Thelin - sitaxentan sodium

PLEASE NOTE: MEDICINAL PRODUCT IS NO LONGER AUTHORIZED (serious side effects in the liver)

What is Thelin?

Thelin comes in capsule-shaped film-coated tablets, yellow-orange colored, containing 100 mg of active ingredient sitaxentan sodium.

What is Thelin used for?

Thelin is used to treat adult patients with class III pulmonary arterial hypertension to improve exercise capacity. Pulmonary arterial hypertension is a disease in which the patient has an abnormally high pressure in the pulmonary arteries; Class III ("moderate") indicates the severity of the disease. Thelin has been shown to be effective in primary pulmonary hypertension (no other cause) and in pulmonary hypertension caused by a connective tissue disease.

Because the number of patients with pulmonary hypertension is low and the disease is rare, Thelin was designated an "orphan medicine" (a medicine used for rare diseases) on 21 October 2004.

The medicine can only be obtained with a prescription.

How is Thelin used?

Treatment with Thelin should only be started and monitored by a doctor who has experience in the treatment of pulmonary arterial hypertension. It is taken daily in doses of 100 mg (one tablet), with or without food, preferably at the same time each day and the dose should not exceed one tablet per day. It should not be taken by patients who present or have severe liver problems. If the patient's condition worsens after 12 weeks, the doctor should review the treatment.

How does Thelin work?

Pulmonary arterial hypertension is a debilitating disease in which there is a strong constriction (narrowing) of the blood vessels of the lungs, which causes a very high pressure in the vessels that carry blood from the right side of the heart to the lungs. The active substance in Thelin, sitaxentan sodium, is an antagonist of a substance naturally present called endothelin-1 (ET-1), which is the cause of a strong constriction of blood vessels. By blocking the effect of endoltelin, it reduces the constriction of blood vessels and this facilitates the decrease in blood pressure.

What studies have been carried out on Thelin?

Before being studied in humans, the safety and efficacy of the medicine were tested in experimental models.

Three main studies were carried out, involving 523 patients. Doses of 50, 100 and 300 mg of sitaxentan sodium have been compared with placebo (a dummy treatment). Efficacy was studied by measuring the distance patients could walk for 6 minutes after 12 weeks of treatment.

What benefit has Thelin shown during the studies?

After treatment with Thelin, patients could travel significantly further. Before treatment with 100mg of sitaxentan sodium, the average distance traveled on foot was between 343 and 394 meters, with an increase of about 33 meters after the treatment. Although not a big increase, it is a significant improvement. Studies have shown that doses of 50 mg did not cause a significant benefit and that doses of 300 mg did not allow for better benefits than the 100 mg dose.

What are the risks associated with Thelin?

The most frequently reported undesirable effect (seen in more than one in 10 patients) was headache. Other common side effects (between 1 and 10 patients in 100) were peripheral edema (swelling of the arms and legs) and nasal congestion (turbulent nose). For the full list of all side effects reported with Thelin, see the package leaflet.

Thelin should not be used in people who may be hypersensitive (allergic) to sitaxentan sodium or other ingredients, to people who have severe liver problems or elevated levels of certain liver enzymes. The patient's liver function must be monitored before and during treatment. Thelin should not be taken with ciclosporin A (a medicine used to treat psoriasis and rheumatoid arthritis as well as to prevent rejection in case of liver or kidney transplantation) and caution should be exercised when taken at the same time as warfarin (a medicine used to treat to thin the blood).

Women who take Thelin must be careful not to get pregnant and use an effective contraceptive method. It is not known whether sitaxentan is excreted in milk or not or whether it can be harmful to an infant. It is advised to avoid breastfeeding while taking Thelin.

Why has Thelin been approved?

The Committee for Medicinal Products for Human Use (CHMP) believes that Thelin has been shown to be effective and that this effectiveness is within the expectations for this class of medicines. He decided that Thelin's benefits outweigh the risks for treating adult patients with primary pulmonary arterial hypertension to improve physical capacity and pulmonary hypertension associated with connective tissue disease. The CHMP therefore recommended that Thelin be given marketing authorization.

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

The company that makes Thelin will have to provide information material to doctors and patients (information sheet for patients). The company will also set up a monitoring system for side effects, suspicious interactions with other medicines and the outcome of any pregnancy that may occur in a woman taking the medicine.