ONE TABLET

Prescription-strength omeprazole with 2 aspirin strengths

81-mg delayed-release aspirin/ 40-mg immediate-release omeprazole

325-mg delayed-release aspirin/ 40-mg immediate-release omeprazole

Product Details

Aspirin and Omeprazole provides CV and GI protection with the coordinated delivery of aspirin and omeprazole.
Aspirin and Omeprazole is designed to sequentially deliver immediate-release omeprazole and delayed-release aspirin for gastro- and cardioprotection.

Indications and Usage

Aspirin and Omeprazole, a combination of aspirin and omeprazole, is indicated for patients who require aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of developing aspirin-associated gastric ulcers.

The aspirin component of Aspirin and Omeprazole is indicated for:

• Reducing the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli
• Reducing the combined risk of death and nonfatal MI in patients with a previous MI or unstable angina pectoris
• Reducing the combined risk of MI and sudden death in patients with chronic stable angina pectoris
• Use in patients who have undergone revascularization procedures (Coronary Artery Bypass Graft [CABG] or Percutaneous Transluminal Coronary Angioplasty [PTCA]) when there is a pre-existing condition for which aspirin is already indicated
The omeprazole component of Aspirin and Omeprazole is indicated for decreasing the risk of developing aspirin-associated gastric ulcers in patients at risk for developing aspirin-associated gastric ulcers due to age (≥ 55) or documented history of gastric ulcers.

Limitations of Use:
• Aspirin and Omeprazole contains a delayed-release formulation of aspirin and it is not for use as the initial dose of aspirin therapy during onset of acute coronary syndrome, acute myocardial infarction, or before percutaneous coronary intervention (PCI), for which immediate-release aspirin therapy is appropriate
• Aspirin and Omeprazole has not been shown to reduce the risk of gastrointestinal bleeding due to aspirin
• Aspirin and Omeprazole is not interchangeable with the individual components of aspirin and omeprazole

Dosage and Administration

Aspirin and Omeprazole is a once-daily tablet containing immediate-release omeprazole and delayed-release aspirin (ASA) indicated for patients who require ASA for secondary prevention of cardiovascular and cerebrovascular events and are at risk for developing ASA-associated gastric ulcers.

Administered at least 1 hour before a meal

81-mg delayed-release aspirin / 40-mg immediate-release omeprazole
325-mg delayed-release aspirin / 40-mg immediate-release omeprazole

*The tablets are to be swallowed whole with liquid. Do not split, chew,

IMPORTANT CONSIDERATIONS 
Remember these points when treating with Aspirin and Omeprazole

Use the lowest effective dose of Aspirin and Omeprazole based on the individual patient’s treatment goals and to avoid potential dose-dependent adverse reactions, including bleeding.

If a dose of Aspirin and Omeprazole is missed, advise patients to take it as soon as it is remembered. If it is almost time for the next dose, skip the missed dose. Take the next dose at the regular time. Patients should not take 2 doses at the same time unless advised by their doctor.

Do not stop taking Aspirin and Omeprazole suddenly as this could increase the risk of heart attack or stroke.

Information for the Patient

Aspirin and Omeprazole is a prescription medicine used:
• in people who have had heart problems or strokes caused by blood clots, to help reduce their risk of further heart problems or strokes, and
• who are at risk of developing stomach ulcers with aspirin use

Aspirin and Omeprazole should not be used to treat sudden signs and symptoms of a heart attack or stroke. Aspirin and Omeprazole should only be used as directed by your doctor to help reduce the risk of further heart problems or strokes.

You should not take an aspirin tablet and an omeprazole tablet together instead of taking Aspirin and Omeprazole, because they will not work the same way.

You should take Aspirin and Omeprazole exactly as prescribed.

Aspirin and Omeprazole may help reduce the risk of stomach ulcers from aspirin use, but you could still have bleeding and stomach or intestine ulcers, or other serious stomach or intestine problems. Talk with your doctor if you experience any of these problems.

Do not use Aspirin and Omeprazole if you: 
• are allergic to aspirin, omeprazole, or any of the ingredients in Aspirin and Omeprazole
• are allergic to any non-steroidal anti-inflammatory drug (NSAID)
• have a medical condition with severe shortness of breath, chest tightness or pain, coughing or wheezing (asthma), sneezing, runny nose or itchy nose (rhinitis), and growths inside of your nose or sinuses (nasal polyps)
• are taking a medicine that contains rilpivirine (EDURANT®, COMPLERA®, ODEFSEY®) used to treat HIV-1 (Human Immunodeficiency Virus)

Do not give Aspirin and Omeprazoleto a child who has a suspected viral infection, even if they do not have a fever. There is a risk of Reye’s syndrome with Aspirin and Omeprazole because it contains aspirin.

