Aspirin-Omeprazole

Aspirin-Omeprazole is a combination medication used for patients requiring aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of developing aspirin-associated gastric ulcers.

• Aspirin-Omeprazole is available under the following different brand names: Yosprala

Common side effects of Aspirin-Omeprazole include:

• stomach pain or discomfort caused by gastritis
• nausea
• diarrhea
• gastric polyps
• noncardiac chest pain

Serious side effects of Aspirin-Omeprazole include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• sneezing
• runny or stuffy nose
• wheezing
• severe nausea
• vomiting
• stomach pain
• watery or bloody diarrhea
• bloody or tarry stools
• coughing up blood
• vomit that looks like coffee grounds
• easy bruising
• unusual bleeding (such as a nosebleed)
• any bleeding that will not stop
• sudden pain or trouble moving the hip, wrist, or back
• fever
• rash
• nausea
• loss of appetite
• joint pain
• urinating less than usual
• blood in your urine
• weight gain
• stomach pain
• itching
• dark urine
• yellowing of the skin or eyes (jaundice)
• dizziness
• fast or irregular heart rate
• tremors (shaking)
• jerking muscle movements
• feeling jittery
• muscle cramps
• muscle spasms in the hands and feet
• cough
• choking sensation
• joint pain
• skin rash on the cheeks or arms that worsens in sunlight

Rare side effects of Aspirin-Omeprazole include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

• Aspirin enteric-coated, delayed-release/omeprazole immediate-release
• The tablet consists of an enteric-coated delayed-release aspirin core surrounded by an immediate-release omeprazole layer.

Tablet

• 81 mg/40 mg
• 325 mg/40 mg
• Prevention of cardiovascular and cerebrovascular events

Adult dosage

• 1 tablet orally once a day (available in combinations that contain aspirin 81 mg or 325 mg)
• Cardiovascular secondary prevention: Generally, 81 mg of aspirin has been accepted as an effective dose for secondary cardiovascular prevention.
• Consider the need for the 325-mg combination as current clinical practice guidelines recommend

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Aspirin-Omeprazole has severe interactions with the following drugs:
  • abrocitinib
  • dichlorphenamide
  • erlotinib
  • fezolinetant
  • mavacamten
  • mifepristone
  • nelfinavir
• Aspirin-Omeprazole has serious interactions with at least 69 other drugs.
• Aspirin-Omeprazole has moderate interactions with at least 357 other drugs.
• Aspirin-Omeprazole has minor interactions with at least 168 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Known allergy to aspirin and other NSAIDs
• Patients with the syndrome of asthma, rhinitis, and nasal polyps; aspirin may cause severe urticaria, angioedema, or bronchospasm
• Known hypersensitivity to aspirin, omeprazole, substituted benzimidazoles, or any of the excipients in the formulation
• Proton pump inhibitors (PPIs) are contraindicated with rilpivirine-containing products
• Not indicated for pediatric patients (safety and efficacy not established); Aspirin is contraindicated in children with suspected viral infections, with or without fever, because of the risk for Reye syndrome with concomitant use of Aspirin in certain viral illnesses

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Aspirin-Omeprazole?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Aspirin-Omeprazole?”

