naproxen/esomeprazole

Naproxen

Absorption: Completely absorbed from the GI tract.

Distribution: Crosses the placenta; enters breast milk in low concentrations.

Protein Binding: >99%.

Metabolism/Excretion: Mostly metabolized by the liver.

Half-Life: 10–20 hr.

Esomeprazole

Absorption: 90% absorbed following oral administration; food ↓ absorption.

Distribution: Unknown.

Protein Binding: 97%.

Metabolism/Excretion: Extensively metabolized by the liver (primarily by the CYP2C19 isoenzyme, but also the CYP3A4 isoenzyme) (the CYP2C19 enzyme system exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of White and Black patients may be poor metabolizers and may have significantly ↑ esomeprazole concentrations and an ↑ risk of adverse effects);<1% excreted unchanged in urine.

Half-Life: 1.0–1.5 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
Esomeprazole (blood levels)	rapid	1.6 hr	24 hr
Naproxen (analgesia)	1 hr	unknown	8–12 hr
Naproxen (anti-inflammatory	14 days	2–4 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to either naproxen or esomeprazole;
History of allergic reactions (including asthma or urticaria) to aspirin or other NSAIDs;
Severe hepatic impairment;
Moderate to severe renal impairment;
Coronary artery bypass graft surgery;
OB: Avoid use of NSAIDs after 30 wk gestation;
Lactation: Lactation.

Use Cautiously in:

Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use or use of higher doses); avoid use in patients with recent MI or HF;
History of GI bleeding/ulcer disease (↑ risk of GI bleeding);
History of HF or fluid retention (may worsen);
Renal impairment, hypovolemia, salt depletion, HF, liver dysfunction (↑ risk of adverse renal reactions);
OB: Use at or after 20 wk gestation may cause fetal or neonatal renal impairment; if treatment is necessary between 20 wk and 30 wk gestation, limit use to the lowest effective dose and shortest duration possible;
Pedi: Safety and effectiveness not established in children;
Geri: risk of GI bleeding, adverse cardiovascular or renal reactions in older adults; consider age, hepatic/renal function, body mass, and concurrent chronic illnesses and drug therapy.

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF, MI, STROKE, edema, hypertension, palpitations

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), photosensitivity, rash, sweating

EENT: tinnitus, visual disturbances

F and E: hyperkalemia

GI: DRUG-INDUCED HEPATITIS, GI BLEEDING, constipation, dyspepsia, nausea, abdominal pain, anorexia, diarrhea, dry mouth, flatulence, vomiting

GU: cystitis, hematuria, renal failure

Hemat: blood dyscrasias, prolonged bleeding time

MS: bone fracture

Neuro: dizziness, drowsiness, headache

Resp: dyspnea

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Naproxen may limit cardioprotective (antiplatelet) effects ofaspirin.
Naproxen may ↑ risk of bleeding with anticoagulants, aspirin, clopidogrel, ticagrelor, prasugrel, corticosteroids, fibrinolytics, SNRIs, or SSRIs.
Naproxen has additive adverse GI side effects with aspirin, corticosteroids, alcohol, SSRIs, oral potassium supplements and other NSAIDs.
Probenecid may ↑ naproxen levels and risk of toxicity.
Naproxen may ↑ risk of toxicity from methotrexate, antineoplastics, or radiation therapy.
Naproxen may ↑ levels and risk of toxicity from lithium.
Cyclosporine, ACE inhibitors, angiotensin II receptor blockers, or chronic use of acetaminophen may ↑ naproxen's adverse renal effects.
Naproxen may ↓ response to antihypertensives or diuretics.
Naproxen may ↑ risk of hypoglycemia with insulin or oral hypoglycemic agents.Esomeprazole may ↓ absorption and effectiveness of digoxin, iron salts, and ketoconazole.

Route/Dosage ⬆ ⬇

PO (Adults ): One tablet (naproxen 375 mg/esomeprazole 20 mg or naproxen 500 mg/esomeprazole 20 mg) twice daily; use lowest effective dose.

Availability ⬆ ⬇

(Generic available)

Delayed-release tablets: naproxen 375 mg/esomeprazole 20 mg; naproxen 500 mg/esomeprazole 20 mg

Assessment ⬆ ⬇

Patients who have asthma, aspirin-induced allergy, and nasal polyps are at ↑ risk for developing hypersensitivity reactions. Assess for rhinitis, asthma, and urticaria.
Assess pain (note type, location, and intensity) prior to and 1–2 hr following administration.
Assess routinely for epigastric or abdominal pain and frank or occult blood in the stool, emesis, or gastric aspirate.
Monitor BP during initiation and periodically during therapy. May cause fluid retention and edema leading to new onset or worsening hypertension or HF.
Assess for rash periodically during therapy. May cause SJS or TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling) periodically during therapy. Discontinue therapy if symptoms occur.

Lab Test Considerations:

Monitor liver function tests periodically during therapy. May cause ↑ AST and ALT.
- Monitor CBC and chemistry profiles (particularly BUN and serum creatinine) periodically during prolonged therapy.
- Bleeding time may be prolonged up to 4 days following discontinuation of therapy.
- May cause hypomagnesemia. Monitor serum magnesium prior to and periodically during therapy.
- Vitamin B12 deficiency may occur with prolonged use (>1–2 yr); monitoring recommended.

Implementation ⬆ ⬇

Administration of higher than recommended doses does not provide ↑ effectiveness but may cause ↑ side effects. Use lowest effective dose for the shortest duration possible to minimize risk of cardiovascular thrombotic events.
- Coadministration with opioid analgesics may have additive analgesic effects and may permit lower opioid doses.
- Analgesic is more effective if given before pain becomes severe.
- Antacids may be used while taking naproxen/esomeprazole.
PO: Administer one tablet twice daily 30 min before meals. DNC: Swallow whole; do not crush, break, chew, or dissolve tablet.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of naproxen/esomeprazole to patient. Do not stop taking drug without consulting health care professional. Instruct patient to take medication as directed. Take missed doses as soon as remembered but not if almost time for the next dose. Do not double doses. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness of medication. Periodic lab tests may be needed.
May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
Advise patient to inform health care professional of medication regimen before treatment or surgery.
Caution patient to avoid the concurrent use of alcohol, aspirin, acetaminophen, or other NSAIDs or OTC medications without consulting health care professional. Use of naproxen with three or more glasses of alcohol per day may ↑ risk of GI bleeding.
Advise patient to notify health care professional promptly if rash, GI pain or bleeding, chest pain, shortness of breath, weakness, slurring of speech, unexplained weight gain, edema, or signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) or anaphylaxis (difficulty breathing, swelling of face or throat) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise women to avoid naproxen in the 3rd trimester of pregnancy (after 29 wk); may cause premature closure of the fetal ductus arteriosus. Use of naproxen after 20 wk may cause fetal renal dysfunction leading to oligohydramnios. May cause reversible infertility in women attempting to conceive; may consider discontinuing naproxen.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