Usage
Esomeprazole + Naproxen is prescribed for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in adults and juvenile idiopathic arthritis (JIA) in children 12 years and older. It is specifically indicated for patients at risk of developing NSAID-associated gastric ulcers.
It is a combination drug belonging to the following pharmacological classifications:
- Naproxen: Nonsteroidal anti-inflammatory drug (NSAID) - analgesic, anti-inflammatory, antipyretic.
- Esomeprazole: Proton pump inhibitor (PPI) - antacid.
The mechanism of action involves Naproxen’s inhibition of cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, thereby diminishing inflammation and pain. Esomeprazole suppresses gastric acid secretion by inhibiting the H+/K+-ATPase in gastric parietal cells, thus protecting the gastric mucosa from NSAID-induced damage.
Alternate Names
- Generic Name: Esomeprazole/Naproxen
- Brand Name: Vimovo
How It Works
Pharmacodynamics: Naproxen exerts its analgesic and anti-inflammatory effects by inhibiting COX-1 and COX-2 enzymes, reducing prostaglandin production. Esomeprazole, a proton pump inhibitor, irreversibly binds to H+/K+-ATPase, blocking the final step in gastric acid secretion, thus reducing intragastric acidity.
Pharmacokinetics:
- Absorption: Naproxen and esomeprazole are both absorbed orally. Naproxen’s absorption is delayed when taken with food. Esomeprazole is formulated as an enteric-coated component in Vimovo to protect it from degradation in the stomach acid and to delay its release. The enteric coating dissolves at higher intestinal pH, triggering the release of esomeprazole in the intestine. This is necessary to ensure appropriate absorption of esomeprazole and to minimize acid-related side effects.
- Metabolism: Naproxen is extensively metabolized in the liver primarily via CYP450 enzymes (CYP1A2 and CYP2C9). Esomeprazole is also metabolized in the liver, primarily by CYP2C19 and to a lesser extent by CYP3A4.
- Elimination: Naproxen is primarily excreted in the urine, with a small amount eliminated in the feces. Esomeprazole is also mainly excreted in the urine, as metabolites.
Dosage
Standard Dosage
Adults: One tablet (375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole) twice daily, taken orally at least 30 minutes before a meal.
Children:
- 12 years and older and weighing 38 kg to less than 50 kg: One tablet (375 mg naproxen/20 mg esomeprazole) twice daily.
- 12 years and older and weighing 50 kg or more: One tablet (375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole) twice daily.
- Younger than 12 years: Use and dose must be determined by a doctor.
Special Cases:
- Elderly Patients: Elderly patients are more susceptible to adverse events associated with NSAIDs. Close monitoring is recommended, and dosage adjustments may be necessary.
- Patients with Renal Impairment: Use is not recommended in patients with severe renal impairment (creatinine clearance <30 mL/min). Dose adjustment may be necessary in mild to moderate renal impairment.
- Patients with Hepatic Dysfunction: Use is not recommended in patients with severe hepatic impairment. Dose adjustment of the naproxen component may be considered in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring is recommended in patients with conditions such as hypertension, heart failure, diabetes, asthma, or a history of gastrointestinal bleeding.
Clinical Use Cases
The combination of esomeprazole and naproxen is not specifically indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for chronic management of inflammatory arthritis.
Dosage Adjustments
Dosage adjustments should be made based on patient-specific factors like renal function, hepatic function, and other comorbid conditions as described above. Individualized therapy is crucial for optimizing efficacy and minimizing risks.
Side Effects
Common Side Effects
- Stomach discomfort
- Diarrhea
- Headache
- Nausea
- Vomiting
- Indigestion
- Upper abdominal or stomach pain
- Loss of appetite
- Stomach bloating, cramping, pain, tenderness, or upset
- Weight loss
Rare but Serious Side Effects
- Allergic reactions (hives, difficulty breathing, swelling)
- Signs of a heart attack or stroke (chest pain, numbness, weakness)
- Severe stomach pain, bloody or tarry stools, bloody vomit
- Kidney problems (decreased urination, blood in urine, swelling)
- Liver problems (jaundice, dark urine, loss of appetite)
- Anemia (fatigue, shortness of breath)
- Serious skin reactions (blistering, peeling, skin rash)
Long-Term Effects
- Fundic gland polyps (stomach growths)
- Vitamin B-12 deficiency
- Increased risk of bone fractures
Contraindications
- Hypersensitivity to naproxen, esomeprazole, or other substituted benzimidazoles
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
- Active peptic ulcer or gastrointestinal bleeding
- Severe heart failure
- Peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery
- Concomitant use with rilpivirine-containing products
Drug Interactions
Esomeprazole + Naproxen interacts with numerous medications, including:
- CYP450 substrates: May alter the metabolism of drugs metabolized by CYP2C19 and CYP3A4.
