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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/629965/2014

EMEA/H/C/001129

EPAR summary for the public

Leflunomide Winthrop

leflunomide

This is a summary of the European public assessment report (EPAR) for Leflunomide Winthrop. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Leflunomide Winthrop.

What is Leflunomide Winthrop?

Leflunomide Winthrop is a medicine that contains the active substance leflunomide. It is available as tablets (10, 20 and 100 mg).

This medicine is the same as Arava, which is already authorised in the European Union (EU). The company that makes Arava has agreed that its scientific data can be used for Leflunomide Winthrop ('informed consent').

What is Leflunomide Winthrop used for?

Leflunomide Winthrop is used to treat adults with active rheumatoid arthritis (an immune system disease causing inflammation of the joints) or active psoriatic arthritis (a disease causing red, scaly patches on the skin and inflammation of the joints).

The medicine can only be obtained with a prescription.

How is Leflunomide Winthrop used?

Leflunomide Winthrop treatment should be started and supervised by a specialist who has experience in the treatment of rheumatoid arthritis and psoriatic arthritis. The doctor should carry out blood tests to check the patient's liver, white blood cell counts and platelet counts before prescribing Leflunomide Winthrop, and regularly during treatment.

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Leflunomide Winthrop treatment usually starts with a 'loading dose' of 100 mg once a day for three days, followed by a maintenance dose. The recommended maintenance dose is 10 to 20 mg once a day in patients with rheumatoid arthritis, and 20 mg once a day in patients with psoriatic arthritis. The medicine usually starts to have an effect after four to six weeks. Its effect may improve further for up to six months.

How does Leflunomide Winthrop work?

The active substance in Leflunomide Winthrop, leflunomide, is an immunosuppressant. It reduces inflammation by reducing the production of immune cells called 'lymphocytes', which are responsible for inflammation. Leflunomide does this by blocking an enzyme called 'dihydroorotate dehydrogenase', which is necessary for the lymphocytes to multiply. With fewer lymphocytes, there is less inflammation, helping to control the symptoms of arthritis.

How has Leflunomide Winthrop been studied?

In rheumatoid arthritis, Leflunomide Winthrop has been studied in four main studies involving over 2,000 patients, in which it was compared with placebo (a dummy treatment), or with methotrexate or sulphasalazine (other medicines used to treat rheumatoid arthritis). Two of the studies lasted six months, and two lasted a year. The two longer studies were then extended, with patients remaining on the medicines for at least one more year.

In psoriatic arthritis, Leflunomide Winthrop has been compared with placebo in 186 patients over six months.

In all of the studies, the main measure of effectiveness was the number of patients who responded to treatment, as defined by disease-specific criteria (American College of Rheumatology response rates for rheumatoid arthritis, and the Psoriatic Arthritis treatment Response Criteria for psoriatic arthritis).

What benefit has Leflunomide Winthrop shown during the studies?

In rheumatoid arthritis, Leflunomide Winthrop was more effective than placebo and as effective as sulphasalazine. Between 49 and 55% of the patients taking Leflunomide Winthrop responded to treatment, compared with 26 to 28% of those taking placebo, and 54% of those taking sulphasalazine. These results were maintained in the extension studies. Over the first year of treatment, Leflunomide Winthrop was as effective as methotrexate, but only when it was taken with folate (a type of vitamin B). Leflunomide Winthrop was not as effective as methotrexate in the extension study.

In psoriatic arthritis, Leflunomide Winthrop was more effective than placebo, with 59% of the patients taking Leflunomide Winthrop responding to treatment, compared with 30% of those taking placebo.

What is the risk associated with Leflunomide Winthrop?

The most common side effects with Leflunomide Winthrop (seen in between 1 and 10 patients in 100) are leucopenia (low white blood cell counts), mild allergic reactions, increased creatine phosphokinase levels (a marker of muscle damage), paraesthesia (abnormal sensations like pins and needles), peripheral neuropathy (nerve damage in hands and feet), headache, dizziness, mild increases in blood pressure, diarrhoea, nausea (feeling sick), vomiting, inflammation of the mouth such as mouth ulcers, abdominal pain (stomach ache), increased liver enzyme levels, hair loss, eczema, rash, pruritus (itching), dry skin, tenosynovitis (inflammation of the sheath surrounding the tendons), loss of appetite, weight loss and asthenia (weakness). For the full list of all side effects reported with Leflunomide Winthrop, see the package leaflet.

Leflunomide Winthrop must not be used in people who may be hypersensitive (allergic) to leflunomide, to teriflunomide (a breakdown product of leflunomide) or to any of the other ingredients. Leflunomide Winthrop must not be used in patients with:

•    liver disease;

•    severe immunodeficiency states, such as acquired immune deficiency syndrome (AIDS);

•    poor bone marrow function or low blood cell counts (red cells, white cells or platelets) caused by conditions other than rheumatoid or psoriatic arthritis;

•    serious infections;

•    moderate to severely impaired    kidney function;

•    severe hypoproteinaemia    (low    blood protein    levels).

Leflunomide Winthrop must not be used in pregnant women, in women who can become pregnant and who are not using reliable contraception or during breast-feeding.

Doctors prescribing Leflunomide Winthrop need to be aware of the risk of liver problems associated with the medicine. They also need to take special care when switching a patient to Leflunomide Winthrop, or when switching a patient who is receiving Leflunomide Winthrop to another treatment.

Why has Leflunomide Winthrop been approved?

The CHMP decided that Leflunomide Winthrop's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe use of Leflunomide Winthrop?

A risk management plan has been developed to ensure that Leflunomide Winthorp is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Leflunomide Wintho, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Leflunomide Winthrop will ensure that doctors who are expected to prescribe the medicine receive an information pack containing important information on the risks with Leflunomide Winthrop and the monitoring that should be carried out in patients.

Other information about Leflunomide Winthrop

The European Commission granted a marketing authorisation valid throughout the European Union for Leflunomide Winthrop on 8 January 2010.

The full EPAR for Leflunomide Winthrop can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Leflunomide Winthrop, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 10-2014.