Botox

Botox is an injectable prescription medicine used for both medical and cosmetic purposes. Medically, Botox injections (onabotulinumtoxinA) are used for chronic migraine, excessive underarm sweating (hyperhidrosis), overactive bladder, urinary incontinence, blepharospasm, strabismus (crossed eyes), and spasticity in adults and children 2 years and older. Botox Cosmetic is a separate product, with the same active ingredient, approved to temporarily improve the appearance of frown lines, crow's feet, forehead lines, and neck bands.

Botox is an acetylcholine release inhibitor and a neuromuscular blocking agent. It received its initial U.S. approval in 1989. Botox and Botox Cosmetic are supplied as a vacuum-dried powder in single-dose vials that a healthcare provider reconstitutes with sterile saline before injecting.

There is no generic version of Botox. Other botulinum toxin products include Dysport, Xeomin, Jeuveau, Daxxify, Myobloc, and Letybo. These products are not interchangeable. The units of one botulinum toxin product cannot be compared with or converted into the units of another.

• Botox is given by a healthcare provider. The person injecting needs to understand the muscle and structural anatomy of the area, and any changes to that anatomy from previous surgery or disease. Electromyographic guidance, nerve stimulation, or ultrasound is recommended for locating muscles when treating strabismus and limb spasticity, and may be useful for cervical dystonia.
• Botox is injected into muscle, into the skin, or into the bladder wall, depending on what is being treated.
• Botox Cosmetic is injected into the muscles of the face or neck.
• Your provider may change your dose until you and your provider find the dose that works best for you.
• Your provider will tell you how often you will receive your injections.

Before bladder injections: you must not have a urinary tract infection at the time of treatment. Preventive antibiotics are usually given 1 to 3 days before, on the day of, and 1 to 3 days after treatment. Anti-platelet medicines should be stopped at least 3 days before, and blood thinners need to be managed to reduce the risk of bleeding. You will be observed for at least 30 minutes after the injections.

State rules on who can inject. Botox Cosmetic may be administered by a licensed medical professional such as a physician. In some states registered nurses or physician assistants may administer it under physician supervision. Dentists may also administer Botox, though some states limit this to treatment that is part of a dental plan.

Botox may cause loss of strength, general muscle weakness, vision problems, or dizziness within hours to weeks of an injection. If this happens, do not drive a car, operate machinery, or do other dangerous activities.

Botox carries a Boxed Warning, the FDA's strongest warning, for distant spread of toxin effect. Call your doctor or get medical help right away if you have any of the problems below after treatment with Botox or Botox Cosmetic.

Spread of toxin effects

The effects of Botox and all botulinum toxin products may spread from the injection area and produce symptoms of botulism. These have been reported hours to weeks after injection and may include:

• Loss of strength and muscle weakness all over the body (asthenia)
• Double vision, blurred vision, and drooping eyelids
• Hoarseness or change or loss of voice (dysphonia)
• Trouble saying words clearly (dysarthria)
• Loss of bladder control
• Trouble breathing
• Trouble swallowing.

Swallowing and breathing difficulties can be life-threatening, and there have been reports of death. The risk is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in people with an underlying condition that predisposes them to these symptoms. Cases have been reported at doses comparable to, or lower than, the doses used to treat cervical dystonia and spasticity.

There have been no definitive serious reports of distant spread of toxin effect with Botox given at the recommended dose for blepharospasm (30 Units and below), severe underarm sweating (100 Units), strabismus, or chronic migraine.

Problems swallowing, speaking, or breathing

These problems can happen hours, days, or weeks after a Botox injection, usually because the muscles used to breathe and swallow become weak.

• Swallowing problems may last several months. People who cannot swallow well may need a feeding tube for food and water. If swallowing problems are severe, food or liquid may go into the lungs (aspiration).
• People who already have swallowing or breathing problems before receiving Botox have the highest risk.
• Botulinum toxins can weaken neck muscles that some people with breathing problems rely on to breathe. These people may be at greater risk of serious breathing problems.
• People with a smaller neck muscle mass and people who need injections into both sternocleidomastoid muscles for cervical dystonia are at greater risk of swallowing problems.

