ketorolac

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) used for short-term (less than 5 days) management of acute pain that requires opioid level of pain relief (analgesia).

Ketorolac relieves pain by inhibiting inflammatory activity in the body. Ketorolac is typically used as a pain reliever before or after medical procedures or after surgeries.

Ketorolac controls inflammation by inhibiting the activity of enzymes known as cyclooxygenases (COX-1 and COX-2), essential for biosynthesis of prostaglandin. Prostaglandin is a fatty compound that promotes inflammation, leading to symptoms including pain, fever and swelling. Ketorolac also inhibits the movement and aggregation of inflammatory cells, and the release of proinflammatory proteins (cytokines). Ketorolac inhibits platelet aggregation, which can increase the risk of bleeding, a major side effect of the drug.

• Do not use ketorolac for treating minor or chronic pain
• Do not use for perioperative pain in major surgeries and coronary artery bypass graft (CABG) surgery
• Do not use during labor and delivery, it may adversely affect fetal circulation, inhibit uterine contractions and increase the risk of uterine hemorrhage
• Do not use in patients with known or suspected hypersensitivity to ketorolac, aspirin or other NSAIDs
• Do not use simultaneously with other NSAIDs because of the cumulative risk
• Do not use ketorolac concomitantly with the following drugs:
• probenecid
• pentoxifylline
• Do not administer as epidural or intrathecal injections into the spine due to the alcohol content in ketorolac

Gastrointestinal risk:

• Do not use in patients with active peptic ulcer disease, recent gastrointestinal (GI) bleeding or perforation, or history of peptic ulcer disease or GI bleeding.
• Ketorolac can cause serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation
• GI adverse events may occur at any time during use and without warning symptoms
• Elderly patients are at greater risk for serious GI events

Cardiovascular risk:

• Ketorolac may increase the risk of serious cardiovascular clotting (thrombotic) events, heart attack (myocardial infarction), and stroke
• Risk for the above may increase with duration of use
• Do not use ketorolac in patients with existing cardiovascular disease or risk factors for such disease, they may have greater cardiovascular risk
• Ketorolac has the potential to trigger heart failure by prostaglandin inhibition which can lead to sodium and water retention, increase in blood pressure, and reduced response to diuretics
• Patients treated with NSAIDs such as ketorolac following heart attack are reported to be more likely to die in the first year of heart attack compared to patients not treated with NSAIDs after first heart attack

Renal risk:

• Do not use in patients with advanced renal impairment and in patients at risk for renal failure due to blood volume depletion (hypovolemia)

Risk of bleeding:

• Do not use in patients with bleeding disorders such as suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and those at a high risk of bleeding. Ketorolac inhibits platelet functions and increases bleeding risks

Common side effects of ketorolac include:

• Headache
• Increase in liver enzymes
• Gastrointestinal symptoms such as:
  • Abdominal pain
  • Indigestion (dyspepsia)
  • Nausea
  • Vomiting
  • Constipation
  • Diarrhea
  • Gas (flatulence)
  • Heartburn
  • Gastrointestinal fullness
  • Gastrointestinal ulcers
  • Sore and inflamed mouth (stomatitis)
• Dizziness
• Drowsiness (somnolence)
• Abnormal kidney function
• Increase in blood urea nitrogen (BUN)
• Increase in serum creatinine
• Swelling (edema)
• High blood pressure (hypertension)
• Pain at injection site
• Skin reactions such as:
  • Excessive sweating (diaphoresis)
  • Itching (pruritus)
  • Skin rash
• Blood disorders such as:
  • Low red blood cell count (anemia)
  • Increased bleeding time
  • Bruising (purpura)
• Ringing in ears (tinnitus)

Serious side effects include:

• Gastrointestinal bleeding
• Gastrointestinal perforation
• Congestive heart failure
• Heart attack (myocardial infarction), rare
• Liver failure
• Kidney failure
• Coma (rare)

Less common side effects include:

• Fever
• Infections
• Sepsis
• Changes in appetite
• Changes in weight
• Dry mouth
• Blood in vomit
• Rectal bleeding
• Dark, tarry stools (melena)
• Gastrointestinal inflammation (esophagitis, gastritis, hepatitis)
• Nasal bleeding (epistaxis)
• Palpitations
• Irregular heartbeat (arrhythmia)
• Rapid or slow heartbeat (tachycardia or bradycardia)
• Chest pain
• Fainting (syncope)
• Pale skin (pallor)
• Flushing
• Hives (urticaria)
• Light sensitivity
• Bronchospasm
• Shortness of breath (dyspnea)
• Throat/tongue swelling
• Blurred vision
• Hearing loss
• Abnormal taste
• Bladder infection (cystitis)
• Painful urination (dysuria)
• Urinary retention
• Urinary frequency
• Blood in urine (hematuria)
• Damage to blood vessels in the kidney (hemolytic-uremic syndrome)
• Confusion
• Depression
• Abnormal thinking
• Anxiety
• Euphoria
• Insomnia
• Abnormal dreams
• Lack of concentration
• Tremors
• Vertigo

Rare side effects include:

• Hypersensitivity reactions including
  • Swelling of tissue under the skin and mucous membranes (angioedema)
  • Severe allergic reaction (anaphylaxis)
• Severe skin reactions including:
  • Exfoliative dermatitis
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Exacerbation of inflammatory bowel diseases (ulcerative colitis, Crohn’s disease)
• High blood glucose levels (hyperglycemia)
• High blood potassium levels (hyperkalemia)
• Low blood sodium levels (hyponatremia)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 10 mg

