Naproxen-Esomep 500/20mg DR Tablets
WARNING: This drug may raise the risk of heart and blood vessel problems like heart attack and stroke. These effects can be deadly. The risk may be greater if you have heart disease or risks for heart disease. However, it can also be raised even if you do not have heart disease or risks for heart disease. The risk can happen within the first weeks of using this drug and may be greater with higher doses or long-term use. Do not use this drug right before or after bypass heart surgery.This drug may raise the chance of severe and sometimes deadly stomach or bowel problems like ulcers or bleeding. The risk is greater in older people, and in people who have had stomach or bowel ulcers or bleeding before. These problems may occur without warning signs. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat ankylosing spondylitis.It is used to treat or prevent nonsteroidal anti-inflammatory drugs (NSAID)- associated gastric ulcers in patients with a history of ulcers. Examples of NSAIDs include ibuprofen and naproxen.
Drug Class
Nonsteroidal Anti-inflammatory Drug (NSAID) / Proton Pump Inhibitor (PPI) Combination
Pharmacologic Class
Cyclooxygenase Inhibitor / Proton Pump Inhibitor
Pregnancy Category
Category D (3rd Trimester); Category C (1st & 2nd Trimester)
FDA Approved
Apr 2010
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medication is a combination of two drugs: naproxen, which is a pain reliever and anti-inflammatory (like ibuprofen), and esomeprazole, which is a stomach protector (like Nexium). It's used to treat pain and inflammation, especially in conditions like arthritis, while also helping to prevent stomach ulcers that can be caused by naproxen.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take this medication at least 30 minutes before meals. Swallow the tablet whole with a glass of water or another drink. Do not chew, break, crush, or dissolve the tablet.
Storing and Disposing of Your Medication
Keep the tablets in their original container at room temperature, with the cap tightly closed. Store them in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take this medication at least 30 minutes before meals. Swallow the tablet whole with a glass of water or another drink. Do not chew, break, crush, or dissolve the tablet.
Storing and Disposing of Your Medication
Keep the tablets in their original container at room temperature, with the cap tightly closed. Store them in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take exactly as prescribed, usually twice a day, at least 30 minutes before a meal.
- Swallow the tablet whole; do not crush, chew, or split it.
- Avoid alcohol, as it can increase the risk of stomach problems.
- Limit caffeine and spicy foods if they worsen stomach upset.
- Stay hydrated, especially if you are elderly or have kidney problems.
- Inform your doctor about all other medications, supplements, and herbal products you are taking.
- Do not take other NSAIDs (like ibuprofen, celecoxib, or other naproxen products) or aspirin (unless low-dose aspirin for heart protection, as directed by your doctor) while taking this medication.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
One tablet (naproxen 500 mg/esomeprazole 20 mg) orally twice daily
Dose Range:
500 - 1000 mg
Condition-Specific Dosing:
osteoarthritis_rheumatoid_arthritis_ankylosing_spondylitis:
One tablet (500 mg/20 mg) orally twice daily
pain_dysmenorrhea:
One tablet (500 mg/20 mg) orally twice daily for short-term use
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (Safety and efficacy not established in patients under 12 years of age)
Adolescent:
Not established (Safety and efficacy not established in patients under 12 years of age)
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment for mild impairment, but monitor renal function.
Moderate:
Use with caution; consider lower doses and close monitoring of renal function. Avoid in advanced renal disease.
Severe:
Contraindicated in patients with advanced renal disease due to naproxen component.
Dialysis:
Not recommended; naproxen is not dialyzable. Esomeprazole is minimally dialyzable.
Hepatic Impairment:
Mild:
No specific dose adjustment for mild impairment, but monitor.
Moderate:
Use with caution; consider lower doses and close monitoring of liver function. Naproxen exposure may be increased. Esomeprazole dose reduction may be needed for severe impairment.
Severe:
Avoid use in severe hepatic impairment due to increased risk of adverse effects and altered pharmacokinetics of both components.
Pharmacology
Mechanism of Action
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that exerts its anti-inflammatory, analgesic, and antipyretic effects by inhibiting prostaglandin synthesis, primarily through the inhibition of cyclooxygenase (COX-1 and COX-2) enzymes. Esomeprazole is a proton pump inhibitor (PPI) that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase (proton pump) in the gastric parietal cells. This specific action leads to inhibition of both basal and stimulated acid secretion.
