Ketoprofen (Anafen) - Uses, Dose, MOA, Brands, Side effects

A non-steroidal anti-inflammatory medicine called ketoprofen (Anafen) prevents the production of prostaglandins. It is utilised to treat fever and pain in people with rheumatoid arthritis and osteoarthritis.

Ketoprofen Uses:

  • Osteoarthritis:

    • Treatment of the signs and symptoms of osteoarthritis
  • Pain (immediate release only):

    • Treatment of pain
  • Primary dysmenorrhea (immediate release only):

    • Management of primary dysmenorrhea
  • Rheumatoid arthritis:

    • Treatment of the signs and symptoms of rheumatoid arthritis
  • Off Label Use of Ketoprofen in Adults:

    • Ankylosing spondylitis

Ketoprofen Dose in Adults:

Note: It is not recommended to use the ER formulation or enteric-coated tablets to treat really bad pain. Little or weak patients should be given lower doses to consider.

Ankylosing spondylitis (off-label):

  • Every day, two doses of 100 mg.

Ketoprofen (Anafen) dose in rheumatoid arthritis or osteoarthritis:

  • Immediate release:

    • 75 mg three times day or 50 mg four times daily; the daily limit is 300 mg.
  • Enteric-coated [Canadian product]:

    • Typical dose: 50 mg three or four times daily; after the maintenance dose is established, a regimen of up to 200 mg twice daily (for example, 100 mg twice daily) may be considered;
    • The daily dosing cap is 300 mg.
  • Extended-release:

    • 200 mg once day; 200 mg daily maximum.

Ketoprofen (Anafen) dose in pain due to dysmenorrhea:

  • Immediate release:

    • Up to 300 mg per day, or 25 to 50 mg every 6 to 8 hours.

Ketoprofen (Anafen) Rectal suppository [Canadian product]:

Ankylosing spondylitis, osteoarthritis, or rheumatoid arthritis:

  • Put one rectally into each morning and evening (twice a day), or at night (once a day).
  • A combined rectal/oral dose of up to 300 mg daily may be taken into consideration for acute rheumatic activity or in cases where lesser dosages
  • are ineffective. Divided oral dosing may be used as a supplement up to a combined rectal/oral maximum of 200 mg daily.

Use in Children:

Not indicated.


Ketoprofen Pregnancy Risk Factor C

  • Cross-over of Ketoprofen and the placenta
  • Some studies have shown that birth defects can be caused by in utero NSAID use. However, the data is inconsistent.
  • Following in utero NSAID use, nonteratogenic effects such as prenatal constriction, persistent pulmonary hypertension, oligohydramnios and necrotizing enterocolitis have been seen in the fetus/newborn.
  • Additionally, the ductus arteriosus may not close after birth and can be resilient to medical treatment.
  • They may lead to premature closure of the ductus Arteriosus. It is important not to use NSAIDs during pregnancy.
  • NSAIDs may be used to treat mild rheumatoid-arthritis flare-ups in pregnant patients. However, it should be avoided or minimized early in pregnancy.
  • Women of reproductive age who continue to use NSAIDs may experience infertility. This can be reversed by stopping the medication.
  • The possibility of miscarriage may increase if NSAIDs are used close to the time of conception.

Ketoprofen use during breastfeeding:

  • Breast milk contains Ketoprofen.
  • Between 1984 and 2011, one case of each esophageal, erosive, and meningeal ulcer was reported to the French Pharmacoviligance Database.
  • The manufacturer does not recommend breastfeeding.
  • NSAIDs can be used postpartum by women who want to breastfeed.
  • However, agents other than ketoprofen should not be used by women breastfeeding infants with platelet dysfunction and thrombocytopenia.

