Consumer medicine information

1 Name of Medicine

Ticagrelor.

2 Qualitative and Quantitative Composition

Each tablet contains 90 mg of ticagrelor.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Round, biconvex, yellow, film-coated tablets. The tablets are marked with "90" above "T" on one side and plain on the other.

4 Clinical Particulars

4.9 Overdose

ARX-Ticagrelor is well tolerated in single doses up to 900 mg. GI toxicity was dose-limiting in a single ascending dose study. Other clinically meaningful adverse effects which may occur with overdose include dyspnoea and ventricular pauses.
In the event of overdose, observe for these potential adverse effects and consider ECG monitoring.
There is currently no known antidote to reverse the effects of ticagrelor, and ARX-Ticagrelor is not dialysable (see Section 5.2 Pharmacokinetic Properties, Special populations, Patients with renal impairment). Treatment of overdose should follow local standard medical practice. The expected effect of excessive ARX-Ticagrelor dosing is prolonged duration of bleeding risk associated with platelet inhibition. If bleeding occurs appropriate supportive measures should be taken.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Ticagrelor showed no genotoxic potential in assays for gene mutations (bacterial reverse mutation, mouse lymphoma TK) and chromosomal damage (rat micronucleus in vivo).
Carcinogenicity. No compound-related tumours were observed in a 2-year mouse study at oral doses up to 250 mg/kg/day (ca.18-fold the maximum human therapeutic exposure to ticagrelor). There was no increase in tumours in male rats at oral doses up to 120 mg/kg/day (ca. 15-fold the maximum human therapeutic exposure). Increases in uterine adenocarcinomas and hepatocellular adenomas/adenocarcinomas and decreases in pituitary adenomas and mammary fibroadenomas were observed in female rats at more than 25 times the maximum human therapeutic exposure to ticagrelor, with no change in tumour incidence seen at around 8 times the maximum human therapeutic exposure. The uterine tumours seen only in rats were hypothesised to result from a hormonal imbalance present in rats given high doses of ticagrelor. The benign liver tumours are considered secondary to the response by the liver to the metabolic load placed on the liver from the high doses of ticagrelor.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Ticagrelor is a white or off-white to pale pink crystalline powder. The log P (octanol/water) has been measured to > 4.0 at pH 7.4. The molecule has no pKa values within physiological range and does not demonstrate pH dependent solubility. It is non-hygroscopic, exhibiting no significant increase in water content after exposure at 40°C/75% RH.
Chemical structure. Chemical name (IUPAC): (1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol.
The chemical structure of ticagrelor is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSTICAGR.gif Molecular weight: 522.57.
CAS number. The CAS number for ticagrelor is 274693-27-5.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/TICARXST.gif