Sitaxsentan Sodium (Thelin®)

SPECIAL NOTICE:  December 10, 2010 - Pfizer Inc. announced today that, in the interest of patient safety, it is voluntarily withdrawing Thelin® (sitaxentan) for the treatment of pulmonary arterial hypertension (PAH) in regions where it is approved (the European Union, Canada and Australia).  In addition, Pfizer is discontinuing clinical studies of Thelin worldwide.  Please see the company's news release for further information.

The following description is for informational purposes only.

ET is an endogenous peptide vasoconstrictor that is present in excessive concentrations in patients with PAH. Sitaxsentan, an ET-receptor antagonist undergoing FDA review in the US but approved in much of the rest of the developed world, is selective for the ETA receptors. By selectively antagonizing the ETA receptors, sitaxsentan causes pulmonary arterial vasodilation and allows normal functioning of the ETB receptor, thus reducing the effects of ET. Bosentan, a similar drug, targets ETA and ETB receptors.

FDA Approval:
Thelin has been approved for marketing in both the European Union, Germany, The Netherlands, the United Kingdom, Ireland, Canada, Sweden and Australia. The medication is currently undergoing clinical trials within the United States.

Recommended for

Sitaxsentan sodium is indicated in WHO functional class II, III and IV (mild to severe symptoms) and is often given in combination with other medications.

How administered

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 as 100 mg (one tablet) a day, with or without food, preferably at the same time of the day, and the dose should not be increased to more than one tablet a day. It should not be taken by patients who have or have had a serious liver problem. If after 12 weeks the patient's condition is getting worse, then the doctor should review the treatment.

Risks/Side Effects

Because of the risks of liver injury and birth defects, Thelin is available only through a special restricted distribution.
Thelin is contraindicated in pregnant women or women intending to become pregnant, nursing women, people with prior liver impairment or elevated liver enzymes, and people taking the drug cyclosporine.

Because liver enzymes rise in some people taking Thelin, monthly liver enzyme test are required.

If you take the drug Warfarin, your dose will be adjusted when you add Thelin to your regiment. See drug information below for a more in-depth discussion of this.

Common Side Effects include:

  • Liver enzyme abnormalities (Increases in ALT and SSI)
  • Edema
  • Constipation
  • Nasal congestion
  • Upper respiratory tract infection
  • Dizziness
  • Insomnia
  • Flushing

More Serious Side Effects include:

  • Birth defects
  • Liver damage

Drug-Drug Interactions

Cyclosporine: THELIN 100 mg once daily co-administered with cyclosporine 3.5 mg/kg twice daily did not alter the pharmacokinetic disposition of cyclosporine, which is extensively metabolized by CYP3A4/5. However, this co-administration resulted in a 6-fold increase in the pre-dose concentrations of sitaxsentan. The mechanism for this interaction is not known. Because of this increase in sitaxsentan exposure, the use of THELIN in patients receiving cyclosporine is contraindicated.

Warfarin: Sitaxsentan is an inhibitor of CYP2C9 and increases the AUC and Cmax of drugs metabolized by CYP2C9. The AUC8 of S-warfarin was increased by approximately 96%, and clearance was decreased by approximately 63% when a single 25 mg dose was co-administered with THELIN 100 mg once daily. An enhanced effect on PT and INR was observed, consistent with the increase in exposure to S-warfarin.

In clinical trials, it was recommended that the warfarin dose be decreased by 80% when starting THELIN and then increased in increments of no greater than 0.5 mg/day while titrating to the desired INR. The mean dose of warfarin at study endpoint in STRIDE 2 (18 weeks of dosing) was 2.2 mg/day for patients receiving THELIN, compared to 3.6 mg/day for patients treated with placebo. In STRIDE 2, the need to change the warfarin dose due to changes in INR was similar among the THELIN-treated and, placebo-treated patients.


Thelin may increase exercise tolerance and delay the worsening of pulmonary arterial hypertension. Functional class has also been known to improve in some patients.

How quickly will I respond to Thelin?
This will vary from person to person, but may take many months. Some improvement in exercise tolerance (6-minute walk test results) was observed after 12 weeks in clinical trial.


The cost of Thelin varies from country to country. It has not been priced for the U.S. market.

Because Thelin is classified as a drug, instead of a treatment, it is covered differently by insurance companies and Medicare. Co-pay rates varied widely. At this time, arrangements with individual insurance companies vary.

Manufactured by
Encysive Pharmaceuticals until 2008, Pfizer since February 2008

Visit the Official Drug Company Website

Page Reviewed/Edited: November 2012

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