Approaches for understanding and predicting drug interactions in human immunodeficiency virus-infected patients.

INTRODUCTION: Knowledge of drug interactions is vital to maximize antiretroviral efficacy and avoid drug-related toxicities. Treatment of co-morbidities has become a difficult task in HIV-infected individuals because pharmacokinetic and/or pharmacodynamic interactions are common when other medications are prescribed along with antiretroviral agents. AREAS COVERED: This article provides an update of the most relevant drug interactions that occur between antiretroviral agents and other drugs. The article additionally revisits how these drug interactions can be prevented from occurring as well as how they can be managed. EXPERT OPINION: Interactions between antiretrovirals and other drugs are frequent in clinical practice. The most common are those affecting drug metabolism due to induction or inhibition of the CYP450, leading to abnormal drug exposure. It is by this mechanism that most HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors and maraviroc often interact with other medications. In contrast, nucleoside reverse transcriptase inhibitors and some integrase inhibitors, which do not or only marginally affect CYP450, are relatively free of significant pharmacokinetic interactions, although nucleoside analogs might be involved in some pharmacodynamic interactions.

Clostridium difficile colitis associated with valaciclovir.

OBJECTIVE: To report a case of Clostridium difficile colitis associated with valaciclovir treatment. CASE SUMMARY: A 73-year-old man with lumbar herpes-zoster started valaciclovir 1 g tid. After three days he began vomiting and developed diarrhea, three to four stools per day. Symptoms worsened over the following days and he was admitted. Valaciclovir was stopped and fluid and electrolyte replacement was started. He continued 6 days later with diarrhea of 7 to 13 stools per day and a stool test for diagnosis of C. difficile infection was performed with a positive result. The patient received oral metronidazole (500 mg/t.i.d. for 10 days) and rapid improvement and eventual resolution of his diarrhea was observed after 3 days of therapy. DISCUSSION: Although no conclusive reports of this reaction exist, we think this is a case of C difficile colitis that appeared three days after valaciclovir was initiated. Colitis improved with metronidazole. Other causes of diarrhea were excluded, such as diabetes mellitus, renal failure, intestinal surgery and intestinal obstruction. Infection was confirmed by a positive test for C. difficile. The application of Naranjo's algorithm asserts the reaction as 'probable'. CONCLUSIONS: Valaciclovir-associated C. difficile colitis, although rare, can have severe consequences for the patient's health. It should be included as a possible adverse effect of valaciclovir treatment by health professionals.