Version May 2024
The FDA has issued a drug safety communication to announce safety-related updates to the prescribing information for immediate-release (IR) and extended-release (ER)/long-acting (LA) opioid analgesics, including updates to Boxed Warnings, Indications and Usage, Dosage and Administration, Warnings and Precautions, and the Medication Guide. These safety labeling changes are intended to provide clarity on appropriate patient populations for opioid treatment, appropriate dosage and administration, and updated information on the risks associated with opioid use. The required safety labeling changes include stating:
the risk of overdose increases as the dosage increases for all opioid pain medicines;
IR opioids should not be used for an extended period of time unless a patient's pain remains severe enough to require them and alternative treatment options continue to be inadequate;
many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine;
it is recommended to reserve ER/LA opioid pain medicines for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate; and
a warning about opioid-induced hyperalgesia (OIH), including information on differentiating OIH symptoms from those of opioid tolerance and withdrawal.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-prescribing-information-all-opioid-pain-medicines-provide-additional-guidance-safe-use.
Because the use of oxycodone/aspirin exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient's risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions.
Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription.
Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone/aspirin, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone/aspirin are essential.
Accidental ingestion of even one dose of oxycodone/aspirin, especially by children, can result in a fatal overdose of oxycodone.
If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome (NOWS), which may be life threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.
The concomitant use of oxycodone/aspirin with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Regularly evaluate patients receiving oxycodone/aspirin and any CYP3A4 inhibitor or inducer frequently.
Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone/aspirin and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
Dosage guidance:
Safety: Consider prescribing naloxone for patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, patients with sleep-disordered breathing, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally [equivalent to ≥33 mg oral oxycodone/day]), and/or concomitant benzodiazepine use (Ref).
Dosing: Dosing provided is based on typical doses; some patients may require higher or lower doses. Individualize dosing based on patient-specific factors (eg, comorbidities, severity of pain, degree of opioid experience/tolerance) and titrated to patient-specific treatment goals (eg, improvement in function and quality of life, decrease in pain using a validated pain rating scale). Use the lowest effective dose for the shortest period of time.
Clinical considerations: Opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for managing severe pain. Maximize nonopioid analgesia (when appropriate) prior to initiation of opioid analgesia (Ref).
Pain management: Note: Oxycodone and aspirin has been discontinued in the United States for >1 year.
Oral: Initial: One tablet (oxycodone 4.835 mg/aspirin 325 mg) every 6 hours as needed for pain; maximum: 12 tablets (oxycodone 58.02 mg/aspirin 3,900 mg) per day.
Discontinuation of therapy: When reducing the dose, discontinuing, or tapering long-term opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established. Individualize tapering based on discussions with patient to minimize withdrawal, while considering patient-specific goals and concerns and the opioid's pharmacokinetics. Proposed initial schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of long-term therapy) to rapid (eg, 25% to 50% reduction every few days) (CDC 2015; CDC [Dowell 2022]). Slower tapers may be appropriate after long-term use (eg, >1 year), whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects. During tapering, patients may be at an increased risk of overdose if they return to their original (or higher) opioid dose or use illicit opioids, due to rapid loss of tolerance; consider prescribing naloxone. Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt autonomic withdrawal symptoms and other adjunctive agents to treat GI symptoms and muscle spasms, as needed. Continue to offer nonopioid analgesics as needed for pain management during the taper (CDC [Dowell 2022]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
GFR ≥10 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
GFR <10 mL/minute: Avoid use.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Severe impairment: Avoid use.
Note: Minimize opioid use in older adults unless for the management of severe acute pain. Opioids are associated with an increased risk of falls and inducing or worsening delirium in older adults. Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use of aspirin at more than 325 mg/day in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Beers Criteria [AGS 2023]).
Refer to adult dosing.
(For additional information see "Oxycodone and aspirin (United States: Not available): Pediatric drug information")
Note: Oxycodone and aspirin has been discontinued in the United States for >1 year. Dosed based on total oxycodone content; titrate dose to appropriate analgesic effects; one tablet contains oxycodone 4.835 mg and aspirin 325 mg. Do not use aspirin in pediatric patients <18 years who have or who are recovering from chickenpox or flu symptoms (eg, viral illness) due to the association with Reye syndrome (APS 2016).
