Ketorolac

Usage

Ketorolac is prescribed for the short-term (up to 5 days) management of moderately severe acute pain that requires analgesia at the opioid level. It is not indicated for minor or chronic pain conditions. It belongs to the pharmacological classification of nonsteroidal anti-inflammatory drugs (NSAIDs). Ketorolac works by inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, which are responsible for producing prostaglandins, substances that mediate pain and inflammation. By reducing prostaglandin synthesis, ketorolac exerts its analgesic and anti-inflammatory effects.

Alternate Names

Ketorolac tromethamine is the generic name. A popular brand name is Toradol.

How It Works

Pharmacodynamics: Ketorolac exerts its analgesic effect primarily through peripheral inhibition of COX, leading to a decrease in prostaglandin synthesis. It also possesses anti-inflammatory and antipyretic properties, though these are less prominent.

Pharmacokinetics:

• Absorption: Rapidly and completely absorbed after oral administration. IM administration results in peak plasma levels within 1-2 hours. IV administration achieves peak plasma levels within minutes.
• Metabolism: Hepatic metabolism via glucuronidation.
• Elimination: Primarily renal excretion (approximately 92%), with about 40% eliminated as metabolites. The elimination half-life is around 5-6 hours in adults.

Mode of Action: Ketorolac binds to COX-1 and COX-2 enzymes, preventing the conversion of arachidonic acid to prostaglandin precursors. This reduces the formation of prostaglandins, thus diminishing pain and inflammation.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Ketorolac primarily works through enzyme inhibition (COX-1 and COX-2). It does not have significant receptor binding or neurotransmitter modulation activity.

Elimination Pathways: Primarily renal excretion, as mentioned above.

Dosage

Standard Dosage

Adults:

• IV/IM: Initial dose: 30 mg. Subsequent doses: 30 mg every 6 hours, not to exceed 120 mg/day.
• Oral: Initial dose: 20 mg after IV/IM therapy. Subsequent doses: 10 mg every 4-6 hours, not to exceed 40 mg/day. Oral ketorolac should only be used as a continuation of IV/IM therapy.

Children:

Ketorolac is not FDA-approved for use in children under 17. Off-label use in pediatric patients should be carefully considered, weighing the benefits against potential risks.

• Off-label (2-16 years): Single dose: 0.5 mg/kg IV/IM (max 15 mg). Multiple doses: 0.5 mg/kg IV/IM every 6 hours (max 5 days).

Special Cases:

• Elderly Patients (≥65 years): Reduced dosages are recommended. IV/IM: 15 mg every 6 hours, not exceeding 60 mg/day. Oral: 10 mg every 4-6 hours, not exceeding 40 mg/day.
• Patients with Renal Impairment: Contraindicated in severe renal impairment. Moderate impairment: reduce dose by 50%, not to exceed 60 mg/day IM/IV.
• Patients with Hepatic Dysfunction: Use with caution. Discontinue if signs of liver toxicity appear.
• Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, cardiovascular disease, and other conditions that may be exacerbated by NSAID use.

Clinical Use Cases

Ketorolac is primarily used for postoperative pain management. Its use in other settings, while possible, should be carefully evaluated. It is not recommended for long-term use or for chronic pain conditions. The provided sources do not specify different dosing strategies for situations like intubation, surgical procedures, mechanical ventilation, ICU use, or specific emergency situations. The general dosing guidelines for adults and special populations should be followed.

Dosage Adjustments

Dose modifications may be required as outlined above for elderly patients, those with renal impairment, hepatic dysfunction, or other relevant conditions. Close monitoring is essential in all cases.

Side Effects

Common Side Effects:

Headache, dizziness, drowsiness, nausea, diarrhea, constipation, gastrointestinal discomfort.

Rare but Serious Side Effects:

Gastrointestinal bleeding, peptic ulcer, renal impairment, myocardial infarction, stroke, allergic reactions, Stevens-Johnson syndrome.

Long-Term Effects:

Long-term use (beyond 5 days) significantly increases the risk of serious side effects, including cardiovascular and gastrointestinal complications.

Adverse Drug Reactions (ADR):

Any serious adverse event related to ketorolac, such as anaphylaxis, severe GI bleeding, or acute renal failure, constitutes a clinically significant ADR and requires immediate medical intervention.