Dose in Kidney Disease:

  • In general, NSAIDs are not advised for use in patients with advanced renal disease.
  • Manufacturer’s labeling:

    • GFR ≥25 mL/minute/1.73 m²:
      • There are no defined dosage modifications given in the manufacturer’s labeling.
      • In patients with mild impairment, the manufacturer’s labeling suggests a maximum dose of 150 mg/day.
    • GFR <25 mL/minute/1.73 m²:
      • There are no defined dosage modifications given in the manufacturer’s labeling.
      • Maximum dose: 100 mg/day
  • KDIGO 2012 guidelines provide the following recommendations for NSAIDs:

    • eGFR 30 to <60 mL/minute/1.73 m²:
      • for a limited period of time discontinue in patients with intercurrent disease that increase the risk of acute kidney injury. Prolonged treatment is not recommended.
    • eGFR <30 mL/minute/1.73 m²:
      • Avoid use.

Dose in Liver Disease:

  • Hepatic impairment and serum albumin <3.5 g/dL:
    • Maximum starting dose: 100 mg/day

Common Side Effects of Ketoprofen (Anafen):

  • Gastrointestinal:

    • Dyspepsia
  • Hepatic:

    • Abnormal hepatic function tests

Less Common Side Effects of Ketoprofen (Anafen):

  • Cardiovascular:

    • Peripheral Edema
  • Central Nervous System:

    • Headache
    • Dizziness
    • Abnormal Dreams
    • Depression
    • Drowsiness
    • Insomnia
    • Malaise
    • Nervousness
  • Dermatologic:

    • Skin Rash
  • Gastrointestinal:

    • Abdominal Pain
    • Constipation
    • Diarrhea
    • Flatulence
    • Nausea
    • Gastrointestinal Hemorrhage
    • Peptic Ulcer
    • Anorexia
    • Stomatitis
    • Vomiting
  • Genitourinary:

    • Urinary Tract Irritation
  • Ophthalmic:

    • Visual Disturbance
  • Otic:

    • Tinnitus
  • Renal:

    • Renal Insufficiency

Contraindications to Ketoprofen (Anafen):

  • Sensitivity of ketoprofen and any other component of the formulation
  • History of asthma, urticaria or allergic-type reactions following aspirin use or any other NSAIDs
  • Use in the CABG setting

Canadian labeling: Additional contraindications not in US labeling

  • Active peptic ulcer, active inflammatory disease of GI tract
  • Recent bleeding or inflammation of the rectum, anus or rectum (suppository only).

Warnings and precautions

  • Anaphylactoid reactions

    • Anaphylactoid reactions can occur even in patients who have never been exposed to the drug.
    • Patients with "aspirin triad" (bronchial asthma and aspirin intolerance, rhinitis, etc.) are at higher risk.
    • Contraindicated in patients who suffer from bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin treatment.
  • Cardiovascular events: [US Boxed Warn]

    • The increased risk of serious (and potentially fatal) cardiovascular thrombotic events such as MI and stroke from NSAIDs is a concern.
    • This risk may be evident at the beginning of treatment and may increase over time.
    • Comparative risk seems to be the same for people with and without proven cardiovascular disease or cardiovascular disease risk factors.
    • Nonetheless, those with known cardiovascular disorders or risk factors had a higher absolute incidence of major cardiovascular events than those getting higher dosages (which can happen early during treatment).
    • High blood pressure can be caused by new-onset or aggravation. NSAIDs can also cause a decrease in response to ACE inhibitors or thiazide or loop diuretics.
    • Patients with edema may experience sodium and fluid retention.
    • Avoid using in the event of heart failure.
    • If there are any benefits to patients who have had a recent MI, do not use it unless they are at greater risk for cardiovascular thrombotic events.
    • To reduce cardiovascular events, use the lowest effective dose for the shortest time possible, in accordance with the individual patient's goals.
    • Alternate therapies should be considered if patients are at high risk.
  • CNS effects

    • This may cause blurred vision, blurred vision, drowsiness, or other neurologic effects that can affect your mental or physical abilities.
    • Patients should be aware of tasks that require mental attention (e.g. driving or operating machinery).
  • GI events: [US Boxed Warning]

