Aspirin + Esomeprazole

Usage

Aspirin + Esomeprazole is prescribed to prevent cardiovascular and cerebrovascular events (like heart attack and stroke) in patients who need continuous low-dose aspirin therapy and are at risk of developing aspirin-associated gastric or duodenal ulcers.

• Pharmacological Classification: This combination drug falls into two classifications:

  • Aspirin: Nonsteroidal anti-inflammatory drug (NSAID), antiplatelet agent, analgesic (pain reliever), antipyretic (fever reducer)
  • Esomeprazole: Proton pump inhibitor (PPI)

• Mechanism of Action: Aspirin works by irreversibly inhibiting cyclooxygenase-1 (COX-1), which reduces thromboxane A2 production, thereby inhibiting platelet aggregation and clot formation. Esomeprazole inhibits the H+/K+ ATPase in gastric parietal cells, reducing gastric acid secretion and protecting the stomach lining from aspirin-induced damage.

Alternate Names

The combination of aspirin and esomeprazole itself doesn’t have an international nonproprietary name (INN). It’s known by the components’ names. Regionally, aspirin may be known as acetylsalicylic acid (ASA).

• Brand Names: A common brand name is Axanum (available in some regions, primarily the European Union).

How It Works

• Pharmacodynamics: Aspirin exerts antiplatelet effects, preventing clot formation. Esomeprazole suppresses gastric acid secretion.

• Pharmacokinetics:

  • Aspirin is rapidly absorbed in the small intestine. It is metabolized in the liver to salicylic acid, then conjugated and excreted renally.
  • Esomeprazole is also absorbed in the small intestine, but it’s formulated as enteric-coated to prevent degradation in the stomach’s acidic environment. It’s metabolized primarily by CYP2C19 and to a lesser extent by CYP3A4 in the liver, and the metabolites are excreted renally.

• Mode of Action: Aspirin irreversibly acetylates a serine residue near the active site of COX-1 in platelets, inhibiting its activity. Esomeprazole binds to the H+/K+ ATPase (proton pump) on the luminal surface of gastric parietal cells, inhibiting acid secretion into the stomach lumen.

• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Aspirin inhibits COX-1 enzyme. Esomeprazole inhibits the H+/K+ ATPase.

• Elimination Pathways: Aspirin: Renal excretion of metabolites. Esomeprazole: Renal excretion of metabolites.

Dosage

Standard Dosage

Adults: One capsule/tablet containing 81 mg or 325 mg of aspirin and 20 mg or 40 mg of esomeprazole is taken orally once a day, at least 30-60 minutes before a meal.

Children: The combination is not recommended for pediatric use. Aspirin use in children is generally avoided due to the risk of Reye’s syndrome.

Special Cases:

• Elderly Patients: The elderly may be more susceptible to adverse effects, especially gastrointestinal bleeding, so careful monitoring is recommended. Dose adjustment might be considered based on individual patient factors.
• Patients with Renal Impairment: Dose adjustments are generally not necessary for esomeprazole in mild to moderate renal impairment. Caution is advised in severe renal impairment. Aspirin should be used cautiously in patients with significant renal dysfunction.
• Patients with Hepatic Dysfunction: Dose adjustments for esomeprazole are generally not needed in mild to moderate hepatic impairment, but in severe hepatic impairment, the daily dose should not exceed 20 mg. Aspirin should be used with caution in patients with severe liver disease.
• Patients with Comorbid Conditions: Patients with asthma, bleeding disorders, or a history of peptic ulcers should be monitored closely.

Clinical Use Cases

The use of this combination is specifically for the prevention of cardiovascular events in patients at risk of aspirin-associated ulcers. It’s not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose modifications may be necessary in certain situations, as outlined above for special cases.

Side Effects

Common Side Effects:

Headache, diarrhea, abdominal pain, nausea, vomiting, flatulence, indigestion.

Rare but Serious Side Effects:

Gastrointestinal bleeding, allergic reactions (urticaria, angioedema, bronchospasm), low magnesium levels (hypomagnesemia), kidney problems, severe skin reactions.

Long-Term Effects:

Long-term use of PPIs like esomeprazole may increase the risk of bone fractures, infections (such as Clostridium difficile-associated diarrhea), and vitamin B12 deficiency.

Adverse Drug Reactions (ADR):

Anaphylaxis, severe bleeding, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Contraindications

Hypersensitivity to aspirin, NSAIDs, esomeprazole, or substituted benzimidazoles; asthma, rhinitis, nasal polyps (aspirin triad); concomitant use with rilpivirine-containing products.

