varicella
Valacyclovir (Valtrex) Contraindications and Precautions
Valacyclovir is not currently approved for use in patients with immunosuppression. Trials regarding the effectiveness of valacyclovir in the treatment and prophylaxis of CMV in renal and bone marrow transplant patients are currently underway. However, in clinical trials using valacyclovir 8 g/day in patients with advanced HIV disease or following allogeneic bone marrow transplantation or renal transplantation, cases of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) have been reported; some of these cases were fatal. Efficacy of valacyclovir has not been established in immunocompromised patients or in those with disseminated herpes zoster (varicella). The CDC does not recommended valacyclovir for cytomegalovirus (CMV) prophylaxis in patients with acquired immunodeficiency syndrome (AIDS). During clinical studies, there was an unexplained trend towards increased mortality in persons with AIDS treated with valacyclovir for the prevention of CMV infection.
Valacyclovir should be used with caution in patients with renal dysfunction. Patients with renal impairment or renal failure should receive lower doses at longer intervals (see Dosage). Acute renal failure and CNS toxicity have been reported in patients with underlying renal dysfunction who have received inappropriately high doses of valacyclovir for their level of renal function. Patients receiving potentially nephrotoxic drugs together with valacyclovir may have an increased risk of renal dysfunction.
In a clinical study of herpes zoster, the duration of pain after healing (post-herpetic neuralgia) was longer in elderly patients ( >= 65 years) compared with younger adults. Elderly patients are more likely to have impaired renal function and may require lower doses of valacyclovir. Elderly patients are also more likely to have renal or CNS adverse events. With respect to CNS adverse events observed during clinical practice, agitation, hallucinations, confusion, delirium, and encephalopathy were reported more frequently in elderly patients.
In order to prevent crystalluria, patients should be well-hydrated to maintain a high urine volume and avoid dehydration during treatment with valacyclovir.
The safe use of valacyclovir in children has not been established. Oral administration of the related drug acyclovir has been studied in children over 2 years old.
Valacyclovir has been classified as FDA pregnancy category B. No complete or well-controlled pregnancy studies have been performed in humans. Acyclovir, the active component of valacyclovir, was not found to be teratogenic in standard animal studies. A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 756 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate the risk for specific defects or to permit definitive conclusions regarding the safety of acyclovir in pregnant women. Valacyclovir should be avoided during pregnancy unless the potential benefits outweigh the possible risks to the fetus.
In a small study of 5 lactating women, valacyclovir was administered orally as a single 500 mg dose. Peak acyclovir concentrations in breast milk ranged from 0.5 to 2.3 times (median 1.4) the corresponding maternal acyclovir serum concentrations and the acyclovir AUC in breast milk ranged from 1.4 to 2.6 times (median 2.2) maternal serum AUC. The administration of valacyclovir 500 mg twice daily to a breast-feeding woman would provide the nursing infant with an oral acyclovir dosage of approximately 0.6 mg/kg/day, resulting in less than 2% of the exposure obtained after administering a standard neonatal intravenous dose of 30 mg/kg/day. In the study, unchanged valacyclovir was not detected in maternal serum, breast milk, or infant urine. Valacyclovir should be administered to a woman breast-feeding her infant with caution and only when indicated. Women who have active herpetic lesions on or near the breast should avoid nursing.
Valacyclovir is rapidly converted to acyclovir; avoid use in patients with acyclovir hypersensitivity or valacyclovir hypersensitivity. Also, use with caution in patients with ganciclovir hypersensitivity; these drugs have similar chemical structures and there may be cross sensitivity.
Patients with moderate or severe hepatic disease have a slower valacyclovir to acyclovir conversion rate. However, the extent of conversion is not affected, or the half-life of acyclovir. No dosage adjustments are recommended for patients with hepatic disease.
[ Last revised: 9/28/2005 6:23:00 PM ]
References
. Centers for Disease Control and Prevention (CDC). The Living Document: USPHS/IDSA Guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Retrieved November 28, 2001. Available on the World Wide Web at http://www.hivatis.org.
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