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Section Number
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Subject
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Change
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2
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Qualitative and Quantitative Composition
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Text deleted:
Vial of 100 units
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4.2
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Posology and method of administration
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Text deleted:
100U/2.5mL
Text edited:
Care should be taken to ensure that VISTABEL is not injected into a blood vessel when it is injected in the vertical lines between the eyebrows also called Glabellar Lines.
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4.4
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Special warnings and precautions for use
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Text added:
“This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”.
“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.
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4.6
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Pregnancy and lactation
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Text deleted:
VISTABEL should not be used during pregnancy unless clearly necessary.
Text added:
VISTABEL should not be used during pregnancy unless clearly necessary
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4.8
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Undesirable effects
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Text edited: (≥ replace >)
The frequency is defined as follows: Very Common (≥ 1/10); Common (≥ 1/100, <1/10); Uncommon (≥ 1/1,000, <1/100); Rare (≥ 1/10,000, <1/1,000); Very Rare (<1/10,000).
Eye lid ptosis – replace blepharoptosis
Text deleted:
Additional information Post-Marketing data (frequency not known)
Text edited:
The following adverse reactions have been reported rarely since the drug has been marketed for the treatment of Glabellar Lines and other clinical indications: skin rash (including erythema multiforme urticaria and psoriasiform eruption),
urticaria, pruritus, erythema multiforme, psoriasiform eruption, and allergic reaction anaphylactic reaction (angiodema, bronchospasm), alopecia, madarosis, tinnitus and hypoacousia.
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5.3
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Preclinical safety data
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Text removed:
Acute toxicity in rats with intramuscular administration occurred at around 39 U/kg. Repeated administration in rats and monkeys caused muscle atrophy and degeneration and respiratory paralysis. The No Observed Adverse Effect Levels (NOAEL), expressed in U/kg, are estimated at 16 (rat, 6 monthly injections), 4 (adult monkey, 7 monthly x 1 injection every other month), and 8 (juvenile monkey, 3 x 1 injection every 8 weeks).
In rats, decreased fertility was observed at 8 to 16 U/kg, probably related to paralysis of the male’s hindquarters and to alteration of the ovulation cycle in females. The NOAEL was 4 U/kg for males and 8 U/kg for females. Administration during the organogenesis period in rats and mice, resulted in delayed ossification and reduced foetal bodyweight at maternotoxic doses. No malformative effects nor effects on foetal viability were observed. In a peri-post natal study, low birth weight and reduced newborn viability were observed. The dose with no toxic effect on development was 4 U/kg and < 4 U/kg for maternotoxic effects. After administration during the organogenesis period in rabbits, 0.5 U/kg/day caused maternal death and abortion but no teratogenic effects. The developmental NOAEL was 0.125 U/kg/day.
There is no mutagenic or clastogenic potential.
Text added:
In reproductive studies in mice, rats, and rabbits, embryo toxicity was observed with high doses (delayed ossification and reduced foetal bodyweight). No teratogenic effects were observed in these species. In rats adverse effects on male fertility and female estrous cycling and fertility occurred only at high doses.
Studies on acute toxicity, repeated dose toxicity, local tolerance, mutagenicity, antigenicity and blood compatibility did not show unusual adverse local or systemic effects at clinically relevant dose levels.
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6.3
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Shelf life
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Text edited
2 3 years
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6.5
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Nature and content of container
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Text edited:
Powder in a vial (Type I glass) fitted with a stopper (chlorobutyl rubber) and a seal (aluminium)
Text deleted
Vial of 100 Allergan Units of Botulinum toxin type A – pack of one
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6.6
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Special precautions for disposal and other handling
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Text added
Reconstitution should be performed in accordance with good practices rules, particularly for the respect of asepsis.
Text deleted
Amount of solvent added (0.9% sodium chloride solution) to a 100 U vial. Resulting dose (Units per 0.1 ml) 2.5 ml 4.0 U.
Text edited
Used vials, syringes and materials should not be emptied and must be discarded into appropriate containers and disposed of as a Medical Biohazardous Waste in accordance with local requirements.
Text edited
Ophthalmic eye wash solution
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10
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Date of revision of the text
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Delete edited:
16 May 2008 replace 14 June 2007
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