Drug Interactions between asparaginase escherichia coli and itraconazole

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

Switch to consumer interaction data

MONITOR: Concomitant use of asparaginase with other hepatotoxic agents may potentiate the risk of liver injury. Asparaginase-associated hepatotoxicity has been reported more commonly in adults than in children and has been strongly associated with obesity. Hepatomegaly, acute severe hepatotoxicity, and fatal liver failure have been reported with asparaginase treatment in adults. Also, asparaginase may increase the toxicity of drugs bound to plasma proteins or metabolized by the liver.

MANAGEMENT: The risk of additive hepatotoxicity should be considered when asparaginase is used with other hepatotoxic agents (e.g., alcohol, androgens, antituberculosis agents, azole antifungal agents, ACE inhibitors, macrolide antibiotics, nonsteroidal anti-inflammatory agents, nucleoside reverse transcriptase inhibitors, sulfonamides, thiazolidinediones, and statins). Liver function tests should be monitored at regular intervals during asparaginase treatment with or without other hepatotoxic drugs. Patients should be advised to seek medical attention if they experience potential symptoms of hepatotoxicity such as right upper quadrant pain, increasing abdominal size, fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, dark urine, pale stools, and jaundice.

Switch to consumer interaction data