Analgesia, severe: Limited data available on combination product: Children and Adolescents: Oral: Initial dose: 0.2 mg/kg/dose; doses typically given every 6 hours as needed. Maximum initial oxycodone dose: 1 tablet (~5 mg/dose); maximum daily aspirin dose: 4,000 mg/day (~12 tablets/day) (APS 2016)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents: In general, oxycodone clearance may be decreased in patients with renal impairment. See individual agents. There are no dosage adjustments provided in the manufacturer's labeling; use with caution. While no dosing recommendations are available for the combination product, the following guidelines have been recommended for oxycodone (Aronoff 2007). Note: Renally adjusted dose recommendations are based on immediate-release oxycodone doses of 0.05 to 0.2 mg/kg/dose every 4 to 6 hours.
GFR ≥50 mL/minute/1.73 m2: No dosage adjustment necessary
GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of usual recommended dose
GFR <10 mL/minute/1.73 m2: Avoid use due to aspirin component
Mild to moderate impairment: There are no dosage adjustments in the manufacturer’s labeling; based on experience in pediatric patients with individual agents, use with caution and initiate at the low end of the dosing range; titrate carefully and monitor closely. See individual agents.
Severe impairment: Avoid use due to aspirin component
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
Frequency not defined:
Cardiovascular: Circulatory depression, shock
Central nervous system: Dizziness, dysphoria, euphoria, sedation
Dermatologic: Pruritus
Gastrointestinal: Constipation
Respiratory: Apnea, respiratory depression
<1%, postmarketing, and/or case reports: Abdominal pain, accidental injury, acidosis, agitation, alkalosis, allodynia (opioid-induced hyperalgesia) (FDA Safety Communication 2023), anaphylactoid reaction, anaphylaxis, angioedema, anxiety, aspiration, asthma, bradycardia, bronchospasm, cerebral edema, coma, confusion, decreased mental acuity, dehydration, depression, diaphoresis, diarrhea, disseminated intravascular coagulation, drowsiness, drug dependence, duodenal ulcer, dyspepsia, dyspnea, ecchymoses, eructation, eye redness, fever, flushing, gastric ulcer, gastrointestinal hemorrhage, hallucination, headache, hearing loss, hemorrhage, hemorrhage (subdural), hepatitis, hyperglycemia, hyperkalemia, hypersensitivity reaction, hyperventilation, hypoglycemia, hypogonadism (Brennan 2013; Debono 2011), hypotension, hypothermia, hypoventilation, increased liver enzymes (transient), increased thirst, interstitial nephritis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, laryngeal edema, lethargy, malaise, metabolic acidosis, miosis, nausea, nervousness, orthostatic hypotension, palpitations, pancreatitis, paresthesia, prolonged prothrombin time, proteinuria, pulmonary edema, purpura, renal failure, renal insufficiency, renal papillary necrosis, respiratory alkalosis, reticulocytosis, Reye syndrome, rhabdomyolysis, seizure, skin rash, stupor, tachycardia, tachypnea, thrombocytopenia, tinnitus, urinary retention, urticaria, visual disturbance, vomiting, weakness, xerostomia
Hypersensitivity (eg, angioedema) to oxycodone, aspirin, or any component of the formulation; use in children and teenagers for viral infections, with or without fever; significant respiratory depression; gastrointestinal obstruction, including paralytic ileus (known or suspected); acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; hemophilia.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Constipation: Oxycodone may cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.
• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
• Hyperalgesia: Opioid-induced hyperalgesia (OIH) has occurred with short-term and prolonged use of opioid analgesics. Symptoms may include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli; symptoms may be suggestive of OIH if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Consider decreasing the current opioid dose or opioid rotation in patients who experience OIH.
• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).
• Respiratory depression: Fatal respiratory depression may occur. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.
• Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and asthma may have an increased risk of salicylate sensitivity.
• Tinnitus: Discontinue use if tinnitus or impaired hearing occurs.
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.
• Bleeding disorders: Use aspirin with caution in patients with platelet and bleeding disorders.
• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.
• Delirium tremens: Use with caution in patients with delirium tremens.
• Ethanol use: Heavy ethanol use (>3 drinks/day) can increase bleeding risks.
• Gastrointestinal disease: Use with caution in patients with erosive gastritis or peptic ulcer disease.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment; avoid use in severe impairment.
• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (CDC [Dowell 2022]).
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychosis: Use with caution in patients with toxic psychosis.