Drug Interactions

Aspirin can interact with anticoagulants, increasing bleeding risk. Esomeprazole can interact with clopidogrel, reducing its effectiveness. It can also affect the absorption of drugs dependent on gastric pH, such as ketoconazole and iron salts. Both aspirin and esomeprazole can interact with other medications metabolized by CYP2C19 and CYP3A4. Alcohol should be avoided as it increases the risk of gastrointestinal bleeding with aspirin.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Aspirin is contraindicated during the third trimester of pregnancy. Esomeprazole use during pregnancy should be limited to situations where benefit outweighs risk.

• Fetal risks: Aspirin can cause premature closure of the ductus arteriosus in the fetus.

• Drug excretion in breast milk: Aspirin is excreted in breast milk and may cause Reye’s syndrome in infants. Esomeprazole may also be excreted in breast milk; breastfeeding is not recommended while taking this medication.

Drug Profile Summary

• Mechanism of Action: Aspirin inhibits COX-1, reducing platelet aggregation. Esomeprazole inhibits the proton pump, reducing gastric acid secretion.

• Side Effects: Common: headache, diarrhea, abdominal pain. Serious: GI bleeding, allergic reactions, hypomagnesemia.

• Contraindications: Aspirin triad, hypersensitivity, concomitant use with rilpivirine.

• Drug Interactions: Anticoagulants, clopidogrel, drugs metabolized by CYP2C19/3A4.

• Pregnancy & Breastfeeding: Aspirin is contraindicated in the third trimester. Breastfeeding is not recommended while taking this combination.

• Dosage: Adults: 81-325 mg aspirin + 20-40 mg esomeprazole once daily before meals. Not recommended for children.

• Monitoring Parameters: Signs of bleeding, kidney function, liver function, magnesium levels.

Popular Combinations

This combination itself is a popular strategy for patients requiring aspirin who are at high risk of gastrointestinal ulcers.

Precautions

Screen patients for allergies, bleeding disorders, asthma, and renal/hepatic impairment. Avoid alcohol. Advise patients to report any unusual bleeding or bruising. Pregnant women should avoid aspirin, especially in the third trimester. Breastfeeding is not recommended.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Aspirin + Esomeprazole?

A: The standard adult dose is one tablet/capsule containing 81 or 325 mg of aspirin and 20 or 40 mg of esomeprazole, taken once daily at least 30-60 minutes before a meal.

Q2: Can children take Aspirin + Esomeprazole?

A: No, this combination is not recommended for pediatric patients due to the risk of Reye’s syndrome associated with aspirin use in children.

Q3: What are the major side effects to watch out for?

A: Serious side effects include gastrointestinal bleeding (look for black, tarry stools, coffee-ground emesis, or persistent abdominal pain), allergic reactions (rash, itching, swelling, difficulty breathing), and signs of hypomagnesemia (muscle cramps, tremors, irregular heartbeat).

Q4: Are there any contraindications to Aspirin + Esomeprazole?

A: Yes. This medication is contraindicated in patients with hypersensitivity to aspirin, other NSAIDs, or esomeprazole; those with asthma, rhinitis, and nasal polyps (aspirin triad); and patients taking rilpivirine-containing products.

Q5: How does this combination protect the stomach?

A: Esomeprazole, a proton pump inhibitor, reduces gastric acid secretion, protecting the stomach lining from the irritating effects of aspirin.

Q6: Can patients crush or chew the combined pill?

A: No, the medication should be swallowed whole. Crushing or chewing can interfere with the enteric coating of esomeprazole, reducing its effectiveness and potentially increasing side effects.

Q7: What if a dose is missed?

A: The missed dose should be taken as soon as remembered, unless it is close to the time for the next dose. Do not double the dose.

Q8: Are there any drug interactions I should be aware of?

A: Yes, this combination can interact with several medications, including anticoagulants (like warfarin), clopidogrel, and certain antifungals. It can also interact with drugs metabolized by CYP2C19 and CYP3A4. A thorough medication review is essential before prescribing this combination.

Q9: Can pregnant or breastfeeding women take Aspirin + Esomeprazole?

A: Aspirin is contraindicated in the third trimester of pregnancy. Esomeprazole should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Breastfeeding is not recommended while taking this combination as both aspirin and esomeprazole can be excreted in breast milk.

Q10: What are the long-term implications of using a PPI like esomeprazole?

A: Long-term use of PPIs has been associated with a slightly increased risk of bone fractures, infections (such as C. difficile infection), and vitamin B12 deficiency. These risks should be considered, especially in elderly patients and those with other risk factors for these conditions.