Consumer medicine information

1. Why am I using APO-LEFLUNOMIDE?

APO-LEFLUNOMIDE contains the active ingredient leflunomide. APO-LEFLUNOMIDE is used to treat rheumatoid or psoriatic arthritis. For more information, see Section 1. Why am I using APO-LEFLUNOMIDE? in the full CMI.

2. What should I know before I use APO-LEFLUNOMIDE?

Do not use if you have ever had an allergic reaction to leflunomide, teriflunomide or any of the ingredients listed at the end of the CMI. Do not use if you are pregnant or plan to become pregnant, are not using reliable birth control, or are breastfeeding.
There are a number of other circumstances in which a person must not use this medicine. Check if these apply to you before taking APO-LEFLUNOMIDE (see the full CMI for more details).
Talk to your doctor if you have any other medical conditions, take any other medicines. For more information, see Section 2. What should I know before I use APO-LEFLUNOMIDE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with APO-LEFLUNOMIDE 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 APO-LEFLUNOMIDE?

• The standard dose for this medicine is 100 mg per day for the first 3 days, and after that one 10 mg or 20 mg tablet daily.

• Swallow the tablets whole with a full glass of water, at about the same time each day. You can take it with or without food.

5. What should I know while using APO-LEFLUNOMIDE?

6. Are there any side effects?

Common side effects include: diarrhoea; nausea and vomiting; abdominal pain; weight loss; rashes, itchy skin; hair loss; unusual tiredness or weakness. Serious side effects include: fever; severe upper stomach pain; severe skin rash or sores in your mouth; pale skin, fatigue or increased infections and bruising; cough or trouble breathing; blisters and bleeding in the lips, eyes, mouth, nose and genitals; skin ulcer. Very serious side effects include: allergic reaction symptoms.
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

Leflunomide.

2 Qualitative and Quantitative Composition

Each tablet contains 10 mg or 20 mg of leflunomide, as the active ingredient.
Excipients with known effect. Sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

10 mg tablets. White, round biconvex tablet.
20 mg tablets. Yellow, round biconvex tablets with a scoreline on one side.

4 Clinical Particulars

4.9 Overdose

Symptoms. There have been reports of chronic overdose in patients taking leflunomide at daily dose up to five times the recommended daily dose and reports of acute overdose. There were no adverse events reported in the majority of case reports of overdose. Adverse events were consistent with the safety profile for leflunomide. The most frequent adverse events observed were diarrhoea, abdominal pain, leukopenia, anaemia and elevated liver function tests.
Treatment. In the event of a significant overdose or toxicity, cholestyramine or charcoal administration is recommended to accelerate elimination. Cholestyramine given orally at a dose of 8 g three times a day for 24 hours to three healthy volunteers decreased plasma levels of A771726 by approximately 40% in 24 hours and by 49 - 65% in 48 hours.
Administration of activated charcoal (powder made into a suspension) orally or via nasogastric tube (50 g every 6 hours for 24 hours) has been shown to reduce plasma concentrations of the active metabolite A771726 by 37% in 24 hours and by 48% in 48 hours.
These washout procedures may be repeated if clinically necessary.
Studies with both haemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicated that A771726 the primary metabolite of leflunomide is not dialyzable.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Leflunomide (A771726) was not mutagenic in bacteria (Salmonella typhimurium and Escherichia coli) or Chinese hamster ovary cells, did not cause chromosomal damage in vivo (mouse and Chinese hamster bone marrow cells) and did not induce unscheduled synthesis of DNA in vitro in mammalian cells. A minor metabolite of leflunomide, trifluoromethylaniline, was mutagenic and caused chromosomal damage in in vitro assays, but it did not cause chromosomal damage in vivo (Chinese hamster bone marrow cells) at concentrations higher than those expected in humans.
Carcinogenicity. A two-year carcinogenicity study of oral leflunomide in mice showed an increased incidence of malignant lymphoma in males given leflunomide 15 mg/kg/day [associated with plasma A771726 concentrations (AUC) similar to that expected in humans], an increase in bronchioalveolar adenomas in males given ≥ 5 mg/kg/day (A771726 AUC similar to or about 50% lower than that expected in humans) and an increase in bronchioalveolar adenomas and carcinomas in females given 1.5 mg/kg/day (A771726 AUC at least 10 - 20 times lower than that expected in humans). The increase in the development of malignant lymphomas was probably due to the immunosuppressant effect of leflunomide. A no-effect dose or AUC for the development of lung tumours in female mice was not established, but the relevance of these findings for humans was not clear. Leflunomide showed no carcinogenicity activity in rats given oral leflunomide at doses up to 6 mg/kg/day (associated with A771726 AUC 25 - 65 times lower than that expected in humans).
The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppression medications. There is a potential for immunosuppression with leflunomide. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the clinical trials of leflunomide, but larger and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with leflunomide.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Leflunomide is a white to off white powder, practically insoluble in water and freely soluble in ethanol or acetone.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSLEFLUN.gif Chemical name: N-(4-trifluoromethylphenyl)-5-methylisoxazol-4-carboxamide).
Molecular formula: C₁₂H₉F₃N₂O₂.
Molecular weight: 270.2.
CAS number. 75706-12-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

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