Medical Staff Pulse is
a Publication of the Chief of Staff
Pharmacy Focus 1

Liver Failure with Propylthiouracil

There is a risk of serious and possibly fatal liver injury associated with propylthiouracil, an anti-thyroid drug used to treat Graves' disease, according to the FDA. Propylthiouracil is considered a second-line therapy in Graves' disease. The drug of choice in most cases is methimazole, because it has been associated with fewer cases of serious liver damage than propylthiouracil.

Children are especially vulnerable to liver damage with the drug. The risk profile is different for patients in the first trimester of pregnancy, however, since methimazole has been associated with embryopathy and propylthiouracil has not.

The FDA is recommending that clinicians reserve the use of propylthiouracil for patients who cannot take methimazole because of allergy or intolerance, or for patients in the first trimester of pregnancy. Propylthiouracil should not be used in children unless they cannot take methimazole and there are no other treatment options available.

Increased Mortality in Liver Transplant Patients Treated with Rapamune

Stable liver transplant patients may have an increased risk of death if they are switched from an immunosuppressive regimen based on a calcineurin inhibitor (CNI) to sirolimus, which is marketed as Rapamune, according to the FDA.

The drug is approved to prevent organ rejection in patients 13 and older who receive kidney transplants. It is not approved to treat patients with liver or lung transplants.

The higher mortality risk was found in a clinical trial conducted by Wyeth, the manufacturer of Rapamune. The trial also suggested that patients converted to Rapamune were more likely to experience treatment failure at one year, and more likely to discontinue the drug because of adverse events, than patients who remained on CNI-based therapy.

Serious Fungal Infections with Simponi

There is a risk of serious fungal infections with TNF blockers, including the recently approved Simponi (golimumab), according to the FDA.

TNF blockers are immunosuppressants used to treat chronic inflammatory diseases, including rheumatoid arthritis.

The FDA previously warned about the risk of such infections associated with TNF blockers, including Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab) and Remicade (infliximab). FDA said that invasive fungal infections, including histoplasmosis, have not been consistently recognized in patients taking these drugs, resulting in delayed treatment and, in some cases, death.

TNF blockers, including Simponi, should be discontinued if such infections occur, and clinicians should consider empiric antifungal therapy until the specific pathogens can be identified, according to Centocor Ortho Biotech, the manufacturer of Simponi.

For more information on any of the items above, visit www.fda.gov/psn.