Botox
Botox Information
Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex is a sterile, vacuum-dried form of purified botulinum toxin type A, produced from a culture of the Hall strain of Clostridium botulinum grown in a medium containing N-Z amine and yeast extract. Botox is purified from the culture solution by a series of acid precipitations to a crystalline complex consisting of the active high molecular weight toxin protein and an associated hemagglutinin protein. The crystalline complex is re-dissolved in a solution containing saline and albumin and sterile filtered (0.2 microns) prior to vacuum-drying.
Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex 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.
However, since FDA ruled Botox use legal, it has been used as an anti-aging drug, in the form of Botox Cosmetic.
Botox Cosmetic is the product name for Allergans cosmetic wrinkle removing drug. Botox Cosmetic is a therapeutic muscle-relaxing agent that works at motor nerve endings (nerves that lead to muscles). Botox Cosmetic is a drug used for the temporary improvement in the appearance of moderate to severe glabellar lines (frown lines). These frown lines come from muscles called corrugator and/or procerus muscles. Botox Cosmetic is the name used for the process of injecting the Botox Cosmetic product into the patient.
The efficacy of Botox Purified Neurotoxin Complex 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 is doubtful, or multiple injections over time may be required. Botox is ineffective in chronic paralytic strabismus except to reduce antagonist contracture in conjunction with surgical repair. Presence of antibodies to botulinum toxin type A may reduce the effectiveness of Botox Purified Neurotoxin Complex therapy. In clinical studies, reduction in effectiveness due to antibody production has occurred in one patient with blepharospasm receiving three doses of Botox over a six week period totaling 92 U, and in several torticollis patients who received multiple doses experimentally, totaling over 300 U in a one month period. For this reason, the dose of Botox for strabismus and blepharospasm should be kept below 200 U in a one month period.
How Does Botox Work?
Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, Botox produces a localized chemical denervation muscle paralysis. When the muscle is chemically denervated, it atrophies and may develop extrajunctional acetylcholine receptors. There is evidence that the nerve can sprout and reinnervate the muscle, with the weakness thus being reversible.
The paralytic effect on muscles injected with Botox Purified Neurotoxin Complex is useful in reducing the excessive, abnormal contractions associated with blepharospasm. When used for the treatment of strabismus, it is postulated that the administration of Botox affects muscle pairs by inducing an atrophic lengthening of the injected muscle and a corresponding shortening of the muscle's antagonist. Following peri-ocular injection of Botox, distant muscles show electrophysiologic changes but no clinical weakness or other clinical change for a period of several weeks or months, parallel to the duration of local clinical paralysis.
Botox Ingredients and Composition
How To Take Botox and Botox Dosage and Administration
Strabismus
Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex 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. Botox Injection without surgical exposure or electromyographic guidance should not be attempted. Physicians should be familiar with electromyographic technique.
An injection of Botox Purified Neurotoxin Complex is prepared by drawing into a sterile 1.0 mL tuberculin syringe an amount of the properly diluted toxin slightly greater than the intended dose. Air bubbles in the syringe barrel are expelled and the syringe is attached to the electromyographic injection needle, preferably a 1.5 inch, 27 gauge needle. Injection volume in excess of the intended dose is expelled through the needle into an appropriate waste container to assure patency of the needle and to confirm that there is no syringe-needle leakage. A new sterile, needle and syringe should be used to enter the vial on each occasion for dilution or removal of Botox.
To prepare the eye for Botox Purified Neurotoxin Complex 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 Purified Neurotoxin Complex injected for treatment of strabismus should be between 0.05 mL to 0.15 mL per muscle.
Strabismus dosage: The initial listed doses of the diluted Botox Purified Neurotoxin Complex 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. Botox 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.
Initial doses for Strabismus treatment in units (abbreviated as U).
Use the lower listed doses for treatment of small deviations. Use the larger doses only for large deviations.
- For vertical muscles, and for horizontal strabismus of less than 20 prism diopters: 1.25 U to 2.5 U in any one muscle.
- For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5 U to 5.0 U in any one muscle.
- For persistent VI nerve palsy of one month or longer duration: 1.25 U to 2.5 U in the medial rectus muscle.
Subsequent doses for residual or recurrent Strabismus.
- It is recommended that patients be re-examined 7-14 days after each injection to assess the effect of that dose.
- Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose comparable to the initial dose.
- Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to twice the size of the previously administered dose.
- 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.
- The maximum recommended dose as a single injection for any one muscle is 25 U.
Blepharospasm
For blepharospasm, diluted Botox Purified Neurotoxin Complex is injected using a sterile, 27 - 30 gauge needle without electromyographic guidance. 1.25 U to 2.5 U ( 0.05 mL to 0.1 mL volume 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 is the initial recommended dose. In general, the initial effect of the Botox 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 indefinitely. 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 U per site. Some tolerance may be found when Botox isused 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 Purified Neurotoxin Complex in a 30-day period should not exceed 200 U.
