 31 32 37 72 73 75 194

  • 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;4 296 297 additional study needed to elucidate mechanism in glandular and non-muscle tissue.4

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Inform patients with cervical dystonia of possibility of dysphagia (typically mild to moderate);9 14 57 69 rarely, severe dysphagia occurs, sometimes associated with aspiration, dyspnea, pneumonia, and need to reestablish an airway.2

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

  • Advise patients and/or caregivers to seek immediate medical attention if unexpected muscle weakness or swallowing, speech, or respiratory disorders occur.2 371

  • 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).

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

  • 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.

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Botulinum Toxin Type B

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

5000 units/mL (of Clostridium botulinum Toxin Type B)

Myobloc

Solstice Neurosciences

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. 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

1. Allergan. Botox (botulinum toxin type A) purified neurotoxin complex prescribing information. Irvine, CA; 2006 Oct.

2. Solstice Neurosciences. Myobloc (botulinum toxin type B) injectible solution prescribing information. South San Francisco, CA; 2008 Sep.

3. Bell MS, Vermeulen LC, Sperling KB. Pharmacotherapy with botulinum toxin: harnessing nature’s most potent neurotoxin. Pharmacotherapy. 2000; 20:1079-91. [IDIS 453589] [PubMed 10999501]

4. Munchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ. 2000; 320:161-5. [IDIS 441486] [PubMed 10634738]

5. Allergan. Botox Cosmetic (botulinum toxin type A) purified neurotoxin complex prescribing information. Irvine, CA; 2008 Apr.

6. Arthurs B, Flanders M, Codere F et al. Treatment of blepharospasm with medication, surgery and type A botulinum toxin. Can J Ophthalmol. 1987; 22:24-8. [PubMed 3815152]

7. Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: double-blind, placebo-controlled study. Neurology. 1987; 37:616-23. [IDIS 228452] [PubMed 3561773]

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