- Anticoagulants (e.g., warfarin): May increase the risk of bleeding.
- Antiplatelet agents (e.g., clopidogrel): Increased risk of bleeding.
- Methotrexate: May enhance methotrexate toxicity.
- Tacrolimus: May increase tacrolimus levels.
- Antihypertensives: May reduce the effectiveness of antihypertensive medications.
- Diuretics: May lead to impaired response to diuretic therapy.
- Lithium: May increase lithium levels.
- Rilpivirine: Contraindicated due to potential for interaction.
Additionally, alcohol, smoking, and certain foods (e.g., grapefruit juice) may also interact with this medication. Consult a detailed drug interaction resource for comprehensive information.
Pregnancy and Breastfeeding
- Pregnancy: Use is not recommended after 20 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus. Use between 20 and 30 weeks should only be considered if the potential benefit outweighs the risk. Use is contraindicated after 30 weeks of gestation.
- Breastfeeding: Naproxen is excreted in breast milk. It is unknown if esomeprazole is excreted in breast milk. Use during breastfeeding is not recommended.
Drug Profile Summary
- Mechanism of Action: Naproxen inhibits COX-1 and COX-2, reducing prostaglandin synthesis. Esomeprazole inhibits gastric acid secretion.
- Side Effects: Common: Gastrointestinal upset, diarrhea, headache. Serious: Allergic reactions, cardiovascular events, gastrointestinal bleeding, renal/hepatic dysfunction.
- Contraindications: Hypersensitivity, history of aspirin/NSAID allergy, active peptic ulcer, severe heart failure, CABG surgery, rilpivirine use, late pregnancy.
- Drug Interactions: Anticoagulants, antiplatelet agents, methotrexate, tacrolimus, antihypertensives, diuretics, lithium, rilpivirine.
- Pregnancy & Breastfeeding: Not recommended during pregnancy after 20 weeks and during breastfeeding.
- Dosage: Adults: One tablet (375 mg/20 mg or 500 mg/20 mg) twice daily. Pediatric dosing available for specific age/weight groups.
- Monitoring Parameters: Blood pressure, renal function, liver function, complete blood count, signs and symptoms of gastrointestinal bleeding.
Popular Combinations
Esomeprazole + Naproxen is itself a combination product. Combining it with other medications should be done with caution and careful consideration of potential interactions.
Precautions
- General Precautions: Assess for allergies, renal/hepatic impairment, cardiovascular risk factors, and history of gastrointestinal bleeding before initiating therapy.
- Specific Populations: See Dosage section for details on elderly, renal/hepatic impairment, and comorbid conditions. Use is not recommended during pregnancy after 20 weeks or during breastfeeding.
- Lifestyle Considerations: Avoid alcohol as it may increase the risk of gastrointestinal bleeding. Smoking may also increase cardiovascular risk.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Esomeprazole + Naproxen?
A: For adults, one tablet (375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole) twice daily. Pediatric and special population dosing varies; see the Dosage section for specific details.
Q2: What are the most common side effects?
A: Common side effects include stomach discomfort, diarrhea, headache, nausea, and vomiting.
Q3: Can Esomeprazole + Naproxen be used during pregnancy?
A: No, it’s contraindicated after 30 weeks and not recommended after 20 weeks.
Q4: What are the major drug interactions?
A: Significant interactions occur with anticoagulants, antiplatelet agents, methotrexate, and certain antihypertensives. It’s contraindicated with rilpivirine.
Q5: What should I monitor in patients taking Esomeprazole + Naproxen?
A: Monitor blood pressure, renal function, liver function tests, and complete blood counts, as well as for any signs or symptoms of gastrointestinal bleeding.
Q6: What is the mechanism of action of this combination drug?
A: Naproxen inhibits COX enzymes, reducing inflammation and pain, while esomeprazole reduces gastric acid production, protecting against ulcers.
Q7: Can this medication be crushed or chewed?
A: No, the tablets should be swallowed whole and not crushed, chewed, or broken.
Q8: Who should not take this medication?
A: Individuals with hypersensitivity to the components, a history of aspirin/NSAID-induced asthma/urticaria, active GI bleeding, severe heart failure, and those undergoing CABG surgery or taking rilpivirine should not take this medication. Also contraindicated in late pregnancy.
Q9: What are signs of a serious allergic reaction to this medication?
A: Hives, difficulty breathing, swelling of the face, lips, tongue, or throat are signs of a serious allergic reaction that require immediate medical attention.
