Novartis Updates Safety Label of Egaten

Novartis has updated the warnings and precautions section of the label of Egaten (triclabendazole), which is used to treat infections caused by Fasciola parasites, flatworms referred to as liver flukes. Egaten can increase the QTc interval, especially after prolonged use. This can result in a heart rhythm condition that can cause chaotic heartbeats.

The change was made to reflect the results from a phase 1 clinical study conducted to assess the effects of Egaten on the heart rate-corrected QT intervals in healthy volunteers, according to a spokesperson for Novartis, the company that manufactures Egaten.

“The main revision entailed the replacement of the nonclinical information with the results from the QT/QTc clinical study, which confirmed that Egaten prolongs the QTc interval. The QT/QTc study was conducted to fulfill a postmarketing requirement requested by the FDA, which has been fulfilled as of February 17, 2022,” the spokesperson told FormularyWatch®.

The FDA approved Egaten in February 2019 for patients 6 years of age and older, and is the treatment of choice for this infection.

Egaten is not on formularies, as Novartis supplies Egaten in the United States for the treatment of fascioliasis in patients at no cost. The company also supplies it to the World Health Organization at no cost for distribution globally. Novartis has been donating Egaten to the WHO since 2005 as part of its commitment to neglected tropical diseases.

These infections are caused by two species of parasitic flatworms that mainly affect the liver (Fasciola hepatica or Fasciola gigantica). Left untreated, fascioliasis can result in pain and discomfort. The acute phase of the disease is manifested with fever, abdominal pain, nausea, diarrhea, and eosinophilia. The disease later progresses to a latent phase with less symptoms and ultimately into a chronic or obstructive phase. In children, fascioliasis can be a serious infection with high fever, enlarged tender liver, and anemia.

Fasciola parasites are found in more than 50 countries, especially where sheep and cattle are reared, according to the CDC. People can become infected when drinking water or eating vegetables contaminated with the parasite. Although more common outside the United States, Fasciola infections can be found in Hawaii, California, and Florida.

The updated warnings section now reads (changes are underlined):

“Egaten prolongs the QTc interval [see Clinical Pharmacology (12.2)]. The magnitude of QTc prolongation can increase with increasing treatment duration of Egaten Administration of Egaten concurrently with CYP1A2 inhibitors and use in patients with hepatic impairment may result in increased exposures of triclabendazole and/or its metabolites, and, therefore, may increase the risk for QT prolongation.

“Monitor electrocardiogram (ECG) in patients with a history of prolongation of the QTc interval or a history of symptoms compatible with a long QT interval or with electrolyte imbalance like hypokalemia, or when Egaten is used in patients who receive drugs that are known to prolong the QTc interval, or patients taking CYP1A2 inhibitors, or in patients with hepatic impairment. If signs of cardiac arrhythmia occur during treatment with Egaten, stop the treatment and monitor ECG.”