Brivudine

Brivudine is a nucleoside analog that is used as an antiviral agent for infections with herpes simplex type 1 and herpes zoster. It is the drug of choice for these indications for patients over 50 years of age.

What is brivudine?

Brivudine is a substance from the group of nucleoside analogues and is used for herpes simplex type 1 and herpes zoster (shingles). Compared to other common nucleoside analogues (e.g. acyclovir), the substance has a significantly stronger antiviral potency. The half-life and the intracellular residence time are also significantly longer.

The molecular formula of brivudine is C11H13BrN2O5. The substance has a molar mass of 333.135g x mol ^ -1. Brivudine was already produced in the 1970s, but it has only been widely used since 2001. Since then, brivudine has been approved for the treatment of herpes zoster. Previously, there was only approval for the treatment of infections caused by the herpes simplex virus type 1.

Pharmacological effect

Brivudine is administered orally in the form of tablets. The usual dose is 125 mg per day for seven days. The brivudine must first be activated, the active substance in the body is the brivudine triphosphate. This has an intracellular residence time of ten hours.

Brivudine only works in cells that have been infected by viruses. This is due to the fact that the brivudine is catalyzed by the viral thymidine kinase. This means that the viral thymidine kinase activates the brivudine by converting it to triphosphate. Due to the long intracellular residence time of ten hours, there is enough time to act against the viruses in the affected cell.

The triphosphates of brivudine ensure the antiviral effect. They inhibit the viral DNA polymerase and ensure the incorporation of modified nucleobases into the DNA. Ultimately, this leads to chain termination during DNA elongation.

It should be noted, however, that the brivudine triphosphate only inhibits the reproduction of the virus, but does not work against the virus itself. So the virus cannot be killed and remains in the body. The typical reactivation of the herpes viruses cannot be prevented by brivudine either. The initiation of therapy therefore makes the most sense in the virus replication stage, since this is where the active ingredient unfolds its effect. Therapy with brivudine should therefore be started within 72 hours after the appearance of skin symptoms.

Brivudine is effective against herpes simplex type 1 and herpes zoster viruses. There is no adequate effect against other herpes viruses. Brivudine is also not effective against herpes simplex type 2, which causes genital herpes.

After oral ingestion, 85% of brivudine is absorbed in the intestine. The plasma protein binding of brivudine is 95%. Brivudine is subject to a high first pass effect and is therefore only 30% bioavailable. The half-life is about 16 hours. Excretion takes place primarily through the kidneys, but partly also through the stool.

Medical application & use

Brivudine is medically indicated for the treatment of infections with herpes simplex type 1 and herpes zoster. In practice, brivudine is the drug of choice for treating these infections, especially in patients over 50 years of age. Brivudine therapy should be started within 72 hours of the appearance of skin symptoms in order to be most effective.

After these 72 hours, the therapy is still useful if there are fresh blisters on the skin, if there is visceral spread, if zoster ophthalmicus is florid (fully developed herpes zoster of the eye) and zoster oticus (herpes zoster of the ear). Before starting therapy with brivudine, check for cross-resistance with acyclovir.

Risks & side effects

Brivudine side effects are rare. They mainly affect the gastrointestinal tract. Above all, this can lead to nausea and diarrhea. Furthermore, fatigue, sleep disorders, dizziness, headaches, hypersensitivity reactions of the skin, reversible changes in the blood count and the increase in creatinine and urea in the blood serum are possible as undesirable effects.

Brivudine must in no case be administered simultaneously with 5-fluorouracil, prodrugs of 5-fluorouracil or flucytosine. Brivudine inhibits the enzyme responsible for the breakdown of these substances, so that an accumulation occurs, whereby a toxic concentration of these substances is reached. This side effect is potentially fatal. After therapy with brivudine, an interval of at least 4 weeks must be observed before the substances mentioned can be administered.

Brivudine should not be administered during pregnancy and breastfeeding. Brivudine therapy is also contraindicated in immunocompromised patients.

There is cross-resistance with acyclovir: if the patient is allergic to acyclovir, he is also allergic to brivudine and vice versa.