Medical uses of Botox

Botox is FDA-approved for:

• Overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication
• Urinary incontinence due to detrusor overactivity associated with a neurologic condition, such as spinal cord injury or multiple sclerosis, in adults who have an inadequate response to or are intolerant of an anticholinergic medication
• Neurogenic detrusor overactivity (NDO) in children 5 years of age and older who have an inadequate response to or are intolerant of anticholinergic medication
• Prevention of headaches in adults with chronic migraine (15 or more days per month with headache lasting 4 hours a day or longer)
• Spasticity in adults and children 2 years of age and older
• Cervical dystonia in adults to reduce the severity of abnormal head position and neck pain
• Severe primary axillary hyperhidrosis (excessive underarm sweating) that is inadequately managed with topical agents
• Blepharospasm associated with dystonia in patients 12 years of age and older
• Strabismus in patients 12 years of age and older

Limitations of use. Botox has not been shown to work for preventing episodic migraine (14 headache days or fewer per month), or for excessive sweating in areas other than the underarms. Botox has not been shown to improve upper limb function, or the range of motion of a joint affected by a fixed contracture.

Cosmetic uses of Botox

Botox Cosmetic is FDA-approved in adults for the temporary improvement in the appearance of moderate to severe:

• Glabellar lines (frown lines) associated with corrugator and/or procerus muscle activity
• Lateral canthal lines (crow's feet) associated with orbicularis oculi activity
• Forehead lines associated with frontalis muscle activity
• Platysma bands (neck bands) associated with platysma muscle activity.

Frown lines, crow's feet, forehead lines, and neck bands may be treated in the same session.

Do not receive Botox or Botox Cosmetic if you:

• Are allergic to onabotulinumtoxinA or to any of the other ingredients in the injection
• Had an allergic reaction to any other botulinum toxin product, such as Dysport (abobotulinumtoxinA), Xeomin (incobotulinumtoxinA), Myobloc (rimabotulinumtoxinB), Jeuveau (prabotulinumtoxinA-xvfs), Daxxify (daxibotulinumtoxinA-lanm), or Letybo (letibotulinumtoxinA-wlbg)
• Have an infection at the planned injection site
• Are being treated for a bladder condition and have a urinary tract infection
• Are being treated for a bladder condition, do not routinely self-catheterize, and cannot empty your bladder on your own or have a post-void residual urine volume over 200 mL

Before receiving Botox or Botox Cosmetic, tell your healthcare provider about all your medical conditions, including if you:

• Have a disease that affects your muscles and nerves, such as ALS (Lou Gehrig's disease), myasthenia gravis, or Lambert-Eaton syndrome
• Have heart disease or a history of an irregular heart rhythm or heart attack
• Have allergies to any botulinum toxin product, or had any side effect from one in the past
• Have or have had a breathing problem, such as asthma or emphysema
• Have or have had swallowing problems
• Have or have had bleeding problems, or take medicines that thin the blood
• Have plans to have surgery, or have had surgery on your face
• Have weakness of your forehead muscles, such as trouble raising your eyebrows
• Have drooping eyelids, significant dry eye, or any other change in the way your face normally looks
• Have symptoms of a urinary tract infection, or problems emptying your bladder on your own, and are being treated for a bladder condition
• Are pregnant or plan to become pregnant. In animal studies, Botox given during pregnancy reduced fetal weight and skeletal bone formation at clinically relevant doses, alongside toxic effects in the mother. There are no adequate data in pregnant women.
• Are breastfeeding or plan to breastfeed. There are no data on whether Botox passes into human milk.

Age limits

It is not known whether Botox is safe and effective in people younger than:

• 18 years for overactive bladder, chronic migraine, or underarm sweating
• 16 years for cervical dystonia
• 12 years for strabismus or blepharospasm
• 5 years for bladder overactivity due to a neurologic condition
• 2 years for spasticity

A trial in 123 adolescents aged 12 to under 18 with chronic migraine did not show that Botox worked better than placebo. A trial in adolescents aged 12 to 17 with overactive bladder also did not demonstrate efficacy.

