Usage
Dexamethasone + Ketorolac combination is prescribed for short-term management of moderate to severe pain, particularly post-operative pain, where both anti-inflammatory and analgesic effects are desired. It is also prescribed for acute renal colic. It is not for chronic or minor pain.
Pharmacological Classification:
- Dexamethasone: Corticosteroid, Anti-inflammatory
- Ketorolac: Nonsteroidal anti-inflammatory drug (NSAID), Analgesic
Mechanism of Action:
Dexamethasone reduces inflammation by inhibiting inflammatory mediators. Ketorolac inhibits prostaglandin synthesis, reducing pain and inflammation. The combination provides synergistic pain relief and reduces inflammation.
Alternate Names
There is no official alternate name for the combination, however the drugs are often referred together as “Decadron and Toradol” due to popular brand names.
Brand Names:
There are no combined brand names for this drug combination, each medication is available under individual brand names.
- Dexamethasone: Decadron, Dexamethasone Intensol, Dexpak and others.
- Ketorolac: Toradol
How It Works
Pharmacodynamics: Dexamethasone exerts its anti-inflammatory effects by binding to glucocorticoid receptors, modulating gene expression, and suppressing inflammatory pathways. Ketorolac inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, thereby decreasing pain and inflammation.
Pharmacokinetics:
- Dexamethasone: Well-absorbed orally, IM, and IV. Metabolized in the liver and excreted renally. Long half-life (36-54 hours).
- Ketorolac: Well-absorbed orally, IM, and IV. Peak plasma concentration occurs in about 1 hour (IM) or 30 minutes (IV). Highly protein-bound. Metabolized in the liver to inactive metabolites and excreted primarily in the urine. Short half-life (2.5-9 hours).
Mode of Action/Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dexamethasone binds to glucocorticoid receptors, influencing gene transcription. Ketorolac inhibits COX enzymes non-selectively.
Elimination Pathways: Both are primarily eliminated by hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults:
- Weight ≥ 50 kg:
- IM/IV: Initial dose 30 mg IV/IM followed by 15 to 30 mg IV or IM every 6 hours; maximum daily dose: 120 mg for up to 5 days.
- Oral: 20 mg once after IV/IM therapy, then 10 mg every 4-6 hours; maximum daily dose 40mg for up to 5 days total.
- Intranasal: 15.75 mg every 6 to 8 hours (one spray in 1 nostril); Maximum dose: 63 mg/day.
- Weight < 50 kg:
- IM/IV: Initial dose 15 mg IV/IM followed by 15 mg IV/IM every 6 hours; maximum daily dose: 60 mg for up to 5 days.
- Oral: 10 mg once after IV/IM therapy, then 10 mg every 4-6 hours; maximum daily dose 40mg for up to 5 days total.
Children:
- 1 month to <2 years: 0.5 mg/kg IV every 6-8 hours.
- 2 to 16 years: Single dose: 1 mg/kg IM (max 30 mg) or 0.5 mg/kg IV (max 15 mg). Multiple dose: 0.5 mg/kg IM/IV every 6 hours (max 15 mg/dose) for up to 5 days.
- For moderately severe acute pain (off-label): Single dose: 0.5 mg/kg IV/IM once (not to exceed 15 mg). Multiple dose: 0.5 mg/kg IV/IM every 6 hours (not to exceed 5 days).
Pediatric safety: Use with caution; monitor for gastrointestinal and renal adverse effects. Total duration of therapy should not exceed 5 days.
Special Cases:
- Elderly Patients: Reduced doses are recommended due to decreased renal and hepatic function. Start with the lowest dose and titrate as needed. Maximum dose should not exceed 60 mg/day IM/IV or 40 mg/day oral.
- Patients with Renal Impairment:
- Moderate: 50% of the recommended dose; not to exceed 60 mg/day IM/IV.
- Severe: Contraindicated.
- Patients with Hepatic Dysfunction: Use with caution and at reduced doses. Monitor closely for adverse effects.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, cardiovascular disease, or other relevant conditions. Adjust dose as needed.
Clinical Use Cases
Dosing is generally as outlined above. Duration of therapy should not exceed 5 days.
- Intubation: Premedication with Dexamethasone might reduce incidence of postoperative sore throat.
- Surgical Procedures: Commonly used for post-operative pain management.
- Mechanical Ventilation: Use with caution, especially in patients at increased risk for gastrointestinal bleeding.
- Intensive Care Unit (ICU) Use: Careful monitoring is required due to the potential for renal and gastrointestinal complications.
- Emergency Situations: Ketorolac may be used for short-term pain control in emergencies.
Dosage Adjustments: Adjustments are necessary based on renal function, hepatic function, age, weight, and comorbidities. Consult package insert or clinical guidelines for specific adjustments.
