Consumer medicine information

1 Name of Medicine

Pantoprazole (as pantoprazole sodium sesquihydrate).

2 Qualitative and Quantitative Composition

Each Chemists' Own Heartburn Relief Pantoprazole Tablet contains 22.7 mg pantoprazole sodium sesquihydrate equivalent to 20 mg of pantoprazole.
Excipients of known effect. Contains soya bean products as a component of the Opadry AMB Coating System (Proprietary Ingredient No. 106688).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Chemists' Own Heartburn Relief Pantoprazole Tablets are available as 20 mg (yellow, oval shaped, plain on both sides) biconvex, enteric-coated tablets: 7's, 14's (blister pack).

4 Clinical Particulars

4.9 Overdose

There are no known symptoms of overdosage in humans. In individual cases, 240 mg was administered i.v or p.o. and was well tolerated. As pantoprazole is extensively protein bound, it is not readily dialyzable. Treatment should be symptomatic and supportive measures should be utilised.
For information on the management of overdose, contact the Poisons Information Centre 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. A number of in vitro and in vivo genotoxicity assays covering mutagenicity, clastogenicity and DNA damage end points were conducted on pantoprazole and the results were generally negative. Exposures achieved in the in vivo tests in mice and rats were well in excess of exposures expected clinically. However, pantoprazole was clearly positive in carefully conducted cytogenetic assays in human lymphocytes in vitro, both in the presence and absence of metabolic activation. Omeprazole was also positive in a comparable test conducted in the same laboratory, suggesting a possible class effect. A minute amount of radioactivity was bound to rat hepatic DNA after treatment with 200 mg/kg/day pantoprazole for 14 days. This is an estimated exposure 24-fold the clinical exposure from the 40 mg tablet. No distinct DNA-adduct has been detected.
Pantoprazole was found to be negative in the following studies: in vivo chromosome aberration assay in rat and bone marrow (126E/95), mouse lymphoma test (222E/95) and a gene mutation test in Chinese hamster ovary cells (in vitro) (188E/95). In addition, toxicokinetic studies were conducted in rats at the doses used in the bone marrow assay (50 to 1200 mg/kg) (56E/96) and in mice at the high dose from the earlier micronucleus test (710 mg/kg) (89E/96). In both species, pantoprazole exposure was high with the AUCs being 26 to 30 times higher in the rat or mouse respectively, than humans using the 20 mg tablet.
Carcinogenicity. A two year oral carcinogenicity study in Sprague Dawley rats at doses up to 200 mg/kg/day gastric carcinoids were found after pantoprazole treatment at doses greater than 0.5 mg/kg/day in females and greater than 5 mg/kg/day in males, with none observed in controls. The estimated exposure (based on AUC) from these doses are at, or below, clinical exposure from a 40 mg tablet. The development of gastric tumours is attributed to chronic elevation of serum gastrin levels with associated histopathological changes in the gastrointestinal system.
In both male and female rats, the development of hepatocellular adenomas was increased at doses greater than 5 mg/kg/day and the development of hepatocellular carcinomas was increased at doses greater than 50 mg/kg/day. Hepatocellular tumours, which were also observed in female mice at oral doses greater than 25 mg/kg/day, may be associated with pantoprazole-induced increases in hepatic enzyme activity.
Treatment with pantoprazole at doses greater than 50 mg/kg/day also increased the development of thyroid follicular cell adenomas in male and female rats. Several studies in rats were conducted to investigate the effect of pantoprazole on the thyroid, the results of which suggested that the effect may be secondary to the induction of enzymes in the liver.
In a more recent carcinogenicity study, Fischer rats were studied using lower doses (5, 15 and 50 mg/kg. Gastric carcinoids were detected at all doses in females and at the 15 and 50 mg/kg doses in males, while none were detected in controls. No metastases of these carcinoids were detected. There was no increase in incidence of liver tumours. The dose of 15 mg/kg is seen to be the no-effect level for liver tumours in rodents.
Consideration of the possible mechanisms involved in the development of the above drug-related tumour types suggests that it is unlikely that there is any carcinogenic risk in humans at therapeutic dose levels of pantoprazole for short term treatment.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

It is a white to off white crystalline powder. Solubility is low at neutral pH and increases with increasing pH.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSPANSOS.gif Chemical name. Sodium 5-(difluoromethoxy)-2-[(RS)-[(3,4-dimethoxypyridin-2-yl)methyl]sulphinyl]benzimidazol-1-ide sesquihydrate.
Molecular formula. C₁₆H₁₄F₂N₃NaO₄S.1½H₂O.
Molecular weight. 432.4.
CAS number. 164579-32-2.

7 Medicine Schedule (Poisons Standard)

S3 (Pharmacist only medicine): 14-pack size.
S2 (Pharmacy medicine): 7-pack size.

Summary Table of Changes

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