BOTOX^® is indicated for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia.

BOTOX^® is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents.

BOTOX^® is indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above.

The efficacy of BOTOX^® treatment in deviations over 50 prism diopters, in restrictive strabismus, in Duane's syndrome with lateral rectus weakness, and in secondary strabismus caused by prior surgical over-recession of the antagonist has not been established. BOTOX^® is ineffective in chronic paralytic strabismus except when used in conjunction with surgical repair to reduce antagonist contracture.

BOTOX^® is supplied in a single use vial. Because the product and diluent do not contain a preservative, once opened and reconstituted, store in a refrigerator and use within four hours. Discard any remaining solution. Do not freeze reconstituted BOTOX^®.

BOTOX^® is to be reconstituted with sterile, non-preserved saline prior to intramuscular injection.

An injection of BOTOX^® is prepared by drawing into an appropriately sized sterile syringe an amount of the properly reconstituted toxin (see Dilution Table) slightly greater than the intended dose. Air bubbles in the syringe barrel are expelled and the syringe is attached to an appropriate injection needle. Patency of the needle should be confirmed. Anew, sterile, needle and syringe should be used to enter the vial on each occasion for removal of BOTOX^®.

The method utilized for performing the potency assay is specific to Allergan’s Botulinum Toxin Type A. Due to specific details of this assay such as the vehicle, dilution scheme and laboratory protocols for the various potency assays, Units of biological activity of Botulinum Toxin Type Acannot be compared to nor converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method. Therefore, differences in species sensitivities to different botulinum neurotoxin serotypes precludes extrapolation of animal dose-activity relationships to human dose relationships.

The phase 3 study enrolled patients who had extended histories of receiving and tolerating BOTOX^® injections, with prior individualized adjustment of dose. The mean BOTOX^® dose administered to patients in the phase 3 study was 236 Units (25th to 75th percentile range 198 Units to 300 Units). The BOTOX^® dose was divided among the affected muscles (see Clinical Studies: Cervical Dystonia). Dosing in initial and sequential treatment sessions should be tailored to the individual patient based on the patient’s head and neck position, localization of pain, muscle hypertrophy, patient response and adverse event history.

The initial dose for a patient without prior use of BOTOX^® should be at a lower dose, with subsequent dosing adjusted based on individual response. Limiting the total dose injected into the sternocleido-mastoid muscles to 100 Units or less may decrease the occurrence of dysphagia (see Precautions: Cervical Dystonia).

A 25, 27 or 30 gauge needle may be used for superficial muscles, and a longer 22 gauge needle may be used for deeper musculature. Localization of the involved muscles with electromyographic guidance may be useful.

Clinical improvement generally begins within the first two weeks after injection with maximum clinical benefit at approximately six weeks post-injection. In the phase 3 study most subjects were observed to have returned to pre-treatment status by 3 months post-treatment.

The recommended dose is 50 Units per axilla. The hyperhidrotic area to be injected should be defined using standard staining techniques, e.g., Minor’s Iodine-Starch Test. BOTOX^® is reconstituted with 0.9% non-preserved sterile saline (100 Units/4 mL). Using a 30 gauge needle, 50 Units of BOTOX^® (2mL) is injected intradermally in 0.1 to 0.2 mL aliquots to each axilla evenly distributed in multiple sites (10-15) approximately 1-2 cm apart.

Repeat injections for hyperhidrosis should be administered when the clinical effect of a previous injection diminishes.

Instructions for the Minor’s Iodine Starch Test Procedure : Patients should shave underarms and abstain from use of over-the-counter deodorants or antiperspirants for 24 hours prior to the test. Patient should be resting comfortably without exercise, hot drinks, etc. for approximately 30 minutes prior to the test. Dry the underarm area and then immediately paint it with iodine solution. Allow the area to dry, then lightly sprinkle the area with starch powder. Gently blow off any excess starch powder. The hyperhidrotic area will develop a deep blue-black color over approximately 10 minutes.

Each injection site has a ring of effect of up to approximately 2 cm in diameter. To minimize the area of no effect, the injection sites should be evenly spaced as shown in Figure 1:

Figure 1:

Each dose is injected to a depth of approximately 2mm and at a 45° angle to the skin surface with the bevel side up to minimize leakage and to ensure the injections remain intradermal.

If injection sites are marked in ink do not inject BOTOX^® directly through the ink mark to avoid a permanent tattoo effect.

For blepharospasm, reconstituted BOTOX^® (see Dilution Table) is injected using a sterile, 27 - 30 gauge needle without electromyographic guidance. The initial recommended dose is 1.25 - 2.5 Units (0.05 mL to 0.1 mLvolume at each site) injected into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid. Avoiding injection near the levator palpebrae superioris may reduce the complication of ptosis. Avoiding medial lower lid injections, and thereby reducing diffusion into the inferior oblique, may reduce the complication of diplopia. Ecchymosis occurs easily in the soft eyelid tissues. This can be prevented by applying pressure at the injection site immediately after the injection.

