Botox

BOTOXÆ belongs to a class of drugs called botulinum toxins. BOTOXÆ, a focal muscle-relaxing agent, is the brand of botulinum toxin type A made by Allergan. BOTOXÆ is the most studied brand of botulinum toxins and has been used to treat over 1 million patients worldwide for more than 11 years.
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What is Botox?

BOTOXÆ is a formulation of botulinum toxin type A. It is derived from the bacterium Clostridium botulinum. More than 100 years of research have expanded our knowledge of botulinum toxin type A from the identification of the bacterium Clostridium botulinum to the commercialization of botulinum toxin type A as BOTOXÆ.

In the 1960s, the muscle-relaxing properties of botulinum toxin type A were tapped for investigational use in realigning crossed eyes. These early studies paved the way for treating other conditions caused by overactive muscles with botulinum toxin type A.

Today, BOTOXÆ is produced in controlled laboratory conditions and given in extremely small therapeutic doses. It has helped over 1 million patients worldwide with conditions caused by overactive muscles.

Is Botox a new treatment?

No. BOTOXÆ has been used for more than 11 years to treat over 1 million patients worldwide, and it is approved by the health ministries of at least 70 countries.

How is Botox different from other botulinum toxin treatments?

BOTOXÆ is Allergan's brand of botulinum toxin type A. A brand of botulinum toxin type B is also now available. The two toxins are different in several ways:

… They are different serotypes

… They have different manufacturing processes

… They work differently

… They require different doses

How is Botox different from oral treatments?

BOTOXÆ differs from oral therapies in that it is a non-systemic, focal therapy. When drugs are taken orally, they are distributed throughout the body by the blood system. The drugs reach not only their desired site of action but also many additional sites. In contrast, BOTOXÆ is administered directly into the desired site of action. BOTOXÆ is not expected to be present in the blood stream at measurable levels following injection at the recommended doses.

Why should you have confidence in Botox?

BOTOXÆ provides targeted relief of symptoms for the treatment of neck pain and abnormal head position in Cervical Dystonia with

… No GI upset

… No fatigue

… No confusion

… No depression

… No liver toxicity

BOTOXÆ has been proven as a safe and effective therapy, and has been widely used for more than 11 years.

Over the past 20 years, BOTOXÆ has been evaluated in more than 200 studies specific to approved indications in the US. Currently, little clinical data are published about botulinum toxin type B.

How does Botox work?

Normally, your brain sends electrochemical messages to your muscles to make them contract and move. These messages are transmitted from a nerve to the muscle by a substance called acetylcholine. When too much acetylcholine is released, muscles become overly active and spasm or tense up.

BOTOXÆ blocks the nerve from releasing acetylcholine. As a result, the muscle spasms stop or are greatly reduced, providing relief from symptoms. Your health care provider will know how much BOTOXÆ is needed to treat you effectively.

It's important to remember that botulinum toxin treatment is not a cure. For many people, however, its effects have been dramatic. With BOTOXÆ, the nerve will take about 3 months to recover and begin to release acetylcholine, and the muscles may become overactive again. At that point, another injection will be needed to provide relief, as long as no allergic reactions or other significant side effects occurred and clinical response was obtained.

How long can I be treated with Botox?

Each treatment typically lasts 3 months and can be repeated as long as your condition responds to BOTOXÆ and you do not have any serious allergic reactions or other significant side effects. BOTOXÆ has been used for more than 11 years to treat more than 1 million patients worldwide, and although formal, long-term clinical evaluations have not been conducted, its safety in long-term use has been well established.

Although most people continue to respond to BOTOXÆ injections, some people have experienced a diminished response over time. There may be several explanations for this:

1. Changes in your condition - If the pattern of your muscle activity changes, your health care provider may need to inject new muscles and/or change your dose. Identifying and injecting the affected muscle can be difficult, complicated by the changing pattern of muscle involvement and progression of the disorder.

2. Setting appropriate expectations - You may believe your first BOTOXÆ injection was more helpful than subsequent injections. That's because your condition was perhaps quite severe when you had your first injection. Subsequent injections are usually given before your condition becomes that severe again. Therefore, the relief you experienced with subsequent injections may not have been as dramatic as the first time.

3. Antibody formation - When foreign proteins, like botulinum toxins, enter your body, antibodies may form. If antibodies to botulinum toxin develop, you may no longer respond to treatment.

Because botulinum toxins are usually used to treat chronic conditions, it's important to preserve responsiveness to therapy.

How can I help maintain my response to Botox?

While the critical factors for neutralizing antibody formation have not been well characterized, you may be able to help maintain your response to BOTOXÆ by minimizing your total exposure. The potential for antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between injections.