Botox Cosmetic has not been established as safe and effective in anyone under 18 years of age.

In general, side effects occur within the first week after injection. They are usually temporary, but can last several months or longer. Pain, infection, inflammation, tenderness, swelling, redness, bleeding, or bruising may occur at the injection site. Flu-like symptoms such as nausea, fever, and muscle aches have been reported. Needle-related pain or anxiety can cause fainting or a drop in blood pressure.

Weakness of the injected muscle is the expected effect of botulinum toxin. Weakness of nearby muscles can also happen because of toxin spread.

Common side effects by condition

In people treated for severe underarm sweating, the most frequently reported side effects (3% to 10%) were injection site pain and bleeding, sweating elsewhere on the body, infection, sore throat, flu-like symptoms, headache, fever, neck or back pain, itching, and anxiety.

In people treated for cervical dystonia, the most common severe side effect is difficulty swallowing, and about 20% of those cases also report shortness of breath. Most swallowing problems are mild or moderate.

Serious side effects and warnings

Beyond the boxed warning above, Botox and Botox Cosmetic can cause the following.

Allergic reactions

Serious and immediate allergic reactions have been reported, including anaphylaxis, serum sickness, hives, soft tissue swelling, and shortness of breath. Get medical help right away if you develop itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint.

Cardiovascular events

There have been reports of cardiovascular events after botulinum toxin injection, including irregular heart rhythm and heart attack, some with fatal outcomes. Some of these people had existing risk factors including cardiovascular disease. Botox should be used with caution in people with pre-existing cardiovascular disease.

Existing nerve and muscle conditions

People with conditions such as amyotrophic lateral sclerosis (ALS), myasthenia gravis, Lambert-Eaton syndrome, or peripheral motor neuropathy may be at increased risk of serious effects including generalized muscle weakness, double vision, drooping eyelids, voice and speech changes, severe swallowing difficulty, and breathing problems, even at normal doses.

Breathing problems in people treated for spasticity or bladder conditions

People with compromised breathing should be monitored closely. In adults with reduced lung function treated for upper limb spasticity, drops in forced vital capacity of 15% or more were more common with Botox than with placebo. Bronchitis and upper respiratory tract infections were also reported more often with Botox in people treated for spasticity, including 17% of children treated with 6 Units/kg for upper limb spasticity, compared with 9% on placebo.

Bladder problems

• Inability to empty the bladder. Only people willing and able to start catheterizing after treatment, if needed, should be treated. In people who are not catheterizing, post-void residual urine volume should be checked within 2 weeks of treatment and then periodically up to 12 weeks, especially in people with multiple sclerosis or diabetes.
• Urinary tract infections. Botox increases the rate of urinary tract infection. Rates were higher in people with diabetes and in people 65 years and older, reaching 38% in those aged 75 and over.
• Autonomic dysreflexia. In people treated for bladder overactivity due to a neurologic condition, this occurred in 1.5% on Botox compared with 0.4% on placebo, and can need urgent treatment.

Eye problems

• Corneal exposure and ulceration can occur in people treated for blepharospasm, because reduced blinking leaves the eye surface exposed. Serious corneal exposure, persistent epithelial defect, corneal ulceration, and one case of corneal perforation have been reported.
• Retrobulbar hemorrhage severe enough to compromise blood flow to the retina has occurred during injections for strabismus. It occurred in 0.3% of a series of 5587 injections.
• Dry eye has been reported with Botox Cosmetic injected in or near the muscle around the eye. Persistent eye irritation, light sensitivity, or visual changes should be reviewed by an ophthalmologist.
• Spatial disorientation, double vision, or past-pointing can occur when an eye muscle is paralyzed during strabismus treatment.

Serious reactions with unapproved uses

Serious reactions, including excessive weakness, swallowing difficulty, and aspiration pneumonia, some with fatal outcomes, have been reported in people who received Botox for uses that are not FDA-approved. The safety and effectiveness of Botox for unapproved uses have not been established.

Human albumin

Botox contains albumin, a product derived from human blood. It carries an extremely remote risk of transmitting viral diseases and variant Creutzfeldt-Jakob disease. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Side effects reported after approval

The following have been reported since Botox came onto the market. Because they are reported voluntarily, it is not always possible to estimate how often they happen or confirm they were caused by Botox.