    • NSAIDs increase the risk of severe GI inflammation, ulceration and bleeding (may be fatal); patients older than 65 years old and those with a history peptic ulcer disease or GI bleeding are more at risk.
    • These events can occur at any moment during treatment, and without warning.
    • Patients with active GI bleeding should not be given this medication.
    • NSAIDs other than aspirin shouldn't be used to patients who have a history of significant lower GI bleeding. This is particularly valid if the patient has diverticulosis, angioectasia, or both.
    • Exercise caution if you have a history of gastrointestinal ulcers, are taking a medication at the same time that is known to increase your risk of bleeding in the GI tract (such as aspirin, steroids, or selective serotonin reuptake inhibitors), have advanced liver disease, coagulopathy, smoke, or consume alcohol, or in elderly or debilitated patients.
    • To reduce the risk of GI adverse reactions, use the smallest dose possible for the shortest time. Patients at high risk should consider alternate treatments.
    • When used alongside aspirin, a significant increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.
  • Hematologic effects

    • Patients with coagulation disorders and those on anticoagulants need to be closely monitored for platelet adhesion or aggregation.
    • Anemia can occur; patients receiving long-term NSAID therapy for chronic conditions should be evaluated for anemia.
    • Occasionally has the use of NSAIDs been associated with serious blood disorders including agranulocytosis or thrombocytopenia.
  • Hepatic effects

    • Use has been associated with transaminase elevations; ensure that you carefully examine any patients suffering from abnormal LFT.
    • Uncommon, sometimes fatal, severe hepatic reactions have been reported with NSAIDs.
    • Stop immediately if you notice any signs or symptoms of hepatic diseases or if there are systemic manifestations.
  • Hyperkalemia:

    • NSAIDs can increase hyperkalemia risk, particularly in elderly people, diabetics, patients with kidney disease and those who use ACE-inhibitors or other agents that induce hyperkalemia.
    • Monitor potassium closely.
  • Ophthalmic events

    • Reports of blurred/reduced vision have been made. If symptoms persist, consult an ophthalmologist immediately.
    • Extended use may require periodic ophthalmic examinations.
  • Effects on the renal system:

    • NSAIDs can affect the function of the kidneys. Dose-dependent decreases in prostaglandin synthesis could result from NSAIDs.
    • This may lead to decreased renal blood flow, which can cause renal decompensation.
    • Patients with impaired renal function, dehydration and hypovolemia, heart disease, hepatic impairment, diuretics and ACE inhibitors, as well as the elderly, are more at risk for renal toxicity.
    • Before beginning treatment, hydrate the patient and monitor your renal function.
    • Long-term NSAID treatment can cause renal damage, including renal papillary necrosis.
  • Reactions to skin:

    • NSAIDs can cause potentially lethal skin adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis and exfoliative dermatitis (TEN). These may occur without warning. Stop using NSAIDs immediately if you notice any skin rash or hypersensitivity.
  • Aseptic meningitis

    • Aseptic meningitis may increase in patients with systemic Lupus Erythematosus (SLE), and mixed connective tissue disorders.
  • Asthma

    • Patients with asthma that is aspirin-sensitive should not use this product. Bronchospasm can be fatal and severe.
    • Patients with other forms or asthma should be treated carefully.
  • Bariatric surgery

    • Gastric ulceration: refrain long-term use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may happen.
    • As part of a multimodal pain management strategy, short-term celecoxib and IV ketorolac are recommended.
  • Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]

    • In the case of coronary bypass graft (CABG), surgery, it is not recommended to use.
    • Following CABG surgery, the risk of stroke and MI may increase.
  • Hepatic impairment

    • Patients with hepatic impairment should be cautious; patients suffering from advanced hepatic disease have a greater risk of GI bleeding when using NSAIDs.
    • Patients with hypoalbuminemia and chronic disease may have higher levels of systemic exposure.
    • Patients with abnormal liver function tests (LFT) should be watched carefully.
  • Renal impairment

    • Patients with advanced kidney disease should abstain from using this medication. If you have persistent or worsening abnormalities in your renal function, stop using it.

