Brivudine is a nucleoside analog used as a virostatic agent for herpes simplex type 1 and herpes zoster infections. It is the drug of choice for these indications in patients older than 50 years.
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 with other common nucleoside analogues (e.g., aciclovir), the substance has a significantly stronger antiviral potency. The half-life and intracellular residence time are also significantly higher. 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 seventies of the 20th century, but widespread use has only taken place since 2001. Since that time, brivudine has been approved for the therapy of herpes zoster. Previously, there was only an approval for the therapy of infections caused by the herpes simplex viruses of type 1.
Pharmacologic Action
Brivudine is administered orally in the form of tablets. The usual dose is 125 mg per day for a period of seven days. Brivudine must first be activated, and the active substance in the body is brivudine triphosphate. This has an intracellular residence time of ten hours. Brivudine only acts in cells that are infected by viruses. This is because brivudine is catalyzed by viral thymidine kinase. This means that viral thymidine kinase activates brivudine by converting it to triphosphate. Due to the long intracellular residence time of ten hours, there is sufficient time to act against the viruses in the affected cell. The triphosphates of brivudine provide the antiviral effect. They inhibit viral DNA polymerase and ensure the incorporation of modified nucleic bases into the DNA. Ultimately, this leads to chain termination during DNA elongation. It should be noted, however, that the brivudine triphosphate thus only inhibits the reproduction of the virus, but is not effective against the virus itself. Thus, the virus cannot be killed and remains in the body. The typical reactivation of the herpes viruses can therefore not be prevented by brivudine. The initiation of therapy therefore makes the most sense at the stage of viral replication, since this is where the active ingredient takes effect. Therapy with brivudine should therefore be started within 72 hours of the appearance of skin symptoms. Brivudine is effective against herpes simplex type 1 and herpes zoster viruses. There is insufficient efficacy against other herpes viruses. Brivudine is also not effective against herpes simplex type 2, which causes genital herpes. Brivudine is 85% absorbed in the intestine after oral absorption. 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 approximately 16 hours. Excretion occurs primarily via the kidney, but also to some extent via the stool.
Medical use and application
Medically, brivudine is indicated for the treatment of infections with herpes simplex type 1 and herpes zoster. In practice, brivudine is the agent of choice for therapy of these infections, especially in patients older than 50 years. Therapy with brivudine should be started within 72 hours of the onset of skin symptoms to achieve maximum efficacy. After these 72 hours, therapy is still useful if fresh vesicles are present on the skin, visceral spread, florid zoster ophthalmicus (full-blown herpes zoster of the eye), and zoster oticus (herpes zoster of the ear). Before therapy with brivudine, check for the presence of cross-resistance with aciclovir.
Risks and Side Effects
Side effects from brivudine are rare. They mainly affect the gastrointestinal tract. Here, nausea and diarrhea (diarrhea) may occur in particular. Furthermore, fatigue, sleep disturbances, dizziness, headache, hypersensitivity reactions of the skin, reversible changes in the blood count and the increase of creatinine and urea in the blood serum are possible as adverse effects. Brivudine should never be administered concomitantly with 5-fluorouracil, prodrugs of 5-fluorouracil, or flucytosine. Brivudine inhibits the enzyme responsible for the degradation of these substances, so that accumulation occurs, resulting in a toxic concentration of these substances.This side effect is potentially fatal. After therapy with brivudine, an interval of at least 4 weeks must be observed before the aforementioned substances may be administered. Brivudine must not be administered during pregnancy and lactation. Therapy with brivudine is also contraindicated in immunocompromised patients. There is cross-resistance with aciclovir: if the patient is allergic to aciclovir, he or she is also allergic to brivudine and vice versa.
