1 Name of Medicine
Amisulpride.
2 Qualitative and Quantitative Composition
Each table contains amisulpride as the active ingredient (50 mg, 100 mg, 200 mg or 400 mg).
Excipients with known effect. Contains phenylalanine, trace amounts of sulfites and sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Sulprix 50 mg tablets are white round shaped tablets with 'AA 50' on one side and 'G' on the reverse, approximately 6 mm in diameter.
Sulprix 100 mg tablets are white round shaped tablets with 'AMI' breakline '100' on one side and 'G' on the reverse, approximately 7.5 mm in diameter.
Sulprix 200 mg tablets are white round shaped tablets with 'AMI' breakline '200' on one side and 'G' on the reverse, approximately 10 mm in diameter.
Sulprix 400 mg tablets are white film-coated, 18 ± 0.5 mm capsule shaped tablet, debossed with "AS 400" on one side and a break-line on the reverse.
4 Clinical Particulars
4.9 Overdose
Symptoms. Experience with amisulpride in overdosage is limited. Exaggeration of the known pharmacological and adverse effects of amisulpride have been reported. These may include drowsiness, sedation, hypotension, extrapyramidal symptoms and coma.
Fatal outcomes have been reported mainly in combination with other psychotropic agents.
Treatment. In cases of acute overdose, the possibility of multiple drug intake should be considered.
There is no specific antidote to amisulpride. Appropriate supportive measure should therefore be instituted: close supervision of vital functions and, because of the risk of prolongation of QT interval, continuous cardiac monitoring until the patient recovers.
If severe extrapyramidal symptoms occur, anticholinergic agents should be administered.
Since amisulpride is weakly dialysed, haemodialysis is not recommended as a method of elimination.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
An overall review of the completed safety studies indicates that amisulpride is devoid of any general, organ-specific, teratogenic, mutagenic or carcinogenic risk. Changes observed in rats and dogs at doses below the maximum tolerated dose are either pharmacological effects or are devoid of major toxicological significance under these conditions. Compared with the maximum recommended dosages in man, maximum tolerated doses are 2 and 7 times greater in the rat (200 mg/kg/d) and dog (120 mg/kg/d) respectively in terms of AUC. No carcinogenic risk, relevant to man, was identified in the mouse (up to 120 mg/kg/d) and in the rat (up to 240 mg/kg/d), corresponding for the rat to 1.5 to 5 times the expected human AUC.
Reproductive studies performed in the rat, rabbit and mouse did not show any teratogenic potential.
Genotoxicity. Amisulpride showed no genotoxicity in in vitro tests for bacterial gene mutation, or in in vitro and in vivo tests for clastogenic activity.
Carcinogenicity. In carcinogenicity studies, amisulpride was administered in the diet of mice and rats for up to two years. Treatment of mice was associated with increases in malignant mammary gland tumours and pituitary adenomas in females at all dose levels, but there was no tumourigenic response in males (doses were equivalent to 0.1, 0.2 and 0.5 times the maximum human dose of 1200 mg/day on a body surface area basis). Treatment of rats resulted in increased incidences of malignant mammary gland tumours in both sexes, malignant pituitary tumours and adrenal medullary phaeochromocytomas in males, and malignant pancreatic islet cell tumours in both sexes, at doses achieving lower systemic drug exposure (plasma AUC) than in humans at the maximal recommended dose. Increases in mammary gland, pituitary, adrenal and pancreatic endocrine tumours in rodents have been reported for other antipsychotic medicines, and are considered to result from increased prolactin secretion.
The relevance of prolactin-mediated endocrine tumours in rodents for human risk is unknown. In clinical trials, amisulpride substantially elevated plasma prolactin concentrations, although to date neither clinical nor epidemiological studies have shown an association between chronic administration of neuroleptic medicines and mammary tumourigenesis. However, since tissue culture experiments indicate that about one-third of human breast cancers are prolactin-dependent in vitro, amisulpride should be used cautiously in patients with previously-detected breast cancer or in patients with pituitary tumours (see Section 4.3 Contraindications).
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSAMSULP.gif Chemical name: (R,S)-4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-ethylsulfonyl-2-methoxybenzamide.
Molecular formula: C17H27N3O4S.
Molecular weight: 369.48.
Amisulpride is a white to off-white powder, which is practically insoluble in water, sparingly soluble in ethanol, soluble in methanol and freely soluble in dichloromethane.
CAS number. 71675-85-9.
7 Medicine Schedule (Poisons Standard)
S4 (Prescription Only Medicine).
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/SULPRIST.gif
