Safety

Side effects after BTX-A injection are generally related to pain, tenderness, and bruising after injection as well as to paresis of adjacent muscles, seen primarily with facial and palmar treatment. [80,117,122] Neurophysiological study of 37 patients treated for palmar hyperhidrosis showed a decrease in compound muscle action potential (CMAP) of several intrinsic hand muscles.[138] The decrease of CMAP was noted 3 weeks after injection, ranged from 36% to 64% compared to baseline, and returned to normal by 37 weeks.[138] The authors of this study conclude that even with careful intradermal injection it is possible for BTX-A to diffuse into adjacent intrinsic muscles; they recommend using Botox doses no higher than 0.8 U per square centimeter in the skin overlying the thenar and hypothenar eminence.[138]

Contraindications include infection in the injection site, peripheral motor neuron disease (amyotrophic lateral sclerosis), or neuromuscular junction disease (myasthenia gravis, Lambert-Eaton disease), pregnancy, and lactation.[122]

There are several drugs known to interact with botulinum toxins:

• Aminoquinolones
• Aminoglycosides
• Cyclosporine
• D-penicillamine
• Tubocurarine
• Pancuronium
• Gallamine
• Succinylcholine

Some of these agents increase muscle weakness (aminoglycosides and cyclosporine). Other drugs interfere with toxin effect by inhibiting binding, intracellular transport, or lysosomal processing of the botulinum toxin.[61,122]

A major concern about use of botulinum toxins is that development of neutralizing antibodies will lessen the effectiveness of repeat treatments.[122] The only published study that addresses this question in the treatment of hyperhidrosis is the 16-month open-label follow-up study of 207 patients treated with BTX-A (Botox, 50 U per axilla) for axillary sweating.[103] Only 1 patient developed neutralizing antibodies to BTX-A. However, this patient had a negative test for antibodies and had a good clinical response to repeat BTX-A treatment after the study was completed.

Further information regarding antibody formation in BTX-treated patients is based on experience treating cervical dystonia and facial spasm.[61] The development of antibodies appears to be related to the cumulative dose of BTX-A; frequency of injections and use of booster injections are also a factor.[8] Less than 5% of patients treated with BTX-A for various neurologic problems develop neutralizing antibodies.[8,61] In one study, 22% of patients treated with BTX-F at high doses in order to achieve similar duration of action to that achieved with the more-potent BTX-A were no longer responsive to the toxin after 12 to 66 months.[8] To decrease the risk for neutralizing antibody formation, it is recommended that clinicians use the lowest effective dose, intervals of at least 3 months, and no booster injections.[61]

Although approved for use only in cervical dystonia, BTX-B (Myobloc, Elan Pharmaceticals) is reported to be used “off-label” for hyperhidrosis and facial wrinkles.[11] There are no published reports on BTX-B in hyperhidrosis, but a case report of its use in a patient with palmar hyperhidrosis who did not respond to BTX-A is of interest.[11] After 2 treatments with 100 U of Botox to each palm 3 months apart and little response, the patient was treated with 2500 U of BTX-B to each palm. He stopped having excessive palmar sweating, but 2 days after injection complained of blurred vision, indigestion, and dysphagia with a “dry sore throat.” The indigestion and dysphagia cleared within 10 days, but the blurred vision lasted for 3 weeks. Since BTX-B has been reported to cause dysphagia and a dry mouth when used at a dose of 5000 to 10000 U for cervical dystonia, this patient’s symptoms were thought to be due to the toxin. Further study of BTX-B with regard to both safety and efficacy in the treatment of hyperhidrosis is clearly needed.[11]

Although approved for use only in cervical dystonia, BTX-B (Myobloc, Elan Pharmaceticals) is reported to be used “off-label” for hyperhidrosis and facial wrinkles.[11] There are no published reports on BTX-B in hyperhidrosis, but a case report of its use in a patient with palmar hyperhidrosis who did not respond to BTX-A is of interest.[11] After 2 treatments with 100 U of Botox to each palm 3 months apart and little response, the patient was treated with 2500 U of BTX-B to each palm. He stopped having excessive palmar sweating, but 2 days after injection complained of blurred vision, indigestion, and dysphagia with a “dry sore throat.” The indigestion and dysphagia cleared within 10 days, but the blurred vision lasted for 3 weeks. Since BTX-B has been reported to cause dysphagia and a dry mouth when used at a dose of 5000 to 10000 U for cervical dystonia, this patient’s symptoms were thought to be due to the toxin. Further study of BTX-B with regard to both safety and efficacy in the treatment of hyperhidrosis is clearly needed.[11]