1. Clinical Overview
A fixed-dose combination (FDC) of Ketorolac Tromethamine, a potent non-steroidal anti-inflammatory drug (NSAID), and Dexamethasone, a potent synthetic glucocorticoid. This combination provides synergistic anti-inflammatory, analgesic, and anti-edema effects, primarily used for short-term management of moderate to severe acute pain and inflammation, particularly in post-operative, musculoskeletal, and ophthalmic conditions. The combination aims to reduce the total dose of each component, potentially minimizing individual side effects while enhancing therapeutic efficacy.
| Onset | Duration | Bioavailability |
|---|---|---|
| Ketorolac: 30-60 minutes (oral/IM). Dexamethasone: Rapid, within 1-2 hours. | Ketorolac: 4-6 hours. Dexamethasone: 36-54 hours (due to long biological half-life). | Ketorolac: ~100% (IM), ~80-100% (Oral). Dexamethasone: ~78% (Oral). |
2. Mechanism of Action
The combination exerts a multi-modal action. Ketorolac is a non-selective, reversible inhibitor of cyclooxygenase (COX-1 and COX-2) enzymes, thereby inhibiting the synthesis of prostaglandins (PGs), thromboxanes, and prostacyclins from arachidonic acid. This reduces pain, fever, and inflammation at the site. Dexamethasone acts as a potent glucocorticoid receptor agonist. The drug-receptor complex translocates to the nucleus, modulating gene transcription. It induces the synthesis of anti-inflammatory proteins (like lipocortin) and inhibits the production of pro-inflammatory mediators (cytokines, chemokines, adhesion molecules, COX-2). The synergy results in enhanced suppression of inflammation and pain with a potential steroid-sparing effect.
3. Indications & Uses
- Short-term management of moderate to severe acute pain with significant inflammatory component
- Post-operative pain and inflammation (e.g., dental, orthopedic, abdominal surgery)
- Acute musculoskeletal disorders (e.g., acute low back pain, tendonitis, bursitis)
- Ophthalmic inflammation (post-operative or non-infectious) - in specific formulations
4. Dosage & Administration
Adult Dosage: Dosage must be individualized. Typical: 1 tablet (Ketorolac 10 mg + Dexamethasone 0.5 mg) orally every 8 to 12 hours. For IM use: As directed by physician, typically once or twice daily. MAXIMUM DURATION: 5 DAYS for Ketorolac component.
Administration: Take with food or a full glass of milk to minimize GI upset. Do not crush or chew sustained-release formulations. For IM injection, administer deep into a large muscle mass. Do not use for more than 5 days. Do not switch from parenteral to oral therapy (leads to excessive total dose).
5. Side Effects
Common side effects may include:
- Nausea, dyspepsia, abdominal pain
- Headache, dizziness
- Fluid retention, edema
- Insomnia, nervousness (Dexamethasone)
- Increased appetite
- Injection site pain (IM)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Anticoagulants (Warfarin, NOACs) | Increased risk of bleeding due to antiplatelet effect of Ketorolac and potential GI ulceration. | Major |
| Anti-platelets (Aspirin, Clopidogrel) | Additive risk of GI bleeding. Ketorolac may antagonize antiplatelet effect of aspirin. | Major |
| Other NSAIDs or Corticosteroids | Increased risk of GI toxicity and renal impairment. | Major |
| ACE Inhibitors (Enalapril), ARBs (Losartan), Diuretics | Reduced antihypertensive efficacy; increased risk of renal impairment. | Moderate |
| Methotrexate | Decreased renal clearance of Methotrexate, leading to increased toxicity. | Major |
| Lithium | Decreased renal clearance of Lithium, leading to toxicity. | Major |
| Antidiabetics (Insulin, Metformin) | Dexamethasone causes hyperglycemia; may require dose adjustment. | Moderate |
| Cyclosporine, Tacrolimus | Increased risk of nephrotoxicity and seizures. | Major |
| Enzyme Inducers (Phenytoin, Rifampicin) | Increased metabolism of Dexamethasone, reducing its efficacy. | Moderate |
| Ketoconazole, Itraconazole | Inhibit CYP3A4, increasing Dexamethasone levels and toxicity. | Moderate |
| Probenecid | Markedly increases Ketorolac plasma levels; contraindicated. | Major |
7. Patient Counselling
- DO take with food or milk to reduce stomach upset.
- DO inform all your doctors and dentists you are taking this medicine before any surgery or new prescription.
- DO report any signs of stomach pain, black tarry stools, or vomiting blood immediately.
- DO monitor blood sugar if diabetic.
- DO NOT take for more than 5 days unless specifically instructed by your doctor.
- DO NOT take other over-the-counter NSAIDs (like ibuprofen, naproxen) or aspirin while on this medication.
- DO NOT consume alcohol.
- DO NOT use in pregnancy or breastfeeding without consulting your doctor.
8. Toxicology & Storage
Overdose: Ketorolac: Nausea, vomiting, epigastric pain, GI bleeding, lethargy, drowsiness, acute renal failure, metabolic acidosis, coma, seizures. Dexamethasone: Cushingoid symptoms (moon face, central obesity), severe hypertension, hyperglycemia, psychosis, fluid and electrolyte disturbances.
Storage: Store below 30°C. Protect from light and moisture. Keep out of reach of children. Do not freeze. For injections, store in original packaging. Do not use if solution is discolored or contains particulate matter.