naproxen (Rx, OTC)

1-10%

Abdominal pain (3-9%)

Constipation (3-9%)

Dizziness (3-9%)

Drowsiness (3-9%)

Headache (3-9%)

Heartburn (3-9%)

Nausea (3-9%)

Edema (3-9%)

GI bleeding (1-4%)

GI perforation (1-4%)

Lightneadedness (<3%)

GI ulcers (1-4%)

Fluid retention (3-9%)

Diarrhea (1-3%)

Stomatitis (<3%)

Diverticulitis (1-3%)

Dyspnea (3-9%)

Hearing disturbances (<3%)

<1%

Meaningful (3 × upper limit of normal) elevation of serum alanine aminotransferase or aspartate aminotransferase

Contraindications

Absolute: Aspirin allergy; perioperative pain in setting of coronary artery bypass graft (CABG) surgery

Relative: Bleeding disorders, delayed esophageal transit, hepatic disease, peptic ulcer, renal impairment, stomatitis, late pregnancy (may cause premature closure of ductus arteriosus)

Cautions

Use caution in congestive heart failure (CHF), hypertension, renal/hepatic impairment, or aspirin sensitive asthma

May increase risk of aseptic meningitis, especially in patients with systemic lupus erythematosis and mixed connective tissue disorders

Prolonged use may increase risk of adverse cardiovascular events

May cause anaphylactoid reactions, even in patients with no prior exposure to NSAIDs

Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers

May cause drowsiness, dizziness, and blurred vision

Platelet aggregation and adhesion may be decreased; may prolong bleeding time; monitor closely patients with coagulation disorders

May increase risk of hyperkalemia in the elderly, renal disease, or diabetics, especially when used concomitantly with drugs that increase hyperkalemia

May cause serious skin reactions including exfoliative dermatitis, toxic epidermal syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue therapy at first sign of skin rash

May cause new-onset of hypertension; monitor blood pressure closely throughout therapy

OTC use not for children <12 years

Withhold for at least 4-6 half-lives prior to surgery or dental procedure

Heart failure risk

• NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
• NSAIDS should be avoided or withdrawn whenever possible
• Heart failure: risk is higher if you administer more than directed or for longer than directed
• AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134

Pregnancy

There are no adequate and well-controlled studies in pregnant women; data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive; NSAIDs inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth

Lactation

The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2

May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity

Absorption

Bioavailability: 95%

Onset: 30-60 min

Duration: < 12 hr

Peak serum time: 1-4 hr (tablets); 2-12 hr (delayed release empty stomach); 4-24 hr (delayed relase with food)

Peak plasma concentration: 62-96 mcg/mL

Distribution

Protein bound: <99%

Vd: 0.16 L/kg

Metabolism

Metabolized in liver via conjugation

Metabolites: 6-Desmethylnaproxen, glucuronide conjugates

Enzymes inhibited: COX-1, COX-2

Elimination

Half-life: 12-17 hr

Dialyzable: No value

Clearance: 0.13 mL/min/kg

Excretion: Urine (95%), feces (<3%)