Drug Interactions between imatinib and Tylenol Severe Cold & Flu Night Time

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Switch to consumer interaction data

MONITOR: In vitro inhibition data suggest that coadministration with imatinib may increase the plasma concentrations of acetaminophen. The proposed mechanism is imatinib inhibition of acetaminophen clearance via O-glucuronidation. However, no specific pharmacokinetic studies in humans have been performed. Pharmacodynamically, the potential may exist for additive adverse effects on the liver, since both agents individually are associated with hepatotoxicity. Cases of liver injury, including hepatic failure and hepatic necrosis, have been observed with imatinib use, particularly when combined with high-dose chemotherapy regimens. Most cases have been reversible, although approximately 0.5% have required permanent discontinuation of imatinib. In a phase 2 clinical trial, a patient who received a bone marrow transplant and had been taking acetaminophen (3000 to 3500 mg/day) regularly for fever died of acute liver failure 12 days after starting treatment with imatinib 600 mg/day. In a postmarketing case report, a patient developed severe hepatitis associated with coagulopathy five months after starting imatinib 400 mg/day for chronic myeloid leukemia. She began taking acetaminophen 500 to 1000 mg/day after the onset of symptoms. During hospitalization, her condition progressed to encephalopathy and she subsequently died of a cardiac arrest. Whether acetaminophen affected the clinical course and outcome of her hepatitis cannot be determined.

MANAGEMENT: Caution is advised if imatinib is used in combination with acetaminophen, particularly at higher dosages of the latter. All patients treated with imatinib should have liver function tests (transaminases, bilirubin, and alkaline phosphatase) prior to initiation of therapy and monthly thereafter or as clinically indicated. If elevations in bilirubin greater than 3 times institutional upper limit of normal (IULN) or liver transaminases greater than 5 times IULN occur, imatinib should be withheld until bilirubin levels decline to less than 1.5 times IULN and transaminase levels to less than 2.5 times IULN. Treatment may then be resumed at a reduced daily dosage (e.g., in adults: 400 mg to 300 mg, 600 mg to 400 mg, or 800 mg to 600 mg; in children: 340 to 260 mg/m2/day or 260 mg/m2/day to 200 mg/m2/day). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. In addition, they should not take over-the-counter medications such as analgesics containing acetaminophen, flu preparations, or herbal products without first talking to their healthcare provider.

Switch to consumer interaction data

MONITOR: Coadministration with CYP450 2D6 inhibitors may increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. Coadministration of dextromethorphan (60 mg orally, once) with the CYP450 2D6 inhibitor panobinostat (20 mg orally once a day on days 3, 5, and 8) in 14 patients with advanced cancer had a highly variable effect on dextromethorphan levels, increasing the peak plasma concentration (Cmax) of dextromethorphan by 20% to 200%, and total systemic exposure (AUC 0 to infinity) by 20% to 130%, compared to dextromethorphan given alone. In addition, multiple doses of the potent CYP450 2D6 inhibitor cinacalcet (50 mg daily), increased the AUC of a single 30 mg dextromethorphan dose by 11-fold in extensive metabolizers of this isoenzyme. The moderate CYP450 2D6 inhibitor asunaprevir, given at 200 mg twice daily, also increased Cmax and AUC of a single 30 mg dose of dextromethorphan by 2.7- and 3.9-fold, respectively, in 17 study subjects.

MANAGEMENT: Caution should be exercised if these drugs must be used together. Patients should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

Switch to consumer interaction data