Efavirenz Valproate

Clinically important, potentially hazardous interactions with alcohol, amprenavir, barbiturates, chlorpheniramine, clarithromycin, CNS depressants, efavirenz, erythromycin, esomeprazole, imatinib, MAO inhibitors, narcotics, nelfinavir, phenothiazines, valproate... 

Zidovudine (AZT) is an HIV reverse transcriptase inhibitor and chain terminator that is extensively glucuronidated (70% of the dose) primarily by UGT2B7. Metabolism of AZT is induced by rifampin (PXR), ritonavir, tipranavir, and efavirenz. Zidovudine clearance is inhibited by methadone (McCance-Katz, 1998) (opiates like codeine and morphine are UGT2B7 substrates), fluconazole Trapnell, 1998, atovaquone (Lee, 1996), and valproate (Lertora, 1994). Rifampin increased the formation clearance to AZT-glucuronide by twofold (Gallicano, 1999). 

The findings of the study suggest that valproate can be used with efa-virenz-based regimens without any anticipated pharmacokinetic drug interaction. However, the case report introduces a note of caution. It may be appropriate to monitor valproate levels in patients taking efavirenz. It is unclear whether the case of hepatotoxicity was a result of a drug interaction. Note that there has been some concern about using valproate in HIV infection but there seems to be no established reason to avoid or specifically promote the use of valproate in HlV-infection per se. 

Saraga M, Preisig M, Zullino DF. Reduced valproate plasma levels possible after introduction of efavirenz in a bipolar patient. Bipolar Disord (2006) 8, 415-17. 

Efavirenz levels were not altered by valproic acid in one study in mV-positive patients, and valproic acid levels were not different to those in a control group not taking efavirenz. However, one patient had a marked decrease in valproate levels after starting efavirenz. A case of hepatotoxicity has occurred in a patient taking valproic acid with nevirapine and saquinavir/ritonavir. 

However, a bipolar patient with multidrug addiction had a decrease in plasma valproic acid levels of more than 50% shortly after starting an antiretroviral regimen including efavirenz. Even though the valproate dose was increased to 4 g daily, it was found diffrcult to achieve a target plasma level of 50 mg/dL. About 3 months later, following a valproate dose reduction to 1.5 g daily due to adverse effects, his level was unaltered, at 52 mg/dL. ... 

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See also in sourсe #XX -- [ ]

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