Skip to main content

Interactions between Aceta-Gesic (old formulation) and Avelumab

1 drug interaction and 27 additional warnings found for the following 2 drugs:

Add/remove drugs

Drug interactions

Moderate drug interactions

Moderate:

acetaminophen avelumab

Applies to: Aceta-Gesic (old formulation) (acetaminophen / phenyltoloxamine) and avelumab
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)
  1. 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
  2. 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
  3. Najeebullah, ali ma, Naveed R, Khatri G, Priya, hasan mm (2022) "Acetaminophen: a hazard to immunotherapy." Ann Med Surg (Lond), 80, p. 104272

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

acetaminophen Food/Lifestyle

Applies to: Aceta-Gesic (old formulation) (acetaminophen / 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.

References (1)
  1. (2022) "Product Information. Acetaminophen (acetaminophen)." Camber Pharmaceuticals, Inc

Moderate food/lifestyle interactions

Moderate:

phenyltoloxamine Food/Lifestyle

Applies to: Aceta-Gesic (old formulation) (acetaminophen / 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 (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. 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.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Disease interactions

25 potential interactions Applies to: 22 conditions, including Asthma, COPD, Hypotension, Hyperthyroidism, and Inflammatory Bowel Disease.

Adrenal Insufficiency

Moderate:

avelumab

Avelumab has a moderate potential interaction with Adrenal Insufficiency.

Avelumab can cause immune-mediated adrenal insufficiency. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients with prolonged periods of stress due to major surgery, intensive care, etc. It is recommended to administer corticosteroids as appropriate for adrenal insufficiency. Monitor patients for clinical signs and symptoms of adrenal insufficiency and institute appropriate measures as necessary. Withhold avelumab for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. If appropriate modify the dose according to manufacturer recommendations. Monitor as clinically indicated prior to and periodically during treatment. Care should be taken when using avelumab in these patients.

Alcoholism

Major:

Aceta-Gesic (old formulation)

The acetaminophen in Aceta-Gesic (old formulation) 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.

Asthma

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Asthma.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Autoimmune Disorders

Moderate:

avelumab

Avelumab has a moderate potential interaction with Autoimmune Disorders.

Programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies can cause immune-mediated adverse reactions, which may be severe or fatal. Immune-mediated adverse reactions can occur in any organ system or tissue at any time after starting therapy. This may be considered when using PD-1/PD-L1 blocking antibodies in patients with immune system disorders (e.g., ulcerative colitis, Crohn's disease, lupus) or with conditions affecting the nervous system (e.g., myasthenia gravis, Guillain-Barre syndrome). It is recommended to monitor patients closely for signs/symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions.

Bone Marrow Transplantation

Moderate:

avelumab

Avelumab has a moderate potential interaction with Bone Marrow Transplantation.

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. It is recommended to follow patients closely for evidence of transplant-related complications and intervene promptly. The benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT should be considered.

Cardiovascular Conditions and Disorders

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

COPD

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with COPD.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Dehydration

Major:

Aceta-Gesic (old formulation)

The acetaminophen in Aceta-Gesic (old formulation) 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:

avelumab

Avelumab has a moderate potential interaction with Diabetes Mellitus.

Avelumab can cause type 1 diabetes mellitus. Monitor for hyperglycemia or other signs and symptoms of diabetes. Withhold treatment in cases of severe hyperglycemia until metabolic control is achieved. Permanently discontinue avelumab for life-threatening hyperglycemia. If appropriate modify the dose according to manufacturer recommendations. Care should be exercised when using avelumab in diabetic patients.

Gastrointestinal Obstruction

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Gastrointestinal Obstruction.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

Glaucoma/Intraocular Hypertension

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

Hyperthyroidism

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Hyperthyroidism.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Hypotension

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Hypotension.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Inflammatory Bowel Disease

Moderate:

avelumab

Avelumab has a moderate potential interaction with Inflammatory Bowel Disease.

Immune-mediated colitis has been reported with the use of avelumab. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents followed by corticosteroid taper for moderate or severe or life-threatening colitis. If appropriate modify the dose according to manufacturer recommendations. Monitor patients for signs and symptoms of colitis. Permanently discontinue avelumab for life-threatening or for recurrent colitis. Care should be taken when using avelumab in patients with inflammatory bowel disease.

Liver Disease

Major:

Aceta-Gesic (old formulation)

The acetaminophen in Aceta-Gesic (old formulation) 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.

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Liver Disease.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Moderate:

avelumab

Avelumab has a moderate potential interaction with Liver Disease.

No clinically meaningful differences in pharmacokinetics were observed in the clearance of avelumab based on mild or moderate hepatic impairment. Caution should be exercised when avelumab is used in patients with severe hepatic impairment as there are limited data from patients. The effect of severe hepatic impairment on the pharmacokinetics of avelumab is unknown.

Malnourishment

Major:

Aceta-Gesic (old formulation)

The acetaminophen in Aceta-Gesic (old formulation) 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.

Organ Transplant

Moderate:

avelumab

Avelumab has a moderate potential interaction with Organ Transplant.

Solid organ transplant rejection and other transplant (including corneal graft) rejection have been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. This may be considered when using PD-1/PD-L1 blocking antibodies in patients who have received a solid organ or other transplant.

Phenylketonuria

Moderate:

Aceta-Gesic (old formulation)

The acetaminophen in Aceta-Gesic (old formulation) 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).

Pleuropulmonary Infection

Moderate:

avelumab

Avelumab has a moderate potential interaction with Pleuropulmonary Infection.

Immune-mediated pneumonitis, including fatal cases have been reported with the use of avelumab. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for moderate or more severe pneumonitis, followed by corticosteroid taper. Withhold treatment with avelumab for moderate pneumonitis and permanently discontinue therapy for severe, life-threatening, or recurrent moderate pneumonitis. If appropriate modify the dose according to manufacturer recommendations. Care should be taken when using avelumab in patients with pulmonary infections.

Renal Dysfunction

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Renal Dysfunction.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Moderate:

avelumab

Avelumab has a moderate potential interaction with Renal Dysfunction.

Avelumab can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents followed by corticosteroid taper for life-threatening increased serum creatinine. Withhold avelumab for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to <= Grade 1. Permanently discontinue avelumab for life-threatening (Grade 4) nephritis. If appropriate modify the dose according to manufacturer recommendations. Care should be taken when using avelumab in patients with renal dysfunction.

Thyroid Disease

Moderate:

avelumab

Avelumab has a moderate potential interaction with Thyroid Disease.

Avelumab can cause autoimmune thyroid disorders. Monitor thyroid function prior to and periodically during treatment. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. It is recommended to withhold avelumab for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Care should be taken when using this agent in patients with thyroid disease.

Urinary Retention

Moderate:

Aceta-Gesic (old formulation)

The phenyltoloxamine in Aceta-Gesic (old formulation) has a moderate potential interaction with Urinary Retention.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

More resources

Aceta-Gesic (old formulation)

A total of 760 drugs are known to interact with Aceta-Gesic (old formulation).

avelumab

A total of 613 drugs are known to interact with avelumab.

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.