General precautions: This drug contains albumin, a derivative of human blood. When a medicinal product derived from human blood or serum is administered in human body, the theoretical risk of infectious diseases by transmissible agents cannot be completely excluded, though is considered extremely remote. It may include any pathogenic agent that is still unknown. In order to decrease the risks of infection by transmissible agents, particular cares including appropriate assay methods are given to the controls of the donors and donation site, to the manufacturing process and to the virus removal/inactivation process.
Cerebral Palsy: NEURONOX treatment is used for local seizure studied in association with the standard treatment; it does not replace these treatment modalities. NEURONOX does not appear that it will be effective in improving limited movement of joints permanently.
Glabellar Wrinkles: In the phase III clinical trial study, those patients who have the history of facial nerve paralysis or the symptoms of eyelid ptosis, history of treatment of glabellar pan like face lifting and permanent implant or with scars which may affect the treatment results, satisfactorily not improved with physical method since the lines are not flattened even using hands, they were excluded; therefore warnings should be given. The interval between administrations of NEURONOX should not be less than 3 months, and the minimum effective dose must be used.
Muscle Spasticity: NEURONOX is used only for treating localized spasticity studied in association with typical standard treatment. NEURONOX is not effective in improving the range of movement in joints affected by fixed limitation.
NEURONOX should be administered with caution for the following patients: Patients who are taking a muscle relaxant (Sodium Tubocurarine, Dantrolen Sodium, etc.) [may be at risk of developing dysphagia or increasing muscle relaxing effect].
Patients who are taking Spectinomycin Hydrochloride, aminoglycoside antibiotics (Gentamycin Sulfate, Neomycin Sulfate, etc.), polypeptide antibiotic (Polymixin B Sulfate, etc.), tetracycline antibiotics, lincosamide antibiotics, muscle relaxant (Baclofen, etc.), anticholinergics (Butylscopolamine Bromide, Trihexyphenidyl Hydrochloride, etc.), benzodiazepines and similar drugs (Diazepam, Etizolam, etc.), benzamides (Tiapride Hydrochloride, Sulpiride, etc.), and such drugs with muscle relaxing effect may be at risk of developing dysphagia or increasing muscle relaxing effect.
Effects on the Ability to Drive or Operate Machinery: Due to the nature of the disease being treated, the effects of the drug on the ability to drive or to operate machines cannot be predicted.
Carcinogenesis, mutagenesis, impairment of fertility, Animal toxicity: Long term studies in animals have not been performed to evaluate carcinogenic potential of botulinum toxin. The result of the animal toxicology with other botulinum toxin product is following. In a study to evaluate inadvertent peribladder administration, bladder stones were observed in 1 of 4 male monkeys that were injected with a total of 6.8 Units/kg divided into the prostatic urethra and proximal rectum (single administration). No bladder stones were observed in male or female monkeys following injection of up to 36 Units/kg (~12X the human dose) directly to the bladder as either single or 4 repeat dose injections or in female rats for single injections up to 100 Units/kg (~33X the human dose).
Use in Pregnancy & Lactation: Safety in pregnant women and nursing mothers has not been established in this drug. Other botulinum toxin injection has been shown to produce abortions and effects at daily doses of 0.125 U/kg/day and at 2 U/kg and higher in rabbits; whereas in rats and mice, no abortions or effects were observed when up to 4 U/kg of botulinum toxin were injected. Doses of 8 and 16 U/kg in rats and mice have been shown to be associated with reduced fetal body weight and/or delayed ossification of the hyoid bone, which may be reversible.
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 NEURONOX is administered to a nursing woman.
NEURONOX is contraindicated in pregnancy and lactation.
Use in Children: Blepharospasm: Safety and effectiveness in children below the age of 18 years have not been established.
Pediatric cerebral palsy: Safety and effectiveness in children over the age of 11 years have not been established.