NNRTIs; Delavirdine + Acids - Drug Interactions

In patients with poor gastric acid production, orange juice andglutamic acid increase absorption of delavirdine.

Clinical evidence,mechanism, importance and management

When glutamic acid 1.36 g three times daily was given with delavirdine 400mg three times daily to 8 HIV-positive subjects with gastric hypoacidity, AUC of delavirdine was increased by 50 % (See reference number 1). Similarly,orange juice increased delavirdine absorption by 50 % to 70 % in subjects with gastric hypoacidity, but had less effect (0 to 30%) in those with normal gastric acidity. However, despite use of orange juice, AUC of delavirdine was still about 50 % lower in patients with gastric hypoacidity than those without (See reference number 2).

Delavirdine is a weak base that is poorly soluble at neutral pH (note that antacids reduce its absorption,see NNRTIs + Drugs that affect gastric pH interaction). Therefore, in subjects with gastric hypoacidity, absorption of delavirdine is reduced, and substances that lower gastric pH increase its absorption.

The clinical value of using glutamic acid or acidic beverages with delavirdine is unknown. Nevertheless, manufacturer recommends that, in patients with achlorhydria, delavirdine should be taken with an acidic beverage such as orange or cranberry juice (See reference number 3).

Morse GD,Adams JM, Shelton MJ, Hewitt RG, Cox SR, Chambers JH. Gastric acidification increases delavirdine mesylate (DLV) exposure in HIV+ subjects with gastric hypoacidity(GH). Clin Pharmacol Ther (1996) 59, 141.

Shelton MJ,Hewitt RG, Adams JM, Cox SR, Chambers JH, Morse GD. Delavirdine malabsorption in HIV-infected subjects with spontaneous gastric hypoacidity. J Clin Pharmacol (2003) 43, 171–9.

Rescriptor (Delavirdine mesylate). Pfizer Inc. US Prescribing information,June 2006.