Cautions

• Aspirin
  • Even low doses of aspirin can inhibit platelet function, leading to an increase in bleeding time; monitor for signs of bleeding
  • Aspirin is associated with serious GI adverse reactions, including inflammation, bleeding ulceration, and perforation of the upper and lower GI tract; other adverse reactions with aspirin include stomach pain, heartburn, nausea, and vomiting
  • Avoid severe renal failure (GFR below 10 mL/min); regular use of aspirin is associated with a dose-dependent increased risk of chronic renal failure; aspirin decreases GFR and renal blood flow, especially with preexisting renal disease
  • Long-term moderate-to-high doses of aspirin may result in elevations in serum ALT levels; avoid with any degree of hepatic impairment
  • Aspirin may elevate hepatic enzymes, blood urea nitrogen, and serum creatinine; may cause hyperkalemia, proteinuria, and prolonged bleeding time
  • NSAIDs, including aspirin, may cause premature closure of the fetal ductus arteriosus; avoid use in pregnant women starting at 30 weeks of gestation 
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Drug Reactions reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
  • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
  • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
  • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately
• Omeprazole
  • Avoid use in Asian patients with unknown CYP2C19 genotype or those who are known to be poor metabolizers 
  • Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; TIN may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (eg, fever, rash, or arthralgia); discontinue the drug and evaluate patients with suspected acute TIN
  • PPIs are possibly associated with an increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider the diagnosis of CDAD for patients taking PPIs who have diarrhea that does not improve
  • Published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, particularly with prolonged (longer than 1 year), high-dose therapy
  • Daily long-term use (eg, for more than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin
  • Cutaneous lupus erythematosus and systemic lupus erythematosus (SLE) were reported with PPIs; SLE typically occurred within days to years after initiating treatment, but some cases occurred days or years after initiating treatment; SLE occurred primarily in patients ranging from young adults to the elderly; the majority of patients presented with rash; however, arthralgia and cytopenia were also reported; discontinue therapy and refer the patient to the appropriate specialist for evaluation; most patients improve with discontinuation of PPI alone in 4 to 12 weeks; serological testing (eg, antinuclear antibodies) may be positive, and elevated serological test results may take longer to resolve than clinical manifestations
  • Hypomagnesemia may occur with prolonged use (for more than 1 year); adverse effects may result and include tetany, arrhythmias, and seizures; Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients; in most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued
  • Consider monitoring magnesium and calcium levels before initiation of therapy and periodically while on treatment in patients with a preexisting risk for hypocalcemia (eg, hypoparathyroidism); supplement with magnesium and/or calcium, as necessary; if hypocalcemia is refractory to treatment, consider discontinuing therapy
  • Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels.
  • PPI therapy is associated with an increased risk for fundic gland polyp; risk increases with long-term use 1 year and above); the patient may be asymptomatic; the problem is usually identified incidentally on endoscopy; use the shortest duration of therapy, appropriate to the condition being treated
• Drug interaction overview
  • Also see Interactions Section and Drug Interaction Checker
  • Aspirin
    • Because of its ability to inhibit platelet aggregation, low-dose Aspirin is often used in conjunction with anticoagulants for the prevention of thrombotic cardiovascular events; closely monitor INR and for signs and symptoms of bleeding
    • Maintenance doses of Aspirin below 100 mg reduce the ticagrelor effect in preventing thrombotic cardiovascular events; avoid coadministration of ticagrelor with the 325-mg/40-mg tablet strength
    • Counsel patients who consume more than 3 alcoholic drinks/day about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin
    • Aspirin may decrease the antihypertensive effect of ACE inhibitors, beta-blockers, or diuretics.
    • Moderate aspirin doses may increase the effect of oral hypoglycemics
  • Omeprazole
    • PPIs are contraindicated with rilpivirine-containing products
    • Omeprazole inhibits hepatic isoenzyme CYP2C19 and may decrease the metabolism of drugs that are CYP2C19 substrates (eg, citalopram, cilostazol, phenytoin, diazepam, tacrolimus)
    • Coadministration of clopidogrel with 80-mg omeprazole reduces clopidogrel’s pharmacological activity, even when administered 12 hours apart; avoid coadministration; clopidogrel’s antiplatelet effect is entirely due to an active metabolite; the metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications (eg, omeprazole) that interfere with CYP2C19 activity
    • CYP2C19 or CYP3A4 inducers (eg, St John’s Wort or rifampin) can substantially decrease omeprazole concentrations; avoid coadministration
    • Coadministration of PPIs with methotrexate (primarily at high doses) may elevate and prolong methotrexate serum levels and/or its metabolite, possibly leading to toxicity
    • May increase exposure to digoxin; monitor digoxin concentrations and adjust the dose as needed to maintain therapeutic serum concentrations
    • For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), healthcare professionals may consider monitoring magnesium levels before initiation of PPI treatment and periodically
    • May reduce the absorption of drugs that are dependent on gastric pH for absorption (eg, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Pregnancy and Lactation

• Aspirin
  • Use of NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
  • Because of these risks, limit the dose and duration of drug combination between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy
  • The use of NSAIDs, including this drug combination, at about 30 weeks gestation or later in pregnancy increases the risk for premature closure of the fetal ductus arteriosus
  • The administration of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment
  • If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit its use to the lowest effective dose and shortest duration possible; if drug combination treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue drug use and follow up according to clinical practice
  • Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive
  • Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors, such as Aspirin, resulted in increased pre-and post-implantation loss
  • Prostaglandins also have been shown to have an important role in fetal kidney development; in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses
  • Reproductive potential
  • Based on their mechanism of action, the use of prostaglandin-mediated NSAIDs may delay or prevent the rupture of ovarian follicles, which has been associated with reversible infertility in some women
  • Published animal studies have shown that the administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
  • Small studies in women treated with NSAIDs have also demonstrated a reversible delay in ovulation; consider withdrawal of NSAIDs in women who have trouble conceiving or who are undergoing investigation of infertility
• Omeprazole
  • Four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women not exposed to the drug
  • The number of infants exposed in utero to omeprazole who had any malformation, low birth weight, low Apgar score, or hospitalization was similar to those of women not exposed in each study
  • Exceptions were the number of infants born with ventricular septal defects and the number of stillborn infants, which were both slightly higher in the omeprazole-exposed infants
• Lactation
  • Individual components, aspirin, and omeprazole, are secreted in human milk
  • Limited data describe the presence of aspirin in human milk at relative infant doses of 2.5%-10.8% of the maternal weight-adjusted dosage
  • Case reports of breastfeeding infants whose mothers were exposed to aspirin during lactation describe adverse reactions, including metabolic acidosis, thrombocytopenia, and hemolysis
  • Limited data describe the presence of omeprazole in human milk at a relative infant dose of 0.9% of the maternal weight-adjusted dosage; there are no reports of adverse effects of omeprazole on the breastfed infant
  • Because of the potential for serious adverse reactions in infants, including the potential for aspirin to cause metabolic acidosis, thrombocytopenia, hemolysis, or Reye syndrome, breastfeeding is not recommended during treatment
  • Not known if maternal exposure to aspirin during lactation increases the risk of Reye’s syndrome in breastfed infants; the direct use of aspirin in infants and children is associated with Reye’s syndrome, even at low plasma levels