CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.
When you choose BOTOX® Cosmetic, you can trust in its established track record. Backed by over 15 years of clinical studies, BOTOX® Cosmetic is the most widely researched and studied treatment of its kind, approved for use in 96 countries. The safety and efficacy of BOTOX® Cosmetic has been described in more than 495 peer-reviewed articles in scientific and medical journals.
This is where Botox comes into play. When you get consistent Botox injections, you prevent potential wrinkle formations from getting deeper or worse. Botox limits the range of facial muscle movement (when done skillfully, your face will not get that frozen look) so that wrinkles don't worsen over time. If you have a bad habit of frowning or lifting your brows for no reason, consistent Botox injections can also help your face kick these bad habits and therefore prevent any potential lines from getting etched in your skin. Getting frequent Botox injections may also help relax your facial muscles so that you don't need as a high a dose or as frequent as an injection to maintain your results.
Unlike a face lift or other kind of invasive facial rejuvenation procedure, treatment takes minutes and requires zero downtime. Using a very fine needle, Botox is injected into the facial muscles that are responsible for unsightly wrinkles and fine lines and relaxes the muscles. The ingredients in Botox block the signal from the nerve to the muscle, and therefore reduce it’s ability to contract, and form unsightly wrinkles.
The safety and effectiveness for the treatment of anatomic regions other than the mid-face with JUVÉDERM VOLUMA® XC; facial wrinkles and folds with JUVÉDERM® Ultra XC, JUVÉDERM® Ultra Plus XC, and JUVÉDERM VOLLURE™ XC; and the lips and perioral area with JUVÉDERM® Ultra XC and JUVÉDERM VOLBELLA® XC have not been established in controlled clinical studies
The American Migraine Foundation recently launched the American Registry for Migraine Research, or ARMR. ARMR collects information and biospecimens from patients living with migraine and other disorders that cause head pain. ARMR will be used to help health care providers and scientists better understand the causes, characteristics, and management of migraine and other headache types. Anonymized ARMR data will be made available to researchers who apply for access, enhancing the efficiency by which headache research can be conducted. Dr. Todd Schwedt, Professor of Neurology at the Mayo Clinic in Scottsdale, Arizona, and co-principal investigator of ARMR, expands on the registry.
Botox is so commonplace these days that you can get it done at some gyms and spas, but in these cases, you never know what you’re getting, how old the product is, with what it's mixed, and whether the injector knows what he or she is doing. Dr. Matarasso suggests only getting it done by what he calls the “core four”: a board-certified physician who is either a dermatologist, a plastic surgeon, an ear-nose-and-throat doctor, or an ophthalmologist.
In patients who are not catheterizing, post-void residual (PVR) urine volume should be assessed within 2 weeks post treatment and periodically as medically appropriate up to 12 weeks, particularly in patients with multiple sclerosis or diabetes mellitus. Depending on patient symptoms, institute catheterization if PVR urine volume exceeds 200 mL and continue until PVR falls below 200 mL. Instruct patients to contact their physician if they experience difficulty in voiding as catheterization may be required.
In many children, there are a few muscle groups that can have very active spasticity. A more focal approach to these muscles would be better than a widespread approach. In this case a doctor may advise a nerve block to interrupt the signal to the muscle that is spastic. Once the signal that is carried to the muscle by the nerve is interrupted, the spasticity will decrease.
The number of headache days determines whether the patient has episodic migraine (EM) (14 or fewer headache days a month) or CM (more than 15 days of headache a month). The best method of determining the actual number of headache days is to subtract this from the number of completely headache-free days in a month. If headache is present on more than half the days in the month, and there are migraine features on at least 8 days a month, the condition is termed CM. The migraine features only have to be present on 8 days out of the month and not on every headache day. The other headache days in this condition are considered to be milder forms of migraine, and they do not have all the typical migraine features. If headache is present on fewer than 15 days a month, this is referred to as EM. EM can transform to CM over time. If analgesics are used on 10 or more days per month, this can lead to a transformation to CM. The patient’s headache pattern over a 12-month period should be determined, and during this time, there should be at least 3 months with 15 headache days; 8 of these days should meet migraine criteria.1-3
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Galli’s winning film presents herself, and people with migraine, as superheroes, living with a secret identity: migraine. “Other than me laying down on my couch, and knowing what's going on inside my body, nobody sees what's happening,” she says. “It's all happening inside. It's like that same struggle that superheroes have.” The migraine symptoms are superpowers, albeit ones that you don’t want. When her migraine attacks first began, Galli recalls an increased sensitivity to sound, odors, light and “all these things that feel not normal.” Many people with migraine are fighting the disease on their own, because their peers can’t relate to what their feeling on a daily basis. “It's time that we create better awareness and we tell the world that no, we don't need to be alone,” she says. “We don't need to fight alone and hide in the dark.” The film, she hopes, will add to the conversation and bring this disease out of the shadows. For the more than 37 million Americans living with migraine, Galli says: “You’re all superheroes. I hear you, I feel you.”
Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, serum sickness, urticaria, soft-tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX® should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined.
But even if the laws remain unchanged, as long as off-label uses are permitted by law, expect doctors to keep pushing the boundaries of Botox's applications--sometimes in the name of medical progress and sometimes with remarkable results.Norman Rosenthal, the Maryland psychiatrist who recommended Botox for his suicidal patient, says he's seen the upside firsthand. The patient, persuaded by Rosenthal, did indeed get Botox shots on his forehead and between his brows. Days later, Rosenthal got an email from the patient. It was a thank-you note. Finally, the patient wrote, he was feeling better.
Botox, or onabotulinumtoxinA, is used for three main purposes: muscle spasm control, severe underarm sweating and cosmetic improvement. In this article we concentrate on the third use, achieved with the product called Botox Cosmetic, which contains botulinum toxin type A (the active ingredient), human albumin (a protein found in human blood plasma) and sodium chloride.
Forehead – The horizontal lines and furrows on your forehead will not magically disappear. Which is why you should consider getting a Botox injection before they start to set in permanently. These lines will become more excessive with age, and will age to your appearance.Over time by repeatedly injecting these lines the deeply etched lines will become progressively improved
Other than that, there don’t seem to be any specific groups of people or health conditions that are contraindicated for Botox injections. As with all treatments, general health guidelines apply. People with a healthy body-mass index who are non-smokers, moderate or non-drinkers, and physically active will nearly always tolerate any type of medical treatment well.
Laser tattoo removal has minimal side effects. Lasers break up the pigment of the tattoo with a high-intensity light beam. During the procedure, the patient wears protective eye shields and may be giving anesthesia. The pulse of the laser feels like the snapping of a rubber band against the skin. Possible side effects include a risk of infection, hypopigmentation, and hyperpigmentation.
“I don’t think it is physically addictive,” says Dr. Matarasso. “But, I have to be very frank with you, when I get a new patient I tell them (and I say this tongue-in-cheek) this product is truly addictive. I make jokes with my patients that we need a 12-step program for it, because when it’s done correctly, it’s a very simple office procedure, with impressive cosmetic results.”
For blepharospasm, reconstituted BOTOX is injected using a sterile, 27-30 gauge needle without electromyographic guidance. The initial recommended dose is 1.25 Units-2.5 Units (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. Avoiding injection near the levator palpebrae superioris may reduce the complication of ptosis. Avoiding medial lower lid injections, and thereby reducin g 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.
Some doctors and dermatologists recommend lying down and resting after a treatment, but Ravitz says she doesn't think there's any need for downtime unless a patient experiences pain. It can take about two weeks to work, though some patients start to feel relief from chronic migraines sooner than that. Ravitz tells me, "If it’s going to work for a patient, one round of the treatment typically lasts for around three months." Though everybody metabolizes it at a different rate, getting it done every three months or so has been found to be effective.
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BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP -25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle resulting in a localized reduction in muscle act ivity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX.
After working out techniques for freeze-drying, buffering with albumin, and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility in 1980, and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner").
In the third study, 25 patients with chronic migraine were injected with 12.5 doses of botox into each trigger point twice, during a period of 3 months. Frequency (main variable), intensity and scales of migraine crises were recorded one month before and one month after the treatment to compare the changes experienced. In addition, side effects were also recorded during the experiment, and they were found to be mild and temporary.
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Lastly, a Botox treatment does not offer permanent results. Botox is most effective when treatments are carried out at regular intervals before the results fully wear off. On average, the results last for three to four months, although Botox metabolizes at different rates in different individuals. The first ever Botox treatment you receive may not last as long as subsequent treatments, plus you may require touch-ups two weeks after the procedure as your injector determines the right dosage for you. Over time, however, many patients notice that they can wait longer intervals between treatments as their treated facial muscles weaken.