Warnings

Contraindications 

Aspirin and Omeprazole is contraindicated in:

• Patients with known allergy to aspirin and other nonsteroidal anti-inflammatory drug products (NSAIDs) and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma)
• Pediatric patients with suspected viral infections, with or without fever, because of the risk of Reye’s syndrome with concomitant use of aspirin in certain viral illnesses
• Patients with known hypersensitivity to aspirin, omeprazole, substituted benzimidazoles, or to any of the excipients in the formulation
• Proton pump inhibitor (PPI)–containing products, including Yosprala, are contraindicated in patients receiving rilpivirine-containing products

Warnings and Precautions 

Coagulation Abnormalities 
Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect patients with inherited (hemophilia) or acquired (liver disease or vitamin K deficiency) bleeding disorders. Monitor patients for signs of increased bleeding.

Gastrointestinal Adverse Reactions
Aspirin is associated with serious gastrointestinal (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.

Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, monitor patients for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Inform patients about the signs and symptoms of GI adverse reactions.

If active and clinically significant bleeding from any source occurs in patients receiving Aspirin and Omeprazole, discontinue treatment.

Bleeding Risk with Use of Alcohol
Counsel patients who consume three or more alcoholic drinks every day about the bleeding risks involved with chronic, heavy alcohol use while taking Aspirin and Omeprazole.

Interaction with Clopidogrel 
Avoid concomitant use of Aspirin and Omeprazole with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that interfere with CYP2C19 activity. Co-administration of clopidogrel with 80-mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using Aspirin and Omeprazole, consider alternative anti-platelet therapy.

Interaction with Ticagrelor 
Maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor in preventing thrombotic cardiovascular events. Avoid concomitant use of ticagrelor with the 325-mg/40-mg tablet strength of Aspirin and Omeprazole.

Renal Failure 
Avoid Aspirin and Omeprazole in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute). Regular use of aspirin is associated in a dose-dependent manner with an increased risk of chronic renal failure. Aspirin use decreases glomerular filtration rate and renal blood flow especially with patients with pre-existing renal disease.

Presence of Gastric Malignancy 
In adults, response to gastric symptoms with Aspirin and Omeprazole does not preclude the presence of gastric malignancy. Consider additional gastrointestinal follow-up and diagnostic testing in adult patients who experience gastric symptoms during treatment with Yosprala or have a symptomatic relapse after completing treatment. In older patients, also consider an endoscopy.

Acute Interstitial Nephritis
Acute interstitial nephritis has been observed in patients taking PPIs including omeprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue Aspirin and Omeprazole if acute interstitial nephritis develops.

Clostridium difficile-Associated Diarrhea
Published observational studies suggest that PPI-containing therapy like Yosprala may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve.

Use the lowest dose and shortest duration of Aspirin and Omeprazole appropriate to the condition being treated.

Bone Fracture 
Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Use the lowest dose and shortest duration of Aspirin and Omeprazole therapy appropriate to the condition being treated.

Cutaneous and Systemic Lupus Erythematosus 
Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Aspirin and Omeprazole, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks.

Hepatic Impairment 
Long-term moderate to high doses of aspirin may result in elevations in serum ALT levels. These abnormalities resolve rapidly with discontinuation of aspirin. Systemic exposure to omeprazole is increased in patients with hepatic impairment. Avoid Aspirin and Omeprazole in patients with any degree of hepatic impairment.

Cyanocobalamin (Vitamin B12) Deficiency 
Daily treatment with any acid-suppressing medications over a long period of time (eg, longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with Aspirin and Omeprazole.

Hypomagnesemia 
Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take Yosprala with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), consider monitoring magnesium levels prior to initiation of Aspirin and Omeprazole and periodically during treatment.

Reduced Effect of Omeprazole with St. John’s Wort or Rifampin
Drugs which induce the CYP2C19 or CYP3A4 (such as St. John’s Wort or rifampin) can substantially decrease concentrations of omeprazole. Avoid concomitant use of Aspirin and Omeprazole with St. John’s Wort or rifampin.

Interactions with Diagnostic Investigations for Neuroendocrine Tumors 
Serum chromogranin A (CgA) levels increase secondary to omeprazole-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic interventions for neuroendocrine tumors. Temporarily discontinue treatment with Yosprala at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (eg, for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

Interaction with Methotrexate 
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of Aspirin and Omeprazole may be considered in some patients.

Premature Closure of Fetal Ductus Arteriosus 
NSAIDs including aspirin, may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Aspirin and Omeprazole, in pregnant women starting at 30 weeks of gestation (third trimester).

Abnormal Laboratory Tests 
Aspirin has been associated with elevated hepatic enzymes, blood urea nitrogen and serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time.

Adverse Reactions 
Most common adverse reactions in adults (incidence ≥2% and more common in Aspirin and Omeprazole treated patients) are: gastritis, nausea, diarrhea, gastric polyps, and non-cardiac chest pain. Less common adverse reactions were 2 patients with upper GI bleeding (gastric or duodenal) and 2 patients with lower GI bleeding (hematochezia and large intestinal hemorrhage) and one additional patient experienced obstruction in the small bowel.

Drug Interactions 
See the full prescribing information for the complete list of drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Aspirin and Omeprazole and instructions for preventing or managing them.

Use in Specific Populations 
• Pregnancy: Use during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of Aspirin and Omeprazole in pregnant women starting at 30 weeks of gestation (third trimester)
• Lactation: Breastfeeding not recommended

To report SUSPECTED ADVERSE EVENTS, contact Pharm-Olam at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.