• Renal impairment: Use with caution in patients with renal impairment; avoid use in severe renal impairment (GFR <10 mL/minute).
• Respiratory disease: Use oxycodone with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.
• Seizures: Use with caution in patients with a history of seizure disorders.
• Sleep-related disorders: Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing (CDC [Dowell 2022]).
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• Benzodiazepines or other CNS depressants: Concomitant use may result in respiratory depression and sedation, which may be fatal. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.
Special populations:
• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.
• Older adult: Use opioids with caution in older adults; may be more sensitive to adverse effects. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increased adverse effects. Monitor closely for adverse effects associated with opioid therapy (eg, respiratory and CNS depression, falls, cognitive impairment, constipation) (CDC [Dowell 2022]). Consider the use of alternative nonopioid analgesics in these patients when possible.
• Neonates: Neonatal withdrawal syndrome: Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.
• Surgery: Aspirin should be avoided (if possible) in surgical patients for 1 to 2 weeks prior to surgery, to reduce the risk of excessive bleeding (except in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy [aspirin, clopidogrel]; patient specific situations need to be discussed with cardiologist; AHA/ACC/SCAI/ACS/ADA Science Advisory provides recommendations). Opioids decrease bowel motility; monitor for decreased bowel motility in postoperative patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.
Other warnings/precautions:
• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent to opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances; provide care as needed. Concurrent use of agonist/antagonist (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.
• Abuse/misuse/diversion: Use with caution in patients with a history of substance abuse disorder; potential for drug dependency exists. Other factors associated with increased risk for misuse include concomitant depression or other mental health conditions, higher opioid dosages, or taking other CNS depressants. Consider offering naloxone prescriptions in patients with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), concomitant benzodiazepine use, and patients at risk for returning to a high dose after losing tolerance (CDC [Dowell 2022]).
• Appropriate use: Outpatient setting: Opioids should not be used as first-line therapy for acute (<1-month duration), subacute (1- to 3-month duration), or chronic pain (>3-month duration [outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment]). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications and antidepressants) as appropriate for the specific condition. If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks and realistic benefits of opioid therapy should be discussed with the patient. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). For the treatment of acute pain, therapy should only be given for the expected duration of pain severe enough to require opioids and prescribed as needed (not scheduled). For the treatment of subacute and chronic pain, realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Risk to patients increases with higher opioid dosages. Dosages ≥50 MME/day are likely to not have increased benefit to pain relief or function relative to overall risk to patients; before increasing dosage to ≥50 MME/day, readdress pain and reassess evidence of individual benefits and risks (CDC [Dowell 2022]).
• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced opioid-induced respiratory depression/opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.
• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.
Oxycodone and aspirin has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Generic: Oxycodone hydrochloride 4.8355 mg and aspirin 325 mg [DSC]
Yes
Tablets (oxyCODONE-Aspirin Oral)
4.8355-325 mg (per each): $1.94
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: Oxycodone 5 mg and aspirin 325 mg
C-II
Oral: Administer without regard to meals.
Oral: May administer without regard to meals; if GI upset occurs, may administer with food or milk
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Percodan: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/007337s054lbl.pdf#page=31
Pain management: Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of use: Because of the risks of substance use disorder, abuse, and misuse with opioids, which may occur at any dosage or duration, reserve oxycodone/aspirin for use in patients for whom alternative treatment options (eg, nonopioid analgesics) have not been tolerated or are not expected to be tolerated; have not provided adequate analgesia or are not expected to provide adequate analgesia. Not intended to be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
Percodan may be confused with Decadron, Percocet, Percogesic, Periactin.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Beers Criteria: Aspirin, when used chronically at doses more than 325 mg/day, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high-risk category (eg, older than 75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents) In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).