The one side effect that we most commonly see with Botox for migraine, ironically, is increased headache pain in the days immediately following the injections. Interestingly, some patients have the opposite effect, noticing immediate pain relief. That may be due to an acupuncture-like response, where poking needles into unhappy muscles actually makes them feel better.
Unopened vials of BOTOX should be stored in a refrigerator (2° to 8°C) for up to 36 months. Do not use after the expiration d ate on the vial. Administer BOTOX within 24 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.
Much like other fillers, Botox is slowly metabolized in the system, so for it to remain effective, patients have to get the procedure every three months or so (however, as Ravitz told me during a recent visit, you can't get it done too frequently or your body will develop antibodies). I've now had four additional rounds of Botox since my initial procedure and have learned a lot about how my body reacts to it. Read on for both Ravitz's insight and information about my experience with five rounds of Botox.
Proper refrigeration at temperatures below 3 °C (38 °F) retards the growth of Clostridium botulinum. The organism is also susceptible to high salt, high oxygen, and low pH levels. The toxin itself is rapidly destroyed by heat, such as in thorough cooking. The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time.
As you noted in your question, the effects of Botox don't last forever. For some patients the short term effects of Botox are a ‘good thing,’ as it means that trying Botox is a relatively low risk/low commitment procedure. If you don't like your Botox results, there's not much to worry about: They will fade on their own in a few months. Generally speaking, the results last between three to five months -- but the duration of the Botox effect depends on the individual and on how many Botox units were used.
Postmarketing reports indicate that the effects of BOTOX® Cosmetic and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses, including spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and spasticity and at lower doses.
In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Preventio n (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local o r state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100. More information can be obtained at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.
I tell my patients that it is not the total price that is important, but how many units are used. For instance, if a patient goes to a spa and pays $150 per area, that may sound like a great deal. However, when the patient ask how long the treatment is supposed to last, the spa responds "2 months". I have seen that many of those less expensive treatments often consist of around 10 units (and therefore carrying a "non-deal" $15 cost per unit!). So, what initially looks like a great bargain, is in fact just a treatment with an inadequate amount of Botox. Always ask your injector how many units they are using, so you can determine what price/unit you are getting. Experienced injectors know that there is no such thing as a standard amount of units, as everyone's facial anatomy and muscular strengths are variable, even from one side of the face to the other.
According to the PREEMPT injection paradigm, a total of 5 units of onabotulinumtoxinA is injected into each corrugator muscle. To confirm the location of the muscle, the patient is asked to furrow the brow in order to activate the corrugator. Once the muscle has been located, the muscle should be palpated and pinched by holding it between the thumb and index finger. Five units of onabotulinumtoxinA is injected at an approximate 90° angle with the bevel of the needle pointing upward into the medial belly of the muscle. As the needle is inserted, there is skin resistance, which lessens when the muscle is penetrated. This decrease in resistance is termed a muscle pop. Once the muscle pop occurs, inject into the superficial muscle. If the injection is too far superior or above the corrugator muscle, brow ptosis can occur due to depression of the medial brow as the frontalis elevating function is lost and the corrugator depressing function remains unopposed. Whereas weakening the corrugator muscle will cause elevation of the medial eyebrow, alternatively, if the corrugator injection is done too low, then diffusion to the levator palpebral muscle could lead to lid ptosis.
The recommended dilution is 200 Units/4 mL or 100 Units/2 mL, with a final concentration of 5 Units per 0.1 mL (see Table 1). The recommended dose for treating chronic migraine is 155 Units ad ministered intramuscularly using a sterile 30-gauge, 0.5 inch needle as 0.1 mL (5 Units) injections per each site. Injections should be divided across 7 specific head/neck muscle areas as specified in the diagrams and Table 2 below. A one inch needle may be needed in the neck region for patients with thick neck muscles. With the exception of the procerus muscle, which should be injected at one site (midline), all muscles should be injected bilaterally with half the number of injection sites administered to the left, and half to the right side of the head and neck. The recommended re-treatment schedule is every 12 weeks.
Many people who experience excessive sweating, whether on their hands, hairline, or even under their breasts or butt, are turning to Botox and other neuromodulators (like Xeomin or Dysport). "They help prevent excessive sweating by acting on the sweat glands directly," says NYC board-certified plastic surgeon Z. Paul Lorenc, MD. "The neuromodulator is injected into the sweat glands to relax the muscle and help combat excessive sweating."
