Ancotil 2.5g/250ml Solution for Infusion - - (eMC)

Sorivudine (1-β-d-arabinofuranosyl-E-5-[2-bromovinyl] uracil; BV-araU; SQ32,756) is an antimetabolite which is a synthetic analogue of thymidine. This drug has demonstrated antiviral activity against varicella zoster virus, herpes simplex type 1 virus, and Epstein-Barr virus. Clinical studies in Japan and subsequently worldwide showed this drug to be a potent agent for treating varicella zoster infections. Although in general well tolerated, a fatal drug interaction with fluoropyrimidine drugs was subsequently observed. While three deaths resulting from this interaction were recognized to have occurred during the initial clinical evaluation in Japan, the full impact of the interaction was not recognized in Japan until post-marketing when an additional 23 cases of severe toxicity were reported including 16 patients who subsequently died from fluoro-pyrimidine toxicity. Worldwide recognition of this potentially fatal drug-drug interaction led to subsequent disapproval in the US and elsewhere. The interaction has been shown to be due to suppression of 5-fluorouracil (5-FU) catabolism, resulting in higher levels of 5-FU than would normally be observed. The mechanism of this interaction is mediated through inhibition of the 5-FU rate-limiting catabolizing enzyme dihydropyrimidine dehydrogenase (DPD) by the BV-araU metabolite BVU. This drug-drug interaction of sorivudine and 5-FU further emphasizes the critical importance of DPD on the clinical pharmacology of 5-FU.

Ancotil 2.5g/250ml Solution for Infusion - by Meda Pharmaceuticals

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Actikerall 5mg/g + 100mg/g Cutaneous Solution - - (eMC)

One of the products of sorivudine metabolism is bromovinyluracil (BVU). In vitro studies conducted long before clinical trials with sorivudine were initiated had identified BVU as a potent inhibitor of dihydropyrimidine dehydrogenase (DPD). Among other enzymatic activities, DPD is involved in the metabolism of 5-FU, a cancer chemotherapeutic agent (). This creates the potential for a significant drug interaction in patients concomitantly receiving sorivudine and 5-FU. With DPD inhibited by BVU, the activity of 5-FU is sustained, which may result in severe bone marrow suppression. In Japan, where sorivudine was originally synthesized, sorivudine was released for use in the treatment of herpes zoster (at a dosage of 50 mg three times daily) in September 1993. Within a few weeks, multiple instances of cancer patients on 5-FU therapy receiving sorivudine for herpes zoster were reported, despite warnings to physicians (). Tragically, this inappropriate prescription of medications resulted in 18 deaths due to severe bone marrow toxicity (). Sorivudine was withdrawn from the Japanese market in October 1993.

Actikerall 5mg/g + 100mg/g Cutaneous Solution - by Almirall Limited

One of the products of sorivudine metabolism is bromovinyluracil (BVU). In vitro studies conducted long before clinical trials with sorivudine were initiated had identified BVU as a potent inhibitor of dihydropyrimidine dehydrogenase (DPD). Among other enzymatic activities, DPD is involved in the metabolism of 5-FU, a cancer chemotherapeutic agent (). This creates the potential for a significant drug interaction in patients concomitantly receiving sorivudine and 5-FU. With DPD inhibited by BVU, the activity of 5-FU is sustained, which may result in severe bone marrow suppression. In Japan, where sorivudine was originally synthesized, sorivudine was released for use in the treatment of herpes zoster (at a dosage of 50 mg three times daily) in September 1993. Within a few weeks, multiple instances of cancer patients on 5-FU therapy receiving sorivudine for herpes zoster were reported, despite warnings to physicians (). Tragically, this inappropriate prescription of medications resulted in 18 deaths due to severe bone marrow toxicity (). Sorivudine was withdrawn from the Japanese market in October 1993.

Anti viral-drug synthesis by Dr Anthony Crasto
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