Ketoprofen

Ketoprofen is approved for use in the following clinical indications

Osteoarthritis: Management of the signs and symptoms of osteoarthritis

Pain (immediate release only): Management of pain

Primary dysmenorrhea (immediate release only): Treatment of primary dysmenorrhea

Rheumatoid arthritis: Management of the signs and symptoms of rheumatoid arthritis.

• Although not approved there have been certain off labelled uses documented for Ketoprofen which includes:

• Ankylosing spondylitis:

Oral (off-label): 100 mg twice daily.

Rectal suppository [Canadian product]: Insert one suppository rectally in the morning and evening (twice daily) or at bedtime (once daily). May supplement with divided oral dosing up to a combined rectal/oral maximum of 200 mg daily; for severe rheumatic activity or an inadequate response to lower dosages, a combined rectal/oral dose up to 300 mg daily may be considered.

Dysmenorrhea, pain: Oral: Immediate release: 25 to 50 mg every 6 to 8 hours up to a maximum of 300 mg/day.

Osteoarthritis, rheumatoid arthritis:

Oral:

Immediate release: 50 mg 4 times daily or 75 mg 3 times daily; maximum: 300 mg/day.

Enteric coated :Usual dose: 50 mg 3 or 4 times daily; up to 200 mg daily; twice daily regimen (eg, 100 mg twice daily) may be considered after maintenance dose is established; maximum: 300 mg/day.

Extended release: 200 mg once daily; maximum: 200 mg/day.

Rectal suppository [Canadian product]: Insert one suppository rectally in the morning and evening (twice daily) or at bedtime (once daily). May supplement with divided oral dosing up to a combined rectal/oral maximum of 200 mg daily; for severe rheumatic activity or an inadequate response to lower dosages, a combined rectal/oral dose up to 300 mg daily may be considered.

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in heart failure. Avoid use in patients with a recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events:. Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

• Ophthalmic events: Blurred/diminished vision has been reported; discontinue therapy and refer for ophthalmologic evaluation if symptoms occur. Periodic ophthalmic exams may be necessary with prolonged use.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity)

• Common Adverse effects:

CNS effects (e.g. drowsiness, dizziness), blurred vision, Na and fluid retention, new-onset or exacerbated hypertension, hyperkalemia, liver function abnormalities (e.g. increased transaminase levels), renal impairment (e.g. increased BUN, oedema), decreased platelet aggregation, prolonged bleeding time, anemia

• Less Common Adverse effects:

Dyspepsia, nausea, abdominal pain, vomiting, constipation, diarrhea, flatulence.

• Rare Adverse effects

Severe anaphylactic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, hepatotoxicity (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure).

• May increase the risk of toxicity of lithium and methotrexate. Increased risk of renal toxicity with ACE inhibitors, diuretics, angiotensin II receptor antagonists, ciclosporin, and tacrolimus.
• May reduce the therapeutic effects of diuretics and antihypertensive agents. Increased serum concentration with probenecid. Increased risk of renal failure when given with tenofovir disoproxil fumarate.
• May elevate the plasma levels of digoxin.
• Potentially Fatal: Increased risk of gastrointestinal ulceration and bleeding with other NSAIDs, aspirin, corticosteroids, SSRIs and anticoagulants (e.g. warfarin, heparin).

• Pharmacodynamic

Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAID) 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.

• Pharmacokinetics