Consumer medicine information

1 Name of Medicine

Australian approved name: romidepsin.

2 Qualitative and Quantitative Composition

Each vial contains 11 mg of romidepsin (inclusive of 10% overfill).
For the full list of excipients, see Section 6.1 List of Excipients.
Description. Romidepsin is a white to off-white powder, with a melting point of 272°C. Romidepsin is generally more soluble in organic solvents and is very slightly soluble in water (about 0.3 mg/mL). The partition coefficient (n-octanol/water) is approximately 1.9.

3 Pharmaceutical Form

Istodax is supplied in a composite pack including a sterile 10 mg single-use vial containing 10 mg of lyophilised romidepsin and 20 mg of povidone, and a second sterile vial containing 2.2 mL of solvent. The solvent vial contains 80% propylene glycol and 20% anhydrous ethanol. Both romidepsin and solvent vials contain an overfill to ensure the recommended volume can be withdrawn at a concentration of 5 mg/mL.

4 Clinical Particulars

4.9 Overdose

Expected manifestations of overdose could include GI disturbances (nausea, vomiting, diarrhoea, and constipation), haematologic toxicity (thrombocytopenia, neutropenia, and anaemia), asthenic conditions (e.g. fatigue, asthenia, and lethargy), infections, and ECG changes. No specific information is available on the treatment of overdosage of Istodax. There is no known antidote for romidepsin and it is not known if romidepsin is dialyzable.
In the event of an overdose, close clinical monitoring may be instituted and supportive therapy given as required. For information on the management of overdose, in Australia, contact the Poisons Advisory Centre on 13 11 26. In New Zealand. Contact the National Poisons Centre on 0800 POISON or 0800 764 766 for advise on management.

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m² in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area.
Carcinogenicity. Carcinogenicity studies have not been performed with romidepsin.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSROMIDE.gif CAS number. 128517-07-7.
Molecular formula: C₂₄H₃₆N₄O₆S₂.
Molecular weight: 540.71.
ATC code: L01XX39.
Chemical name: (1S,4S,7Z,10S,16E,21R)-7-ethylidene- 4,21-bis(1-methylethyl)-2-oxa-12,13-dithia- 5,8,20,23-tetraazabicyclo[8.7.6]tricos- 16-ene-3,6,9,19,22-pentone.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes

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