Contraindications

• Hypersensitivity to ketorolac.
• Active peptic ulcer disease.
• History of GI bleeding or perforation.
• Recent or planned coronary artery bypass graft (CABG) surgery.
• Advanced renal impairment.
• Hypovolemia.
• Labor and delivery.
• Concurrent use of aspirin or other NSAIDs.
• Bleeding diathesis.
• Cerebrovascular bleeding.
• Intrathecal or epidural administration.

Drug Interactions

• Antiplatelet agents (e.g., clopidogrel): Increased bleeding risk.
• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Antihypertensives (e.g., ACE inhibitors, ARBs): Reduced antihypertensive effect and increased risk of renal impairment.
• Lithium: Increased lithium levels.
• Methotrexate: Increased methotrexate toxicity.
• Corticosteroids: Increased GI bleeding risk.
• Diuretics: Reduced diuretic effect.

Pregnancy and Breastfeeding

• Pregnancy: Ketorolac is contraindicated in the third trimester due to the risk of premature closure of the ductus arteriosus. Use during the first and second trimesters should be avoided if possible.
• Breastfeeding: Ketorolac is excreted in breast milk. Alternate analgesics are preferred, particularly during the first few days postpartum and when breastfeeding a newborn or preterm infant.

Drug Profile Summary

• Mechanism of Action: Inhibits COX-1 and COX-2 enzymes, reducing prostaglandin synthesis.
• Side Effects: Headache, dizziness, GI upset, bleeding, peptic ulcer, renal impairment, MI, stroke.
• Contraindications: Hypersensitivity, active peptic ulcer, GI bleeding, CABG, renal impairment, pregnancy (third trimester), breastfeeding.
• Drug Interactions: Anticoagulants, antiplatelets, antihypertensives, lithium, methotrexate.
• Pregnancy & Breastfeeding: Avoid if possible during pregnancy; contraindicated in the third trimester. Use with caution while breastfeeding; alternative analgesics preferred.
• Dosage: Adults: IV/IM 30 mg every 6 hours (max 120 mg/day), Oral 10 mg every 4-6 hours (max 40 mg/day) following IV/IM therapy. Elderly and renal impairment: Lower dosages are recommended.
• Monitoring Parameters: Renal function, signs of GI bleeding, blood pressure.

Popular Combinations

No information is available from the sources provided about popular Ketorolac drug combinations.

Precautions

• General Precautions: Assess renal function, history of GI bleeding, and cardiovascular risk factors before initiating treatment. Monitor for adverse effects throughout therapy.
• Specific Populations: Use with caution in elderly patients, those with renal or hepatic impairment, pregnant women, and breastfeeding mothers.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ketorolac?

A: Adults: IV/IM 30 mg every 6 hours (max 120 mg/day). Oral: 20 mg initially followed by 10 mg every 4-6 hours (max 40 mg/day) as continuation therapy after IV/IM dosing. Elderly patients and those with renal impairment: Lower dosages are necessary. Pediatric use is off-label and requires careful consideration.

Q2: What is the maximum duration of Ketorolac therapy?

A: 5 days, regardless of the route of administration (oral, IV, IM, or nasal).

Q3: Can Ketorolac be used for chronic pain?

A: No, ketorolac is indicated only for the short-term management of moderately severe acute pain.

Q4: What are the most serious side effects of Ketorolac?

A: GI bleeding, peptic ulcer, renal impairment, myocardial infarction, and stroke.

Q5: Can Ketorolac be used during pregnancy?

A: Use should be avoided if possible, especially during the third trimester. It is contraindicated in the third trimester.

Q6: Can Ketorolac be used while breastfeeding?

A: Use with caution. Alternative analgesics are preferred, especially when breastfeeding a newborn or preterm infant.

Q7: How does Ketorolac interact with other NSAIDs?

A: Concurrent use of Ketorolac with other NSAIDs is contraindicated due to increased risk of adverse effects.

Q8: Does Ketorolac affect blood clotting?

A: Yes, Ketorolac inhibits platelet function and can increase the risk of bleeding. It should be used cautiously in patients with bleeding disorders or those taking anticoagulants or antiplatelet medications.

Q9: Can Ketorolac be given epidurally or intrathecally?

A: No, these routes of administration are contraindicated.