Ketoprofen: Drug Interaction

Risk Factor C (Monitor therapy)

5-Aminosalicylic Acid Derivatives

Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives.

Acalabrutinib

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)

May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.

Alcohol (Ethyl)

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination.

Aliskiren

Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction.

Aminoglycosides

Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.

Aminolevulinic Acid (Topical)

Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).

Angiotensin II Receptor Blockers

May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function.

Angiotensin-Converting Enzyme Inhibitors

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.

Anticoagulants

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.

Beta-Blockers

Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol.

Bisphosphonate Derivatives

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern.

Cephalothin

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.

Collagenase (Systemic)

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.

Corticosteroids (Systemic)

May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents (Nonselective).

Dasatinib

May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Deferasirox

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.

Deoxycholic Acid

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.

Desmopressin

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin.

Dichlorphenamide

The serum levels of dichlorphenamide may rise in response to OAT1/3 Inhibitors.

Digoxin

Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin.

Drospirenone

Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone.

Eplerenone

Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone.

Fat Emulsion (Fish Oil Based)

May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.

Felbinac

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Glucosamine

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Haloperidol

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion.

HydrALAZINE

Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE.

Ibritumomab Tiuxetan

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.

Ibrutinib

May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.

Inotersen

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Limaprost

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

MetFORMIN

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN.

Multivitamins/Fluoride (with ADE)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Multivitamins/Minerals (with ADEK, Folate, Iron

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Multivitamins/Minerals (with AE, No Iron)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Naftazone

May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents.

Nitisinone

May increase the serum concentration of OAT1/3 Substrates.

Obinutuzumab

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.

Omega-3 Fatty Acids

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Pentosan Polysulfate Sodium

May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.

Pentoxifylline

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Porfimer

The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents.

Potassium-Sparing Diuretics

Potassium-Sparing Diuretics may have less of an antihypertensive effect when used with Nonsteroidal Anti-Inflammatory Drugs. Potassium-Sparing Diuretics may have a stronger hyperkalemic impact when used with Nonsteroidal Anti-Inflammatory Drugs.

PRALAtrexate

The serum levels of PRALAtrexate may rise in response to non-steroidal anti-inflammatory drugs. More specifically, NSAIDS may lessen pralatrexate's renal excretion. Management: If pralatrexate is used in conjunction with an NSAID, keep a close eye out for elevated serum levels and/or toxicity. While stopping NSAIDs, keep an eye out for dropping pralatrexate serum levels.

Pretomanid

OAT1/3 Substrates' serum concentration can rise.

Probenecid

Ketoprofen serum concentration can rise.

Prostacyclin Analogues

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Prostaglandins (Ophthalmic)

The therapeutic value of prostaglandins may be diminished by nonsteroidal anti-inflammatory drugs (Ophthalmic). The therapeutic effects of prostaglandins may potentially be enhanced by nonsteroidal anti-inflammatory drugs (Ophthalmic).

Quinolones

Quinolones may have a stronger neuroexcitatory and/or seizure-provoking action when used with nonsteroidal anti-inflammatory drugs. Quinolones' serum concentration may rise in response to non-steroidal anti-inflammatory drugs.

Salicylates

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.

Serotonin/Norepinephrine Reuptake Inhibitors

May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).

Tacrolimus (Systemic)

Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic).

Teriflunomide

OAT1/3 Substrates' serum concentration can rise.

Thiazide and Thiazide-Like Diuretics

May enhance the nephrotoxic effect of Nonsteroidal AntiInflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics.

Thrombolytic Agents

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.

Tipranavir

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Tolperisone

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents.

Tricyclic Antidepressants (Tertiary Amine)

May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).

Vancomycin

Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin.

Verteporfin

Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.

Vitamin E (Systemic)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Zanubrutinib

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Risk Factor D (Consider therapy modification)

Apixaban

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.

Bemiparin

Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.

Bemiparin

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.

Bile Acid Sequestrants

May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents.

CycloSPORINE (Systemic)

Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs.

Dabigatran Etexilate

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.

Diclofenac (Systemic)

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs.