In general, the initial effect of the injections is seen within three days and reaches a peak at one to two weeks post-treatment. Each treatment lasts approximately three months, following which the procedure can be repeated. At repeat treatment sessions, the dose may be increased up to two-fold if the response from the initial treatment is considered insufficient-usually defined as an effect that does not last longer than two months. However there appears to be little benefit obtainable from injecting more than 5.0 Units per site. Some tolerance may be found when BOTOX^® is used in treating blepharospasm if treatments are given any more frequently than every three months, and is rare to have the effect be permanent.

The cumulative dose of BOTOX^® treatment in a 30-day period should not exceed 200 Units.

BOTOX^® is intended for injection into extraocular muscles utilizing the electrical activity recorded from the tip of the injection needle as a guide to placement within the target muscle. Injection without surgical exposure or electromyographic guidance should not be attempted. Physicians should be familiar with electromyographic technique.

To prepare the eye for BOTOX^® injection, it is recommended that several drops of a local anesthetic and an ocular decongestant be given several minutes prior to injection.

Note: The volume of BOTOX^® injected for treatment of strabismus should be between 0.05 - 0.15 mLper muscle.

The initial listed doses of the reconstituted BOTOX^® (see Dilution Table below) typically create paralysis of injected muscles beginning one to two days after injection and increasing in intensity during the first week. The paralysis lasts for 2-6 weeks and gradually resolves over a similar time period. Overcorrections lasting over six months have been rare. About one half of patients will require subsequent doses because of inadequate paralytic response of the muscle to the initial dose, or because of mechanical factors such as large deviations or restrictions, or because of the lack of binocular motor fusion to stabilize the alignment.

I. Initial doses in Units. Use the lower listed doses for treatment of small deviations. Use the larger doses only for large deviations.

A. For vertical muscles, and for horizontal strabismus of less than 20 prism diopters: 1.25 - 2.5 Units in any one muscle.

B. For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5 - 5.0 Units in any one muscle.

C. For persistent VI nerve palsy of one month or longer duration: 1.25 - 2.5 Units in the medial rectus muscle.

II. Subsequent doses for residual or recurrent strabismus.

A. It is recommended that patients be re-examined 7-14 days after each injection to assess the effect of that dose.

B. Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose comparable to the initial dose.

C. Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to two-fold compared to the previously administered dose.

D. Subsequent injections should not be administered until the effects of the previous dose have dissipated as evidenced by substantial function in the injected and adjacent muscles.

E. The maximum recommended dose as a single injection for any one muscle is 25 Units.

Prior to injection, reconstitute vacuum-dried BOTOX^®, with sterile normal saline without a preservative; 0.9% Sodium Chloride Injection is the only recommended diluent. Draw up the proper amount of diluent in the appropriate size syringe, and slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently mix BOTOX^® with the saline by rotating the vial. Record the date and time of reconstitution on the space on the label. BOTOX^® should be administered within four hours after reconstitution.

During this time period, reconstituted BOTOX^® should be stored in a refrigerator (2° to 8°C). Reconstituted BOTOX^® should be clear, colorless and free of particulate matter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and whenever the solution and the container permit. Dilution Table

Note: These dilutions are calculated for an injection volume of 0.1 mL. A decrease or increase in the BOTOX^® dose is also possible by administering a smaller or larger injection volume - from 0.05 mL(50% decrease in dose) to 0.15 mL(50% increase in dose.)

BOTOX^® is supplied in a single use vial. Each vial contains 100 Units of vacuum-dried Clostridium botulinum type Aneurotoxin complex. NDC 0023-1145-01.

Vials of BOTOX^® have a holographic film on the vial label that contains the name "Allergan" within horizontal lines of rainbow color. In order to see the hologram, rotate the vial back and forth between your fingers under a desk lamp or fluorescent light source. (Note: the holographic film on the label is absent in the date/batch area.) If you do not see the lines of rainbow color or the name "Allergan", do not use the product and contact Allergan for additional information at (800) 890-4345 from 8:00 a.m. to 4:00 p.m. Pacific time.

Unopened vials of BOTOX^® should be stored in a refrigerator (2°to 8°C) for up to 24 months. Do not use after the expiration date on the vial. Administer BOTOX^® within 4 hours of reconstitution; during this period reconstituted BOTOX^® should be stored in a refrigerator (2° to 8°C). Reconstituted BOTOX^® should be clear, colorless and free of particulate matter.

All vials, including expired vials, or equipment used with the drug should be disposed of carefully as is done with all medical waste.

6. Wang YC, Burr DH, Korthals GJ, Sugiyama H. Acute toxicity of aminoglycoside antibiotics as an aid in detecting botulism. Appl Environ Microbiol 1984;48:951-955.

^® Marks owned by Allergan, Inc., Revised: July 2004, Manufactured by: Allergan Pharmaceuticals Ireland a subsidiary of: Allergan, Inc., 2525 Dupont Dr., Irvine, CA92612

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