Drug Interactions between acetaminophen / caffeine / phenyltoloxamine and Comhist
This report displays the potential drug interactions for the following 2 drugs:
- acetaminophen/caffeine/phenyltoloxamine
- Comhist (chlorpheniramine/phenylephrine/phenyltoloxamine)
Interactions between your drugs
phenylephrine caffeine
Applies to: Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine) and acetaminophen / caffeine / phenyltoloxamine
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
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
- Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
- "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
- "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
- "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
- "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
- "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
chlorpheniramine phenyltoloxamine
Applies to: Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine) and acetaminophen / caffeine / phenyltoloxamine and Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine)
MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.
MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.
References
- Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
- Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
- Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
- Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
- Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
- Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
- Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
- Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
- Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
- Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
- Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
- Cohen MA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry 151 (1994): 619-20
- "Product Information. Cogentin (benztropine)." Merck & Co., Inc PROD (2001):
- Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
- "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
Drug and food interactions
acetaminophen food
Applies to: acetaminophen / caffeine / phenyltoloxamine
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
- 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
- O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
- Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
- Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
- McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
- Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
- Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
- "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
- Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
- Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
- Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
- Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
chlorpheniramine food
Applies to: Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine)
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
- Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
- "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
- "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
phenyltoloxamine food
Applies to: acetaminophen / caffeine / phenyltoloxamine and Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine)
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
- Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
- "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
- "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
phenylephrine food
Applies to: Comhist (chlorpheniramine / phenylephrine / phenyltoloxamine)
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
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
- Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
- "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
- "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
- "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
- "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
- "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
caffeine food
Applies to: acetaminophen / caffeine / phenyltoloxamine
The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.
References
- "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
- Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52
Therapeutic duplication warnings
Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.
Antihistamines
Therapeutic duplication
The recommended maximum number of medicines in the 'antihistamines' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antihistamines' category:
- acetaminophen/caffeine/phenyltoloxamine
- Comhist (chlorpheniramine/phenylephrine/phenyltoloxamine)
Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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