Ketoprofen (Monograph)

Drug class: Reversible COX-1/COX-2 Inhibitors

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Warning

Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).¹ ⁵⁰⁰ ⁵⁰² ⁵⁰⁸ Risk may occur early in treatment and may increase with duration of use.⁵⁰⁰ ⁵⁰² ⁵⁰⁵ ⁵⁰⁶ ⁵⁰⁸ (See Cardiovascular Thrombotic Effects under Cautions.)
Contraindicated in the setting of CABG surgery.⁵⁰⁸

Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).¹ Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.¹ Geriatric individuals are at greater risk for serious GI events.¹ (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA; propionic acid derivative.¹ ² ³ ⁴ ³⁰ ⁵³ ⁹³ ²⁰⁵

Uses for Ketoprofen

Consider potential benefits and risks of ketoprofen therapy as well as alternative therapies before initiating therapy with the drug.¹ Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.¹

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.¹ ³⁶ ⁹⁶ ⁹⁷ ⁹⁸ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹³¹ ¹³² ¹³⁴ ¹³⁵ ¹³⁶ ¹³⁷ ¹³⁸ ¹³⁹ ¹⁴⁷ ¹⁴⁸ ¹⁵⁰ ¹⁵³ ¹⁵⁴ ¹⁵⁸ ²⁰⁵

Has been used in the symptomatic treatment of ankylosing spondylitis^{† [off-label]}.⁹⁷ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹⁰⁹ ¹³⁸ ¹⁴² ¹⁴³ ¹⁴⁴ ¹⁴⁶ ¹⁷⁵ ²⁰⁵

Pain

Relief of pain.¹ ¹²¹ ¹⁶⁰ ¹⁶⁶ ¹⁷¹ ¹⁷³ ¹⁷⁴ ²³⁵ ²³⁶ ²³⁸ ²³⁹

Dysmenorrhea

Symptomatic management of primary dysmenorrhea.¹ ⁵⁰ ¹⁶¹ ¹⁶⁴ ²³⁴

Ketoprofen Dosage and Administration

General

Consider potential benefits and risks of ketoprofen therapy as well as alternative therapies before initiating therapy with the drug.¹

Administration

Oral Administration

Administer orally once daily as extended-release capsules or 3 or 4 times daily as conventional capsules.¹

Administration with antacids,¹ ⁹⁷ ¹⁰² ¹¹⁵ ¹¹⁶ ¹⁴² ¹⁴⁹ food,¹ ¹⁰⁴ or milk¹ may minimize adverse GI effects.

Ketoprofen extended-release capsules are not recommended for the management of acute pain because of slow onset of action.¹

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.¹ Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.¹

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Conventional capsules: Initially, 75 mg 3 times daily or 50 mg 4 times daily.¹ Base subsequent dosage on clinical response and tolerance.¹

Extended-release capsules: Initially, 200 mg once daily.¹ Base subsequent dosage on clinical response and tolerance.¹

Pain

Oral

Conventional capsules: Usual dosage is 25–50 mg every 6–8 hours as needed.¹

Dysmenorrhea

Oral

Conventional capsules: Usual dosage is 25–50 mg every 6–8 hours as needed.¹

Prescribing Limits

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Conventional capsules: Maximum 300 mg daily.¹

Extended-release capsules: Maximum 200 mg daily.¹

Pain or Dysmenorrhea

Oral

Conventional capsules: Maximum 300 mg daily.¹

Special Populations

Hepatic Impairment

Maximum recommended initial total dosage is 100 mg daily in patients with hepatic impairment and serum albumin concentrations <3.5 g/dL.¹

Renal Impairment

Mild renal impairment: Maximum recommended dosage is 150 mg daily.¹

Severe renal impairment (GFR <25 mL/minute per 1.73 m² or end-stage renal impairment): Maximum recommended dosage is 100 mg daily.¹ (See Renal Impairment under Cautions.)