Side Effects
Common Side Effects:
- Gastrointestinal upset (nausea, dyspepsia, diarrhea, constipation)
- Headache
- Dizziness
- Drowsiness
- Fluid retention
- Increased blood pressure
- Increased blood glucose
- Insomnia
Rare but Serious Side Effects:
- Gastrointestinal bleeding or perforation
- Renal failure
- Allergic reactions (rash, itching, swelling, anaphylaxis)
- Cardiovascular events (heart attack, stroke)
- Adrenal insufficiency (with prolonged Dexamethasone use)
Long-Term Effects: Long-term use (greater than 5 days) of Ketorolac is contraindicated. Long-term use of Dexamethasone can lead to Cushing’s syndrome, osteoporosis, cataracts, and increased risk of infections.
Contraindications
- Hypersensitivity to ketorolac, dexamethasone, or other NSAIDs.
- Active peptic ulcer disease or gastrointestinal bleeding.
- History of aspirin-exacerbated respiratory disease.
- Recent myocardial infarction or cerebrovascular accident.
- Pre- or post-operative use with coronary artery bypass graft (CABG) surgery.
- Bleeding disorders.
- Severe renal impairment.
- Intrathecal or epidural use (due to the alcohol content in Ketorolac injection).
- Use after 30 weeks gestation (Ketorolac).
Drug Interactions
- Other NSAIDs (increased risk of gastrointestinal bleeding)
- Anticoagulants (increased risk of bleeding)
- Corticosteroids (increased risk of gastrointestinal bleeding)
- ACE inhibitors, Angiotensin receptor blockers, Diuretics (reduced antihypertensive effect, increased risk of kidney problems).
- Lithium (increased lithium levels)
- Methotrexate (increased methotrexate toxicity)
Pregnancy and Breastfeeding
- Pregnancy: Ketorolac is contraindicated after 30 weeks of gestation. Dexamethasone should be used with caution.
- Breastfeeding: Ketorolac is present in breast milk and should be avoided. Dexamethasone is present in breast milk, but at low levels and is generally considered safe in breastfeeding.
Drug Profile Summary
- Mechanism of Action: Dexamethasone: Glucocorticoid receptor agonist, anti-inflammatory. Ketorolac: COX inhibitor, analgesic and anti-inflammatory.
- Side Effects: GI upset, bleeding, headache, dizziness, fluid retention, increased blood pressure, increased blood glucose.
- Contraindications: Hypersensitivity, active peptic ulcer disease, GI bleeding, asthma exacerbated by NSAIDs, recent MI or stroke, perioperative CABG use, pregnancy (after 30 weeks gestation for Ketorolac)
- Drug Interactions: NSAIDs, anticoagulants, corticosteroids, ACE inhibitors/ARBs, lithium, methotrexate.
- Pregnancy & Breastfeeding: Avoid Ketorolac after 30 weeks of gestation. Caution is advised with both drugs during pregnancy and breastfeeding.
- Dosage: Varies by age, weight, and route of administration. Maximum duration of treatment is 5 days.
- Monitoring Parameters: Renal function, liver function, blood pressure, signs of gastrointestinal bleeding, blood glucose.
Popular Combinations
This combination is often used in clinical practice.
Precautions
- Careful patient selection is crucial, considering the risks of gastrointestinal and renal side effects.
- Close monitoring of patients with renal, hepatic, or cardiac issues.
- Limit therapy to a maximum of 5 days.
- Educating patients about potential side effects and reporting unusual symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dexamethasone + Ketorolac?
A: See dosage section above, as dosage varies greatly by patient-specific factors.
Q2: Can Dexamethasone and Ketorolac be mixed in the same syringe?
A: No, they should not be mixed in the same syringe unless specifically formulated for combined administration (such as certain ophthalmic preparations).
Q3: What are the major contraindications to using this combination?
A: Active peptic ulcer disease, bleeding disorders, severe renal impairment, and hypersensitivity are major contraindications.
Q4: Can this combination be used in pregnancy?
A: Ketorolac is contraindicated after 30 weeks of gestation. Dexamethasone use during pregnancy should be carefully evaluated, balancing risks and benefits.
Q5: Can this drug be used in breastfeeding women?
A: Ketorolac use while breastfeeding is generally discouraged. Dexamethasone use during breastfeeding is generally considered safe at low doses, but maternal and infant should be monitored.
Q6: What monitoring parameters are important when using Dexamethasone + Ketorolac?
A: Renal function, liver function tests, blood pressure, signs of gastrointestinal bleeding, and blood glucose levels should be monitored.
Q7: What are the signs of a severe allergic reaction to this combination?
A: Difficulty breathing, swelling of the face or throat, hives, and rapid heart rate are signs of a severe allergic reaction and require immediate medical attention.
Q8: How long can a patient safely use this combination?
A: Maximum duration of therapy is 5 days due to increased risk of adverse effects with prolonged use.
Q9: What are the most common drug interactions to be aware of?
A: Co-administration with other NSAIDs, anticoagulants, corticosteroids, ACE inhibitors/ARBs may increase the risk of adverse effects.
Q10: What patient education points are important to emphasize?
A: Educate the patient about the importance of taking the medication as prescribed, not exceeding the recommended dose or duration of treatment, and promptly reporting any signs of gastrointestinal bleeding or other adverse effects.