• Abdominal pain, diarrhea, loss of appetite, malaise
• Hair loss, including loss of eyebrows and eyelashes (madarosis)
• Brachial plexopathy, peripheral neuropathy, radiculopathy, nerve and muscle wasting, localized muscle twitching
• Reduced sensation, pins and needles
• Dry eye, eyelid swelling after injections around the eye, strabismus, visual disturbances
• Hearing loss, ringing in the ears, vertigo
• Excessive sweating
• Mephisto sign (an upward arching of the outer eyebrow)
• Erythema multiforme, psoriasis-like skin eruptions and dermatitis
• New or recurrent seizures, typically in people already predisposed to them
• Cardiovascular events including irregular heart rhythm and heart attack, some fatal
• Deaths, sometimes associated with swallowing difficulty, pneumonia, other significant debility, or anaphylaxis

Tell your doctor if you have any side effect that bothers you, or that does not go away. These are not all the possible side effects of Botox. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Botox blocks the transmission of signals between nerves and muscles. It binds to acceptor sites on motor or autonomic nerve endings, enters the nerve ending, and stops the release of acetylcholine, the chemical messenger that tells a muscle to contract. It does this by cleaving SNAP-25, a protein the nerve needs in order to release acetylcholine from its storage vesicles.

The result depends on where it is injected:

• Into muscle, Botox partly and temporarily denervates the muscle, reducing its activity. This is the basis for its use in spasticity, cervical dystonia, blepharospasm, strabismus, and for softening the lines caused by repeated facial muscle movement.
• Into the skin, Botox temporarily denervates the sweat glands, reducing local sweating.
• Into the bladder wall, Botox reduces acetylcholine release in the nerve pathways that drive bladder muscle activity.

The effect is not permanent. The muscle may shrink, nerves may sprout new branches, and there is evidence that reinnervation occurs, slowly reversing the effect.

Botox is classified as an acetylcholine release inhibitor and a neuromuscular blocking agent. On Drugs.com it is listed under skeletal muscle relaxants.

Botox is a protein, so the body can form antibodies against it. If these are neutralizing antibodies, they can inactivate the toxin and make treatment less effective.

In the clinical trials, neutralizing antibodies developed in:

• 1.2% of 326 people treated long term for cervical dystonia. Three of those four people went on to develop clinical resistance.
• 0.2% of 445 people treated for underarm sweating
• 0.5% of 380 adults treated for upper limb spasticity
• None of 406 people treated for migraine
• 0% of 954 people receiving 100 Unit doses for overactive bladder, rising to 1.2% of 260 people who received at least one 150 Unit dose
• 1.0% of 300 adults receiving only 200 Unit doses for neurologic bladder overactivity, rising to 1.9% of 258 people who received at least one 300 Unit dose

The factors that drive antibody formation are not well understood, but some studies suggest that injections given more frequently or at higher doses may increase the risk. The chance of antibodies forming may be reduced by using the lowest effective dose at the longest practical intervals.

The price of Botox varies. Medical uses are often covered by insurance for conditions such as chronic migraine, overactive bladder, or cervical dystonia. Prior authorization may be required. Cosmetic uses are not usually covered by insurance and are generally billed per Unit or per treatment area.

Botox dosing is measured in Units and depends entirely on what is being treated. A provider reconstitutes the vacuum-dried powder with preservative-free 0.9% sodium chloride before injection, and the same vial can be diluted to different strengths depending on the target dose.

Maximum Botox dose

• Adults: the total cumulative dose across all indications should not exceed 400 Units in any 3-month period.
• Children: the total dose should not exceed the lower of 10 Units/kg body weight or 340 Units in any 3-month period.
• The lowest recommended dose should be used when starting treatment.

Botox Cosmetic dose by treatment area

Forehead lines are always treated together with the glabellar lines, because treating the forehead alone can drop the brow. The safety and effectiveness of treating with Botox Cosmetic more often than every 3 months have not been studied.