Geriatric Patients

Consider reduced initial dosage in patients >75 years of age.¹

Cautions for Ketoprofen

Contraindications

Known hypersensitivity to ketoprofen or any ingredient in the formulation.¹
History of asthma, urticaria, or other sensitivity reactions precipitated by aspirin or other NSAIAs.¹ ²⁶ ⁴⁸ ⁸³ ⁸⁶ ⁸⁹ ⁹⁰ ⁹¹ ⁹² ¹⁷⁷
In the setting of CABG surgery.⁵⁰⁸

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.⁵⁰⁰ ⁵⁰² ⁵⁰⁸

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information⁵⁰⁰ ⁵⁰¹ ⁵⁰² indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.⁵⁰⁰

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.⁵⁰⁰ ⁵⁰² ⁵⁰⁶ ⁵⁰⁸

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.⁵⁰⁰ ⁵⁰² ⁵⁰⁵ ⁵⁰⁶ ⁵⁰⁸

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.⁵⁰⁸

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.⁵⁰⁵ ⁵⁰⁸

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;⁵⁰⁰ ⁵⁰⁸ ⁵¹¹ absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.⁵⁰⁸ ⁵¹¹

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.²⁸⁸ ²⁸⁹ ²⁹⁰ ²⁹⁴ ⁵⁰⁰ ⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁶ FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.⁵⁰⁰

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary. ¹ ⁵⁰⁰ ⁵⁰⁸

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.⁵⁰⁵ ⁵¹¹ ⁵¹² ⁵¹⁶ Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.⁵⁰⁸ Contraindicated in the setting of CABG surgery.⁵⁰⁸

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.¹ ⁵⁰² ⁵⁰⁸ (See Specific Drugs under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms;¹ ²⁴¹ ²⁴² ²⁴⁵ increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.¹ ²³³ ²⁷⁰ ²⁸¹

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;²⁴⁴ ²⁷⁰ ²⁷³ ²⁷⁴ alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)²⁴⁴ ²⁷⁰ ²⁷³ or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).²⁷³

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.¹ Use with caution in patients with hypertension; monitor BP.¹

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.¹ ⁵⁰⁸ ⁵⁰⁹ (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.¹ ⁵⁰⁸

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.⁵⁰⁰ ⁵⁰¹ ⁵⁰⁴ ⁵⁰⁷ ⁵⁰⁸

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.⁵⁰⁸ (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.⁵⁰⁸

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.⁵⁰⁷

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.¹

Potential for overt renal decompensation.¹ ⁹ ¹⁵ ²⁶ ⁴⁸ ⁸³ ¹⁷⁷ ¹⁹⁸ Increased risk of renal toxicity in patients with renal¹ ¹⁵ ⁴⁸ ⁸³ ¹⁷⁷ ¹⁹⁸ or hepatic¹ ¹⁵ ²⁶ ⁴⁸ ⁸³ ¹⁷⁷ ¹⁹⁸ impairment or heart failure,¹ ²⁶ ⁴⁸ ⁸³ ¹⁷⁷ ¹⁹⁸ in geriatric patients,¹ ⁴⁸ ¹⁷⁷ in patients with volume depletion,¹ ¹⁶ ²⁶ ⁴⁸ ⁸³ ¹⁷⁷ ¹⁹⁸ ²²⁴ and in those receiving a diuretic,¹ ACE inhibitor,¹ or angiotensin II receptor antagonist.²⁸⁶ (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.¹ Immediate medical intervention and discontinuance for anaphylaxis.¹

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.¹

Potentially fatal or life-threatening syndrome of multi-organ hypersensitivity (i.e., drug reaction with eosinophilia and systemic symptoms [DRESS]) reported in patients receiving NSAIAs.¹²⁰¹ Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy, and/or facial swelling, possibly associated with other organ system involvement (e.g., hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis).¹²⁰¹ Symptoms may resemble those of acute viral infection.¹²⁰¹ Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.¹²⁰¹ If signs or symptoms of DRESS develop, discontinue ketoprofen and immediately evaluate the patient.¹²⁰¹

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported;¹ ¹⁴² can occur without warning.¹ Discontinue at first appearance of rash or any other signs of hypersensitivity (e.g., blisters, fever, pruritus).¹

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.¹

Elevations of serum ALT or AST reported.¹

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.¹ Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.¹ ²⁰⁹ ²¹⁰

Hematologic Effects

Anemia reported rarely.¹ ¹⁴¹ Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.¹ ²⁰⁹ ²¹⁰

May inhibit platelet aggregation and prolong bleeding time.¹ ³⁴ ⁴⁰ ⁴¹ ⁴⁷ ⁵⁴

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.¹

May mask certain signs of infection.¹ ⁸³ ¹⁷⁷ ²⁰⁹ ²¹⁰

Obtain CBC and chemistry profile periodically during long-term use.¹

Specific Populations

Pregnancy

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.¹²⁰⁰ ¹²⁰¹

Effects of NSAIAs on the human fetus during third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.¹²⁰²

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment, and consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.¹²⁰⁰ ¹²⁰¹ (See Advice to Patients.)

