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Valaciclovir, also spelled valacyclovir, is an antiviral drug used in the management of herpes simplex, herpes zoster (shingles), and herpes B.
It is a prodrug, which is converted to aciclovir in a persons body.
Valaciclovir was approved for medical use in 1995.
1 Medical use
2 Adverse effects
3 Mechanism of action
Valtrex brand valaciclovir 500mg tablets
Valaciclovir is indicated for the treatment of HSV and VZV infections, including:
Oral and genital herpes simplex (treatment and prophylaxis )
Reduction of HSV transmission from people with recurrent infection to uninfected individuals
Herpes zoster (shingles): the typical dosage for treatment of herpes is 1,000 mg orally three times a day for seven consecutive days.
Prevention of cytomegalovirus following organ transplantation
Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy)
It has shown promise as a treatment for infectious mononucleosis,
Common adverse drug reactions (≥1% of patients) associated with valaciclovir therapy are the same as for aciclovir, its active metabolite, and include: nausea, vomiting, diarrhea and headache. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, edema, arthralgia, sore throat, constipation, abdominal pain, rash, weakness and/or renal impairment. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic symptoms, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis. Mechanism of action Valaciclovir belongs to a family of molecules first described and patented by Paolo Cornaglia Ferraris in 1982 (patents EP0077460 A2, CA1258149A1, DE3273785D1, EP0077460A3, EP0077460B1, US4567182). Valaciclovir is a prodrug, an esterified version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir (10–20%). It is converted by esterases to the active drug aciclovir, as well as the amino acid valine, via hepatic first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase ; it has approximately 100 times higher affinity to viral than cellular polymerase. Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo- GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases. Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity: Herpes simplex virus type I (HSV-1) Herpes simplex virus type II (HSV-2) Varicella zoster virus (VZV) Epstein–Barr virus (EBV) Cytomegalovirus (CMV) The drug is predominantly active against HSV, and to a lesser extent VZV. It is only of limited efficacy against EBV and CMV; however, valacyclovir has recently been shown to lower or eliminate the presence of the Epstein–Barr virus in subjects afflicted with acute mononucleosis, leading to a significant decrease in the severity of symptoms. To date, It also is used for herpes B virus postexposure prophylaxis. Chemistry Valtrex is offered in 250 mg, 500 mg, and 1 gram tablets, the active ingredient being valacyclovir hydrochloride, with the inactive ingredients carnauba wax, colloidal silicon dioxide, crospovidone, FD&C Blue No. 2 Lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.
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