Botox dose for medical conditions

How often can you have Botox?

• Chronic migraine: every 12 weeks.
• Bladder conditions: no sooner than 12 weeks after the previous bladder injection. In the overactive bladder trials, the median time before people qualified for a second treatment was 169 days (about 24 weeks). For adults treated with 200 Units for neurologic detrusor overactivity it was 295 to 337 days (42 to 48 weeks).
• Spasticity: generally no sooner than 12 weeks after the previous injection.
• Underarm sweating and blepharospasm: when the effect of the previous injection wears off.
• Cosmetic use: treating more often than every 3 months has not been studied.

Onset and duration differ by what is being treated. The figures below come from the placebo-controlled trials in the prescribing information.

For cervical dystonia, improvement generally begins within the first 2 weeks, with maximum benefit at about 6 weeks. In the controlled study, most people had returned to their pre-treatment state by 3 months.

Tell your doctor about all your medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Do not start any new medicines until you have told your doctor that you have received Botox. Tell your doctor, especially if you:

• Have received any other botulinum toxin product in the last four months. Giving a different botulinum toxin product at the same time, or before the effects of a previous one have worn off, can worsen muscle weakness. Be sure your doctor knows exactly which product you received.
• Have recently received an antibiotic by injection. Aminoglycoside antibiotics and other medicines that interfere with nerve-to-muscle signaling, such as curare-like compounds, can strengthen the effect of the toxin.
• Take muscle relaxants. These can exaggerate muscle weakness when given before or after Botox.
• Take anticholinergic medicines. Using these after Botox may increase anticholinergic effects such as dry mouth, constipation, and blurred vision. Many allergy, cold, sleep, and bladder medicines are anticholinergic.
• Take antiplatelet medicines (aspirin-like products) or anticoagulants (blood thinners). These raise the risk of bruising and bleeding at the injection site, and need to be managed before bladder injections.

Ask your doctor if you are not sure whether your medicine is listed above. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine.

Signs of an overdose are not likely to appear straight away. If accidental injection or swallowing occurs, or an overdose is suspected, the person should be medically supervised for several weeks for signs of muscle weakness, which may be local or distant from the injection site. This may require hospitalization. If the muscles of the throat and gullet are affected, food or liquid may enter the lungs. If the breathing muscles are weakened enough, a breathing tube and assisted ventilation may be needed.

An antitoxin is available from the Centers for Disease Control and Prevention, but it will not reverse effects that are already present.

• Unopened vials of Botox are stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 36 months.
• Unopened vials of Botox Cosmetic are stored in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Once reconstituted with saline, Botox and Botox Cosmetic are stored in a refrigerator at 2°C to 8°C and must be used within 24 hours.
• Vials are single-dose. Any unused portion is discarded.
• Do not use after the expiration date on the vial.

Botox and Botox Cosmetic are handled and stored by the clinic, not by the patient.

Botox ingredients

Active ingredient: onabotulinumtoxinA, a purified botulinum toxin type A produced by fermentation of the Hall strain of Clostridium botulinum type A.

Inactive ingredients: human albumin and sodium chloride.

• 100 Unit vial: 100 Units of neurotoxin complex, 0.5 mg human albumin, 0.9 mg sodium chloride
• 200 Unit vial: 200 Units of neurotoxin complex, 1 mg human albumin, 1.8 mg sodium chloride

Botox Cosmetic ingredients

Active ingredient: onabotulinumtoxinA.

Inactive ingredients: human albumin and sodium chloride.

• 50 Unit vial: 50 Units of neurotoxin complex, 0.25 mg human albumin, 0.45 mg sodium chloride
• 100 Unit vial: 100 Units of neurotoxin complex, 0.5 mg human albumin, 0.9 mg sodium chloride

Both are supplied as a sterile, preservative-free, vacuum-dried powder in a single-dose vial for reconstitution. Every Botox and Botox Cosmetic vial label and carton carries U.S. License number 1889. Cartons have tamper-evident features. Products without these features should not be used.

Botox and Botox Cosmetic are manufactured by AbbVie Inc., 1 N Waukegan Road, North Chicago, IL 60064.