How is Botox given?

BOTOXÆ is injected into the affected muscle(s). Your doctor will determine which muscles need to be treated.

Does the injection hurt?

Some people report minor, temporary discomfort from the injection. BOTOXÆ is reconstituted with sterile, preservative-free, normal saline for injection. The neutral pH of the injected solution, in combination with the fine-gauge needle your doctor will use, can help to minimize any injection-related pain.

When will Botox start to work?

If you're receiving BOTOXÆ, you'll usually see the effects within 2 weeks of the injection. If you're receiving BOTOXÆ for blepharospasm, you'll usually see effects within 3 days.

How long will the effect last?

BOTOXÆ offers sustained relief, dose after dose. The relief you'll feel from one treatment of BOTOXÆ will normally last for about 3 months. Treatments can be continued as long as your condition responds to BOTOXÆ, and you do not have any serious allergic reactions or other significant side effects. When the relief begins to fade, you'll return to your doctor for your next treatment.

Usually, BOTOXÆ treatment is required approximately four times per year. Because symptoms can change over time, the amount and duration of relief you'll experience can vary. Consult your doctor, who can determine how to achieve the best possible results with BOTOXÆ.

What side effects have been seen with Botox?

The most frequently reported adverse reactions in patients receiving BOTOXÆ for the treatment of cervical dystonia are dysphagia (difficulty swallowing, 19%), upper respiratory infection (such as a cold or flu,12%), neck pain (11%), and headache (11%). Dysphagia is a commonly reported adverse event following treatment of cervical dystonia patients. In these patients, there are reports of rare cases of dysphagia serious enough to require the insertion of a gastric feeding tube (a tube for introducing nutritious, high-calorie fluids into the stomach.)

The most frequently reported treatment-related adverse reactions in patients receiving BOTOXÆ for the treatment of blepharospasm are ptosis (droopy eyelids, 20.8%), superficial punctuate keratitis (inflammation of the cornea characterized by small erosions of the tissue covering the cornea, 6.3%), and eye dryness (6.3%). Reduced blinking from BOTOXÆ injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect (a defect in the corneal covering) and corneal ulceration (a hollowed-out cavity in the cornea), especially in patients with VII nerve disorders.

In general, adverse reactions occur within the first week following injection of BOTOXÆ and, while generally transient, may last several months. Localized pain, tenderness and/or bruising may be associated with the injection. Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of adjacent muscles may also occur due to spread of toxin.

Please seek immediate medical attention if swallowing, speech, or respiratory (breathing) disorders arise.

Is Botox right for me?

Your health care provider can help you decide if BOTOXÆ is right for you. In order to make the right treatment decision, you should discuss the following with your health care provider before choosing treatment:

… Clinical experience with the drug

… Effectiveness and side effects

Make sure your health care provider knows if you are pregnant, nursing, or taking any medications before receiving BOTOXÆ injections. Additionally, you should not receive BOTOXÆ if you have an infection at the injection site.

BOTOXÆ should be used with caution if you have other neurological diseases or disorders, or if you are taking aminoglycoside antibiotics or other drugs that interfere with neuromuscular transmission. Be sure to tell your health care provider about any prescription or over-the-counter medications you are taking before receiving BOTOXÆ.

How can I find out if my insurance covers Botox?

The BOTOX ADVANTAGETM Program Reimbursement Hotline has been helping patients and physicians get answers to their BOTOXÆ reimbursement questions for years. In addition, BOTOXÆ has more than a decade of reimbursement experience with insurance carriers and health care providers. It is this experience that has resulted in BOTOXÆ coverage by most payers, including Medicare and Medicaid; particularly for cervical dystonia.

Some insurance plans cover BOTOXÆ under the medical benefit and others cover BOTOXÆ under the pharmacy benefit. To find out how BOTOXÆ is covered under your insurance plan, call the BOTOX ADVANTAGETM Program Reimbursement Hotline, toll-free, at 1-800-530-6680. Our knowledgeable Hotline staff is available to assist you with your insurance coverage questions Monday through Friday from 8:00 am to 6:00 pm ET.

Additionally, Hotline representatives will help physicians and patients research alternative coverage for those who do not have insurance or cannot qualify for government assistance. If the Hotline representatives cannot find alternative coverage, they will help determine if patients meet the criteria for the BOTOXÆ Patient Assistance Program. The BOTOXÆ Patient Assistance Program is available to all patients who lack insurance coverage and demonstrate financial need.

What about BOTOXÆ headache Treatment?
The BOTOXÆ headache Treatment has been found to give relief to headache sufferers. The treatment of severe headaches really belongs to neurologists, not plastic surgeons. But the BOTOXÆ headache Treatment help is gaining acceptance.