This is because the discretionary procedures tend to be out of pocket, and providers are used to answering the question: how much does it cost? An MRI, on the other hand, might have several prices: A sticker price, a negotiated or reimbursed rate (what the insurance company pays), the rate that Medicare and Medicaid pay for treatments for people who are older and those who have low income, an out-of-network price, and so on. We know about this because we’ve done pricing surveys for about 35 common procedures in seven U.S. metro areas, collecting cash or self-pay prices for both medically necessary procedures (an MRI, a colonoscopy) and discretionary procedures (Botox, Lasik).
In recent years, a number of high-profile lawsuits have been brought against Allergan in which plaintiffs claimed that off-label uses--for ailments including a child's cerebral-palsy symptoms, for instance, or an adult's hand tremors--resulted in lasting deleterious side effects. Still, the drug's acceptance in a growing number of doctors' offices worldwide, and its revenue growth, show no signs of slowing.
“ARMR is a longitudinal study. We’re collecting data over time, which will allow us to study changes in headache patterns, health care resource utilization, diagnostic and management strategies, development of co-morbidities and responses to therapies,” Dr. Schwedt says. The registry is comprised of multiple components: The first component is an online platform in which participants fill out a baseline and follow-up questionnaires and clinicians enter the participants’ headache diagnoses. There is also an ARMR headache diary mobile app in which participants share daily information about their migraine attacks, their level of function and their treatment, if any. The third component is a blood sample, which is processed and stored in the ARMR biobank and will be used for genetic analyses. Brain imaging data are collected in the ARMR Neuroimaging Repository, and electronic health record data are pulled and confidentially entered into a centralized ARMR database. “Oftentimes, research is done in silos,” Dr. Schwedt says. “So a group at one institution is doing their own work, collecting their own data, doing their own analysis. And a group at another institution is doing their own work. That isn’t the most efficient way to move forward in the field. We believe creating and sharing data from this large and comprehensive study is really going to improve the efficiency of research in the field.”
Lalvani previously worked in organizations dedicated to diabetes, breast cancer and kidney disease, but strongly identifies with our community because she is living with migraine. She recalls first getting what she thought were terribly debilitating headaches when she was 18. “I had no idea what a migraine was,” she said, “and I never saw anyone around me have a migraine, so I had no idea what I was dealing with, and no one else around me knew what I was dealing with.” Lalvani is excited to see the progress that’s been made recently in migraine care and the tremendous effort that AMF has put forth in helping advance research to produce therapies at a faster rate. As you know, the mission for AMF is to drive and support impactful research that translates into treatment advances as well as mobilize the community for patient support and advocacy.
When women in their 20's first consider getting Botox, prevention is often the primary factor, since the early signs of aging—such as crow's feet, forehead wrinkles, and fine lines—are beginning to show. "Lines get deeper and deeper with age," explains Wexler. "If you start [getting Botox] early enough and it's done properly, you're not going to need [as much] in the future." For younger patients wary of the frozen look—remember, youthful faces move—Wexler likes to employ lower doses of Botox via ultra-targeted micro injections administered on specific areas of the face such as the forehead, brows, or around the eyes.
If you find that your Botox wears off really fast, speak to the person who gave you the injections to find out why (i.e. if the Botox was too diluted, not enough was injected, the Botox was old, your anatomy requires a different technique, you might be resistant to Botox, etc). A reputable doctor will work with you to figure out how to make the Botox treatments worth your time and money. Keep in mind that for some people, Botox takes time to kick in - approximately 1-2 days to be noticeable and 1-2 weeks to peak.
In her talk, Lalvani expressed her intent to drive AMF’s mission forward by leveraging the expertise of the American Headache Society and incorporating more patient voices. The Move Against Migraine support community is essential to that goal, and AMF strives to be a trusted partner for support, resources and credible information for everyone in the community. The Move Against Migraine campaign was launched to raise awareness of migraine, but that’s only the beginning. Lalvani pointed to AMF’s advocacy and community-building efforts, specifically the response to Elle’s “Migraine Pose” article and robust partnership program. Whatever the platform and audience, AMF works to ensure the patient voice is always included and heard. Lalvani concluded her talk by stressing that patients have an important role to play as “drivers of change” and encouraged listeners to continue connecting with AMF. Check out our full library of Facebook Live recaps with some of the leading headache specialists and patient advocates in the country, and visit our resource library for more information on how you can better advocate for yourself and the migraine community.
