Pancreatitis and Combination Antiretroviral Therapy
With its durable virological response and convenient once-daily dosing, the nucleotide analogue tenofovir (Viread®, Gilead) is recommended for first-line combination treatment with lamivudine (Generic Epivir, GlaxoSmithKline) and efavirenz (Sustiva drug, Bristol-Myers Squibb). However, combining tenofovir with other nucleotide analogues, such as didano-sine (Videx®, Bristol-Myers Squibb), might result in a toxic interaction, advise researchers from Cleveland Clinic Foundation and Virginia Commonwealth University Medical Center.
They describe a patient with didano-sine-induced pancreatitis secondary to concurrent use of tenofovir. Other cases have been reported about the effects of full-strength didanosine, but this is the third case in which the didanosine dosage was reduced.
The initial antiretroviral therapy consisted of efavirenz 600 mg and tenofovir 300 mg at bedtime; stavudine (Zerit generic, Bristol-Myers Squibb) 30 mg twice daily; lamivudine 150 mg twice daily; and didanosine enteric-coated, 250-mg tablets at 5 a.m. daily. Ten weeks later, the patient was admitted to the emergency department after five days of intractable nausea and vomiting, epigastric abdominal pain without radiation, weight loss, pleuritic chest pain, and chills. He had stopped taking the antiretroviral medications two days before admission.
An abdominal computed tomographic scan revealed fat strands surrounding the pancreas and a small amount of ascites consistent with pancreatitis but no definitive pancreatic necrosis. After three days, the patient was discharged with mild epigastric pain; laboratory values returned to normal. All of the anti-retroviral agents were discontinued for one month and were then restarted without didanosine. Ten months later, the patient’s amylase values remained normal and the pancreatitis symptoms resolved.
Didanosine use is associated with significant adverse drug effects (ADEs) such as peripheral neuropathy and hepatitis in addition to pancreatitis; such toxicities have a dose-dependent relationship.
Two other factors might have contributed to the pancreatitis. Medication Stavudine might have increased the risk of a drug-drug interaction, and the patient was underweight (60 kg, or 160 pounds). The authors say that reducing the dose of didanosine to 125 mg/day should be considered for such patients, although no published pharmacokinetic data are available.