Pharmacokinetics
Absorption:
Bioavailability:
Naproxen: ~95%; Esomeprazole: ~64% (single dose), ~89% (repeated dosing)
Tmax:
Naproxen: 2-4 hours; Esomeprazole: 1.5 hours (for esomeprazole magnesium component, which is released first)
FoodEffect:
Food does not significantly affect the absorption of naproxen or esomeprazole from this combination product, but may delay Tmax for naproxen. The delayed-release formulation ensures esomeprazole is released before naproxen.
Distribution:
Vd:
Naproxen: 0.16 L/kg; Esomeprazole: 0.22 L/kg
ProteinBinding:
Naproxen: >99%; Esomeprazole: ~97%
CnssPenetration:
Naproxen: Limited; Esomeprazole: Limited
Elimination:
HalfLife:
Naproxen: 12-17 hours; Esomeprazole: 1-1.5 hours
Clearance:
Naproxen: ~0.13 mL/min/kg; Esomeprazole: ~0.3-0.6 L/min
ExcretionRoute:
Naproxen: Urine (95% as unchanged drug, 6-O-desmethylnaproxen, and their conjugates); Esomeprazole: Urine (80%), Feces (20%)
Unchanged:
Naproxen: <1%; Esomeprazole: <1%
Pharmacodynamics
OnsetOfAction:
Naproxen: 1 hour (analgesia); Esomeprazole: Within 1 hour (acid suppression)
PeakEffect:
Naproxen: 2-4 hours; Esomeprazole: 1.5 hours (acid suppression)
DurationOfAction:
Naproxen: Up to 12 hours; Esomeprazole: Up to 24 hours (acid suppression)
Safety & Warnings
BLACK BOX WARNING
CARDIOVASCULAR THROMBOTIC EVENTS: NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. NAPROXEN-ESOMEPRAZOLE is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. GASTROINTESTINAL RISK: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic reactions: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Electrolyte problems: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, change in balance, abnormal heartbeat, seizures, loss of appetite, or severe upset stomach or vomiting.
Kidney problems: Inability to pass urine, changes in urine output, blood in the urine, or sudden weight gain.
Bleeding: Vomiting or coughing up blood, vomit that looks like coffee grounds, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
High potassium levels: Abnormal heartbeat, confusion, weakness, lightheadedness, dizziness, numbness or tingling, or shortness of breath.
High blood pressure: Severe headache or dizziness, fainting, or changes in vision.
Cardiovascular issues: Chest pain or pressure, rapid heartbeat, weakness on one side of the body, trouble speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Respiratory problems: Shortness of breath, sudden weight gain, or swelling in the arms or legs.
General weakness: Feeling extremely tired or weak.
Bone pain: Pain in the bones.
Sensory changes: Ringing in the ears or changes in vision.
Mental health changes: Depression or confusion.
Flu-like symptoms: Symptoms similar to the flu.
Liver problems: Dark urine, fatigue, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes. (Note: Liver problems can be fatal.)
C. diff-associated diarrhea (CDAD): Stomach pain or cramps, very loose or watery stools, or bloody stools. Do not treat diarrhea without consulting your doctor.
Severe skin reactions: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or other serious reactions, which can be fatal. Symptoms include red, swollen, blistered, or peeling skin; red or irritated eyes; sores in the mouth, throat, nose, eyes, genitals, or skin; fever; chills; body aches; shortness of breath; or swollen glands.
Lupus: Rash on the cheeks or other body parts, changes in skin color, easy sunburn, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
Low vitamin B-12 levels: Shortness of breath, dizziness, abnormal heartbeat, muscle weakness, pale skin, fatigue, mood changes, or numbness or tingling in the arms or legs. (Note: This can occur with long-term treatment, typically longer than 3 years.)
Other Side Effects
Most people do not experience side effects or only have mild side effects. However, if you notice any of the following symptoms or if they bother you or do not go away, contact your doctor:
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Heartburn
Gas
Dizziness
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic reactions: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Electrolyte problems: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, change in balance, abnormal heartbeat, seizures, loss of appetite, or severe upset stomach or vomiting.
Kidney problems: Inability to pass urine, changes in urine output, blood in the urine, or sudden weight gain.
Bleeding: Vomiting or coughing up blood, vomit that looks like coffee grounds, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
High potassium levels: Abnormal heartbeat, confusion, weakness, lightheadedness, dizziness, numbness or tingling, or shortness of breath.
High blood pressure: Severe headache or dizziness, fainting, or changes in vision.
