What is Leflunomide Winthrop?
Leflunomide Winthrop is a medicine containing leflunomide as an active ingredient and is available as tablets (10 and 100 mg white round; 20 mg yellow triangular).
The medicine is identical to Arava, already authorized for marketing in the European Union (EU). The company that makes Arava has considered that the scientific data related to it could also be used for Leflunomide Winthrop ("informed consent").
What is Leflunomide Winthrop used for?
Leflunomide Winthrop is used to treat adults with active rheumatoid arthritis (a disease of the immune system that causes inflammation of the joints) or active psoriatic arthritis (a disease that causes red and 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 therapy should be started and supervised by a specialist experienced in the treatment of rheumatoid arthritis and psoriatic arthritis. The doctor must perform blood tests to check the patient's liver, white blood cell and platelet counts before prescribing Leflunomide Winthrop, and regularly during treatment.
Treatment with Leflunomide Winthrop should be started with a "loading dose" of 100 mg once a day for three days, followed by a maintenance dose. The recommended maintenance dose is 10-20 mg once a day in patients with rheumatoid arthritis and 20 mg once a day in patients with psoriatic arthritis. Usually the medicine begins to take effect after four to six weeks. The effect can further improve up to six months.
How does Leflunomide Winthrop work?
The active substance in Leflunomide Winthrop, leflunomide, is an immunosuppressant. This substance reduces inflammation by reducing the production of immune cells called "lymphocytes", which are responsible for inflammation. The leflunomide exerts this action by blocking an enzyme called "dihydroorotate dehydrogenase", necessary for the lymphocytes to multiply. With less lymphocytes, inflammation is reduced and the symptoms of arthritis are controlled.
How has Leflunomide Winthrop been studied?
For rheumatoid arthritis Leflunomide Winthrop has been studied in four main studies involving over 2000 patients in which it was compared with a placebo (a dummy treatment), or with methotrexate or sulfasalazine (other medicines used to treat rheumatoid arthritis ). Two of the studies lasted six months and two lasted a year. The two longer studies were subsequently prolonged and the patients continued to take the medicines for at least another year.
Leflunomide Winthrop has been compared with placebo for over six months in 186 patients with psoriatic arthritis.
In all the studies, the main efficacy parameter was the number of patients who responded to treatment, identified by specific criteria for the disease (response rates of the American College of Rheumatology for rheumatoid arthritis and the criteria for response to treatment for psoriatic arthritis).
What benefit has Leflunomide Winthrop shown during the studies?
In rheumatoid arthritis, Leflunomide Winthrop showed an efficacy superior to that of placebo and equivalent to that of sulfasalazine. Between 49 and 55% of the patients taking Leflunomide Winthrop responded to treatment compared to 26-28% of those taking placebo and 54% of those taking sulfasalazine. These results were maintained in the extension studies. During the first year of therapy, Leflunomide Winthrop showed an efficacy equivalent to that of methotrexate, but only if it was taken together with folate (a type of vitamin B). In the extension study Leflunomide Winthrop did not show an efficacy equivalent to that of methotrexate.
In psoriatic arthritis, Leflunomide Winthrop was more effective than placebo, with a treatment response rate of 59% of the patients taking Leflunomide Winthrop compared to 30% of those taking placebo.
What are the risks associated with Leflunomide Winthrop?
The most common side effects with Leflunomide Winthrop (seen in between 1 and 10 patients in 100) are leukopenia (low white blood cell count), mild allergic reactions, increased levels of creatine phosphokinase (a marker of muscle injuries), paraesthesia (sensitivity disorders such as pins and needles), headache, dizziness, slight increase in blood pressure, diarrhea, nausea, vomiting, inflammation of the mouth (eg mouth ulceration), abdominal pain (stomach ache), increased levels of liver enzymes, hair loss, eczema, rash, itching, dry skin, tenosynovitis (inflammation of the sheath that covers 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 should not be used in people who may be hypersensitive (allergic) to leflunomide or any of the other substances. Leflunomide Winthrop should not be used in patients with:
• liver diseases;
• states of severe immunodeficiency, eg. acquired immunodeficiency syndrome (AIDS);
• poor bone marrow function or low level of blood cells (red blood cells, white blood cells or platelets) due to diseases other than rheumatoid or psoriatic arthritis;
• serious infections;
• moderate to severe kidney disease;
• severe hypoproteinemia (low levels of protein in the blood).
Leflunomide Winthrop should not be used in women who are pregnant, women of childbearing potential or breast-feeding.
Doctors who prescribe Leflunomide Winthrop should be aware of the risk of liver problems associated with the medicine. In addition, special caution should be exercised when transferring a patient to Leflunomide Winthrop or passing a patient taking Leflunomide Winthrop to another treatment.
Why has Leflunomide Winthrop been approved?
The Committee for Medicinal Products for Human Use (CHMP) has determined that the benefits of Leflunomide Winthrop are greater than its risks for the treatment of adult patients with active rheumatoid arthritis as a "disease-modifying antirheumatic drug" (DMARD ) and active psoriatic arthritis and recommended the granting of a marketing authorization for Leflunomide Winthrop.
Other information on Leflunomide Winthrop
On 8 January 2010, the European Commission granted a marketing authorization valid throughout the European Union for Leflunomide Winthrop to Sanofi-Aventis Deutschland GmbH. This authorization is valid for five years and is renewable.
The full EPAR for Leflunomide Winthrop can be found here.
Last update of this summary: 11-2009.
