Ketorolac

OVERVIEW

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) primarily used for the short-term management of moderate to severe pain. Below is an overview of its key aspects, including its uses, methods of administration, and properties.

DOSAGE

Adult Dosage

Intravenous (IV) or Intramuscular (IM)

Single Dose:

Patients ≥ 65 years or with renal impairment: 15 mg IV or 30 mg IM

Patients < 65 years: 30 mg IV or 60 mg IM

Multiple-Dose Treatment:

Patients ≥ 65 years or with renal impairment: 15 mg IV/IM every 6 hours (maximum: 60 mg/day)

Patients < 65 years: 30 mg IV/IM every 6 hours (maximum: 120 mg/day)

Oral

Continuation Therapy (only after IV/IM therapy):

Initial: 20 mg once and after that 10 mg every 4 to 6 hours as needed (maximum: 40 mg/day)

Nasal Spray

Weight ≥ 50 kg: 31.5 mg every 6 to 8 hours (maximum: 126 mg/day)

Weight < 50 kg: 15.75 mg every 6 to 8 hours (maximum: 63 mg/day)

Pediatric Dosage (Off-label)

Children < 2 years:

Not recommended.

Ages 2 to <16 years:

Single Dose: 0.5 mg/kg IV/IM (not to exceed 15 mg)

Multiple-Dose: Every 6 hours, not to exceed a total of five days.

Ages ≥16 years and weight <50 kg:

IV: Single dose of 15 mg or every 6 hours (maximum: 60 mg/day)

Ages ≥16 years and weight ≥50 kg:

Same as adult dosing.

Ketorolac – Dosage
Formulation	Patient Type	Single Dose	Multiple Dose	Maximum Daily Dose
Intravenous (IV)	Adults (≥ 65 years)	15 mg	15 mg every 6 hours	60 mg
	Adults (< 65 years)	30 mg	30 mg every 6 hours	120 mg
	Pediatric (2-16 years)	0.5 mg/kg (max 15 mg)	0.5 mg/kg every 6 hours	Not to exceed 5 days
Intramuscular (IM)	Adults (≥ 65 years)	30 mg	15 mg every 6 hours	60 mg
	Adults (< 65 years)	60 mg	30 mg every 6 hours	120 mg
	Pediatric (2-16 years)	0.5 mg/kg (max 15 mg)	0.5 mg/kg every 6 hours	Not to exceed 5 days
Oral	Adults	20 mg after IV/IM therapy	10 mg every 4-6 hours	40 mg
	Geriatric	10 mg after IV/IM therapy	10 mg every 4-6 hours	40 mg
	Pediatric (>16 years, <50 kg)	10 mg after IV/IM therapy	10 mg every 4-6 hours	40 mg
	Pediatric (>16 years, >50 kg)	20 mg after IV/IM therapy	10 mg every 4-6 hours	40 mg
Nasal Spray	Weight ≥50 kg	31.5 mg	Every 6-8 hours	Max: 126 mg
	Weight <50 kg	15.75 mg	Every 6-8 hours	Max: 63 mg

MECHANISM OF ACTION

Inhibition of Cyclooxygenase Enzymes

COX-1: This enzyme is constitutively active and plays a role in maintaining gastric mucosa and regulating platelet function.

COX-2: This enzyme is inducible and is mainly involved in the inflammatory response. It converts arachidonic acid into pro-inflammatory prostaglandins.

Reduction of Prostaglandin Synthesis

By blocking the COX enzyme, ketorolac reduces the production of prostaglandins, thereby reducing inflammation, pain, and fever. This action is important for its analgesic and anti-inflammatory effects.

Analgesic Properties

The analgesic effects of ketorolac are similar to those of opioids, making it effective for the management of moderate to severe pain, especially in postoperative settings. It provides pain relief without the sedative effects associated with opioids.

ADVERSE DRUG REACTIONS

Gastrointestinal Issues:

• Abdominal pain
• Nausea
• Dyspepsia (indigestion)
• Diarrhea
• Constipation
• Heartburn
• Gastrointestinal bleeding or ulcers

Central Nervous System Effects:

• Drowsiness (common, occurring in over 10% of patients)
• Dizziness
• Headaches

Other Effects:

• Edema (swelling)
• Itching or rash
• Increased blood pressure (hypertension)
• Increased serum creatinine and blood urea nitrogen (BUN)

Gastrointestinal Risks:

Serious complications include peptic ulcers, gastrointestinal bleeding, and perforation of the stomach or intestines. These risks are increased in elderly patients and those with a history of gastrointestinal problems.

Cardiovascular Risks:

The risk of serious cardiovascular thrombotic events, including myocardial infarction (heart attack) and stroke, is increased.

Renal Risks:

Possibility of acute kidney failure, especially in patients with pre-existing kidney disease or those who are dehydrated.

Hypersensitivity Reactions:

Serious allergic reactions may occur, including bronchospasm, anaphylaxis, and dermatological reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

DRUG-DRUG INTERACTIONS

Warfarin: Concomitant use increases the risk of gastrointestinal bleeding. While ketorolac does not significantly alter the pharmacokinetics of warfarin, caution is advised due to the potential for increased bleeding time and increased risk of bleeding.

Probenecid: This combination is contraindicated because probenecid decreases the clearance of ketorolac, increasing plasma concentrations and increasing the risk of adverse effects.

Methotrexate: Ketorolac may reduce the renal clearance of methotrexate, thereby increasing its toxicity. This interaction requires careful monitoring of methotrexate levels.

Pentoxifylline: The risk of bleeding increases when used together. This combination should be used with caution.

Lithium: Ketorolac may increase lithium levels, potentially leading to toxicity. Monitoring of lithium levels is recommended during concurrent use.

Diuretics: Ketorolac may reduce the effectiveness of diuretics by inhibiting renal prostaglandin synthesis, which can lead to fluid retention and increased blood pressure.

NSAIDs: Concomitant use increases the risk of gastrointestinal side effects, such as ulcers and bleeding. The effectiveness of ketorolac may also be reduced when taken with aspirin.

USE

Post-operative pain: Ketorolac is usually prescribed to control acute pain following surgery. It is effective in reducing the intensity of pain and improving comfort in recovery.

Acute pain: It is indicated for a variety of acute pain, including pain from injuries, musculoskeletal disorders, and headaches.

Adjunct to Opioids: Ketorolac is often used as an adjunct to opioid medications, thereby reducing the dosage of opioids and minimizing associated side effects, such as nausea and constipation.

Menstrual Pain: It is effective in treating dysmenorrhea and provides relief from cramps and discomfort during menstruation.

Ocular Uses: Ketorolac is available in the form of eye drops and is used to treat eye inflammation and pain, especially after eye surgery. It can also help manage the symptoms of allergic conjunctivitis.

Idiopathic Pericarditis: Ketorolac can be used to reduce inflammation in cases of idiopathic pericarditis.

Combination therapy: It can be combined with other analgesics for pain relief in various clinical conditions.