Cardiovascular issues: Chest pain or pressure, rapid heartbeat, weakness on one side of the body, trouble speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Respiratory problems: Shortness of breath, sudden weight gain, or swelling in the arms or legs.
General weakness: Feeling extremely tired or weak.
Bone pain: Pain in the bones.
Sensory changes: Ringing in the ears or changes in vision.
Mental health changes: Depression or confusion.
Flu-like symptoms: Symptoms similar to the flu.
Liver problems: Dark urine, fatigue, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes. (Note: Liver problems can be fatal.)
C. diff-associated diarrhea (CDAD): Stomach pain or cramps, very loose or watery stools, or bloody stools. Do not treat diarrhea without consulting your doctor.
Severe skin reactions: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or other serious reactions, which can be fatal. Symptoms include red, swollen, blistered, or peeling skin; red or irritated eyes; sores in the mouth, throat, nose, eyes, genitals, or skin; fever; chills; body aches; shortness of breath; or swollen glands.
Lupus: Rash on the cheeks or other body parts, changes in skin color, easy sunburn, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
Low vitamin B-12 levels: Shortness of breath, dizziness, abnormal heartbeat, muscle weakness, pale skin, fatigue, mood changes, or numbness or tingling in the arms or legs. (Note: This can occur with long-term treatment, typically longer than 3 years.)
Other Side Effects
Most people do not experience side effects or only have mild side effects. However, if you notice any of the following symptoms or if they bother you or do not go away, contact your doctor:
Constipation, diarrhea, stomach pain, upset stomach, or vomiting
Heartburn
Gas
Dizziness
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe stomach pain, black or tarry stools, vomit that looks like coffee grounds (signs of stomach bleeding)
- Chest pain, shortness of breath, sudden weakness or numbness on one side of the body, slurred speech (signs of heart attack or stroke)
- Swelling in your ankles, feet, or hands, sudden weight gain (signs of fluid retention or kidney problems)
- Yellowing of the skin or eyes, dark urine, unusual tiredness (signs of liver problems)
- Severe skin rash, blistering, or peeling (signs of severe skin reaction)
- Difficulty breathing or swallowing, swelling of the face, lips, tongue, or throat (signs of allergic reaction)
- Unusual bruising or bleeding
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
Allergies to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen.
A history of asthma triggered by salicylate medications, such as aspirin, or NSAIDs.
Presence of certain health conditions, including:
+ Active bleeding or bleeding in the brain or gastrointestinal (GI) tract.
+ Other bleeding problems.
+ Heart failure (weak heart).
+ Kidney or liver problems.
+ Stomach or bowel ulcers.
Recent heart attack.
Current use of other NSAIDs, salicylate drugs like aspirin, or pemetrexed.
Use of specific medications, including:
+ Atazanavir.
+ Clopidogrel.
+ Methotrexate.
+ Nelfinavir.
+ Rifampin.
+ Rilpivirine.
+ St. John's wort.
+ Warfarin.
Fertility issues or ongoing fertility evaluation.
* Pregnancy, planned pregnancy, or suspected pregnancy. This medication may harm an unborn baby if taken after 20 weeks of gestation. If you are between 20 and 30 weeks pregnant, only take this medication under your doctor's guidance. Do not take this medication if you are more than 30 weeks pregnant.
To ensure your safety, it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. Verify that it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
Allergies to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen.
A history of asthma triggered by salicylate medications, such as aspirin, or NSAIDs.
Presence of certain health conditions, including:
+ Active bleeding or bleeding in the brain or gastrointestinal (GI) tract.
+ Other bleeding problems.
+ Heart failure (weak heart).
+ Kidney or liver problems.
+ Stomach or bowel ulcers.
Recent heart attack.
Current use of other NSAIDs, salicylate drugs like aspirin, or pemetrexed.
Use of specific medications, including:
+ Atazanavir.
+ Clopidogrel.
+ Methotrexate.
+ Nelfinavir.
+ Rifampin.
+ Rilpivirine.
+ St. John's wort.
+ Warfarin.
Fertility issues or ongoing fertility evaluation.
* Pregnancy, planned pregnancy, or suspected pregnancy. This medication may harm an unborn baby if taken after 20 weeks of gestation. If you are between 20 and 30 weeks pregnant, only take this medication under your doctor's guidance. Do not take this medication if you are more than 30 weeks pregnant.
To ensure your safety, it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. Verify that it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.