Dilution Technique
To reconstitute vacuum-dried Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex, use sterile normal saline without a preservative; 0.9% Sodium Chloride Injection is the recommended diluent. Draw up the proper amount of diluent in the appropriate size syringe. Since Botox is denatured by bubbling or similar violent agitation, inject the diluent into the vial gently. Discard the vial if a vacuum does not pull the diluent into the vial. Record the date and time of reconstitution on the space on the label.
Botox should be administered within four hours after reconstitution.
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. The use of one vial for more than one patient is not recommended because the product and diluent do not contain a preservative.
If you suspect a Botox Overdose
In the event of Botox overdosage or injection into the wrong muscle, additional information may be obtained by contacting Allergan, Inc. at (800) 433-8871 from 8:00 a.m. to 4:00 p.m. Pacific Time, or at (714) 246-5954 for a recorded message at other times.
Botox Side Effects
Botox Precautions and Contraindications
The recommended dosages and frequencies of administration for Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex should not be exceeded. There have not been any reported instances of systemic toxicity resulting from accidental injection or oral ingestion of Botox. Should accidental injection or oral ingestion occur, the person should be medically supervised for several days on an office or outpatient basis for signs or symptoms of systemic weakness or muscle paralysis. The entire contents of a vial is below the estimated dose for systemic toxicity in humans weighing 6 kg. or greater.
The safe and effective use of Botox (Botulinum Toxin Type A) Purified Neurotoxin Complex depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering Botox must understand the relevant neuromuscular and orbital anatomy and any alterations to the anatomy due to prior surgical procedures, and standard electromyographic techniques.
As with all biologic products, epinephrine and other precautions as necessary should be available should an anaphylactic reaction occur.
During the administration of Botox Purified Neurotoxin Complex for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred from needle penetrations into the orbit. It is recommended that appropriate instruments to decompress the orbit be accessible. Ocular (globe) penetrations by needles have also occurred. An ophthalmoscope to diagnose this condition should be available.
Reduced blinking from Botox Purified Neurotoxin Complex injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. One case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatmentof any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.
Botox Drug Interactions
The effect of botulinum toxin may be potentiated by aminoglycoside antibiotics or any other drugs that interfere with neuromuscular transmission. Caution should be exercised when Botox Purified Neurotoxin Complex is used in patients taking any of these drugs.
Botox Experiences and Results
In one study, botulinum toxin was evaluated in 27 patients with essential blepharospasm. Twenty-six of the patients had previously undergone drug treatment utilizing benztropine mesylate, clonazepam and/or baclofen without adequate clinical results. Three of these patients then underwent muscle stripping surgery still without an adequate outcome. One patient of the 27 was previously untreated. Upon using botulinum toxin, 25 of the 27 patients reported improvement within 48 hours. One of the other patients was later controlled with a higher dosage. The remaining patient reported only mild improvement but remained functionally impaired.
In another study, 12 patients with blepharospasm were evaluated in a double-blind, placebo-controlled study. All patients receiving botulinum toxin (n=8) were improved compared with no improvements in the placebo group (n=4). The mean dystonia score improved by 72%, the self-assessment score rating improved by 61%, and a videotape evaluation rating improved by 39%. The effects of the treatment lasted a mean of 12.5 weeks.
One thousand six hundred eighty-four patients with blepharospasm evaluated in an open trial showed clinical improvement lasting an average of 12.5 weeks prior to the need for retreatment.
Six hundred seventy-seven patients with strabismus treated with one or more injections of Botox Purified Neurotoxin Complex were evaluated in an open trial. Fifty-five percent of these patients were improved to an alignment of 10 prism diopters or less when evaluated six months or more following injection. These results are consistent with results from additional open label trials which were conducted for this indication.
Taking Botox during Pregnancy or Breast-feeding
Animal reproduction studies have not been conducted with Botox Purified Neurotoxin Complex. It is also not known whether Botox can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Botox should be administered to pregnant women only if clearly needed.
It is not known whether Botox is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Botox Purified Neurotoxin Complex is administered to a nursing woman.
Botox and Children
Safety and effectiveness in children below the age of 12 have not been established.
Storing Botox
Botox should be administered within four hours after reconstitution.
During this time period, reconstituted Botox Purified Neurotoxin Complex should be stored in a refrigerator (2°C to 8°C).
Additional Notes
Patients with blepharospasm may have been extremely sedentary for a long time. Sedentary patients should be cautioned to resume activity slowly and carefully following the administration of Botox Purified Neurotoxin Complex.
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
Articles and information related to Botox
