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Drug Interactions between Coricidin Night Time Cold Relief and Gleevec

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

acetaminophen imatinib

Applies to: Coricidin Night Time Cold Relief (acetaminophen / diphenhydramine) and Gleevec (imatinib)

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.

References

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. Lin NU, Sarantopoulos S, Stone JR, et al. "Fatal hepatic necrosis following imatinib mesylate therapy." Blood 102 (2003): 3455-6

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Drug and food interactions

Major

acetaminophen food

Applies to: Coricidin Night Time Cold Relief (acetaminophen / diphenhydramine)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

imatinib food

Applies to: Gleevec (imatinib)

GENERALLY AVOID: Coadministration of imatinib with strong CYP450 3A4 inhibitors such as grapefruit juice, may significantly increase the plasma concentrations of imatinib, a known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of imatinib by certain compounds present in grapefruits. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In a single-dose study, coadministration of imatinib with ketoconazole (a strong CYP450 3A4 inhibitor) increased imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 40%, respectively.

MANAGEMENT: Patients treated with imatinib should preferably avoid the consumption of grapefruit or grapefruit juice. If coadministration is unavoidable, monitor for prolonged and/or increased pharmacologic effects of imatinib, including edema, hematologic toxicity and immunosuppression.

References

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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Moderate

diphenhydrAMINE food

Applies to: Coricidin Night Time Cold Relief (acetaminophen / diphenhydramine)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.