Precautions & Cautions
Important Information About Your Medication
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
If you are taking this medication long-term, your doctor may recommend regular blood tests to monitor your health. Be sure to discuss this with your doctor.
This medication may interfere with certain laboratory tests. It is essential that you notify all of your healthcare providers and laboratory personnel that you are taking this medication.
There is a risk of developing high blood pressure while taking this medication. Your doctor will likely recommend regular blood pressure checks to monitor your condition.
Before consuming alcohol, consult with your doctor to discuss any potential risks.
If you smoke, it is crucial that you discuss this with your doctor, as smoking may affect your health while taking this medication.
Taking Your Medication Safely
Do not exceed the dosage recommended by your doctor, as taking more than prescribed may increase your risk of severe side effects. Additionally, do not take this medication for longer than your doctor has advised.
Special Considerations
If you have asthma, consult with your doctor before taking this medication, as you may be more sensitive to its effects.
This medication may increase your risk of bleeding easily. To minimize this risk, be careful to avoid injury, use a soft toothbrush, and consider using an electric razor.
If you are taking aspirin to prevent a heart attack, inform your doctor, as this may affect your treatment plan.
Your doctor may recommend taking calcium and vitamin D supplements while taking this medication. Be sure to follow their instructions.
Bone Health
This medication may increase your risk of fractures, particularly in the hip, spine, and wrist, especially if you have weak bones (osteoporosis). This risk may be higher if you take high doses of this medication, take it for more than a year, or are over 50 years old.
If you have risk factors for osteoporosis, such as drinking alcohol, smoking, taking steroids, or having a family history of osteoporosis, discuss these with your doctor to assess your individual risk.
Rare but Serious Side Effects
In rare cases, people taking this medication for an extended period (at least 3 months) may develop low magnesium levels, which can lead to other electrolyte problems. Your doctor may recommend regular blood tests to monitor your magnesium levels.
Heart Health
The use of this medication may increase your risk of heart failure. If you already have heart failure, your risk of heart attack, hospitalization, and death may be higher. Discuss these risks with your doctor.
Additionally, people who have had a recent heart attack may be at higher risk of heart attack and heart-related death while taking this medication. Your doctor can help you understand these risks and make informed decisions about your treatment.
Other Potential Risks
Long-term use of this medication (more than 1 year) may increase your risk of developing stomach growths called fundic gland polyps. If you have concerns, discuss them with your doctor.
This medication may also affect ovulation (egg release) in women, which can impact fertility. However, this effect is typically reversible when the medication is stopped. If you are planning to become pregnant, discuss this with your doctor.
Breastfeeding
If you are breastfeeding, inform your doctor, as they will need to discuss any potential risks to your baby.
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
If you are taking this medication long-term, your doctor may recommend regular blood tests to monitor your health. Be sure to discuss this with your doctor.
This medication may interfere with certain laboratory tests. It is essential that you notify all of your healthcare providers and laboratory personnel that you are taking this medication.
There is a risk of developing high blood pressure while taking this medication. Your doctor will likely recommend regular blood pressure checks to monitor your condition.
Before consuming alcohol, consult with your doctor to discuss any potential risks.
If you smoke, it is crucial that you discuss this with your doctor, as smoking may affect your health while taking this medication.
Taking Your Medication Safely
Do not exceed the dosage recommended by your doctor, as taking more than prescribed may increase your risk of severe side effects. Additionally, do not take this medication for longer than your doctor has advised.
Special Considerations
If you have asthma, consult with your doctor before taking this medication, as you may be more sensitive to its effects.
This medication may increase your risk of bleeding easily. To minimize this risk, be careful to avoid injury, use a soft toothbrush, and consider using an electric razor.
If you are taking aspirin to prevent a heart attack, inform your doctor, as this may affect your treatment plan.
Your doctor may recommend taking calcium and vitamin D supplements while taking this medication. Be sure to follow their instructions.
Bone Health
This medication may increase your risk of fractures, particularly in the hip, spine, and wrist, especially if you have weak bones (osteoporosis). This risk may be higher if you take high doses of this medication, take it for more than a year, or are over 50 years old.
If you have risk factors for osteoporosis, such as drinking alcohol, smoking, taking steroids, or having a family history of osteoporosis, discuss these with your doctor to assess your individual risk.
Rare but Serious Side Effects
In rare cases, people taking this medication for an extended period (at least 3 months) may develop low magnesium levels, which can lead to other electrolyte problems. Your doctor may recommend regular blood tests to monitor your magnesium levels.
