Secondary prevention of cardiovascular and cerebrovascular events: Oral: One tablet (aspirin 81 mg/omeprazole 40 mg or aspirin 325 mg/omeprazole 40 mg) once daily. Note: Generally 81 mg of aspirin has been accepted as an effective dose for secondary cardiovascular prevention; refer to current clinical practice guidelines when considering the need for 325 mg of aspirin.
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: No dosage adjustment necessary.
GFR <10 mL/minute: Avoid use.
Avoid use in patients with hepatic impairment.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
>10%: Gastrointestinal: Gastritis (18%)
1% to 10%:
Gastrointestinal: Diarrhea (3%), gastric polyp (2%), nausea (3%)
Nervous system: Noncardiac chest pain (2%)
<1%: Gastrointestinal: Duodenal ulcer with hemorrhage, gastric ulcer with hemorrhage, gastrointestinal hemorrhage (including hematochezia and large intestinal hemorrhage), intestinal obstruction (small bowel)
Frequency not defined: Gastrointestinal: Dyspepsia, upper abdominal pain
Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, urticaria) to aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), omeprazole, other substituted benzimidazole proton pump inhibitors, or to any component of the formulation; history of asthma, urticaria, rhinitis, and nasal polyps or other allergic-type reactions after taking aspirin or other NSAIDs; pediatric patients with suspected viral infections, with or without fever; concurrent use with rilpivirine-containing products.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Atrophic gastritis: Long-term omeprazole therapy has caused atrophic gastritis (identified by biopsy).
• Carcinoma: In long-term (2-year) studies in rats, omeprazole produced a dose-related increase in gastric carcinoid tumors. While available endoscopic evaluations and histologic examinations of biopsy specimens from human stomachs have not detected a risk from short-term exposure to omeprazole, further human data on the effect of sustained hypochlorhydria and hypergastrinemia are needed to rule out the possibility of an increased risk for the development of tumors in humans receiving long-term therapy.
• Clostridioides difficile–associated diarrhea: Use of proton pump inhibitors (PPIs) may increase risk of Clostridioides difficile–associated diarrhea (CDAD), especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.
• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of omeprazole.
• Dermatologic reactions: Severe cutaneous adverse reactions, including acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported.
• 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 nonsteroidal anti-inflammatory drugs (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.
• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with PPI therapy. Patients on high-dose (multiple daily doses) or long-term (≥1 year) therapy should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.
• Fundic gland polyps: Use of PPIs increases risk of fundic gland polyps, especially with long-term use (>1 year). May occur without symptoms, but nausea, vomiting, or abdominal pain may occur; GI bleeding and/or anemia may occur with ulcerated polyps. Diagnosis of polyps may also increase risk for small intestinal blockage. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.
• GI effects: Aspirin may cause serious GI adverse reactions, including inflammation, bleeding ulceration and perforation. Other adverse reactions include stomach pain, heartburn, nausea, and vomiting. Monitor patients for signs of ulceration and bleeding. Discontinue therapy if active and significant bleeding occurs. Use aspirin with caution in patients with erosive gastritis; avoid use in patients with active peptic ulcer disease.
• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of >3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Hypomagnesemia may lead to or exacerbate hypocalcemia in patients at risk (eg, hypoparathyroidism). Hypomagnesemia may also lead to hypokalemia. Hypomagnesemia and hypocalcemia may be corrected by magnesium/calcium supplementation, although discontinuation of omeprazole may be necessary.
• 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.
• Tubulointerstitial nephritis: Acute tubulointerstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy. Patients may present with symptomatic hypersensitivity reaction to nonspecific symptoms of impaired renal function (eg, anorexia, malaise, nausea); may be diagnosed with biopsy and in the absence of extra-renal manifestations (eg, fever, rash, arthralgia). Discontinue and evaluate patients if acute tubulointerstitial nephritis is suspected.
• Upper gastrointestinal events (eg, symptomatic or complicated ulcers): Low-dose aspirin for cardioprotective effects is associated with a two- to fourfold increase in upper gastrointestinal (UGI) events. The risks of these events increase with increasing aspirin dose; during the chronic phase of aspirin dosing, doses >81 mg are not recommended unless indicated (Bhatt 2008).
