Interactions between Acetaminophen / guaifenesin / phenylephrine and Restasis
No drug interactions found, but 15 warnings to review for the following 2 drugs:
- acetaminophen/guaifenesin/phenylephrine
- Restasis (cyclosporine ophthalmic)
Drug interactions
There were no interactions found between acetaminophen / guaifenesin / phenylephrine and Restasis. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
acetaminophen Food/Lifestyle
Applies to: acetaminophen / guaifenesin / phenylephrine
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.
References (1)
- (2022) "Product Information. Acetaminophen (acetaminophen)." Camber Pharmaceuticals, Inc
Moderate food/lifestyle interactions
Moderate:
phenylephrine Caffeine
Applies to: acetaminophen / guaifenesin / phenylephrine
Monitor
Coadministration of two or more sympathomimetic or noradrenergic agents may increase the risk of nervousness, irritability, tachycardia, and/or increased blood pressure. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic and/or noradrenergic agents, including norepinephrine transporter inhibitors. 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 or noradrenergic agents are coadministered. Pulse and blood pressure should be closely monitored. Consultation with individual product labeling, as well as relevant institutional protocols, may be advisable for further guidance.
References (20)
- 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
- (2024) "Product Information. Ephedrine (ephedrine)." Hameln Pharma Ltd
- (2023) "Product Information. Ephedrine Hydrochloride (ephedrine)." Wockhardt UK Ltd
- (2026) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
- (2025) "Product Information. Atomoxetine (atomoxetine)." Zentiva Pharma UK Ltd
- (2026) "Product Information. Atomoxetine (Apo) (atomoxetine)." Arrotex Pharmaceuticals Pty Ltd
- Angita Pharma, Inc (2026) AG-ATOMOXETINE Product Monograph (Health Canada) https://pdf.hres.ca/dpd_pm/00059014.PDF
- (2026) "Product Information. Boots Decongestant (Pseudoephedrine) (pseudoephedrine)." The Boots Company Plc
- (2023) "Product Information. Sinus and Nasal Decongestant (Trust) (pseudoephedrine)." Noumed Pharmaceuticals Pty Ltd
- (2019) "Product Information. Ephedrine (ephedrine)." Pfizer Australia Pty Ltd
- (2024) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Amneal Pharmaceuticals LLC
- (2024) "Product Information. Lemsip Cough Max for Mucus Cough and Cold (guaifenesin/paracetamol/phenylephrine)." Reckitt Benckiser Healthcare (UK) Ltd
- emc (2026) Product information: sudafed plus blocked nose 1mg/50mg/ml nasal spray. https://www.medicines.org.uk/emc/product/14256/smpc?utm_source=chatgpt.com
- (2023) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Baxter Corporation
- Neo Health (OTC) Pty Ltd (2026) Product information: pseudoephedrine hydrochloride-paracetamol capsules. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2024-PI-02603-1&d=20260804172310101&d=20260827172310101
Disease interactions
13 potential interactions Applies to: 13 conditions, including Benign Prostatic Hyperplasia, Hyperthyroidism, Diabetes Mellitus, Liver Disease, and Dehydration.
Alcoholism
Major:
acetaminophen / guaifenesin / phenylephrine
The acetaminophen in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Alcoholism.
Chronic alcohol abusers may be at increased risk of hepatotoxicity during treatment with acetaminophen (APAP). Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously, if at all, in patients who consume three or more alcoholic drinks a day. In general, patients should avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure. They should also be advised to seek medical attention if they experience signs and symptoms of liver injury such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.
Benign Prostatic Hyperplasia
Moderate:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a moderate potential interaction with Benign Prostatic Hyperplasia.
Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.
Cardiovascular Conditions and Disorders
Major:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Cardiovascular Conditions and Disorders.
Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.
Cerebrovascular Insufficiency
Major:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Cerebrovascular Insufficiency.
Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.
Dehydration
Major:
acetaminophen / guaifenesin / phenylephrine
The acetaminophen in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Dehydration.
Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.
Diabetes Mellitus
Moderate:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a moderate potential interaction with Diabetes Mellitus.
Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.
Glaucoma/Intraocular Hypertension
Moderate:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a moderate potential interaction with Glaucoma/Intraocular Hypertension.
Sympathomimetic agents can induce transient mydriasis via stimulation of alpha-1 adrenergic receptors. In patients with anatomically narrow angles or narrow-angle glaucoma, pupillary dilation can provoke an acute attack. In patients with other forms of glaucoma, mydriasis may occasionally increase intraocular pressure. Therapy with sympathomimetic agents should be administered cautiously in patients with or predisposed to glaucoma, particularly narrow-angle glaucoma.
Hyperthyroidism
Major:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Hyperthyroidism.
Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.
Liver Disease
Major:
acetaminophen / guaifenesin / phenylephrine
The acetaminophen in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Liver Disease.
Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.
Malnourishment
Major:
acetaminophen / guaifenesin / phenylephrine
The acetaminophen in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Malnourishment.
Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.
Phenylketonuria
Moderate:
acetaminophen / guaifenesin / phenylephrine
The acetaminophen in acetaminophen / guaifenesin / phenylephrine has a moderate potential interaction with Phenylketonuria.
Several oral acetaminophen and acetaminophen-combination products, particularly flavored chewable tablets, contain the artificial sweetener, aspartame (NutraSweet). Aspartame is converted to phenylalanine in the gastrointestinal tract following ingestion. Chewable and effervescent formulations of acetaminophen products may also contain phenylalanine. The aspartame/phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).
Pheochromocytoma
Major:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a major potential interaction with Pheochromocytoma.
Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.
Prostate Tumor, Benign
Moderate:
acetaminophen / guaifenesin / phenylephrine
The phenylephrine in acetaminophen / guaifenesin / phenylephrine has a moderate potential interaction with Prostate Tumor, Benign.
Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.
More resources
acetaminophen / guaifenesin / phenylephrine
A total of 721 drugs are known to interact with acetaminophen / guaifenesin / phenylephrine.
- Acetaminophen / guaifenesin / phenylephrine is in the drug class upper respiratory combinations.
- Acetaminophen / guaifenesin / phenylephrine is used to treat Cough and Nasal Congestion.
Restasis
A total of 16 drugs are known to interact with Restasis.
- Restasis is in the drug class miscellaneous ophthalmic agents.
- Restasis is used to treat Dry Eye Disease.
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.