SkinMedica® TOTAL DEFENSE + REPAIR Broad Spectrum/PA++++ Sunscreens (SPF 34, SPF 34 Tinted, and SPF 50+) and Essential Defense Broad Spectrum/PA++++ Sunscreens (Everyday Clear SPF 47, Mineral Shield Tinted SPF 32, and Mineral Shield SPF 35) are over-the-counter drug products that are formulated and marketed pursuant to the FDA's governing regulations set forth at 21 CFR § 352.
After an exam by a therapist and doctor, botulinum toxin for focal relief of muscle spasticity can be advised as the best way to address a child's functional problems. The problem muscle groups are identified, and goals for that child are discussed. Then the injection of botulinum toxin can be done if there are no permanent contractures of the muscle groups.
Botox should only be injected with sterile instruments in a doctor's office or a medical spa — not at Botox parties at your local nail salon or neighbor's living room. Botox injection is usually performed with some local anesthesia or a numbing cream. You may feel some minimal discomfort from the shot, but today's needles are so thin and fine that the procedure is often painless. Depending on the extent of treatment, the procedure can take anywhere from a few minutes to 20 minutes.
Jump up ^ Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, Gravas S, Madersbacher S (October 2011). "Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)". European Urology. 60 (4): 784–95. doi:10.1016/j.eururo.2011.07.001. PMID 21782318.
Botox for migraines has been something that has flown under the radar, as many people know Botox as a procedure simply aimed at hiding fine lines. We turned to Matthew S. Robbins, MD, director of inpatient services at Montefiore Headache Center and the chief of neurology at the Jack D. Weiler Hospital, Montefiore, to break down the procedure for us. Scroll down to see what he has to say.
No definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of BOTOX® Cosmetic at the labeled dose of 20 Units (for glabellar lines), 24 Units (for lateral canthal lines), 40 Units (for forehead lines with glabellar lines), 44 Units (for simultaneous treatment of lateral canthal lines and glabellar lines), and 64 Units (for simultaneous treatment of lateral canthal lines, glabellar lines, and forehead lines) have been reported.
Botox must be used only under a doctor's care. It's important that injections be placed precisely in order to avoid side effects. Botox therapy can be dangerous if it's administered incorrectly. Ask for a referral from your primary care doctor or look for a doctor who specializes in your condition and who has experience in administering Botox treatments.
Other things to know about Botox treatments: Some providers charge a consultation fee, which is waived if you choose to proceed with the injections but charged if you decline. Also, who is doing the injection? Make sure it’s a trained, certified professional. As in many other things, training and credentials are important. In some practices, a junior employee may perform the procedure for a lesser rate. Make sure that’s what you want.
Safety and effectiveness of BOTOX® have not been established for the treatment of other upper or lower limb muscle groups or for the treatment of spasticity in pediatric patients under age 18 years. BOTOX® has not been shown to improve upper extremity functional abilities, or range of motion at a joint affected by a fixed contracture. Treatment with BOTOX® is not intended to substitute for usual standard of care rehabilitation regimens.
A randomized, multi-center, double-blind, placebo-controlled study of the treatment of cervical dystonia was conducted. This study enrolled adult patients with cervical dystonia and a history of having received BOTOX in an open label manner with perceived good response and tolerable side effects. Patients were excluded if they had previously received surgical or other denervation tre atment for their symptoms or had a known history of neuromuscular disorder. Subjects participated in an open label enrichment period where they received their previously employed dose of BOTOX. Only patients who were again perceived as showing a response were advanced to the randomized evaluation period. The muscles in which the blinded study agent injections we re to be administered were determined on an individual patient basis.
I always tell my patients that you get what you pay for. However, you need to advocate for yourself and understand what you are getting for your dollars. Ensure that your injector is experienced and properly trained; that you are getting FDA approved Botox Cosmetic from Allergan; and know how many units you receive. As well, a physician's office should maintain a medical record of your treatments so you can optimize and customize your Botox to achieve the best effect and value. Good Luck!
In 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As supplies became exhausted, patients who had come to rely on periodic injections became desperate. For 4 months, as liability issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.