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Interactions between Excedrin Sinus Headache and Smallpox vaccine

1 drug interaction and 15 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

acetaminophen smallpox vaccine

Applies to: Excedrin Sinus Headache (acetaminophen / phenylephrine) and smallpox vaccine
Monitor

Prophylactic administration of antipyretics at the time of vaccination may reduce certain antibody responses. Some studies suggest that prophylactic antipyretics (e.g., paracetamol/acetaminophen or ibuprofen) may reduce antibody responses to certain pediatric vaccines, particularly during primary infant series. However, some pediatric studies showed no effect, finding that prophylactic antipyretics did not reduce seroconversion. In a randomized study of healthy young adults receiving hepatitis B vaccine, prophylactic acetaminophen started at vaccination was associated with lower antibody concentrations than no acetaminophen, whereas starting acetaminophen hours after vaccination did not show this effect. Adult data are mixed; one hepatitis B study showed an effect with prophylactic acetaminophen, while several influenza studies did not. Findings vary by antipyretic agent, timing (prophylactic vs therapeutic), vaccine, and population. Also, there is no evidence that antipyretics prevent febrile seizures. Therapeutic use initiated after symptom onset has generally not shown clinically meaningful reductions in immunogenicity. The mechanism is not well established.

Management

Caution is advised if prophylactic acetaminophen or other antipyretics are used concurrently or within the same day of viral or bacterial vaccine administration. If needed for symptom relief, the lowest effective dose for the shortest duration is recommended. Local guidelines and prescribing information for the products involved should be consulted for further recommendations.

References (14)
  1. Prymula R. (2009) "Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials." Lancet, 374, p. 1339-50
  2. wysocki m (2017) "A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations." Vaccine, 35, p. 1926
  3. Falup-Pecurariu O (2017) "Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine (PHiD-CV) co-administered with DTPa-combined vaccines" Hum Vaccin Immunother, 13, p. 649
  4. Doedee M (2014) "Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials." PLoS ONE, 9, e98175
  5. Walter EB (2017) "The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children." Vaccine, 35, p. 6664
  6. Sil A (2017) "Effect of prophylactic or therapeutic administration of paracetamol on immune response to DTwP-HepB-Hib combination vaccine in Indian infants." Vaccine, 35, p. 2999
  7. long ss (1990) "Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy." Pediatrics, 85, p. 294
  8. uhari m (1988) "Effect of prophylactic acetaminophen administration on reaction to DTP vaccination." Acta Paediatr Scand, 77, p. 747
  9. Aoki FY (1993) "Effects of acetaminophen on adverse effects of influenza vaccination in health care workers." CMAJ, 149, p. 1425
  10. gross pa (1994) "Vaccine immune response and side effects with the use of acetaminophen with influenza vaccine." Clin Diagn Lab Immunol, 1, p. 129
  11. Chernesky M (1993) "Immunogenicity and adverse reactions of influenza vaccination in elderly patients given acetaminophen or placebo." Clin Diagn Virol, 1, p. 129
  12. Ezeanolue E General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP) https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf
  13. Immunisation Against Infections Disease-"The Green Book". Chapter 8: Vaccne safety and the management of adverse events following immunisation. https://assets.publishing.service.gov.uk/media/686d5f2cfe1a249e937cbe53/Green_Book_chapter_8_28May25.pdf
  14. Australian Immunisation Handbook: Administraiton of vaccines https://immunisationhandbook.health.gov.au/contents/vaccination-procedures/administration-of-vaccines

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

acetaminophen Food/Lifestyle

Applies to: Excedrin Sinus Headache (acetaminophen / 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)
  1. (2022) "Product Information. Acetaminophen (acetaminophen)." Camber Pharmaceuticals, Inc

Moderate food/lifestyle interactions

Moderate:

phenylephrine Caffeine

Applies to: Excedrin Sinus Headache (acetaminophen / 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)
  1. 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
  2. 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
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2024) "Product Information. Ephedrine (ephedrine)." Hameln Pharma Ltd
  8. (2023) "Product Information. Ephedrine Hydrochloride (ephedrine)." Wockhardt UK Ltd
  9. (2026) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
  10. (2025) "Product Information. Atomoxetine (atomoxetine)." Zentiva Pharma UK Ltd
  11. (2026) "Product Information. Atomoxetine (Apo) (atomoxetine)." Arrotex Pharmaceuticals Pty Ltd
  12. Angita Pharma, Inc (2026) AG-ATOMOXETINE Product Monograph (Health Canada) https://pdf.hres.ca/dpd_pm/00059014.PDF
  13. (2026) "Product Information. Boots Decongestant (Pseudoephedrine) (pseudoephedrine)." The Boots Company Plc
  14. (2023) "Product Information. Sinus and Nasal Decongestant (Trust) (pseudoephedrine)." Noumed Pharmaceuticals Pty Ltd
  15. (2019) "Product Information. Ephedrine (ephedrine)." Pfizer Australia Pty Ltd
  16. (2024) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Amneal Pharmaceuticals LLC
  17. (2024) "Product Information. Lemsip Cough Max for Mucus Cough and Cold (guaifenesin/paracetamol/phenylephrine)." Reckitt Benckiser Healthcare (UK) Ltd
  18. 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
  19. (2023) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Baxter Corporation
  20. 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:

Excedrin Sinus Headache

The acetaminophen in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The acetaminophen in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The acetaminophen in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The acetaminophen in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The acetaminophen in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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:

Excedrin Sinus Headache

The phenylephrine in Excedrin Sinus Headache 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

Excedrin Sinus Headache

A total of 721 drugs are known to interact with Excedrin Sinus Headache.

smallpox vaccine

A total of 392 drugs are known to interact with smallpox vaccine.

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.