Dr. Richard Glogau, MD, UCSF professor of dermatology had produced a small study of 24 patients and reported that 75 percent of patients in his case study experienced 4 to 6 months of headache relief following injections of BOTOXÆÆ (botulinum toxin A) to muscles of the face and head in a presentation at the American Society of Dermatologic Surgery meeting (held November 2-5). This adds weight to previous reports that botulinum toxin A can relieve headaches. Two previous studies were presented at the 1999 meeting of the American Association for the Study of Headache. One study was reported by researchers at the Michigan Head Pain and Neurological Institute in Ann Arbor and Michigan State University spoke of dosage. Another study, reported by researchers at the University of California, Los Angeles, reported 51 percent of 96 patients reported complete improvement of their headache pain.

Following this discovery, Glogau and other researchers began to evaluate BOTOXÆ injection points and dosages that could alleviate headaches. Glogau's results indicate that botulinum toxin A injected into the muscles of the brow, eyes, forehead, side of the head and back of the head near the neck (a point that earlier investigators have neglected) induce sometimes immediate headache relief and provide benefit for up to six months. BOTOXÆ dosage in his case studies averaged 80 units per patient.

Dr. Glogau's case studies had long-standing diagnoses of headaches, had all seen neurologists, and were taking standard headache medications, including sumatriptan (Imitrex). Some required narcotic medication to relieve the pain of their frequent headaches. Most suffered headaches on a minimum of once a week and several suffered on a daily basis.

In addition to use in prevention of wrinkles, BOTOXÆ has been used to treat uncontrolled eye twitching, crossed eyes, muscle spasms and, most recently, excessive underarm sweating (reported by Dr. Glogau in the September, 1998 issue of Dermatologic Surgery).

"I think it was accepted pretty quickly," said Emory University neurologist Dr. David Hewitt. "There are a number of people around the country who are using it off-label to treat headache."

In using BOTOXÆ to treat headaches and other severe headaches, there are still some questions -- such as what is the optimal dose, and where should BOTOXÆ be injected to get the best results? Two large studies are under way at headache clinics around the country that may provide those answers.

What is a BOTOXÆ Injection?

"BOTOXÆ injection" or "botox shot" is the term most widely used to describe the procedure of adminstering the Allergan BOTOXÆ Cosmetic treatement. BOTOXÆ injections utilize Botulinum Toxin Type A to treat wrinkles. BOTOXÆ Injections were originally slated to treat neurological disorders; today, BOTOXÆ injections are widely used to remove facial lines, especially frown lines, "crow's feet," and forehead lines.

BOTOX ³ FOR HEADACHE

Migraine headache and associated headaches such as muscle contraction and chronic tension headache and neck pain are all potentially relieved with the use of BOTOX ³. This medication was originally used to treat crossed eyes and later for conditions such as blepharospasm and torticollis (twisting necks) .Ý More recently, BOTOX ³ was used by cosmetic surgeons to produce minor paralysis of facial muscles around the eyes and smooth out wrinkles.Ý Many of the patients reported significant relief of a variety of types of headaches and various trials were instituted to prove that it works for the treatment of headache. 

Headaches are extremely common in the United States with an estimate of 30 million people affected such that they miss days from work or have chronic disability. 

BOTOX ³ (Botulinum Toxin Type A) for Headache

Botulinum Toxin Type A is a new therapeutic option for the preventive treatment of migraine and chronic tension type headache.Ý It offers several advantages over current drug therapy.Ý Injections are given in doses up to 100-300 units every three to four months.Ý When it is effective, the need for daily medications or acute medicines for severe attacks are significantly reduced or entirely eliminated.Ý There are few side effects from the injections, except for minimal discomfort at the time of injection, including a sensation of pinprick and a little burning with minor bleeding which is likened to a mosquito bite.  On rare occasions patients get aching in injected muscles, usually just for a few days. I have now performed over 1885 patient injections in more than 550 patients with an 75-87% improvement rate. 
( 05-29-2003 ).

Mechanism of Action

It is known that Botulinum toxin (BOTOX ³) can partially paralyze muscles.Ý Patients with blepharospasm and torticollis (so-called cervical dystonia) have been treated and have had significant improvement in motor activity with reduction of either the blepharospasm or the torticollis.Ý What has been noted is that there is often a reduction in pain that is more significant than the motor effect and the pain effect lasts longer.Ý It is quite likely that small fibers containing pain-producing chemicals such as Substance P are affected by Botulinum toxin.Ý It is also likely that there are other mechanisms, not yet understood, for the effect of Botulinum injections.Ý None of these theories are yet proven. 