• Vitamin B12 deficiency: Prolonged treatment (>3 years) of PPIs may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam 2013).
Disease-related concerns:
• Bleeding disorders: Use aspirin with caution in patients with platelet and bleeding disorders.
• Dehydration: Use aspirin with caution in patients with dehydration.
• Gastric malignancy: Relief of gastric symptoms does not preclude the presence of a gastric malignancy.
• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of PPIs may increase risk of these infections.
• Hepatic impairment: Avoid use in patients with hepatic impairment.
• Renal impairment: Avoid use in patients with glomerular filtration rate (GFR) <10 mL/minute.
Concurrent drug therapy issues:
• Clopidogrel: PPIs may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham 2010; Levine 2011).
Special populations:
• Asian ethnicity: Avoid use in Asian patients with unknown CYP2C19 genotype or those who are known to be poor metabolizers.
Dosage form specific issues:
• Interchangeability: Aspirin/omeprazole combination product is not interchangeable with the individual components of aspirin and omeprazole.
Other warnings/precautions:
• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop omeprazole treatment at least 14 days before CgA test; if initial CgA levels are high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet Delayed Release, Oral:
Yosprala: Aspirin 81 mg and omeprazole 40 mg, Aspirin 325 mg and omeprazole 40 mg [contains corn starch, fd&c blue #2 (indigotine,indigo carmine)]
Generic: Aspirin 325 mg and omeprazole 40 mg [DSC], Aspirin 81 mg and omeprazole 40 mg [DSC]
Yes
Tablet, EC (Yosprala Oral)
81-40 mg (per each): $26.10
325-40 mg (per each): $26.10
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.
Administer at least 1 hour before a meal. Swallow tablet whole with liquid; do not split, chew, crush, or dissolve.
Bariatric surgery: Tablet, delayed release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Consider switching to separate components.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Yosprala: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205103s009lbl.pdf#page=30
Secondary prevention of cardiovascular and cerebrovascular events: Reduction of the risk of aspirin-associated gastric ulcers in patients at risk of developing gastric ulcers due to age (≥55 years) or documented history of gastric ulcers who require aspirin for the secondary prevention of cardiovascular and cerebrovascular events.
Limitations of use: Not for use as the initial dose of aspirin therapy during onset of acute coronary syndrome, acute myocardial infarction or before percutaneous coronary intervention; has not been shown to reduce the risk of gastrointestinal bleeding due to aspirin.
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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Acalabrutinib. This interaction is only applicable to acalabrutinib capsules. Risk X: Avoid combination
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
Alcohol (Ethyl): May enhance the adverse/toxic effect of Aspirin. Specifically, alcohol may increase the bleeding risk of aspirin. Alcohol (Ethyl) may diminish the therapeutic effect of Aspirin. Specifically, alcohol may interfere with the controlled release mechanism of extended release aspirin. 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
Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
Amphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the absorption of Amphetamine. 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
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
Atazanavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Atazanavir. Management: Avoid use in treatment-experienced patients. In treatment-naive patients, administer boosted atazanavir 12 hours after the PPI and the PPI dose should not exceed the equivalent of 20 mg omeprazole. Monitor for reduced atazanavir efficacy. Risk D: Consider therapy modification
Belumosudil: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with inhibitors of the proton pump (PPIs and PCABs). Risk D: Consider therapy modification
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
Bisphosphonate Derivatives: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Bosutinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors and potassium-competitive acid blockers, such as short-acting antacids or histamine-2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Risk D: Consider therapy modification
Calcium Channel Blockers (Nondihydropyridine): May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Capecitabine: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Capecitabine. 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
CarBAMazepine: May decrease the serum concentration of Omeprazole. Omeprazole may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
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
Cefditoren: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefditoren. Risk X: Avoid combination
Cefpodoxime: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy
Cefuroxime: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Cefuroxime. Risk X: Avoid combination
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
Cilostazol: Omeprazole may increase serum concentrations of the active metabolite(s) of Cilostazol. Omeprazole may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving omeprazole. Monitor clinical response to cilostazol closely. Risk D: Consider therapy modification
Citalopram: Omeprazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with omeprazole. Monitor for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation) in patients receiving this combination. Risk D: Consider therapy modification
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy
Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
ClomiPRAMINE: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Clopidogrel: Omeprazole may diminish the antiplatelet effect of Clopidogrel. Omeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk X: Avoid combination
CloZAPine: Omeprazole may decrease the serum concentration of CloZAPine. Omeprazole may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
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
CycloSPORINE (Systemic): Omeprazole may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C19 Inducers (Moderate): May decrease the serum concentration of Omeprazole. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May decrease the serum concentration of Omeprazole. Risk X: Avoid combination
CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Omeprazole. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May increase the serum concentration of Omeprazole. Risk C: Monitor therapy
Cysteamine (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Cysteamine (Systemic). 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
Dacomitinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with PPIs and PCABs. Antacids may be used. Histamine H2-receptor antagonists (HR2A) may be used if dacomitinib is given at least 6 hours before or 10 hours after the H2RA. Risk X: Avoid combination
Darunavir: May decrease the serum concentration of Omeprazole. Risk C: Monitor therapy
Dasatinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of PPIs or PCABs if some acid-reducing therapy is needed. Risk X: Avoid combination
Delavirdine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Delavirdine. Management: Chronic therapy with PPIs or PCABs should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI or PCAB therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination
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
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
Dextroamphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Risk C: Monitor therapy
Doxycycline: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the bioavailability of Doxycycline. Risk C: Monitor therapy
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
Enoxacin: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Enoxacin. Risk C: Monitor therapy
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
Erlotinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Erlotinib. Risk X: Avoid combination
Escitalopram: Omeprazole may increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Gefitinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Gefitinib. Management: Avoid use of inhibitors of the proton pump (PPIs or PCABs) with gefitinib when possible. If required, administer gefitinib 12 hours after the PPI/PCAB or 12 hours before the next dose of the PPI/PCAB. Closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
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
Gliclazide: Omeprazole may increase the serum concentration of Gliclazide. Risk C: Monitor therapy
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
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
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Indinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Infigratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Infigratinib. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
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
Itraconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Itraconazole. This specifically applies to the super bioavailable itraconazole products (eg, Tolsura brand). Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Itraconazole. This specifically applies to the non-super bioavailable itraconazole products (eg, Sporanox brand and its generics). Management: Exposure to Tolsura brand itraconazole may be increased by PPIs or PCABs ; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole may be decreased. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs or PCABs. Risk D: Consider therapy modification
Ketoconazole (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Management: Administer ketoconazole with an acidic beverage, such as non-diet cola, to increase gastric acidity and improve absorption if concomitant use with proton pump inhibitors or potassium-competitive acid blockers is necessary. Risk D: Consider therapy modification
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
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Ledipasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Ledipasvir. Management: PPI or PCAB doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Use of ledipasvir with higher doses or with food, or 2 hours after a these agents, may reduce ledipasvir bioavailability. Risk D: Consider therapy modification
Levoketoconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Levoketoconazole. Levoketoconazole may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk X: Avoid combination
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
Loop Diuretics: Salicylates may diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk C: Monitor therapy
Macimorelin: Aspirin may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification
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
Methotrexate: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Methotrexate. Management: Consider temporarily interrupting PPI or PCAB therapy in patients receiving high-dose methotrexate. If coadministered, monitor for increased methotrexate toxicity (eg, mucositis, myalgias) and/or delayed methotrexate elimination. Risk D: Consider therapy modification
Moclobemide: May increase the serum concentration of Omeprazole. Omeprazole may increase the serum concentration of Moclobemide. Risk C: Monitor therapy
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 ADEK, Folate, Iron): Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be decreased. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Mycophenolate: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Nelfinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nelfinavir. Management: Due to potentially significant reductions in nelfinavir exposure, avoid concurrent use of nelfinavir with a PPI or PCAB when possible. If unavoidable, consider PPI or PCAB use for a short duration (less than 30 days) and closely monitor viral load. Risk D: Consider therapy modification
Neratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Risk X: Avoid combination
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
Nilotinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nilotinib. Management: Avoid this combination. Histamine H2 receptor antagonists (H2RAs) given 10 hours before or 2 hours after nilotinib, or antacids given 2 hours before or 2 hours after nilotinib are acceptable alternatives. Risk D: Consider therapy modification
Nirogacestat: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
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
Octreotide: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Octreotide. Risk C: Monitor therapy
