Safety of Botox and Dysport

The LD₅₀ of Botox in humans is estimated to be 2500 to 3000 U of toxin for a 70-kg human, or approximately 40 U/kg. For cosmetic purposes, doses of Botox are limited to 100 U; therefore, Botox Cosmetic can be considered a safe and useful chemical. No irreversible clinical effects have been reported.

Similarly, the suggested limit for cosmetic uses of Dysport is 300 U, but up to 1000 U may be used to treat cervical dystonia if needed. No formal drug interaction studies have been conducted with Dysport. However, the package insert lists much the same suggested interactions as could occur with other types of BTX-A.

Indications

Contraindications

Equipment

• 1-mL syringes and 30-gauge, -inch needles for injection, or 0.3-mL insulin syringes with 30- or 31-gauge needles

Preprocedure Patient Preparation

Botox is delivered by overnight transport in a thick Styrofoam container packed with dry ice to keep the potent toxin stable. Allergan recommends storage of the unmixed toxin at 5° C or lower (frozen). Potency of the toxin is measured in units (U), where 1 U is the amount of toxin that kills 50% (LD₅₀) of a standardized mouse model when injected intraperitoneally. Each vial of Botox contains either 50 U or 100 U of toxin, plus 0.5 mg of human albumin and 0.9 mg of sodium chloride. The toxin is lyophilized and sealed in the vial under negative pressure.

Dysport is supplied in a single-use, sterile vial for reconstitution intended for intramuscular injection. Each vial contains 500 U or 300 U of lyophilized abobotulinumtoxinA, 125 µg human serum albumin, and 2.5 mg lactose. Dysport may contain trace amounts of cow’s milk proteins.

The FDA-recommended dose for treatment of dynamic glabellar rhytids with Botox is 20 U, compared with the recommended dose of 50 U for Dysport.

BTX-B (Myobloc) is delivered premixed in several quantities: 2500 U in 0.5 mL, 5000 U in 1 mL, and 10,000 U in 2 mL. (BTX-B may be stored undiluted in the refrigerator at 2° C to 8° C for up to 21 months. If diluted, it should be used promptly because it contains no preservatives.)

An injection site record (Fig. 56-1) should be available before the procedure begins.

Figure 56-1 Sample record of injection sites.

Reconstitution and Handling of Botox and Dysport

Alcohol used to cleanse the rubber stoppers and injection sites can inactivate the toxin. Allow it to evaporate completely before proceeding. Allergan recommends that from 1 to 10 mL of sterile saline without preservatives (single-dose vials do not contain preservatives—see previous comment) be mixed in the vial of Botox, using the large needle to reconstitute it. A vial that does not demonstrate a vacuum should not be used and will be replaced by the company. The reconstituted Botox should be mixed by gently rolling or swirling the vial. Shaking the vial (i.e., causing foaming) was thought to denature Botox, leading to decreased potency of the solution, but this has proven not to be an issue. Once reconstituted, the toxin should be kept at 2° C to 8° C (refrigerated) and used as quickly as possible. Practitioners may choose to store the solution in the glass vial and use a larger needle to fill the solution into 1-mL syringes as needed or remove the rubber stopper and withdraw the fluid with the small needle on insulin syringes to inject the solution. The package insert recommends using this “single-use vial” of toxin within 4 hours when mixed with sterile saline without preservatives. Group consensus and studies have shown minimal loss of potency in either refrigerated or frozen solution made with saline, with or without preservatives, at 30 days. However, most patients agree that injections reconstituted with saline with preservatives are more comfortable.

Botox dilution varies by use and personal preference. More concentrated dilutions seem to cause effects sooner, but may be more difficult for a clinician to inject accurately and last no longer than injections of more dilute solutions. Most clinicians dilute 100 U of lyophilized Botox with 1 to 6 mL of saline. Dilutions of 100 U/1 mL (10 U/0.1 mL), 100 U/2 mL (5 U/0.1 mL), or 100 U/3 mL (3.3 U/0.1 mL) are commonly used for cosmetic procedures, headache treatments, and hyperhidrosis (Table 56-1). The area of effect associated with each injection point can be up to 2 to 3 cm in diameter.

TABLE 56-1 Dilutions of Botox (100 Units/Bottle as Supplied)

Dysport can be reconstituted with 1 to 3 mL of saline, depending on the clinician’s preference, and used in a similar fashion.

Patient Education

Before injection, the patient should review and sign the informed consent (see the patient consent form online at www.expertconsult.com). The patient should appreciate that the treatment produces temporary results (3 to 4 months) and will take up to 10 days for the full effect. The FDA has recently added a revised form, included with the BTX-A vial, for patient distribution every time BTX-A injections are to be given. It discusses the risk of “potentially life threatening distant spread effects after local injection” because these injections have become so commonplace that some patients may underestimate the associated risk. Conversely, by minimizing the amount of toxin used (to decrease risk of side effects), some wrinkles may not be totally eradicated. However, a “natural” rather than “frozen” face is aesthetically desirable. Efficacy and duration of action vary from patient to patient, but both generally increase with serial injections over time as a result of increasing muscle atrophy. At times, a “touch up” could be of value 2 to 3 weeks after the initial injections, should there be areas where the muscles have not been affected enough or with bilateral symmetry.

Caution the patient against prior use of aspirin, large doses of vitamin E, garlic, ginger, and diet pills, which increase the risk of bruising. Cosmetics covering treatment areas can be removed just before injection and reapplied immediately after, provided the patient does not rub the treatment areas afterward. Rubbing the treatment areas can spread the Botox into areas not intended for treatment, increasing the risk of complications such as ptosis. Conversely, the clinician may massage Botox toward or away from areas intentionally.