Dosing and uses of Nexcede (ketoprofen)
Adult dosage forms and strengths
tablet/capsule
- 50mg
- 75mg
capsule, extended-release
- 200mg
oral film
- 12.5mg (OTC)
Pain Management
Immediate-release: 25-50 mg PO q6-8hr as necessary
Extended-release: 200 mg PO qDay; not recommended for acute pain
Rheumatoid Arthritis or Osteoarthritis
Immediate-release: 75 mg PO q8hr or 50 mg PO q6hr
Extended-release: 200 mg PO qDay
Dysmenorrhea
Immediate-release: 25-50 mg q6-8hr PRn
Extended-release: Not recommended for acute pain
Administration
Take with food or 8-12 oz water to avoid GI effects
Other Indications & Uses
Gout
Off-label: vascular headache
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Pain Management
Initial: 25-50 mg PO q6-8hr; increase to 150-300 mg/day; not to exceed 300 mg
Nexcede (ketoprofen) adverse (side) effects
>10%
Increased liver function test (up to 15%)
Dyspepsia (12%)
1-10%
Dizziness (3-9%)
Headache (3-9%)
Impaired renal function disorder (3-9%)
Upper GI ulcers, 3-6 mth treatment; 2-4%,1 yo treatment)
Nausea (>3%)
Diarrhea (>3%)
Abdominal pain (>3%)
Constipation (>3%)
Flatulence (>3%)
Rash (1-3%)
Stomatitis (1-3%)
Insomnia (1-3%)
Malaise (1-3%)
Depression (1-3%)
Ketoprofen-induced peptic ulcer, GI bleeding (>2% in long-term studies);
Peripheral edema (2%)
Bronchospasm (<2%)
Myocardial infarction (<2%)
<1%
Congestive heart failure (<1%)
Hypertension (<1%)
Scaling eczema, Stevens-Johnson syndrome (<0.1%)
Gastrointestinal hemorrhage (<1%)
Gastrointestinal perforation (<1%)
Melena (<1%)
Agranulocytosis (<1%)
Anemia (<1%)
Thrombocytopenia (<1%)
Hepatitis (<1%)
Anaphylactoid reaction (<1%)
Immune hypersensitivity reaction
Cerebrovascular accident
Interstitial nephritis (<1%)
Renal failure (<1%)
Warnings
Black box warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), & stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use & without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Absolute: ASA allergy
Relative: Bleeding disorders, hepatic disease, peptic ulcer, stomatitis, ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of the ductus arteriosus)
Cautions
Use caution in asthma (bronchial), cardiac disease, CHF, HTN, renal impairment, SLe
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs
Heart Failure (HF) risks
- 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
- AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
Pregnancy and lactation
Pregnancy category: B; D in late pregnancy because of inhibition of ductus arteriosus closure
The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)
Lactation: unknown whether excreted in breast milk, not recommended
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.
Pharmacology of Nexcede (ketoprofen)
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2)
May inhibit chemotaxis, may alter lymphocyte activity, decrease proinflammatory cytokine activity, and may inhibit neutrophil aggregation. These effects may contribute to its anti-inflammatory activity
Pharmacokinetics
Bioavailability: 90%
Duration: 6 hr (immediate release)
Onset: <30 min (immediate release)
Peak Plasma Time: 0.5-2 hr (immediate release); 6-7 hr, fasting, ER; 9 hr, non-fasting, Er
Peak Plasma Concentration: 3.2-4.8 mcg/mL, (50 mg); 5.5-10.1 mcg/mL, (100 mg); 13.1 mcg/mL (150 mg); extended-release 3.1 mg/L, fasting, 3.4 mg/L, non-fasting
Protein Bound: 99%
Vd: 0.1 L/kg
Metabolism: Liver
Metabolites: Glucuronide conjugate of ketoprofen, hydroxylated metabolites; at least 3 unidentified conjugates have been detected.
Dialyzable: Yes
Enzymes inhibited: Cyclooxygenase
Half-life:2-4 hr (immediate release); 3-7.5 hr (ER)
Excretion: Urine 50-90% as glucuronide conjugates; feces 1-8%
