Consumer medicine information

1. Why am I using ZEPOSIA?

ZEPOSIA contains the active ingredient ozanimod. ZEPOSIA is used to treat multiple sclerosis and ulcerative colitis in adults.
For more information, see Section 1. Why am I using ZEPOSIA? in the full CMI.

2. What should I know before I use ZEPOSIA?

Do not use if you have ever had an allergic reaction to ozanimod or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, recently had or are planning to have a vaccination, take any other medicines or receive phototherapy, or are pregnant or plan to become pregnant or are breastfeeding. You should avoid becoming pregnant while taking ZEPOSIA or in the 3 months after you stop taking it.
For more information, see Section 2. What should I know before I use ZEPOSIA? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ZEPOSIA and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ZEPOSIA?

You start your ZEPOSIA treatment with an initiation pack that lasts for 7 days. The initiation pack contains lower doses of ZEPOSIA that increase gradually over the first 7 days of treatment.
On Day 8 and thereafter you will take one 920 microgram capsule daily. If you have mild or moderate chronic liver problems, your doctor may need to reduce your 'maintenance' dose to one 920 microgram capsule every other day.
More instructions can be found in Section 4. How do I use ZEPOSIA? in the full CMI.

5. What should I know while using ZEPOSIA?

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.
Common side effects include: viral infections of the nose, mouth, throat, or voice box; low blood levels of a type of white blood cell; sore throat; lung infection; cold sores; headache; swelling of arms, hands, feet, ankles or legs.
Serious side effects include: low heart rate; allergic reaction; changes in blood pressure; serious infections (e.g. urinary, shingles, brain infection); new or worsening breathing problems; significant changes in visions; increased liver enzyme levels in blood tests or yellow pigmentation of the skin, mucus membrane or eyes.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Australian Approved Name: ozanimod.

2 Qualitative and Quantitative Composition

Each 230 microgram capsule contains 230 microgram ozanimod (equivalent to 250 microgram ozanimod hydrochloride).
Each 460 microgram capsule contains 460 microgram ozanimod (equivalent to 500 microgram ozanimod hydrochloride).
Each 920 microgram capsule contains 920 microgram ozanimod (equivalent to 1.00 mg ozanimod hydrochloride).
For the full list of excipients, see Section 6.1 List of Excipients.
Description. Ozanimod hydrochloride is a white to off-white solid with a melting point of ~240°C. Ozanimod hydrochloride is poorly hygroscopic. The solubility of ozanimod hydrochloride in ethanol and methanol is 1.43 and 2.41 mg/mL and in a pH 5.1 aqueous medium is 3.51 mg/mL. The pKa for ozanimod hydrochloride is 7.90 and the partition coefficient (logP) is 3.28.
Ozanimod hydrochloride exists as the (S) configuration with an enantiomeric purity of not less than 99.0%.

3 Pharmaceutical Form

Capsule.
Zeposia 230 microgram capsules. Light grey opaque capsule, size 4, imprinted in black ink with "OZA" on the cap and "0.23 mg" on the body.
Zeposia 460 microgram capsules. Light grey / orange opaque capsule, size 4, imprinted in black ink with "OZA" on the cap and "0.46 mg" on the body.
Zeposia 920 microgram capsules. Orange opaque capsule, size 4, imprinted with "OZA" on the cap and "0.92 mg" on the body.

4 Clinical Particulars

4.9 Overdose

In the event of overdose, patients should be managed by symptomatic and supportive care.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Ozanimod and multiple metabolites were evaluated for bacterial mutagenicity. These mutagenicity assays examined ozanimod, CC112273, CC1084037, RP101124, RP101988, RP101075, and RP101442, which were all negative for mutagenicity. In vitro aneugenicity/clastogenicity assessment included ozanimod (negative in the mouse lymphoma), CC112273 (negative in the human peripheral blood lymphocyte assay), and CC1084037 (positive in the TK6 assay). The positive in vitro TK6 result with CC1084037 was assessed using a two-organ in vivo study (negative bone marrow micronucleus assay and a negative hepatic comet assay at doses up to 1000 mg/kg/day for 3 days in mice). Ozanimod was also negative in the in vivo bone marrow micronucleus assay (at doses up to 800 mg/kg/day for 2 days in rats).
Overall, ozanimod and metabolites did not exhibit any in vitro or in vivo genotoxicity concerns.
Carcinogenicity. Ozanimod was evaluated for carcinogenicity in the 6-month Tg.rasH2 mouse bioassay and the two-year rat bioassay. In the 6-month Tg.rasH2 mouse study, a statistically significant increased incidence of hemangiosarcomas was seen at the mid and high dose (25 mg/kg/day and 80 mg/kg/day) across multiple organs. At the low dose (8 mg/kg/day), the hemangiosarcoma incidence was lower and remained within laboratory background levels.
Hemangiosarcomas in mice have been postulated to be a result of chronic stimulation of endothelial cells through the S1P1 receptor (also known as the endothelial differentiation gene (EDG) 1 receptor). This receptor is abundant on vascular endothelial cells and is important in endothelial cell migration, differentiation, and survival. In mice, S1P1 agonism results in sustained production of placental growth factor 2 (PlGF2) and subsequently, persistent vascular endothelial cell mitoses. In contrast, rat and human vascular endothelial cells do not release PlGF2 or only transiently release PlGF2 in response to S1P1 agonism, and subsequently, sustained stimulation and hemangiosarcoma formation are not observed in these species.
Based upon the evidence that hemangiosarcomas formation by S1P1 agonism is specific to mice and not relevant to humans, the Tg.rasH2 mouse exposure margin for human risk with the top dose of oral ozanimod at 80 mg/kg/day is 17364x. The metabolite exposure margin is 17.3x for CC112273 and is 15.5x for CC1084037. At the NOAEL dose in mice of 8 mg/kg/day, the exposure margins are 1795x for ozanimod, 1.4x for CC112273, and 1.40x for CC1084037.
In the two-year rat bioassay, no incidence of any tumour type was increased at any ozanimod dose (top dose of 2 mg/kg/day).
In rats, the exposure margin at the highest dose tested (2 mg/kg/day), which was the NOAEL, was 135x for ozanimod, 0.29x for CC112273, and 0.176x for CC1084037.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Molecular formula: C₂₃H₂₄N₄O₃.HCl.
Molecular weight: 440.92.
ATC code: L04AA38.
Chemical name: 5-(3-{(1S)-1-[(2-hydroxyethyl)amino]-2,3-dihydro-1H-inden-4- yl}-1,2,4-oxadiazol-5-yl)-2-[(propan-2-yl)oxy]benzonitrile monohydrochloride.
CAS number. Chemical abstract service (CAS) registry number: 1618636-37-5.
Chemical structure.
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7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine.

Summary Table of Changes

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