Edoxaban

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.

Enoxaparin

Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.

Enoxaparin

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.

Heparin

Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required.

Heparin

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)

May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed.

Lithium

Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium.

Loop Diuretics

Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended.

Methotrexate

Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate.

Rivaroxaban

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.

Salicylates

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate.

Selective Serotonin Reuptake Inhibitors

May enhance the antiplatelet effect of Nonsteroidal AntiInflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk.

Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

Sodium Phosphates

May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely.

Tenofovir Products

Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose.

Tolvaptan

OAT1/3 Substrates' serum concentration can rise. Treatment: Individuals taking the Jynarque brand of tolvaptan should refrain from taking OAT1/3 substrates concurrently. With any combined use, it would be predicted that OAT1/3 substrate concentrations and effects would rise.

Vitamin K Antagonists (eg, warfarin

Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising.

Risk Factor X (Avoid combination)

Acemetacin

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Aminolevulinic Acid (Systemic)

Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).

Dexibuprofen

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen.

Dexketoprofen

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Floctafenine

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Ketorolac (Nasal)

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Ketorolac (Systemic)

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Macimorelin

Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin.

Mifamurtide

Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide.

Morniflumate

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).

Omacetaxine

Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL.

Pelubiprofen

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Phenylbutazone

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Talniflumate

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Tenoxicam

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Urokinase

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.

Zaltoprofen

May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

 

Monitoring parameters:

  • CBC 
  • chemistry profile 
  • gaining weight 
  • signs of bleeding 
  • periodic liver function tests;
  • renal function 
  • blood pressure;
  • periodic ophthalmic 

How to administer Ketoprofen (Anafen)?

Oral:

  • Administer alongside food to reduce Gastrointestinal distress.
  • Long-acting pills should not be broken or crushed.

Rectal suppository [Canadian product]:

  • Insert suppository rectally.

Mechanism of action of Ketoprofen (Anafen):

  • It reverses the inhibition of cyclooxygenase-1 (COX-1) enzymes.
  • This results in reduced production of prostaglandin precursors.
    It is anti-inflammatory, analgesic and has antipyretic properties.
  • Additional proposed mechanisms not completely explained (and probably impacting the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, changing lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

The onset of action:

  • Regular release: <30 minutes

Duration:

  • Regular release: Up to 6 hours

Absorption:

  • Almost complete

Protein binding:

  • >99%, primarily to albumin;
  • Hepatic impairment: Unbound fraction has roughly doubled.

Metabolism:

  • Hepatic via glucuronidation;
  • Inactive metabolite has the ability to revert to its parent molecule and may undergo enterohepatic recirculation.

Bioavailability:

  • About 90%

Half-life elimination:

  • Regular release: 2 to 4 hours;
    • Renal impairment: Mild: 3 hours;
    • moderate to severe: 5 to 9 hours
  • Enteric-coated tablet [Canadian product]: 2 hours
  • Extended-release: ~3 to 7.5 hours

Rectal suppository [Canadian product]: ~2 to 2.5 hours Time to peak serum concentration:

  • Regular-release: 0.5 to 2 hours
  • Enteric-coated tablet [Canadian product]: 1 to 2 hours
  • Extended-release capsule: 6 to 7 hours;
  • Extended-release tablet [Canadian product]: 5 to 6 hours
  • Rectal suppository [Canadian product]: ~1 hour

Excretion:

  • Urine (~80%, primarily as glucuronide conjugates)

International Brand Names of Ketoprofen:

