Ketorolac | Pharmacology Mentor

Generic Name

Ketorolac

Mechanism

Ketorolac is a non‑steroidal anti‑inflammatory drug (NSAID) that provides potent analgesia by:
• Potently inhibiting cyclo‑oxygenase (COX‑1 and COX‑2), thereby blocking the conversion of arachidonic acid to prostaglandin H₂.
• Resulting in decreased synthesis of prostaglandins (PGD₂, PGE₂, PGF₂α, and TXA₂), which mediate pain, inflammation, and fever.
• Its analgesic effect is primarily mediated by suppression of peripheral COX‑1‑driven prostaglandin production; it has minimal central nervous system activity.

Pharmacokinetics

Parameter	Key Points
Absorption	Rapid after IV; oral peak 30–60 min; bioavailability ≈ 60‑70 %.
Distribution	Highly protein‑bound (~ 95 % to albumin); volume of distribution ~ 0.5 L/kg.
Metabolism	Predominantly hepatically conjugated (glucuronidation) with minor CYP involvement.
Elimination	Renally excreted (~ 70 % unchanged); renal clearance 0.8–1.0 L/h.
Half‑life	5–6 h (IV); 6–8 h (oral).
Drug‑drugs interactions	↑ risk of nephrotoxicity, GI bleeding, and anticoagulant effects when combined with other NSAIDs, anticoagulants, or ACE inhibitors.

Indications

Short‑term (<5 days) management of moderate‑to‑severe acute pain (post‑operative, trauma, dental procedures).
Alternative to opioids for patients with contraindications or when opioid sparing is desired.
Pre‑operative analgesia to reduce peri‑operative opioid consumption.

Contraindications

Known hypersensitivity to ketorolac or other NSAIDs.
Active or history of gastro‑intestinal ulceration or bleeding.
Severe renal (CrCl < 30 mL/min) or hepatic dysfunction.
Pregnancy (particularly 3rd trimester) – avoid due to risk of premature ductus arteriosus constriction and oligohydramnios.
Bleeding disorders or concurrent anticoagulant therapy (warfarin, heparin).
Pseudomonas cystitis and severe urinary obstruction.
Asthma: possible exacerbation due to leukotriene shift.

Use caution in elderly, renal insufficiency, hepatic impairment, cardiac disease, or when combined with other NSAIDs.

Dosing

Form	Loading Dose	Maintenance	Max Daily	Notes
IV/IM	30 mg once	15 mg q6–8 h	120 mg/day	Use for acute pain; limit total exposure to ≤5 days.
Oral	15 mg q8 h (up to 40 mg/day)	15 mg q8 h	40 mg/day	Requires slow‑release formulation (ketorolac tromethamine).
Topical	5 % ointment/cream	Apply 4×/day	Not studied for systemic toxicity	Use for localized pain (dermatologic inflammation).

• Avoid in patients with CrCl < 30 mL/min; dose adjustment often not meaningful due to increased systemic exposure.
• Start at lowest effective dose; titrate based on pain control.

Adverse Effects

GI: dyspepsia, nausea, abdominal pain, ulceration, hemorrhage.
Renal: AKI, electrolyte disturbances, oliguria, increased serum creatinine (especially with dehydration).
Hematologic: thrombocytopenia, impaired platelet aggregation (evidence for increased bleeding).
Cardiovascular: transient hypertension, fluid retention.
Other: headache, dizziness, urinary retention, rash.

Serious adverse events are rare but may involve peptic ulcer disease with perforation/bleeding, renal failure, or serious hypersensitivity reactions (angioedema, bronchospasm).

Monitoring

Parameter	Rationale
Renal function (Cr, BUN, eGFR)	Detect early AKI; adjust dose or discontinue if >50% drop.
Complete blood count (CBC)	Monitor platelet count and anemia.
Liver function tests (AST, ALT, bilirubin)	Hepatotoxicity monitoring; limited data but advisable.
Blood pressure & urinary output	Assess fluid status and hypertension.
Pain scores (VAS/NRS)	Ensure therapeutic efficacy.
If on anticoagulants	Monitor INR/PTA for bleeding risk.

Clinical Pearls

Limit total therapy to ≤5 days; beyond this, GI and renal complications rise steeply.
Prophylactic PPIs (omeprazole 20 mg) are recommended when oral ketorolac is used in patients at risk of ulcers (e.g., chronic NSAID use, Helicobacter pylori infection).
Avoid co‑administration with ACE inhibitors, ARBs, diuretics, or hydrochlorothiazide in patients with borderline renal function to prevent additive sodium‑water retention and renal impairment.
In elderly patients (≥65 yr), start at the lowest dose (15 mg IV/IM) and monitor renal function closely; consider alternatives such as acetaminophen or opioids if comorbidities are significant.
Warfarin interaction: ketorolac can increase INR by ~20–25 %; hold ketorolac until INR is stable or use alternative analgesics.
Use of topical ketorolac reduces systemic absorption; ideal for superficial musculoskeletal or dermal inflammation when systemic exposure is unnecessary.
For post‑operative pain in patients at high GI risk (e.g., prior ulcer disease), opt for multimodal analgesia combining a limited course of ketorolac with acetaminophen and a short course of opioids rather than ketorolac alone.

> Reference: FDA prescribing information, UpToDate “Ketorolac for acute pain,” and *Review of Clinical Pharmacology* (2025).