Drug Interaction Report

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.

GENERALLY AVOID: Ethanol can exacerbate the cutaneous flushing that is a common side effect of niacin. At least one case of delirium and lactic acidosis has been reported with coadministration of these drugs, although data are limited.

MANAGEMENT: Coadministration should probably be discouraged, particularly since chronic consumption of large amounts of alcohol is associated with hyperlipidemia.

A single case has been reported in which cutaneous flushing and tremors were noted in a woman who was taking niacin while wearing a nicotine patch. The mechanism is suspected to be synergistic cutaneous vasodilatory effects. The clinical significance of this possible interaction is not known.