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.¹²⁰⁰ ¹²⁰¹ Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance.¹²⁰⁰ ¹²⁰¹ Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.¹²⁰⁰ ¹²⁰¹ In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.¹²⁰⁰ ¹²⁰¹ Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).¹²⁰⁰ ¹²⁰¹ Deaths associated with neonatal renal failure also reported.¹²⁰⁰ Limitations of available data (lack of control group; limited information regarding dosage, duration, and timing of drug exposure; concomitant use of other drugs) preclude a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use.¹²⁰¹ Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.¹²⁰¹

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.¹²⁰¹ In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.¹²⁰¹ Maternally toxic ketoprofen dosages associated with embryotoxicity but not teratogenicity in rabbits.¹²⁰¹

Effects of ketoprofen on labor and delivery not known;¹ delayed parturition observed in animal studies.¹

Lactation

Not known whether distributed into milk in humans.¹ Use not recommended.¹

Fertility

NSAIAs may be associated with reversible infertility in some women.¹²⁰³ Reversible delays in ovulation observed in limited studies in women receiving NSAIAs; animal studies indicate that inhibitors of prostaglandin synthesis can disrupt prostaglandin-mediated follicular rupture required for ovulation.¹²⁰³

Consider withdrawal of NSAIAs in women experiencing difficulty conceiving or undergoing evaluation of infertility.¹²⁰³

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

Caution advised.¹ Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.¹ Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.¹

Select dosage with caution because of age-related decreases in renal function.¹ Dosage adjustment recommended in geriatric patients >75 years of age.¹ May be useful to monitor renal function.¹

Hepatic Impairment

Monitor closely.¹ Reduced dosage may be necessary; use lowest effective dosage.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.¹

Reduced maximum dosage recommended.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Dyspepsia,¹ ⁹⁹ ¹⁰⁰ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁰⁹ ¹¹⁴ ¹¹⁸ ¹²³ ¹³⁴ ¹³⁶ ¹³⁹ ²³⁴ nausea,¹ ⁹⁶ ⁹⁹ ¹⁰⁴ ¹⁰⁶ ¹⁰⁹ ¹¹⁵ ¹²³ ¹²⁵ ¹²⁹ ¹³² ¹³⁵ ¹³⁶ ¹³⁷ ¹³⁸ ¹³⁹ ¹⁴⁰ ²³⁴ abdominal pain,¹ ¹⁰⁴ ¹¹⁵ ¹²⁷ ¹³⁵ ¹³⁶ ¹³⁷ ¹³⁸ ¹⁴⁰ ²³⁴ diarrhea,¹ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁰⁷ ¹¹⁴ ¹²⁷ ¹³² ¹³³ ²³⁴ constipation,¹ ⁹⁹ ¹⁰⁴ ¹⁰⁵ ¹⁰⁷ ¹⁰⁹ ¹¹⁸ ¹³² ¹³⁵ ¹⁴³ flatulence,¹ ⁹⁶ ¹⁰⁹ ¹³⁷ ¹⁴⁷ ¹⁴⁹ ¹⁵⁵ anorexia,¹ ¹⁰⁷ ¹⁰⁹ ¹³⁵ ¹³⁷ ¹⁴⁷ vomiting,¹ ¹⁰⁴ ¹⁰⁵ ¹⁰⁹ ¹²⁵ ¹³⁵ ¹³⁶ ¹³⁷ ¹³⁹ stomatitis,¹ ¹⁰⁵ ¹³² ¹⁴⁶ ¹⁴⁹ headache,¹ ⁹⁹ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁹ ¹¹⁸ ¹²³ ¹²⁷ ¹²⁹ ²³⁴ dizziness,¹ ¹⁰⁴ ¹⁰⁶ ¹⁰⁹ ¹¹⁸ ¹²⁷ ¹³¹ ¹³² ¹³⁸ ²³⁴ CNS depression,¹⁰⁶ ¹⁰⁹ ¹³⁸ ¹⁴⁷ ¹⁵⁵ ¹⁵⁸ ¹⁷³ ¹⁹⁰ CNS excitation,¹ ¹⁰⁴ ¹⁰⁵ ¹³² ¹⁵⁰ ¹⁵⁵ ¹⁶¹ tinnitus,¹ ¹¹⁸ ¹¹⁹ ¹⁶⁴ visual disturbances,¹ rash,¹ ⁹⁶ ¹⁰⁴ ¹⁰⁵ ¹²⁷ ¹³² ¹³⁵ ¹⁵⁵ ¹⁹⁰ renal impairment.¹ ¹⁰⁵ ¹¹⁸ ¹²⁵ ¹³⁵ ¹⁵⁸ ¹⁸⁷ ²⁰⁵ ²²⁴

