Co-administration of BOTOX® and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated.
The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
Pregnancy: Pregnancy Category C
When pregnant mice and rats were injected intramuscularly during the period of organogenesis, the developmental NOEL of BOTOX® was 4 U/kg. Higher doses (8 or 16 U/kg) were associated with reductions in fetal body weights and/or delayed ossification which may be reversible.
In a range finding study in rabbits, daily injection of 0.125 U/kg/day (days 6 to 18 of gestation) and 2 U/kg (days 6 and 13 of gestation) produced severe maternal toxicity, abortions and/or fetal malformations. Higher doses resulted in death of the dams. The rabbit appears to be a very sensitive species to BOTOX®.
There are no adequate and well-controlled studies of BOTOX® in pregnant women. Because animal reproductive studies are not always predictive of human response, BOTOX® should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks, including abortion or fetal malformations which have been observed in rabbits.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX®.
The reproductive NOEL following intramuscular injection of 0, 4, 8, and 16 U/kg was 4 U/kg in male rats and 8 U/kg in female rats. Higher doses were associated with dose-dependent reductions in fertility in male rats (where limb weakness resulted in the inability to mate), and an altered estrous cycle in female rats. There were no adverse effects on the viability of the embryos.
Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BOTOX® is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in children below the age of 12 have not been established for blepharospasm or strabismus, or below the age of 16 for cervical dystonia or 18 for hyperhidrosis.
Geriatric Use: Clinical studies of BOTOX® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. There were too few patients over the age of 75 to enable any comparisons. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.