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]