Sorivudine: Effects, Uses & Risks

Sorivudine is a medical drug that was developed in Japan to treat herpes. Sorivudine was marketed under the trade name Usevir and has been unavailable since a drug scandal killed several people in Japan. It did not even receive approval in Europe, so the drug did not have to be withdrawn from the market.

What is sorivudine?

Sorivudine was developed in the early 1990s by the Japanese pharmaceutical company Nippon Shoji. The drug was used to treat herpes infections and functioned as a virostatic agent. This refers to drugs that inhibit the multiplication of viruses and thus enable the treatment of infectious diseases. Sorivudine is effective against infections caused by herpes simplex type 1 viruses. It was also indicated for Epstein-Barr viruses (often called EBV or HHV4). Sorivudine is described in chemistry and pharmacology by the molecular formula C 11 – H 13 – Br – N 2 – O 6 and has a moral mass of 349.13 g/mol. After Usevir, the main sorivudine-containing preparation, caused a national drug scandal in 1994, the substance was withdrawn from the market. It has since been unavailable worldwide as a drug and has no use in human medicine.

Pharmacological action

Sorivudine achieves its activity against herpes and Epstein-Barr viruses by inhibiting the enzyme dihydropyrimidine dehydrogenase (DPD). This is responsible, among other things, for the degradation of various pyrimidines and fluorouracil. Fluorouracil, often also called 5-FU or 5-fluorouracil, is a cytostatic drug. As such, it is administered as part of a comprehensive chemotherapy regimen to treat various cancers. Due to the inhibition of DPD caused by sorivudine, the degradation of fluorouracil is made impossible or considerably slowed down, which can be lethal under certain circumstances. There are therefore massive interactions between sorivudine and fluorouracil. Sorivudine itself is degraded in the body by bromovinyluracil. The degradation process is thus largely the same as that of the antiviral drug brivudine, which continues to be approved as a drug.

Medical application and use

Sorivudine was administered and manufactured for the treatment of herpes. The drug Usevir was indicated to treat infections with herpes zoster (shingles) or herpes simplex type 1. Epstein-Barr viruses could also be treated with sorivudine. It was only taken orally in the form of film-coated tablets. Preparations containing sorivudine were subject to pharmacy and prescription requirements in Japan. Sorivudine was withdrawn from the market following a drug scandal in Japan. Due to the drug’s mode of action, a total of 16 patients died in 1994 after taking sorivudine because they had been treated in advance with fluorouracil. This was possible because Nippon Shoji, the manufacturer of sorivudine, provided inaccurate information to the responsible health ministry during the approval process. This was because there were already deaths caused by the known interaction of fluorouracil and sorivudine when the drug tests required in advance were carried out. Because the manufacturer failed to forward the necessary information after the test phase was completed, sorivudine was approved. No indication of the lethal interaction was provided, resulting in numerous co-administrations with fluorouracil.

Risks and Side Effects

Sorivudine should not be taken if there are known intolerances or allergies to the drug. These may manifest as massive skin reactions such as itching, redness, or rashes. The drug can also cause headaches and general malaise as an undesirable side effect. Gastrointestinal complaints are also conceivable. Sorivudine leads to massive interactions with fluorouracil, as the breakdown of the cancer drug is inhibited by sorivudine. This can be fatal under certain circumstances. From a medical point of view, this is a contraindication, so that combined administration of fluorouracil and sorivudine must be avoided.