Cath Lab Digest

Anaheim—In the past 2 decades, the US Food and Drug Administration (FDA) has approved 4 products containing botulinum toxin; it has also required a risk evaluation and mitigation strategy (REMS) for each product: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB. The FDA warns about the risk of spreading the potent toxin and provides guidelines and advice on how to best care for patients using the products.

Pharmacists discussed the REMS program as well as the safety and efficacy of the products at the ASHP meeting during a symposium titled Current Considerations for the Safe Use of Botulinum Toxin.

Evelyn Hermes DeSantis, PharmD, BCPS, director of the Drug Information Center at the Robert Wood Johnson University Hospital, Piscataway, New Jersey, said there are 7 serotypes of botulinum toxin but only 2 (serotype A and B) are used therapeutically and are commercially available. Botulinum toxin serotype A and B range from 300 to 900 kDa and produce temporary chemical denervation and relaxation of the striated muscle. However, the toxins’ molecular structure and intracellular targets are different. Botulinum toxin serotype A’s receptor target is synaptosomal-associated protein 25, while botulinum toxin serotype B’s receptor target is vesicleassociated membrane protein.

OnabotulinumtoxinA comes in single-use vials of 100 and 200 units, and its average wholesale price (AWP) is $630/100 units. AbobotulinumtoxinA comes in a single-use vial of 100 units, and its AWP is $852/500 units. IncobotulinumtoxinA comes in singleuse vials of 50 and 100 units, and its AWP is $320/50 units. RimabotulinumtoxinB comes in single-use vials of 2500 units (0.5 mL), 5000 units (1 mL), and 10,000 units (2 mL), and its AWP is $609/5000 units.

Joyce Generali, MS, BSPharm, FASHP, clinical professor in the University of Kansas’s School of Pharmacy, Kansas City, discussed the safety concerns related to botulinum toxin products. Public Citizen, a nonprofit organization, distributed a petition in June 2008 requesting the FDA to write warning letters to physicians about botulinum toxin products to emphasize that distant spread is possible, people have died from using botulinum toxin products, and the cosmetic form of botulinum toxin products may cause dysphagia and aspiration. The group asked the FDA to have medication guides dispensed with the products.

In August 2009, the FDA released a safety warning establishing name changes for the products, reinforcing individual potencies and prevention of medication errors, reviewing the boxed warning regarding potentially life-threatening issues, reviewing the REMS program, and making healthcare professionals, patients, family members, caregivers, and the public aware of the issues.

The FDA also made it mandatory for botulinum toxin products to contain a black box warning alerting patients that the products may spread from the area of the injection and produce symptoms associated with botulinum toxin effect that may occur within hours or weeks of the injection. The black box warning also tells patients that there have been cases where people have died and have had life-threatening swallowing or breathing difficulties. Children treated for spasticity are at the highest risk of adverse events, but they can also occur in adults with underlying conditions predisposing them to the symptoms.

The REMS program was created as part of the FDA Amendments Act of 2007. The legislation granted the FDA the authority to require a REMS program be submitted to ensure that a drug’s benefits outweigh its risks. A REMS program includes a medication guide, communication plan for healthcare providers, and elements that ensure safe use of the product as well as requirements for people who prescribe, dispense, or use the drug.

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