Drug Interactions between Flutabs and toripalimab
This report displays the potential drug interactions for the following 2 drugs:
- Flutabs (acetaminophen/dextromethorphan/guaifenesin/pseudoephedrine)
- toripalimab
Interactions between your drugs
acetaminophen toripalimab
Applies to: Flutabs (acetaminophen / dextromethorphan / guaifenesin / pseudoephedrine) and toripalimab
MONITOR: Acetaminophen may reduce the efficacy of immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and/or inhibitors of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1). The mechanism of this interaction has not been fully elucidated, but may involve the ability of acetaminophen to impair proliferation of immune cells and T-cell mediated antitumor immunity, which has been observed in some studies. In the CheckMate 025 trial, patients with advanced renal cell carcinoma (n=297) and detectable serum levels of acetaminophen or its metabolite acetaminophen glucuronide were observed to have significantly poorer overall survival (OS) than patients without detectable acetaminophen levels at treatment onset. Similarly, it was noted during an analysis of plasma samples from patients (n=34) in a separate study who were treated with anti-PD-L1 therapies, with or without anti-CTLA-4 antibodies, that those with a detectable serum acetaminophen level had a significantly lower objective response rate than those without a detectable acetaminophen level (0% vs. 29.4%, respectively). Although OS was numerically shorter for patients with detectable acetaminophen levels compared to those without, this difference was not statistically significant in this study. Likewise, an analysis of plasma samples from patients enrolled in the PREMIS study (n=297) treated with anti-PD-L1 therapies, with or without anti-CTLA-4 antibodies, found that the presence of detectable acetaminophen levels was associated with significantly worse progression-free survival (PFS, median 2.63 months vs. 50.3 months) and OS (median 8.43 months vs. 14.93 months) when compared to those without detectable acetaminophen levels. Similarly, a retrospective single-center study in patients (n=225) with stage IV non-small cell lung cancer (NSCLC) who underwent first-line therapy with pembrolizumab (alone or in combination with platinum-based chemotherapy) or second-line therapy with pembrolizumab, nivolumab, or atezolizumab noted that patients who were exposed to high intensity acetaminophen (defined as therapeutic intake lasting >24 hours or a total intake >60 doses of 1000 mg) between 30 days before to 90 days after the first ICI infusion had an increased risk of treatment failure and a shorter duration of median PFS and OS. Multivariate analyses confirmed that high exposure to acetaminophen was independently associated with a reduction in both PFS and OS. Data are not available for every ICI in combination with acetaminophen in every clinical situation.
MANAGEMENT: Until more information is available, caution and clinical monitoring for reduced efficacy of immune checkpoint inhibitors (ICIs) may be advisable if they are administered with acetaminophen. One study suggests that only a pronounced and/or prolonged intake of acetaminophen is able to reduce the immune response to anti-PD-1/PD-L1 agents in patients with advanced NSCLC and suggests a more restrained and discontinuous intake of acetaminophen (<4 doses of 1000 mg/week) may help avoid worsening patient outcomes in this patient population.
References (3)
- Bessede A, Marabelle A, Guegan JP, et al. (2022) "Impact of acetaminophen on the efficacy of immunotherapy in cancer patients." Ann Oncol, 33, p. 909-15
- Nelli F, Virtuoso A, giannarelli d, et al. (2023) "Effects of acetaminophen exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small-cell lung cancer: a propensity score-matched analysis." Curr Oncol, 30, p. 8117-33
- Najeebullah, ali ma, Naveed R, Khatri G, Priya, hasan mm (2022) "Acetaminophen: a hazard to immunotherapy." Ann Med Surg (Lond), 80, p. 104272
Drug and food interactions
acetaminophen food
Applies to: Flutabs (acetaminophen / dextromethorphan / guaifenesin / pseudoephedrine)
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 (12)
- Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA (1985) "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med, 145, p. 2019-23
- O'Dell JR, Zetterman RK, Burnett DA (1986) "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA, 255, p. 2636-7
- Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med, 104, p. 399-404
- Thummel KE, Slattery JT, Nelson SD (1988) "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther, 245, p. 129-36
- McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA, 244, p. 251-3
- Kartsonis A, Reddy KR, Schiff ER (1986) "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med, 105, p. 138-9
- Prescott LF, Critchley JA (1983) "Drug interactions affecting analgesic toxicity." Am J Med, 75, p. 113-6
- (2002) "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical
- Whitcomb DC, Block GD (1994) "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA, 272, p. 1845-50
- Bonkovsky HL (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
- Nelson EB, Temple AR (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
- Zimmerman HJ, Maddrey WC (1995) "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology, 22, p. 767-73
dextromethorphan food
Applies to: Flutabs (acetaminophen / dextromethorphan / guaifenesin / pseudoephedrine)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete 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.
References (4)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
pseudoephedrine food
Applies to: Flutabs (acetaminophen / dextromethorphan / guaifenesin / pseudoephedrine)
MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.
References (7)
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
- Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
- (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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