Drug Interactions between moxifloxacin / triamcinolone and rifampin

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: Rifampin may induce the hepatic metabolism of corticosteroids, possibly reducing their therapeutic effect. The elimination half-life of corticosteroids has been shown to be reduced by up to 45% when rifampin is coadministered. Theoretically, rifabutin could interact with corticosteroids in a similar manner.

MANAGEMENT: Patients should be monitored for altered corticosteroid effects. Dosage increases may be necessary. Two- to threefold increases in prednisolone dosage have been recommended.

MONITOR: Coadministration of rifampin with agents known to induce hepatotoxicity may potentiate the risk of liver injury. There are various possible mechanisms related to rifampin-associated hepatotoxicity described in product labeling and medical literature, however no consensus has been made. These include increased mitochondrial oxidative stress, apoptotic liver cell injury (in rodent studies), the development of cholestasis, hepatic lipid accumulation, and elevated toxic metabolites caused by rifampin-mediated induction of cytochrome P450 enzymes. Cases of drug-induced liver injury (including fatal cases) have been reported within the first few days to months following rifampin treatment initiation. Additional data suggests that 1-2% of patients receiving rifampin monotherapy for tuberculosis prophylaxis experience hepatotoxicity. The severity of hepatotoxicity from rifampin ranges from asymptomatic elevations in liver enzymes, jaundice and/or hyperbilirubinemia, and symptomatic self-limiting hepatitis to fulminant liver failure and death. In most cases, liver function recovers upon on discontinuation of rifampin treatment, however, progression to acute liver failure requiring liver transplantation is possible. Known risk factors that may predispose the patient to rifampin related hepatotoxicity include: coadministration with other hepatotoxic agents, alcoholism, existing liver disease, malnutrition, extensive liver tuberculosis, liver adenocarcinoma and biliary tract neoplasm. Clinical data have been reported with concurrent use of rifampin with other antituberculosis agents (e.g. isoniazid, pyrazinamide), acetaminophen, antiretroviral agents (e.g., saquinavir/ritonavir) and halothane. Data with other hepatotoxic agents are limited.

MANAGEMENT: Caution and close clinical monitoring should be considered if rifampin is coadministered with other hepatotoxic medications. In addition, the manufacturer recommends patients with impaired liver function only be given rifampin in cases of necessity and then under strict medical supervision. Some authorities consider rifampin treatment in patients with existing liver injury contraindicated (Canada). In cases where coadministration of rifampin with hepatotoxic agents is required, careful monitoring of liver function, especially ALT and AST, should be done prior to therapy and then every 2 to 4 weeks during therapy. If hepatic damage is suspected, rifampin should be immediately discontinued. Furthermore, if hepatitis is attributed to rifampin in patients with tuberculosis, alternative agents should be considered. Patients should be instructed to contact their physician immediately if they experience symptoms such as itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine.