n onset and transient while the rewarding effects as determined in self-administration studies are lower than those of methylphenidate or cocaine.
In repeat dose toxicity studies the major findings were changes in behaviour, such as increased activity typical of stimulant administration, with associated reductions in body weight gain, growth measurements and food intake, considered to be a consequence of an exaggerated pharmacological response.
Lisdexamfetamine dimesylate was not genotoxic when tested in vitro in the Ames test and the mouse lymphoma assay or in vivo in the mouse bone marrow micronucleus test. Carcinogenicity studies of lisdexamfetamine dimesylate have not been performed. No evidence of carcinogenicity was found in studies in which d-, l- amfetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats.
Lisdexamfetamine dimesylate had no effect on embryofoetal development or survival when administered orally to pregnant rats at doses up to 40 mg/kg/day, and rabbits at doses up to 120 mg/kg/day.
No adverse effects on nervous system development or reproductive function were observed following repeat dose administration of lisdexamfetamine dimesylate to juvenile rats and dogs.
Amfetamine (d- to l-enantiomer ratio of 3:1) did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day.
A number of studies in rodents indicate that prenatal or early postnatal exposure to amfetamine (d- or d,l-) at doses similar to those used clinically can result in long-term neurochemical and behavioural alterations. Reported behavioural effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. Similar studies have not been conducted for Elvanse Adult.
6. Pharmaceutical particulars
6.1 List of excipients
Microcrystalline cellulose.
Croscarmellose sodium.
Magnesium stearate.
Capsule shells
Gelatin.
Black ink (shellac and black iron oxide E172).
Capsule shell colourants:
30 mg: titanium dioxide (E171) and erythrosine (E127).
50 mg: titanium dioxide (E171) and brilliant blue FCF (E133).
70 mg: titanium dioxide (E171), brilliant blue FCF (E133) and erythrosine (E127).
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 25°C.
6.5 Nature and contents of container
High density polyethylene bottle and a polypropylene child resistant cap with a foil inner seal.
Pack sizes: 28 or 30.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Shire Pharmaceutical Contracts Limited 1
Kingdom Street
London
W2 6BD
UNITED KINGDOM
8. Marketing authorisation number(s)
PL 08081/0059
9. Date of first authorisation/renewal of the authorisation
03/02/2015
10. Date of revision of the text
20/12/2017 |
