Kynol TR

Approved Indications:

• Rheumatoid Arthritis (RA): Management of signs and symptoms in adults.
• Osteoarthritis (OA): Relief of mild to moderate symptoms.
• Ankylosing Spondylitis (AS): Reduction of spinal inflammation and stiffness.
• Mild to Moderate Pain: Short-term relief of musculoskeletal pain, postoperative pain, dental pain, and traumatic injury.
• Primary Dysmenorrhea: Treatment of menstrual pain and cramping.
• Acute Gouty Arthritis: Relief of acute inflammation and pain during gout attacks.

Topical Use Indications:

• Local pain and inflammation from:
• Tendonitis
• Muscle sprains or strains
• Sports injuries
• Localized soft tissue inflammation

Clinically Accepted Off-label Uses:

• Acute Migraine Attacks: Occasionally used for headache relief.
• Post-traumatic Pain: Used in emergency settings to reduce acute pain and swelling.

Adults:

• Oral (Immediate-release):
  50–100 mg every 6–8 hours; maximum: 300 mg/day.
  Should be taken with food to reduce gastrointestinal side effects.
• Oral (Sustained-release):
  200 mg once daily.
• Rectal (Suppository):
  100 mg twice daily; maximum: 200 mg/day.
• Injectable (IM/IV):
  50–100 mg every 6–8 hours; maximum: 200 mg/day.
  IV infusion should be diluted and administered over 30–60 minutes.
• Topical Gel (2.5%):
  Apply a thin layer to the affected area 2–3 times daily.
  Maximum duration: 14 days without physician reassessment.
  Do not apply to broken or infected skin.

Pediatric Use:

• Not recommended for children under 18 years due to insufficient safety data.

Elderly Patients:

• Use the lowest effective dose.
• Monitor closely for gastrointestinal, cardiovascular, and renal complications.

Renal Impairment:

• Mild to Moderate: Dose reduction may be required.
• Severe (CrCl <30 mL/min): Use is contraindicated.

Hepatic Impairment:

Use cautiously. Monitor liver function regularly during therapy.

Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) that inhibits both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. These enzymes are involved in the synthesis of prostaglandins, which mediate inflammation, pain, and fever. By blocking prostaglandin production, ketoprofen exerts anti-inflammatory, analgesic, and antipyretic effects. It may also stabilize lysosomal membranes and inhibit bradykinin, enhancing its analgesic action.

• Absorption: Rapid and nearly complete after oral administration.
• Bioavailability: Approximately 90%.
• Onset of Action: Oral: 30–60 minutes; IM: 15–30 minutes.
• Peak Plasma Concentration: 0.5 to 2 hours after oral dose.
• Protein Binding: >99%.
• Distribution: Extensively distributed, including into synovial fluid.
• Metabolism: Hepatic glucuronidation (UGT enzymes); no active metabolites.
• Half-life: 1.5 to 2.5 hours (immediate-release); 6–8 hours (sustained-release).
• Excretion: Primarily via urine (50–90% as conjugated metabolites); minor fecal elimination.

Pregnancy:

• Category C (First and Second Trimester): Use only if clearly needed.
• Category D (Third Trimester): Contraindicated due to risk of fetal cardiovascular complications, including premature closure of the ductus arteriosus.

Lactation:

• Ketoprofen is excreted in small amounts into breast milk.
• Short-term use is generally considered safe, but long-term use is not recommended during breastfeeding.
• Monitor the infant for adverse effects if used during lactation.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Propionic acid derivative NSAID (related to ibuprofen and naproxen)

• Hypersensitivity to ketoprofen or other NSAIDs
• History of asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs
• Active gastrointestinal bleeding or peptic ulcer
• Severe hepatic or renal impairment
• Advanced heart failure
• Use during the third trimester of pregnancy
• Use in patients undergoing coronary artery bypass graft (CABG) surgery

• Cardiovascular Risk: NSAIDs may increase the risk of heart attack and stroke. Use the lowest effective dose for the shortest duration.
• Gastrointestinal Risk: May cause serious GI events including bleeding, ulceration, and perforation.
• Renal Risk: Monitor kidney function, particularly in the elderly and dehydrated patients.
• Hepatic Risk: Monitor liver function tests during long-term use.
• Allergic Reactions: May cause anaphylaxis or serious skin reactions (e.g., Stevens-Johnson syndrome).
• Photosensitivity: Particularly with topical forms; avoid excessive sun exposure.
• Masking of Infection: Anti-inflammatory effects may obscure symptoms of underlying infections.

Common Adverse Effects:

• Gastrointestinal: Nausea, vomiting, abdominal pain, dyspepsia, diarrhea, constipation
• Central Nervous System: Headache, dizziness, drowsiness
• Dermatologic: Rash, pruritus, application site reactions (topical)

Serious Adverse Effects:

• Gastrointestinal bleeding or perforation
• Acute renal failure
• Hepatitis and elevated liver enzymes
• Anaphylactic reactions
• Severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Cardiovascular events (e.g., myocardial infarction, stroke)

Timing and Severity:

• Many side effects are dose-related and increase with prolonged use.
• Serious events may occur without warning, especially in high-risk populations.

• ACE Inhibitors, ARBs, Diuretics: Increased risk of renal dysfunction.
• Anticoagulants (e.g., Warfarin): Increased risk of bleeding.
• Aspirin or Other NSAIDs: Increased risk of GI and renal toxicity.
• Corticosteroids: Additive gastrointestinal adverse effects.
• Methotrexate: Risk of toxicity due to reduced clearance.
• Lithium: Increased serum lithium concentrations and toxicity.
• Cytochrome System: Metabolized via glucuronidation; minimal involvement of CYP450 enzymes.

• FDA and EMA have issued class-wide NSAID warnings on cardiovascular and gastrointestinal risks, now required on all ketoprofen products.
• Topical ketoprofen now includes additional warnings regarding photosensitivity, with recommendations to avoid sun exposure for up to 2 weeks after discontinuation.
• Recent clinical guidelines recommend avoiding prolonged NSAID use in patients with cardiovascular disease, chronic kidney disease, or active GI ulcers.

• Oral and Injectable Forms:
  Store below 25°C. Protect from light and moisture.
• Suppositories:
  Store at 2°C to 8°C (refrigerated). Do not freeze.
• Topical Gel:
  Store at room temperature (below 25°C).
  Do not refrigerate or freeze. Protect from heat and direct sunlight.
• Handling Instructions:
  Shake suspensions (if available) before use.
  Do not apply topical gel to broken or infected skin.
  Discard injectable solutions if discolored or if particulate matter is visible.