Heart Health
The use of this medication may increase your risk of heart failure. If you already have heart failure, your risk of heart attack, hospitalization, and death may be higher. Discuss these risks with your doctor.
Additionally, people who have had a recent heart attack may be at higher risk of heart attack and heart-related death while taking this medication. Your doctor can help you understand these risks and make informed decisions about your treatment.
Other Potential Risks
Long-term use of this medication (more than 1 year) may increase your risk of developing stomach growths called fundic gland polyps. If you have concerns, discuss them with your doctor.
This medication may also affect ovulation (egg release) in women, which can impact fertility. However, this effect is typically reversible when the medication is stopped. If you are planning to become pregnant, discuss this with your doctor.
Breastfeeding
If you are breastfeeding, inform your doctor, as they will need to discuss any potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Naproxen overdose: Drowsiness, dizziness, nausea, vomiting, epigastric pain, abdominal discomfort, indigestion, heartburn, acute renal failure, hypoprothrombinemia, metabolic acidosis, apnea, disorientation, coma, GI bleeding.
- Esomeprazole overdose: Limited experience, but symptoms may include drowsiness, blurred vision, tachycardia, nausea, sweating, headache, dry mouth.
What to Do:
Seek immediate medical attention. Call 911 or your local poison control center (e.g., 1-800-222-1222 in the US). Treatment is supportive and symptomatic. Gastric lavage and activated charcoal may be considered. Hemodialysis is not effective for naproxen removal.
Drug Interactions
Contraindicated Interactions
- Other NSAIDs (including aspirin >325mg/day or other naproxen products)
- Ketorolac
- Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
- Advanced renal disease
- Atazanavir, Nelfinavir, Rilpivirine (due to reduced absorption of antiretrovirals by esomeprazole)
Major Interactions
- Anticoagulants (e.g., Warfarin): Increased risk of bleeding
- Antiplatelet agents (e.g., Clopidogrel, Aspirin): Increased risk of bleeding, reduced antiplatelet effect of clopidogrel
- SSRIs/SNRIs: Increased risk of GI bleeding
- Diuretics (e.g., Furosemide, Thiazides): Reduced natriuretic and antihypertensive effects, increased risk of renal impairment
- ACE Inhibitors/ARBs: Reduced antihypertensive effect, increased risk of renal impairment and hyperkalemia
- Lithium: Increased lithium plasma concentrations
- Methotrexate: Increased methotrexate plasma concentrations (especially high-dose)
- Digoxin: Increased digoxin plasma concentrations
- Cyclosporine: Increased nephrotoxicity of cyclosporine
- Tacrolimus: Increased tacrolimus plasma concentrations
- Phenytoin: Increased phenytoin plasma concentrations
- Voriconazole: Increased esomeprazole exposure
- Citalopram: Increased citalopram exposure (due to CYP2C19 inhibition by esomeprazole)
Moderate Interactions
- Corticosteroids: Increased risk of GI ulceration/bleeding
- Rifampin: Decreased esomeprazole exposure
- St. John's Wort: Decreased esomeprazole exposure
- Iron salts: Reduced iron absorption (due to increased gastric pH)
- Mycophenolate Mofetil: Reduced mycophenolic acid exposure
- Erlotinib, Dasatinib, Nilotinib, Pazopanib: Reduced absorption of tyrosine kinase inhibitors (pH-dependent absorption)
Minor Interactions
- Antacids: May delay naproxen absorption, but generally not clinically significant for esomeprazole
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To assess for anemia (due to GI bleeding) or other hematologic abnormalities.
Timing: Prior to initiation
Renal Function (Serum Creatinine, eGFR)
Rationale: To assess baseline kidney function, as NSAIDs can cause renal impairment.
Timing: Prior to initiation
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, as both components are metabolized by the liver and can cause liver injury.
Timing: Prior to initiation
Blood Pressure (BP)
Rationale: To establish baseline, as NSAIDs can cause new onset or worsening hypertension.
Timing: Prior to initiation
Routine Monitoring
Renal Function (Serum Creatinine, eGFR)
Frequency: Periodically, especially in patients at risk for renal impairment (e.g., elderly, heart failure, diuretic use)
Target: Within patient's baseline or normal limits
Action Threshold: Significant increase in creatinine or decrease in eGFR; consider dose adjustment or discontinuation.
Liver Function Tests (LFTs)
Frequency: Periodically, especially with long-term use or in patients with pre-existing hepatic impairment
Target: Within normal limits
Action Threshold: Significant elevation of transaminases (>3x ULN); consider discontinuation.
