Etorac

Systemic (Oral, IM, IV):

Approved Indications:

• Moderate to severe acute pain requiring short-term opioid-level analgesia, especially postoperatively (orthopedic, abdominal, or dental surgery).
• Musculoskeletal pain of acute onset.
• Renal colic or acute flank pain.

Ophthalmic (0.5% solution):

• Postoperative ocular inflammation following cataract extraction.
• Reduction of ocular pain and photophobia after corneal refractive surgery.
• Seasonal allergic conjunctivitis.
• Ocular itching and inflammation associated with allergic or inflammatory eye conditions.

Clinically Accepted Off-Label Uses:

• Acute migraine attacks (parenteral use).
• Acute low back pain.
• Pain related to metastatic bone disease.

Adults (Systemic Use):

• Intramuscular (IM):
• Initial dose: 60 mg as a single dose (patients <65 years), or 30 mg (≥65 years, renally impaired, or low body weight).
• Maintenance: 30 mg every 6 hours as needed.
• Maximum daily dose: 120 mg for adults <65 years, 60 mg for elderly or those with renal impairment.
• Maximum duration: 5 days (IM and oral combined).
• Intravenous (IV):
• 15–30 mg every 6 hours as needed.
• Maximum as above.
• Oral:
• 10 mg every 4–6 hours as needed.
• Maximum daily dose: 40 mg.
• Oral use should only follow IM/IV use and not exceed 5 days total (parenteral + oral).

Ophthalmic (Adults and Children ≥3 years):

• 1 drop of 0.5% solution in the affected eye(s) 4 times daily.
• Duration:
• Up to 2 weeks post-surgery.
• Continue until symptoms resolve in allergic conjunctivitis.

Pediatric Use (Systemic):

• Not recommended for systemic use in children due to high risks of renal and bleeding complications.

Special Populations:

• Elderly (≥65 years):
• Use reduced doses; limit daily IM/IV dose to 60 mg.
• Monitor renal and gastrointestinal function closely.
• Renal Impairment:
• Contraindicated in moderate to severe impairment.
• In mild impairment, reduce dose and monitor renal function.
• Hepatic Impairment:
• Use with caution. Periodic liver function monitoring is advised in prolonged use.

Ketorolac Tromethamine is a potent nonsteroidal anti-inflammatory drug (NSAID) that acts by non-selectively inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. These enzymes are essential for converting arachidonic acid into prostaglandins, which mediate pain, inflammation, and fever. By reducing prostaglandin synthesis, ketorolac provides strong peripheral analgesia comparable to opioids but without the risk of respiratory depression or dependence. Its mechanism also contributes to its anti-inflammatory and antipyretic effects.

• Absorption: Rapid and nearly complete following IM or oral administration.
• Bioavailability: Approximately 100% (IM), 80–100% (oral).
• Onset of Action:
• IV: 10 minutes
• IM: ~30 minutes
• Oral: 30–60 minutes
• Peak Plasma Concentration:
• Oral: ~45 minutes to 1 hour
• IM: ~45 minutes
• Protein Binding: >99%
• Distribution: Widely distributed in body fluids; crosses the placenta and is excreted in breast milk.
• Metabolism: Primarily via hepatic hydroxylation and conjugation (non-CYP450 pathways).
• Half-life: 5–6 hours in healthy adults; up to 8 hours in elderly.
• Elimination: ~90% excreted in urine (as unchanged drug and metabolites); <10% in feces.

Pregnancy:

• FDA Category C (1st and 2nd trimesters): Use only when clearly needed.
• Category D (3rd trimester): Contraindicated due to risk of premature closure of ductus arteriosus and fetal renal toxicity.
• Avoid use during labor and delivery due to bleeding risk.

Lactation:

• Excreted in small amounts in breast milk.
• Not recommended during breastfeeding, especially for repeated or prolonged use, due to potential nephrotoxicity and gastrointestinal effects in infants.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Acetic acid derivative
• Analgesic Role: Non-opioid analgesic for moderate to severe acute pain

• Known hypersensitivity to ketorolac, aspirin, or other NSAIDs
• Active peptic ulcer or history of gastrointestinal bleeding or perforation
• Severe renal impairment or volume depletion
• Recent or active cerebrovascular bleeding
• Use during labor and delivery
• Concurrent use with other NSAIDs or probenecid
• Use in pediatric patients for systemic administration
• Perioperative use in patients undergoing major surgery (especially coronary artery bypass graft surgery)
• Hemorrhagic disorders or high bleeding risk

• Gastrointestinal Risk: Serious GI ulceration, bleeding, or perforation may occur at any time without warning.
• Renal Risk: Ketorolac can cause renal failure, especially in volume-depleted, elderly, or renally impaired patients.
• Bleeding Risk: Inhibits platelet aggregation and may increase surgical bleeding risk.
• Cardiovascular Risk: May increase risk of thrombotic events (e.g., MI, stroke), especially with prolonged use.
• Maximum Duration Warning: Systemic use should not exceed 5 consecutive days due to high toxicity risk.
• Ophthalmic Use: May delay corneal healing; avoid prolonged use in ocular surgery patients.

Common Side Effects:

• Gastrointestinal: Nausea, abdominal pain, dyspepsia, diarrhea
• Central Nervous System: Dizziness, headache, drowsiness
• Injection Site: Pain, burning, or inflammation
• Ophthalmic: Transient burning/stinging, blurred vision, eye irritation

Serious Side Effects:

• Gastrointestinal ulceration and bleeding
• Acute renal failure
• Anaphylaxis or severe hypersensitivity
• Hepatic dysfunction
• Severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Prolonged bleeding time or hemorrhage
• Cardiovascular events (e.g., myocardial infarction, stroke)

Timing and Dose-Dependence:

• Risk increases with dose, duration >5 days, and in high-risk populations (elderly, renally impaired, patients on anticoagulants).

• Anticoagulants/Antiplatelets: Increased risk of bleeding (e.g., warfarin, aspirin, clopidogrel)
• Other NSAIDs: Additive toxicity—should not be co-administered
• Probenecid: Inhibits renal excretion of ketorolac—contraindicated
• ACE inhibitors, ARBs, Diuretics: Increased risk of renal dysfunction
• Methotrexate: Enhanced toxicity due to reduced renal clearance
• Lithium: Elevated serum lithium levels and toxicity
• SSRIs/SNRIs: Increased risk of gastrointestinal bleeding
• CYP Enzymes: Not significantly metabolized by CYP450—low potential for CYP-mediated interactions

• FDA black box warning mandates limiting systemic use to a maximum of 5 days due to GI, renal, and bleeding risks.
• EMA safety updates caution use in patients with cardiovascular or renal disease, reinforcing age and renal dosing limits.
• Updated ophthalmic safety guidance emphasizes corneal toxicity risk, advising caution in patients undergoing corneal surgery.
• Pain management guidelines recognize ketorolac as a preferred opioid-sparing agent for short-term acute pain in emergency and surgical settings.

Tablets and Injection:

• Store below 25°C
• Protect from moisture and light
• Do not freeze injectable solution
• Discard if solution is discolored or contains particulates
• Use opened vials immediately or discard remainder

Ophthalmic Solution:

• Store at 2°C to 25°C
• Do not freeze
• Discard 28 days after opening
• Avoid touching dropper tip to any surface to prevent contamination