Botox and Myobloc Linked to Paralysis and Death

Black Box warnings have been added on four botulinum toxin drug products:

• Botox (new established name: onabotulinumtoxinA)
• Botox Cosmetic (new established name: onabotulinumtoxinA)
• Myobloc (new established name: rimabotulinumtoxinB)
• Dysport (abobotulinumtoxinA) was approved in April 2009 with the boxed warning and is not making any name or label changes at this time.

(On its website, The FDA explains that the established drug names--often referred to as the generic name--have been changed to help reduce the potential for dosing errors. Neither the brand names nor the formulations of the products have changed.)

Between Nov. 1, 1997, and Dec. 31, 2006, the advocacy group Public Citizen reported that 658 people had adverse reactions to botulinum toxin. Of these, 180 people had difficulty swallowing or contracted aspiration pneumonia when food refluxed into the windpipe. Eighty-seven of those people had to be hospitalized and 16 died. All but one of the deaths were associated with therapeutic use.

The FDA was petitioned by Public Citizen to order a black box warning on all Botox products. (A black box warning is the FDA's strongest type: it appears on the package insert for prescription drugs that may cause serious adverse effects.) Public Citizen also requested that every patient receive a pamphlet outlining the risk before each botulinum toxin is administered.

The FDA issued a press release two weeks after the Public Citizen report, acknowledging safety concerns with the botulinum toxin products and revealing that the agency was conducting ongoing reviews of data from the drug companies as well as monitoring reports of adverse events related to the use of the products.

Botox Cerebral Palsy

Several deaths in children, mostly cerebral palsy patients who were administered Botox injections off-label for associated limb spasticity (severe arm and leg muscle spasms), have been reported. The use of these drugs off-label has not been approved by FDA. Although symptoms have also been reported in adults treated both for approved and unapproved uses, Cerebral palsy Botox treatments use much larger doses than cosmetic use of Botox and are applied to areas more likely to allow the toxin to spread to other parts of the body and thereby cause Botox problems.

Symptoms of Botox cerebral palsy treatment problems could include the following:

• Weakness
• Double or Blurred Vision
• Drooping Eyelids
• Slurred Speech
• Dry Mouth
• Difficulty Swallowing
• Respiratory Distress

Botulinum toxin drug products

Botox and Myobloc use botulinum toxin, which blocks nerve impulses to muscles. The FDA only approved the use of botulinum toxin for a limited number of "therapeutic" conditions, including uncontrollable neck and shoulder muscle contractions, crossed eyes, spasmodic blinking of the eyes and excessive underarm sweating. The only approved cosmetic use is for temporary (up to 120 days) smoothing of wrinkles or frown lines between the eyebrows at the recommended doses. Most cosmetic uses of botulinum toxin are unapproved.

Use of botulinum toxins for treatment of limb spasticity in children or adults is not approved in the US, nor have botulinum toxins been approved in any condition in children less than 12 years of age.Myobloc, made by Solstice Neurosciences Inc., was approved in December 2000 for the treatment of adults with cervical dystonia, a movement disorder that causes the muscles to contract and spasm involuntarily.

Botox, manufactured by Allergan, was first approved in December 1989 to treat blepharospasm (spasm of the eyelids) and strabismus (misaligned eyes or "cross-eyed"). In 2000, Botox was approved to treat cervical dystonia (severe neck muscle spasms). In July 20, 2004 it was approved to treat severe primary axillary hyperhydrosis (excess sweating).

Botox and Myobloc still Available

Although Botox products now include a black box warning, healthcare officials have not advised discontinuing prescribing these products. However, the FDA has made the following recommendations to clinicians who administer Botox and/or Myobloc:

• Realize that potency determinations (units) vary among the botulinum toxin products and that clinical doses expressed in units are not comparable from one botulinum product to the next.
• Remain vigilant for systemic effects that may follow administration of botulinum toxins, including dysphagia, dysphonia, weakness, dyspnea, or respiratory distress. These symptoms, which are suggestive of botulism, have been reported from 1 day to several weeks after treatment.
• Inform patients and caregivers regarding how to recognize the signs and symptoms of systemic effects after being injected with a botulinum toxin. Advise patients to seek immediate medical attention for worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness.

Botox Warnings

The Botox label currently warns of the potential for botulinum toxin to spread beyond the injection site and that systemic adverse effects, including severe difficulty swallowing and difficulty breathing and even death, have occurred in patients with neuromuscular disorders such as myasthenia gravis.

The FDA is also warning the public that the botulism toxin seems to be harming people who don't necessarily have neuromuscular diseases. The agency has been investigating reports of illnesses in adults who used the drugs for other conditions, including a woman who was hospitalized after she was given Botox for forehead wrinkles.

The FDA has asked Allergan Inc. and Solstice Neurosciences Inc., makers of the Botox and Myobloc injectables, to provide additional safety records. A Solstice spokesperson said that children with cerebral palsy receive far larger doses injected into their leg muscles than the doses given adults for cosmetic purposes. The FDA said the problems may be related to overdoses but it also has reports of side effects with a variety of doses.

If you have received a botulinum toxin injection for any reason—cosmetic or medical—you should seek immediate care if you have suffered any symptoms of botulism, including difficulty swallowing or breathing; slurred speech; muscle weakness or difficulty holding up your head. And you may also wish to seek legal help.