KIDs List: Salicylates, when used in pediatric patients <18 years of age with suspicion of viral illness (influenza, chickenpox), are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of Reye syndrome (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Aspirin may enhance the antiplatelet effect of Abrocitinib. Management: Do not use aspirin at doses greater than 81 mg/day with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. Risk D: Consider therapy modification
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Blood Glucose Lowering Effects: Salicylates may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Alendronate: Aspirin may enhance the adverse/toxic effect of Alendronate. Specifically, the incidence of upper gastrointestinal adverse events may be increased Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Aspirin may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk D: Consider therapy modification
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Calcium Channel Blockers (Nondihydropyridine): May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Collagenase (Systemic): Aspirin may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy
Dabigatran Etexilate: Aspirin may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling states that low dose aspirin could be considered, but the use of antiplatelets are not recommended for stroke prevention in patients with atrial fibrillation. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexibuprofen: Aspirin may enhance the adverse/toxic effect of Dexibuprofen. Dexibuprofen may diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination
Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen. Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may decrease the serum concentration of Dexketoprofen. Management: The use of high-dose salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable. Consider administering dexketoprofen 30-120 min after or at least 8 hrs before cardioprotective doses of aspirin to minimize any possible interaction. Risk X: Avoid combination
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Edoxaban: Aspirin may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Aspirin may increase the serum concentration of Edoxaban. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Risk D: Consider therapy modification
Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Risk D: Consider therapy modification
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ketorolac (Nasal): May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Nasal) may diminish the cardioprotective effect of Aspirin. Management: Concurrent use of nasal ketorolac with analgesic doses of aspirin is generally not recommended. If using low-dose, cardioprotective aspirin with nasal ketorolac, monitor the patient closely for evidence of adverse GI effects. Risk D: Consider therapy modification
Ketorolac (Systemic): May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Systemic) may diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loop Diuretics: Salicylates may diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Macimorelin: Aspirin may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Management: Consider avoiding coadministration of methotrexate and salicylates. If coadministration cannot be avoided, monitor for increased toxic effects of methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider therapy modification
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modification
Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid combination
Nefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Nicorandil: Aspirin may enhance the adverse/toxic effect of Nicorandil. Specifically, the risk of gastrointestinal ulceration and hemorrhage may be increased. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Aspirin may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Management: Concurrent use of aspirin at doses beyond cardioprotective levels is not recommended. While concurrent use of low-dose aspirin with a COX-2 inhibitor is permissable, patients should be monitored closely for signs/symptoms of GI ulceration/bleeding. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Omacetaxine: Aspirin may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of aspirin with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
PHENobarbital: May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Potassium Phosphate: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Primidone: May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modification
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Rivaroxaban: Aspirin may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: Monitor therapy
Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy
Spironolactone: Aspirin may diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapy
Sucroferric Oxyhydroxide: May decrease the serum concentration of Aspirin. Management: Administer aspirin at least 1 hour before administration of sucroferric oxyhydroxide. Risk D: Consider therapy modification
Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Talniflumate: Aspirin may enhance the adverse/toxic effect of Talniflumate. Management: When possible, consider alternatives to this combination. Concurrent use is generally not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Ticagrelor: Aspirin may enhance the antiplatelet effect of Ticagrelor. Aspirin may diminish the therapeutic effect of Ticagrelor. More specifically, the benefits of ticagrelor relative to clopidogrel may be diminished in adult patients receiving daily aspirin doses greater than 100-150 mg daily. Management: Avoid daily aspirin doses greater than 100 mg in adults receiving ticagrelor. Canadian recommendations are to avoid adult daily aspirin doses greater than 150 mg. Daily low-dose aspirin (U.S.: 75-100 mg; Canada: 75-150 mg) is recommended. Risk D: Consider therapy modification
Tiludronate: Aspirin may decrease the serum concentration of Tiludronate. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Risk C: Monitor therapy
Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Avoid as needed use of salicylates in patients taking vitamin K antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of cardiovascular events. If coadministering salicylates and vitamin K antagonists, monitor for bledding. Risk D: Consider therapy modification
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility in men and women (Brennan 2013).
[US Boxed Warning]: If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome (NOWS), which may be life threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. See individual agents for additional information.
Oxycodone and aspirin are excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended by the manufacturer. See individual agents.
Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and substance use disorder; signs or symptoms of hypogonadism or hypoadrenalism with long-term use (Brennan 2013)
Alternate recommendations: Subacute or chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. In patients with subacute pain initially treated for acute pain, reassess pain and function after 30 days to address potentially reversible causes of pain and prevent unintentional long-term opioid therapy. In patients on long-term therapy, re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Toxicology testing is recommended prior to initiation and at least yearly (includes controlled prescription medications, illicit drugs of abuse, and benzodiazepines). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (CDC [Dowell 2022]).
Oxycodone: Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.
Aspirin: Inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibits the generation of p thromboxane A2
See individual agents.
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