Blood Pressure (BP)
Frequency: Regularly, especially in hypertensive patients
Target: Individualized target BP
Action Threshold: Sustained elevation; consider antihypertensive adjustment or NSAID discontinuation.
Complete Blood Count (CBC)
Frequency: Periodically, especially with long-term use
Target: Within normal limits
Action Threshold: Significant drop in hemoglobin/hematocrit (suggesting GI bleed) or other cytopenias.
Serum Magnesium
Frequency: Periodically (e.g., every 3-6 months) for patients on long-term PPI therapy (âĨ3 months) or those taking other hypomagnesemia-inducing drugs
Target: Within normal limits
Action Threshold: Hypomagnesemia; consider magnesium supplementation or PPI discontinuation.
Symptom Monitoring
- Signs of gastrointestinal bleeding (e.g., black, tarry stools; coffee-ground vomit; severe abdominal pain)
- Symptoms of cardiovascular events (e.g., chest pain, shortness of breath, weakness on one side of the body, slurred speech)
- Signs of renal dysfunction (e.g., decreased urine output, swelling in ankles/feet)
- Symptoms of liver injury (e.g., fatigue, nausea, dark urine, jaundice, right upper quadrant tenderness)
- Signs of allergic reactions (e.g., rash, itching, hives, swelling of face/lips/tongue/throat, difficulty breathing)
- Symptoms of fluid retention (e.g., edema, weight gain)
- New or worsening hypertension
- Symptoms of hypomagnesemia (e.g., muscle cramps, tremors, seizures, arrhythmias)
Special Patient Groups
Pregnancy
Contraindicated in the third trimester of pregnancy due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the newborn. Use in the first and second trimesters should be avoided unless the potential benefit outweighs the potential risk to the fetus, and only under strict medical supervision.
Trimester-Specific Risks:
First Trimester:
Category C (Naproxen): Potential for increased risk of miscarriage and cardiac malformations. Category B (Esomeprazole): No evidence of harm in animal studies, but human data are limited.
Second Trimester:
Category C (Naproxen): Potential for oligohydramnios and fetal renal dysfunction. Category B (Esomeprazole): No evidence of harm.
Third Trimester:
Category D (Naproxen): Risk of premature closure of the fetal ductus arteriosus, persistent pulmonary hypertension, and renal dysfunction in the fetus. Contraindicated.
Lactation
Naproxen is excreted into breast milk. Esomeprazole is also likely excreted into breast milk. Due to the potential for serious adverse reactions in breastfed infants (e.g., cardiovascular, renal, GI effects from naproxen), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Risk level L2 (Safer) for both components individually, but caution is advised for the combination due to potential for adverse effects in the infant, especially with long-term use or high doses.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 12 years of age. Use is generally not recommended.
Geriatric Use
Elderly patients are at a greater risk for serious cardiovascular, gastrointestinal, and renal adverse events with NSAID use. Use the lowest effective dose for the shortest duration possible. Monitor closely for adverse effects, especially GI bleeding, renal impairment, and cardiovascular events.
Clinical Information
Clinical Pearls
- This combination product is designed to reduce the risk of NSAID-induced gastric ulcers in patients who require naproxen for pain/inflammation and are at risk for GI complications.
- The delayed-release formulation ensures that the esomeprazole is released first to provide gastric protection before the naproxen is released.
- Patients should be advised to swallow the tablet whole and not to crush, chew, or split it, as this would compromise the delayed-release properties.
- Despite the PPI component, serious GI events can still occur, especially in high-risk patients. Regular monitoring for GI symptoms is crucial.
- Cardiovascular and renal risks associated with NSAIDs apply to this combination product. Careful consideration of patient comorbidities is essential.
- Long-term use of PPIs (like esomeprazole) has been associated with an increased risk of C. difficile infection, bone fractures (hip, wrist, spine), and hypomagnesemia.
Alternative Therapies
- Other NSAIDs (e.g., ibuprofen, celecoxib, meloxicam) with a separate PPI or H2 blocker
- Acetaminophen (for pain, but no anti-inflammatory effect)
- Opioid analgesics (for severe pain, with different risk profiles)
- Non-pharmacological therapies (e.g., physical therapy, heat/cold therapy, exercise)
Cost & Coverage
Average Cost:
$300 - $600 per 60 tablets (approximate for generic)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for generic versions); Tier 3 or higher (for brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.