  • Anafen
  • Ketoprofen-E
  • NU-Ketoprofen-SR
  • PMS-Ketoprofen
  • PMS-Ketoprofen-E
  • Alketo
  • Arket
  • Ascofan
  • Begsan
  • Bi-Profenid
  • Bi-Rofenid
  • Dexalgin
  • Dolofar
  • Dolofast
  • Dolomax
  • Fastum
  • Fastum Gel
  • Febin
  • Fetik
  • Flexen
  • Gabrilen
  • Gabrilen Retard
  • Helenil
  • Iprofen
  • Kaltrofen
  • Kaprofen
  • Kebanon
  • Kelfen
  • Kenhancer
  • Kenofen
  • Keon EC
  • Keotsan
  • Keprofen
  • Ketadom
  • Ketfren
  • Ketin
  • Ketofain
  • Ketofan
  • Ketofen
  • Ketofen Gel
  • Ketoflam
  • Ketofpan
  • Ketolgin
  • Ketolgin Gel
  • Ketolgin SR
  • Ketomex
  • Ketonal
  • Ketonal Forte
  • Ketoplast
  • Ketor
  • Ketorin
  • Ketospray
  • Ketotop
  • Ketron
  • Ketros
  • Ketum
  • Kop Gel
  • Lantiflam
  • Lolita
  • Mohrus Patch
  • Nazovell
  • Orudis
  • Orudis EC
  • Orudis R-PR
  • Orudis SR
  • Oruvail
  • Oruvail SR
  • Ovurila
  • Profenid
  • Profenid Gel
  • Profika
  • Rhetoflam
  • Rheuna PAP
  • Rofenid
  • Sindol
  • Spondylon
  • Toprec
  • Valusal
  • Xynofen SR

Ketoprofen Brand Names in Pakistan:

Ketoprofen Injection 50 Mg/Ml in Pakistan

Prefen Fynk Pharmaceuticals
Profenid Sanofi Aventis (Pakistan) Ltd.
Stayfen Siza International (Pvt) Ltd.

 

Ketoprofen Cream 2.5 %W/W in Pakistan

Ketodan Danas Pharmaceuticals (Pvt) Ltd

 

Ketoprofen Cream 2.5 % W/W in Pakistan

Ketomax Max Pharmaceuticals

 

Ketoprofen Patches 30 Mg in Pakistan

Ketotop Matrix Pharma

 

Ketoprofen Gel 2.5 %W/W in Pakistan

Dowfen Martin Dow Pharmaceuticals (Pak) Ltd.
Fastum Pharmatec Pakistan (Pvt) Ltd.
Ketoflex Scharper Pharmaceuticals (Pvt) Ltd.
Prifen Prime Labs. (Pvt) Ltd.
Profenid Sanofi Aventis (Pakistan) Ltd.
Proketo Shrooq Pharmaceuticals
Ticon Amarant Pharmaceuticals (Pvt)

 

Ketoprofen Tablets 100 Mg in Pakistan

Alprof Alson Pharmaceuticals
Etopar Rakaposhi Pharmaceutical (Pvt) Ltd.
Ketonel Saydon Pharmaceutical Industries (Pvt) Ltd.
Ketoprofenid Mediate Pharmaceuticals (Pvt) Ltd
Profenid Sanofi Aventis (Pakistan) Ltd.
Protifen Ec Gray`S Pharmaceuticals
Stayfen Siza International (Pvt) Ltd.
Ticon Amarant Pharmaceuticals (Pvt)

 

Ketoprofen Tablets 200 Mg in Pakistan

Alket Alson Pharmaceuticals
Inflo-Ket Valor Pharmaceuticals
Inflo-Ket Valor Pharmaceuticals
Ketonel Saydon Pharmaceutical Industries (Pvt) Ltd.
Protifen Ec Gray`S Pharmaceuticals
Silofen Silver Oak Corporation.

 

Ketoprofen Tablets Sr 200 Mg in Pakistan

Profenid Sanofi Aventis (Pakistan) Ltd.
Stayfen Siza International (Pvt) Ltd.

 

Ketoprofen Capsule 100 Mg in Pakistan

Utofen English Pharmaceuticals Industries

 

Ketoprofen Capsule 200 Mg in Pakistan

Ketoprime Prime Labs. (Pvt) Ltd.
Utofen English Pharmaceuticals Industries

 

Ketoprofen Capsule SR 200 Mg in Pakistan

Gabrilen Akhai Pharmaceuticals.
Mobifen Searle Pakistan (Pvt.) Ltd.