Drug Interactions

Protein-bound Drugs

Potential for ketoprofen to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.⁵² ⁷⁸ Observe for adverse effects.²⁰⁹ ²¹⁰ ²¹¹

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to the ACE inhibitor¹	Monitor BP¹
Angiotensin II receptor antagonists	Reduced BP response to the angiotensin II receptor antagonist²⁹¹	Monitor BP²⁹¹
Antacids (magnesium- or aluminum-containing)	Conventional capsules: Pharmacokinetic interaction unlikely¹
Anticoagulants (warfarin)	Possible bleeding complications¹ Increased PT reported ²⁴⁰	Caution advised ¹
Aspirin	Decreased ketoprofen protein binding¹ ⁵² Increased risk of GI ulceration or other complications ¹ No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs²⁸⁴ ⁵⁰² ⁵⁰⁸	Concomitant use not recommended¹ Clinical importance of pharmacokinetic changes unknown¹
Digoxin	Pharmacokinetic interaction unlikely¹
Diuretics (furosemide, thiazides)	Reduced natriuretic effects¹	Monitor for diuretic efficacy and renal failure¹
Lithium	Increased plasma lithium concentrations¹ ²⁰⁹ ²²⁹	Monitor for lithium toxicity¹ ²⁰⁹ ²²⁹
Methotrexate	Possible increased and prolonged blood concentrations of methotrexate¹ ²⁴ ²¹⁰ ²¹⁶ ²¹⁷ ²¹⁸ ²¹⁹ ²²¹ ²³¹	Use with caution¹
Pemetrexed	Possible increased risk of pemetrexed-associated myelosuppression, renal toxicity, and GI toxicity¹²⁰³	Short half-life NSAIAs (e. g., diclofenac, indomethacin): Avoid administration beginning 2 days before and continuing through 2 days after pemetrexed administration¹²⁰³ Longer half-life NSAIAs (e.g., meloxicam, nabumetone): In the absence of data, avoid administration beginning at least 5 days before and continuing through 2 days after pemetrexed administration¹²⁰³ Patients with Cl_cr 45–79 mL/minute: Monitor for myelosuppression, renal toxicity, and GI toxicity¹²⁰³
Probenecid	Decreased clearance of ketoprofen and/or its conjugates⁷⁸	Concomitant use not recommended¹
Salicylates	Possible altered elimination of ketoprofen; no change in the pharmacokinetics of salicylate⁵²	Clinical importance unknown⁵²
Thrombolytic agents (streptokinase)	Possible bleeding complications³⁹	Use with caution³⁹

Ketoprofen Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; bioavailability is about 90%.¹ Peak plasma concentration usually attained within 0.5–2 hours (conventional capsules) or 6–7 hours (extended-release capsules).¹ ⁵⁸ ⁶⁰ ⁶¹ ⁶² ⁶⁴ ⁶⁶ ⁶⁹ ⁷¹

Food

Food delays time to peak plasma concentration by <1 hour or about 2 hours following administration as conventional capsules or extended-release capsules, respectively.¹

Distribution

Extent

Distributed into synovial fluid⁵⁷ ⁶⁴ ⁶⁷ ⁶⁸ ⁷¹ ²²⁷ and the CNS.⁷⁵

Not known whether ketoprofen is distributed into human milk.¹

Plasma Protein Binding

>99% (mainly albumin).¹ ⁷⁵

Elimination

Metabolism

Rapidly and extensively metabolized in the liver; active metabolites not identified.¹ ² ⁴⁵ ⁵⁹

Elimination Route

Excreted principally in urine.¹ ⁵⁷ ⁵⁹ ⁶⁰ ⁶¹ ⁶² ⁷⁰ ⁷² ⁸⁰ ²²⁸

Half-life

Conventional capsules: 2–4 hours.¹

Extended-release capsules: 5.4 hours.¹

Special Populations

Renal Impairment: Half-life (when given as conventional capsules) prolonged to about 3 hours in patients with mild renal impairment and to about 5–9 hours in patients with moderate to severe renal impairment.¹

Stability

Storage

Oral

Conventional and Extended-release Capsules

Tight¹ , light resistant containers² at 25°C¹ ² ; protect from direct light and excessive heat and humidity.¹

Actions

Inhibits cyclooxygenase-1 (COX-1) and COX-2.²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁶⁷ ²⁶⁸ ²⁶⁹ ²⁷⁰
Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.¹ ³¹ ³⁴ ⁴² ⁴³ ²⁰⁵

Advice to Patients

Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.¹
Risk of serious cardiovascular events (e.g., MI, stroke).¹ ⁵⁰⁰ ⁵⁰⁸
Risk of GI bleeding and ulceration.¹ ²⁴⁷ ²⁵⁵
Risk of serious skin reactions, DRESS, and anaphylactoid and other sensitivity reactions.¹ ¹²⁰¹
Risk of hepatotoxicity.¹
Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.¹ ⁵⁰⁰ ⁵⁰⁸
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.¹
Advise patients to stop taking ketoprofen immediately if they develop any type of rash or fever and to promptly contact their clinician.¹²⁰¹ Importance of seeking immediate medical attention if an anaphylactic reaction occurs.¹
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.¹
Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.⁵⁰⁸
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Importance of avoiding NSAIA use beginning at 20 weeks’ gestation unless otherwise advised by a clinician; importance of avoiding NSAIAs beginning at 30 weeks’ gestation because of risk of premature closure of the fetal ductus arteriosus; monitoring for oligohydramnios may be necessary if NSAIA therapy required for >48 hours’ duration between about 20 and 30 weeks’ gestation.¹²⁰⁰ ¹²⁰¹
Advise women who are trying to conceive that NSAIAs may be associated with a reversible delay in ovulation.¹²⁰³
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.¹
Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ketoprofen
Routes	Dosage Forms	Strengths	Brand Names
Oral	Capsules	25 mg*	Ketoprofen Capsules
		50 mg*	Ketoprofen Capsules
		75 mg*	Ketoprofen Capsules
	Capsules, extended-release	200 mg*	Ketoprofen Extended-release Capsules

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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9. Wolf RE. Nonsteroidal anti-inflammatory drugs. Arch Intern Med. 1984; 144:1658-60. http://www.ncbi.nlm.nih.gov/pubmed/6235791?dopt=AbstractPlus

10. Court H, Volans GN. Poisoning after overdose with non-steroidal anti-inflammatory drugs. Adv Drug React Ac Pois Rev. 1984; 3:1-21.

11. Abramson S, Edelson H, Kaplan H et al. Inhibition of neutrophil activation by nonsteroidal anti-inflammatory drugs. Am J Med. 1984; 10:3-6.

12. McElnay JC, D’Arcy PF. Displacement of albumin-bound warfarin by anti-inflammatory agents in vitro. J Pharm Pharmacol. 1980; 32:709-11. http://www.ncbi.nlm.nih.gov/pubmed/6107346?dopt=AbstractPlus

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283. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. http://www.ncbi.nlm.nih.gov/pubmed/12501230?dopt=AbstractPlus

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291. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

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Pill TEVA 3195 is Ketoprofen 75 mg — Ketoprofen 75 mg (TEVA 3195)

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