- Metabolism: Valaciclovir is rapidly and almost entirely (~99%) converted to the active compound, acyclovir, and L-valine by first-pass intestinal and hepatic metabolism by enzymatic hydrolysis. Neither valaciclovir nor acyclovir is metabolized by cytochrome P450 enzymes. Acyclovir is converted to a small extent to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase. Plasma concentrations of unconverted valacyclovir are low and transient, generally becoming non-quantifiable by 3 hours after administration. Peak plasma valacyclovir concentrations are generally less than 0.5 mcg/mL at all doses. After single-dose administration of 1 gram of VALTREX, average plasma valacyclovir concentrations observed were 0.5, 0.4, and 0.8 mcg/mL in patients with hepatic dysfunction, renal insufficiency, and in healthy volunteers who received concomitant cimetidine and probenecid, respectively. Route of Elimination: Acyclovir accounted for 89% of the radioactivity excreted in the urine. Half Life: 2.5-3.3 hours
- Uses/Sources: For the treatment or suppression of cold sores (herpes labialis), herpes zoster (shingles), genital herpes in immunocompetent individuals, and recurrent genital herpes in HIV-infected individuals. Cold Sores (Herpes Labialis): VALTREX is indicated for treatment of cold sores (herpes labialis). The efficacy of VALTREX initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. Genital Herpes: Initial Episode: VALTREX is indicated for treatment of the initial episode of genital herpes in immunocompetent adults. The efficacy of treatment with VALTREX when initiated more than 72 hours after the onset of signs and symptoms has not been established.
- Health Effects: General: Facial edema, hypertension, tachycardia. Allergic:Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria. CNS Symptoms: Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors. Eye: Visual abnormalities. Gastrointestinal: Diarrhea. Hepatobiliary Tract and Pancreas: Liver enzyme abnormalities, hepatitis. Renal: Renal failure, renal pain (may be associated with renal failure). Hematologic: Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS. Skin: Erythema multiforme, rashes including photosensitivity, alopecia.
- Symptoms: Adverse effects of overexposure might include headache and nausea.
- Treatment: In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored. (L1712)
- Route of Exposure: After oral administration, valaciclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of acyclovir after administration of valaciclovir is 54.5% ± 9.1%.
Mechanism of Action
|Target Name||Mechanism of Action||References|
Propionyl-CoA carboxylase beta chain, mitochondrial
Branched-chain-amino-acid aminotransferase, cytosolic