naproxen/esomeprazole

General

Genetic Implications: Genetic Implications

Pronunciation:
na-prox-en/es-o-mep-ra-zole


Trade Name(s)

  • Vimovo

Ther. Class.
antirheumatics
nonopioid analgesics
antiulcer agents

Pharm. Class.
benzimidazoles
temporary class nonsteroidal anti-inflammatory drugs (NSAIDs)
proton pump inhibitors

Indications

  • Naproxen  provides symptomatic management of osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis; addition of  esomeprazole  decreases the risk of gastric ulcers in patients at risk of NSAID-associated gastric ulcers.
  • Not indicated for acute pain due to delayed absorption of naproxen.

Action

  • Naproxen– Inhibits prostaglandin synthesis.
  • Esomeprazole– binds to an enzyme on gastric parietal cells in the presence of acidic gastric pH, preventing the final transport of hydrogen ions into the gastric lumen.

Therapeutic Effect(s):

Decreased pain/swelling with improved mobility and decreased risk of gastric ulcer in high risk patients.

Pharmacokinetics

Naproxen

Absorption: Completely absorbed from the GI tract.

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

Protein Binding: >99%.

Metabolism and 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 and Excretion: Extensively metabolized by the liver (primarily by the CYP2C19 isoenzyme, but also the CYP3A4 isoenzyme) Genetic implication (the CYP2C19 enzyme system exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of Caucasian 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

ROUTEONSETPEAKDURATION
Esomeprazole (blood levels)rapid1.6 hr24 hr
Naproxen (analgesia)1 hrunknown8–12 hr
Naproxen (anti-inflammatory14 days2–4 wkunknown

Contraindication/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 (CABG) surgery;
  • OB:  Avoid use of NSAIDs after 30 wk gestation;
  • 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, concurrent chronic illnesses and drug therapy.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, headache

CV: HF, MYOCARDIAL INFARCTION, STROKE, edema, hypertension, palpitations

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

Resp: dyspnea

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

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 increased 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.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. 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:

May cause ↑ AST and ALT. monitor liver function tests periodically during therapy.

  • Monitor CBC and chemistry profiles 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.

Implementation

  • Administration in higher than recommended doses does not provide increased effectiveness but may cause increased 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 1 tablet twice daily 30 min before meals.  DNC: Swallow whole; do not crush, break, chew, or dissolve tablet.

Patient/Family Teaching

  • 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.
  • 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 3 or more glasses of alcohol per day may increase 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.
  • 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.

Evaluation/Desired Outcomes

Decreased pain and improved joint mobility with a decreased risk of gastric ulcer in high risk patients.

naproxen/esomeprazoleis the Davis's Drug Guide Word of the day!