History

In the early 1990's,  Dr. William Binder, an Otolaryngologist who used Botulinum toxin for cosmetic purposes in the muscles around the eye noted that a number of patients reported decreases in migraine headache.Ý Thereafter, gradually, the number of physicians using BOTOX ³ for headache has increased.Ý There is significant clinical evidence now that Botulinum toxin type A (BOTOX ³) reduces the pain in migraine, muscle contraction headache, chronic tension headache and neck muscle spasm. 

Types of Injections

Muscles about the eyes and forehead are injected with small amounts of Botulinum toxin.Ý In our practice, usually the muscles between the eyebrows and above the eyes are injected with approximately 4 units in each of 4-6 different injections.Ý Thereafter, a series of three injections are made around the outside of the eye on the side.Ý Then injections are made into the temporal region and sometimes the jaw where the masseter muscle is located.Ý These are the only injections made in patients who only experience frontal pain with their headaches. 

On the other hand, many patients have headaches that involve the entire head, down the back of the neck, into the upper shoulders.Ý In this situation, an additional 50-100 units are injected, 25-35 units on each side, starting at the upper back of the neck and going down onto the shoulders.Ý The shoulder joint is not injected.Ý Sometimes if the pain or muscle spasm goes down between the shoulder blades we inject those muscles as well.

Timing of Injection and Duration of Effect

The majority of studies and treatment patterns to date have been based on earlier experiences with blepharospasm in which patients usually need to be reinjected every three months.Ý However, there are some unusual patients who need to have the blepharospasm muscles about the eye injected only once every two years.Ý After a patient receives a Botulinum toxin injection, there may be an immediate effect just from the use of needles into muscles.Ý In a Scandinavian study, it was found that dry needle injections into muscles such as trigger-point areas in fibromyalgia were significantly improved even though nothing was injected for a period of up to one week.Ý This may be the initial effect sometimes seen in migraine patients.Ý This effect is the exception rather than the rule.Ý Usually, patients do not begin to experience relief from their headache for two to three weeks.Ý Thereafter, however, the effect may increase and have a duration of three to four months.  

When a second injection is performed, the effect appears to last longer--up to four to six months. We speculate, based upon our experience and that of others, that after the third injection, the effect again may last four to six months.Ý Of course, additional information and patient experience is needed before there is definitive proof. 

Summary

BOTOX ³ is a new treatment for migraine.Ý It works in chronic muscle tension-type headache in up to 87 percent.Ý It also is quite effective in some patients who are not responding to any migraine preventive therapy.Ý Our estimate of effect in this population is 75 percent.Ý Overall, this is believed to be an effective, low risk treatment.  In many instances this is a less expensive alternative than chronic daily therapy or frequent use of triptan medication.Ý Nonetheless, BOTOX ³ does not work in every patient and alternative therapies must be kept in mind.

Botox Irons Out Tough Headaches

June 18, 2002 -- New research presented this week at the annual meeting of the American Headache Society offers powerful evidence that the hottest thing in cosmetic medicine is also a powerful new tool for preventing hard-to-treat chronic headaches. Some 13 studies involving more than 650 patients with migraines and frequent tension headaches were presented at the Seattle meeting. Among the major findings:

… Roughly 90% of patients in one study did well on Botox, even though they had responded poorly to an average of three other medications in the past.

… The injections seem to be especially useful for patients who experience more than 15 headaches a month and who get little relief from standard treatments.

… In one study, 68% of those who responded had reductions in migraine-related disability of 75% or more. Responders had an average decrease of 61% in headache frequency and 27% in headache severity.

A purified form of the toxin that causes the deadly food poisoning botulism, Botox is believed to work in migraine patients by deadening the neurotransmitters that cause headache pain in much the same way that it paralyzes facial muscles to reduce wrinkles. Patients typically receive 10 to 25 injections in the head, neck, and shoulders during a treatment cycle, and the effect tends to last for three or four months. Overall, about 84% of all patients reported improvement in their headache pain. Among patients who received four cycles of Botox, 92% improved. Researchers from Houston's Baylor College of Medicine Headache Clinic reported on 60 patients with chronic daily headaches treated with either Botox injections or placebo injections containing only water. After 12 weeks, more than half of those treated with Botox (53%) reported moderate improvement in headaches, compared to 7% of those given the placebo injections. Patients who received two cycles of Botox had better responses than those who received just one cycle. Botox won FDA approval as a wrinkle remedy in April, but it has not been approved for migraines. Most health insurance companies do not currently cover the treatments, which cost between $800 and $1,000 a cycle.