indication

For symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, primary dysmenorrhea and mild to moderate pain associated with musculotendinous trauma (sprains and strains), postoperative (including dental surgery) or postpartum pain.

pharmacology

Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain.

mechanism of action

The anti-inflammatory effects of ketoprofen are believed to be due to inhibition cylooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation. Ketoprofen is a non-specific cyclooxygenase inhibitor and inhibition of COX-1 is thought to confer some of its side effects, such as GI upset and ulceration. Ketoprofen is thought to have anti-bradykinin activity, as well as lysosomal membrane-stabilizing action. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

toxicity

LD₅₀=62.4 mg/kg (rat, oral).

Symptoms of overdose include drowsiness, vomiting and abdominal pain.

Side effects are usually mild and mainly involved the GI tract. Most common adverse GI effect is dyspepsia (11% of patients). May cause nausea, diarrhea, abdominal pain, constipation and flatulence in greater than 3% of patients.

biotransformation

Rapidly and extensively metabolized in the liver, primarily via conjugation to glucuronic acid. No active metabolites have been identified.

absorption

Ketoprofen is rapidly and well-absorbed orally, with peak plasma levels occurring within 0.5 to 2 hours.

half life

Conventional capsules: 1.1-4 hours

Extended release capsules: 5.4 hours due to delayed absorption (intrinsic clearance is same as conventional capsules)

route of elimination

In a 24 hour period, approximately 80% of an administered dose of ketoprofen is excreted in the urine, primarily as the glucuronide metabolite.

drug interactions

Acenocoumarol: The NSAID, ketoprofen, may increase the anticoagulant effect of acenocoumarol.

Acetylsalicylic acid: Concomitant therapy of the NSAID, ketoprofen, and acetylsalicylic acid may result in additive adverse/toxic effects (e.g. GI bleeding). The NSAID may also limit the cardioprotective effect of acetylsalicylic acid. Occasional concomitant use may not cause clinically significant problems, but regular, frequent concomitant therapy is not recommended.

Anisindione: The NSAID, ketoprofen, may increase the anticoagulant effect of anisindione.

Citalopram: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Colesevelam: Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Cyclosporine: The NSAID, ketoprofen, may increase the serum concentration of cyclosporine. Ketoprofen may also increase the nephrotoxicity of cyclosporine.

Dicumarol: The NSAID, ketoprofen, may increase the anticoagulant effect of dicumarol.

Drotrecogin alfa: The antiplatelet effect of ketoprofen may increase the bleed risk associated with drotrecogin alfa. Consider spacing use of the two agents by at least 7 days. Increase monitoring for signs and symptoms of bleeding during concomitant therapy.

Escitalopram: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Fluoxetine: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Fluvoxamine: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Ginkgo biloba: Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Ginseng: Increased risk of bleeding due to additive anticoagulant properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Ketorolac: Concomitant use of ketoprofen and ketorolac, two NSAIDs, is contraindicated due to the risk of additive or synergistic NSAID toxicities (e.g. GI bleeding, ulceration, renal dysfunction, etc).

Lithium: The NSAID, ketoprofen, may increase the serum concentration of lithium by decreasing its renal clearance. Consider a dose reduction in lithium upon initiation of ketoprofen therapy. Monitor for changes in the therapeutic and adverse effects of lithium if ketoprofen is initiated, discontinued or does changed.

Methotrexate: The NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.

Paroxetine: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Pemetrexed: The NSAID, ketoprofen, may increase increase the serum concentration of pemetrexed by decreasing its renal clearance. Patients with mild to moderate renal insufficiency (CrCl 45-79 ml/min) should avoid use of ketoprofen within 2 days of a pemetrexed dose. Patients with better renal function do not appear to be at risk. Monitor for toxicity in all patients during concomitant therapy.

S-Adenosylmethionine: Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Sertraline: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Telmisartan: Concomitant use of Telmisartan and Ketoprofen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.

Timolol: The NSAID, Ketoprofen, may antagonize the antihypertensive effect of Timolol.

Trandolapril: The NSAID, Ketoprofen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Ketoprofen is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Ketoprofen. Monitor for increased bleeding during concomitant thearpy.

Warfarin: The antiplatelet effects of ketoprofen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.