Consumer medicine information

1. Why am I using IMBRUVICA?

IMBRUVICA contains the active ingredient ibrutinib. IMBRUVICA is used to treat the following blood cancers in adults: Mantle Cell Lymphoma (MCL); Chronic Lymphocytic Leukaemia (CLL), including Small Lymphocytic Lymphoma (SLL); Waldenström's macroglobulinemia (WM)
For more information, see Section 1. Why am I using IMBRUVICA? in the full CMI.

2. What should I know before I use IMBRUVICA?

Do not use if you have ever had an allergic reaction to IMBRUVICA or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use IMBRUVICA? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with IMBRUVICA 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 IMBRUVICA?

• The recommended dose of IMBRUVICA for: MCL is 560 mg once a day and for WM and CLL/SLL is 420 mg once a day. Follow your doctor's instructions on the dose appropriate for you.

5. What should I know while using IMBRUVICA?

6. Are there any side effects?

The most common side effects include diarrhoea; feeling very tired; nausea; headache; swollen hands, ankles or feet; being short of breath; dizziness; fainting; constipation; infected nose, sinuses or throat (cold); fever; vomiting; decreased appetite; bleeding; bruises; skin rash; muscle and joint pain; muscle spasms; indigestion (dyspepsia).
Call your doctor or healthcare professional if you have signs or symptoms of serious bleeding, if you have any heart problems like chest discomfort, shortness of breath or palpitations or signs of jaundice.
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

Ibrutinib.

2 Qualitative and Quantitative Composition

Capsules. 140 mg capsules. Imbruvica capsules contain 140 mg ibrutinib as the active ingredient.
Film-coated tablets. Imbruvica tablets contain 140 mg, 280 mg, 420 mg or 560 mg of ibrutinib.
Excipients with known effect. Sugars as lactose.
The characterization data demonstrate that ibrutinib at pH 1.2 is considered slightly soluble and at pH 3 to 8 ibrutinib is considered practically insoluble as defined by USP and European Pharmacopoeia nomenclature. Ibrutinib is non-hygroscopic and the melting onset temperature is 149-158°C. The drug substance has one ionizable group, the protonated pyrimidine moiety, with a pKa of 3.74 in an aqueous solution with methanol as a co-solvent.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Capsules. 140 mg capsules. White opaque, size 0, hard gelatin capsule is marked with "ibr 140 mg" in black ink.
Film-coated tablets. 140 mg tablets. Yellow-green to green round film-coated tablet debossed with "ibr" on one side and "140" on the other.
280 mg tablets. Purple oblong film-coated tablet debossed with "ibr" on one side and "280" on the other.
420 mg tablets. Yellow-green to green oblong film-coated tablet debossed with "ibr" on one side and "420" on the other.
560 mg tablets. Yellow to orange oblong film-coated tablet debossed with "ibr" on one side and "560" on the other.

4 Clinical Particulars

4.9 Overdose

Symptoms and signs. There are limited data on the effects of Imbruvica overdose.
No Maximum Tolerated Dose was reached in the Phase 1 study in which patients received up to 12.5 mg/kg/day (1400 mg/day). In a separate study, one healthy subject who received a dose of 1680 mg experienced reversible Grade 4 hepatic enzyme increases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. There is no specific antidote for Imbruvica. Patients who ingested more than the recommended dosage should be closely monitored and given appropriate supportive treatment.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Ibrutinib has no genotoxic properties when tested for mutagenicity in bacteria or clastogenicity in in vitro assays (chromosomal aberration in Chinese hamster ovary cells) or in vivo (mouse micronucleus test).
Carcinogenicity. Ibrutinib was not carcinogenic in a 6-month study in the transgenic (Tg.rasH2) mouse at oral doses up to 2000 mg/kg/day resulting in exposures approximately 23 (males) to 37 (females) times higher than the exposure in humans at a dose of 560 mg daily based on plasma AUC.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSIBRUTI.gif The chemical name of the ibrutinib is 1 [(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3, 4-d]pyrimidin-1-yl]- 1-piperidinyl]-2-propen-1-one.
Molecular formula: C₂₅H₂₄N₆O₂. Molecular weight: 440.50.
CAS number. 936563-96-1.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

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