Myobloc

This medicine is injected into a muscle. A doctor, nurse, or other healthcare provider will give you this injection. Myobloc injections should be spaced at least 3 months apart.

Your injection may be given into more than one area at a time, depending on the condition being treated.

The effects of a Myobloc injection are temporary. Your symptoms may return completely within 3 months after an injection. After repeat injections, it may take less and less time before your symptoms return, especially if your body develops antibodies to the botulinum toxin.

Do not seek botulinum toxin injections from more than one medical professional at a time. If you switch healthcare providers, be sure to tell your new provider how long it has been since your last botulinum toxin injection.

Using this medicine more often than prescribed will not make it more effective and may result in serious side effects.

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

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 hyperhidrosis†157 160 261 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 lines†156 338 in a limited number of individuals; efficacy evidence and experience are limited.152 156 310 337 338

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

• 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.

• 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.)

In the U.S.

• Myobloc

Available Dosage Forms:

• Solution

Therapeutic Class: Cervical Agent

Pharmacologic Class: Neuromuscular Blocker, Non-Depolarizing

• Tell all of your health care providers that you take Myobloc. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this medicine affects you.
• Do not switch between different forms of Myobloc without first talking with the doctor.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Only 9 subjects without a prior history of tolerating injections of type A botulinum toxin have been studied. Treatment of botulinum toxin naïve patients should be initiated at lower doses of Myobloc (see ADVERSE REACTIONS: Overview).

INFORMATION FOR PATIENTS

The physician should provide a copy of the FDA-Approved Patient Medication Guide and review the contents with the patient. Patients should be advised to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking or breathing), or if any existing symptom worsens.

Patients should be counseled that if loss of strength, muscle weakness, or impaired vision occur, they should avoid driving a car or engaging in other potentially hazardous activities.

DRUG INTERACTIONS

Co-administration of Myobloc and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated.

The effect of administering different botulinum neurotoxin serotypes at the same time or within less than 4 months of each other is unknown. However, neuromuscular paralysis may be potentiated by co-administration or overlapping administration of different botulinum toxin serotypes.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

No long-term carcinogenicity studies in animals have been performed.

PREGNANCY

Animal reproduction studies have not been conducted with Myobloc. It is also not known whether Myobloc can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Myobloc should be given to a pregnant woman only if clearly needed.

NURSING MOTHERS

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Myobloc is administered to a nursing woman.

PEDIATRIC USE

Safety and effectiveness in pediatric patients have not been established.

GERIATRIC USE

In the controlled studies summarized in CLINICAL STUDIES, for Myobloc treated patients, 152 (74.5%) were under the age of 65, and 52 (25.5%) were aged 65 or greater. For these age groups, the most frequent reported adverse events occurred at similar rates in both age groups. Efficacy results did not suggest any large differences between these age groups.

Very few patients aged 75 or greater were enrolled, therefore no conclusions regarding the safety and efficacy of Myobloc within this age group can be determined.

Myobloc is provided as a clear and colorless to light-yellow sterile injectable solution in single-use 3.5-mL glass vials. Each single-use vial of formulated Myobloc contains 5,000 Units1 of botulinum toxin type B per milliliter in 0.05% human serum albumin, 0.01 M sodium succinate, 0.1 M sodium chloride at approximately pH 5.6.

Myobloc is available in the following three presentations.

Store under refrigeration at 2°- 8°C (36°- 46°F).

DO NOT FREEZE. DO NOT SHAKE.

Protect from light. No U.S. Standard of Potency.

Ready to use; no reconstitution required. The recommended storage condition for Myobloc is refrigeration at 2°-8°C.

Myobloc may be diluted with normal saline. Once diluted, the product must be used within 4 hours as the formulation does not contain a preservative.

All vials of expired Myobloc and equipment used in the administration of Myobloc should be carefully discarded according to standard medical waste practices.

Do not use after the expiration date stamped on the vial.

Discard unused portion.

Single-use vial.

Rx ONLY

Manufactured By:

Solstice Neurosciences, Inc., South San Francisco, CA 94080

U.S. License No. 1718

"Myobloc" and the "Myobloc Logo" are registered trademarks of

Solstice Neurosciences, Inc.

Protected by U.S. Patent No. 6,290,961; 6,632,433; 6,872,397; 6,887,476

© 2010 Solstice Neurosciences, Inc.

704361
Rev. 05/10

SNI-MYO424-0410

Applies to botulinum toxin type b: intramuscular solution

Along with its needed effects, botulinum toxin type b (the active ingredient contained in Myobloc) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking botulinum toxin type b:

• Difficulty with swallowing
• infection
• neck pain
• uncontrolled twisting movements of the neck

• Difficulty with breathing or speaking
• muscle weakness

Some side effects of botulinum toxin type b may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• back pain
• belching
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• cough
• difficulty with moving
• dizziness
• dry mouth
• flu-like syndrome
• headache
• heartburn or indigestion
• lack or loss of strength or energy
• muscle pain, stiffness, or weakness
• nausea
• pain, swelling, or redness in the joints
• stomach discomfort, upset, or pain

Some side effects of botulinum toxin type b may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them: