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Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Molecular Formula: C30H26CaO6•2H2O
CAS Number: 53746-45-5
Brands: Nalfon

Medically reviewed by Last updated on Nov 9, 2020.


Special Alerts:

[Posted 10/15/2020]

AUDIENCE: Consumer, Patient, Health Professional, Pharmacy

ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.

For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.

For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: [Web]. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.



  • are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.

  • are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.

  • work by blocking the production of certain chemicals in the body that cause inflammation.

  • are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.

Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.



  • If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.

  • Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: [Web], to find out if the medicines contain NSAIDs.

  • Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.

  • Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.

Health Care Professionals

  • FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

  • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

  • Oligohydramnios is often, but not always, reversible with treatment discontinuation.

  • Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

  • If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.

  • The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.

  • Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.

For more information visit the FDA website at: [Web] and [Web].


    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).137 500 502 508 b 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

    GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).137 b Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.137 b Geriatric individuals are at greater risk for serious GI events.100 137 b (See GI Effects under Cautions.)


Prototypical NSAIA;100 b propionic acid derivative;b structurally and pharmacologically related to flurbiprofen, ibuprofen, ketoprofen, and naproxen.b d

Uses for Fenoprofen

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Consider potential benefits and risks of fenoprofen therapy as well as alternative therapies before initiating therapy with the drug.100 137 b Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.100 137 b


Relief of mild to moderate pain in adults.100 b

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.100 b d

Has been used in the symptomatic treatment of juvenile rheumatoid arthritis.b c

Also has been used with some success in the treatment of ankylosing spondylitis and acute gouty arthritis.b d

Fenoprofen Dosage and Administration


  • Consider potential benefits and risks of fenoprofen therapy as well as alternative therapies before initiating therapy with the drug.100 137 b


Oral Administration

Administer orally.100 b

Administration with meals, milk, or antacids may minimize adverse GI effects.100 b d


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as fenoprofen calcium; dosage expressed in terms of fenoprofen.100 b

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.100 137 b Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.100 137 b



For mild to moderate pain, 200 mg every 4–6 hours as needed.100 b

Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

Initially, 400–600 mg 3 or 4 times daily.146 508 Adjust dose and frequency as necessary based on severity of symptoms and clinical response (maximum 3.2 g daily).100 b

Patients with rheumatoid arthritis may require higher dosages than those with osteoarthritis.100 b

Symptomatic improvement usually begins in a few days, but an additional 2–3 weeks may be needed to determine response.100 b

Prescribing Limits


Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

Maximum 3.2 g daily.100 b

Special Populations

Renal Impairment

No dosage adjustments recommended.100

Use not recommended in patients with advanced renal disease.100

Hepatic Impairment

No dosage adjustments recommended.

Cautions for Fenoprofen


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Known hypersensitivity to fenoprofen or any ingredient in the formulation.100 d

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.100 137 d

  • In the setting of CABG surgery.508

  • History of significant renal impairment.100



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.141 142 143 145 500 501 502 503 506 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.100 137 500 508

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.100 137 138 502 508 (See Specific Drugs under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms;100 104 105 108 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.100 124 127 134

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;107 124 125 126 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)107 124 125 or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).125


Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.100 137 Use with caution in patients with hypertension; monitor BP.100 137

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.100 137 508 (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.100 137 508

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.100 137

Potential for overt renal decompensation.100 137 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.100 137 140 (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.100 137

Immediate medical intervention and discontinuance for anaphylaxis.100 137

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.100 137 d

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.100 137 Discontinue at first appearance of rash or any other signs of hypersensitivity (e.g., blisters, fever, pruritus).100 137

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.100

Elevations of serum ALT or AST reported.100

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.100 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.100

Hematologic Effects

Anemia reported rarely.100 137 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.100 137 d

May inhibit platelet aggregation and prolong bleeding time.100 137 d

CNS Effects

Drowsiness and dizziness reported; may impair ability to perform activities requiring mental alertness.100 b

Ocular Effects

Adverse ocular effects reported in patients receiving NSAIA therapy; ophthalmologic evaluation recommended if visual disturbances occur.100 b

Otic Effects

Safety not established in patients with hearing impairment; auditory function tests should be performed periodically in these patients during prolonged therapy.100 b

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.100

May mask certain signs of infection.b

Obtain CBC and chemistry profile periodically during long-term use.100

Specific Populations


Category C.100 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.100


Fenoprofen is distributed into milk.b d Discontinue nursing or the drug.100 b

Pediatric Use

Safety and efficacy not established in children <18 years of age.100

Geriatric Use

Use with caution in patients ≥65 years of age.100 Geriatric patients appear to tolerate therapy less well (e.g., possible higher incidence of adverse GI effects, greater risk of developing renal decompensation) than younger individuals.100 b Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.100 b

Renal Impairment

Has not been evaluated in patients with severe renal impairment.100 b Use not recommended in patients with advanced renal disease.100 b

Common Adverse Effects

Dyspepsia,100 d nausea,100 d constipation,100 d headache,100 somnolence,100 dizziness,100 nervousness,100 asthenia,100 peripheral edema.100

Interactions for Fenoprofen

Protein-bound Drugs

Possible pharmacokinetic interaction; potential for fenoprofen to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs (e.g., oral anticoagulants, hydantoins, salicylates, sulfonamides, and sulfonylureas).100 b d Observe for adverse effects if used with other protein-bound drugs.100 b

Specific Drugs




ACE inhibitors

Reduced BP response to ACE inhibitor possible 100 137 144

Possible deterioration of renal function in individuals with renal impairment144

Monitor BP100 144 b

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist possible144

Possible deterioration of renal function in individuals with renal impairment144

Monitor BP144 b

Antacids (aluminum- and magnesium-containing)

Did not affect fenoprofen absorption in one study; other antacids not evaluated for possible interactionsa b d

Anticoagulants (e.g., warfarin)

Possible bleeding complications100 137 144

Caution and careful monitoring advised100 144 b


Increased risk of GI ulceration or other complications 100 137

Possible decreased plasma concentrations and half-life of fenoprofen100 b d

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs 100 138 502 508

Concomitant use generally not recommended100 d

Diuretics (furosemide and thiazides)

Reduced natriuretic effects100 137

Monitor for diuretic efficacy and renal failure100 137


Increased plasma lithium concentrations100 137

Monitor for lithium toxicity 100 137


Possible toxicity associated with increased plasma methotrexate concentrations during concomitant NSAIA use100 b

Caution advised100 b


Possible decreased plasma concentrations and plasma half-life of fenoprofen100 b d

Dosage adjustment may be necessary when phenobarbital is initiated or discontinued100 b d

Fenoprofen Pharmacokinetics



Rapidly and almost completely absorbed following oral administration.100 b d Peak plasma concentrations usually attained within 2 hours.100 b


Onset of analgesic activity reportedly occurs within 15–30 minutes following oral administration.b


Duration of analgesic activity: 4–6 hours.b


Food delays and diminishes peak plasma fenoprofen concentrations.100 a b d



Distributed into milk;b d does not appear to cross the placenta.b d

Plasma Protein Binding

Approximately 99% (mainly to albumin).100 b d



Extensively metabolized in the liver.b d Fenoprofen’s major metabolite, 4′-hydroxyfenoprofen, probably is inactive.b

Elimination Route

Eliminated principally in urine as unchanged drug (2–5%), 4′-hydroxyfenoprofen (2–5%), their glucuronide or other conjugates (90%), and unidentified conjugates (2–5%).100 b d


2.5–3 hours.100 b d

Special Populations

Not substantially removed by hemodialysis or peritoneal dialysis.100




Capsules and Tablets

Tight containers at 20–25°C.100


  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.118 119 120 121 122 123 b

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.100 118 119 120 121 122 123 b d

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.100 137

  • Risk of serious cardiovascular events (e.g., MI, stroke).100 500 508 b Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.100 500 508 b

  • Risk of GI bleeding and ulceration.100 111 115 b Importance of notifying a clinician if signs and symptoms of serious adverse GI effects occur.100 b

  • Risk of serious skin reactions.100 b Importance of discontinuing fenoprofen calcium and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.100 b

  • Risk of anaphylactoid and other sensitivity reactions.100 b Importance of seeking immediate medical attention if an anaphylactic reaction occurs.100 b

  • Risk of hepatotoxicity.100 b Importance of discontinuing therapy and contacting a clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.100 b

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.100 508

  • Risk of dizziness and potential for drug to impair mental alertness; use caution when driving or operating machinery until effects on individual are known.100 b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100 Importance of avoiding fenoprofen in late pregnancy (third trimester).100 b

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.100

  • Importance of informing patients of other important precautionary information.100 (See Cautions.)


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

Fenoprofen Calcium


Dosage Forms


Brand Names




200 mg (of fenoprofen)



400 mg (of fenoprofen)



Tablets, film-coated

600 mg (of fenoprofen)*

Fenoprofen Calcium Tablets

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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


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