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
Palbociclib: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Palbociclib. Specifically, this has been reported with the use of palbociclib capsules. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Palbociclib. Specifically, this may occur with the use of palbociclib capsules, and to the greatest extent when taken without food. Management: Carefully evaluate potential risks and benefits of coadministration of palbociclib capsules and proton pump inhibitors or potassium-competitive acid blockers due to the risk of reduced palbociclib efficacy. Palbociclib capsules should be taken with food. Risk D: Consider therapy modification
PAZOPanib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
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
Pexidartinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Pexidartinib. Management: Avoid this combination. If acid-reduction is needed, consider administering an antacid 2 hours before or after pexidartinib, or administer pexidartinib 2 hours before or 10 hours after an H2 receptor antagonist. Risk X: Avoid combination
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Posaconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Posaconazole. Management: Avoid coadministration of PPIs or PCABs and posaconazole oral suspension. Posaconazole delayed-release tablets do not appear to be sensitive to this interaction and do not required dose adjustment if coadministered with PPIs or PCABs. Risk D: Consider therapy modification
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
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Rilpivirine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Riociguat: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Risedronate: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Risedronate. Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Management: Coadministration of PPIs or PCABs with delayed-release risedronate formulations is not recommended. Limit PPI/PCAB dose and duration during coadministration with risedronate as possible. Patients over age 70 are at higher risk of adverse effects. Risk D: Consider therapy modification
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
Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: Monitor therapy
Saquinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Secretin: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of PPIs or PCABs and secretin, and discontinue PPI or PCAB several weeks prior to secretin administration, with the duration of separation determined by the specific acid suppressant. See full monograph for details. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Selpercatinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Selpercatinib. Management: Coadministration of selpercatinib and PPIs or PCABs should be avoided. If coadministration cannot be avoided, selpercatinib and PPIs or PCABs should be administered simultaneously with food. Risk D: Consider therapy modification
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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
SORAfenib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of SORAfenib. Risk C: Monitor therapy
Sotorasib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Sparsentan: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Sparsentan. Risk X: Avoid combination
Spironolactone: Aspirin may diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Omeprazole. Risk X: Avoid combination
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
Tacrolimus (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
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
Technetium Tc 99m Sestamibi: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Technetium Tc 99m Sestamibi. Management: Consider holding/stopping proton pump inhibitor therapy for at least 3 days prior to the use technetium Tc 99m sestamibi in cardiac imaging procedures. Risk D: Consider therapy modification
Technetium Tc 99m Tetrofosmin: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Technetium Tc 99m Tetrofosmin. Risk C: Monitor therapy
Thiazolidinediones: Inhibitors of the Proton Pump (PPIs and PCABs) may enhance the adverse/toxic effect of Thiazolidinediones. Specifically, the risk of osteoporosis or fracture may be increased. Risk C: Monitor therapy
Thiopental: Aspirin may decrease the protein binding of Thiopental. Risk C: Monitor therapy
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 decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). These data are derived from studies with Ritonavir-boosted Tipranavir. 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
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
Velpatasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Velpatasvir. Management: Sofosbuvir/velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Sofosbuvir/velpatasvir/voxilaprevir can be administered with omeprazole 20 mg. Use with other PPIs or PCABs has not been studied. Risk D: Consider therapy modification
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
Voriconazole: Omeprazole may increase the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Omeprazole. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Maternal use aspirin may be associated with dose-related adverse pregnancy outcomes.
Refer to individual monographs for additional information.
Aspirin and omeprazole are present in breast milk.
Due to the potential for adverse events following aspirin exposure, breastfeeding is not recommended by the manufacturer. Refer to individual monographs for additional information.
Magnesium (baseline and periodically thereafter; especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia) and calcium (baseline and periodically in patients at risk [eg, hypoparathyroidism]).
Aspirin: Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, via acetylation, which results in decreased formation of prostaglandin precursors; irreversibly inhibits formation of prostaglandin derivative, thromboxane A2, via acetylation of platelet cyclooxygenase, thus inhibiting platelet aggregation; has antipyretic, analgesic, and anti-inflammatory properties.
Omeprazole: Suppresses gastric basal and stimulated acid secretion by inhibiting the parietal cell H+/K+ ATP pump
See individual agents.
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