Injectable solution

• 15 mg/mL
• 30 mg/mL

Prefilled syringe

• 15 mg/mL
• 30 mg/mL
• 60 mg/mL

Moderately Severe Acute Pain

• Short-term (up to 5 days) management of moderately severe acute pain that requires analgesia at opioid level; not indicated for minor or chronic painful conditions

Adult

• Intravenous (IV): 30 mg as a single dose or 30 mg every 6 hours; not to exceed 120 mg/day
• Intramuscular (IM): 60 mg as a single dose or 30 mg every 6 hours; not to exceed 120 mg/day
• Oral: 20 mg once after IV or IM therapy, THEN 10 mg every 4-6 hours; not to exceed 40 mg/day

Dosing Considerations

• Always begin with parenteral therapy; oral administration indicated only as a continuation of intravenous/intramuscular (IV/IM) dosing, if necessary
• Use the lowest effective dose for the shortest duration based on individual patient needs, to minimize risk of gastrointestinal adverse events
• Duration of therapy should not exceed 5 days
• Dosage beyond maximum or labeled doses will not provide better efficacy but will increase the risk of serious adverse events
• Decrease daily dose in patients over 65 years, less than 50 kg, or with moderately elevated serum creatinine

Dosing Modifications

Renal impairment

• Severe: Contraindicated
• Moderate (moderately elevated serum creatinine): Use 50% of recommended dosage; not to exceed 60 mg/day intramuscular/intravenous (IM/IV)

Hepatic impairment

• Not studied; use caution; discontinue if symptoms of liver toxicity develop

Geriatric

• Intravenous (IV): 15 mg as a single dose or 15 mg every 6 hours; not to exceed 60 mg/day
• Intramuscular (IM): 30 mg as a single dose or 15 mg every 6 hours; not to exceed 60 mg/day
• Oral: 10 mg once after IV or IM therapy, THEN 10 mg every 4-6 hours; not to exceed 40 mg/day

Dosing considerations

• Long-term use should be avoided because of asymptomatic, pathologic gastrointestinal (GI) conditions; duration of therapy should not exceed 5 days
• Dosage adjustment required for patients over 65 years or less than 50 kg

Pediatric

(Off-label)

Children below 2 years of age

• Safety and efficacy not established

Children 2-16 years of age

• 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

Children above 16 years of age, less than 50 kg

• Intravenous (IV): 15 mg as a single dose or 15 mg every 6 hours; not to exceed 60 mg/day
• Intramuscular (IM): 30 mg as a single dose or 15 mg every 6 hours; not to exceed 60 mg/day
• Oral: 10 mg once after IV/IM therapy, then 10 mg every 4-6 hours; not to exceed 40 mg/day

Children above 16 years of age, greater than 50 kg

• Intravenous (IV): 30 mg as a single dose or 30 mg every 6 hours; not to exceed 120 mg/day
• Intramuscular (IM): 60 mg as a single dose or 30 mg every 6 hours; not to exceed 120 mg/day
• Oral: 20 mg once after IV/IM therapy, then 10 mg every 4-6 hours; not to exceed 40 mg/day

Dosing Considerations

• Not FDA-approved for use in pediatric patients
• Duration of therapy should not exceed 5 days

• Overdose can cause several symptoms including lethargy, abdominal pain, nausea and vomiting, hypertension and acute renal failure.
• There is no specific antidote for ketorolac and overdose must be treated with symptomatic and supportive care, such as administering activated charcoal and/or inducing vomiting (emesis).

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of ketorolac include:
  • None
• Ketorolac has serious interactions with at least 47 different drugs.
• Ketorolac has moderate interactions with at least 228 different drugs.
• Ketorolac has mild interactions with at least 78 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies of ketorolac in pregnant women. Use ketorolac with caution during the first and second trimester of pregnancy only if the potential benefits outweigh the potential risk to the fetus.
• Use ketorolac only in life-threatening emergencies in late pregnancy (third trimester), it may cause fetal harm by interfering with the fetal blood circulation (premature closure of ductus arteriosus).
• Do not use ketorolac during labor and delivery, it may adversely affect fetal blood circulation, inhibit uterine contractions and increase the risk for uterine hemorrhage.
• Ketorolac may impair fertility and is not recommended for use in women trying to conceive.
• Ketorolac is excreted in breast milk, avoid use in nursing mothers

• Use with caution before, during and after surgeries, or tonsillectomy in children; ketorolac may interfere with stoppage of bleeding (hemostasis).
• Use with caution in patients with gastric perforation, kidney/liver impairment or disease, or hypertension (may cause new onset of hypertension or worsening of existing hypertension), and patients on blood thinners (anticoagulant).
• Long-term administration of NSAIDs may result in kidney damage or injury; patients at the greatest risk include elderly individuals, those with impaired renal function, low blood volume (hypovolemia), heart failure, liver dysfunction, or salt depletion; and those taking medication such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers.
• Ketorolac may increase the risk of hyperkalemia (elevated potassium in blood), especially in renal disease, patients with diabetes, the elderly, and when used simultaneously with other medications capable of inducing hyperkalemia.
• Use of ketorolac is associated with a risk of severe skin reactions.
• Oral ketorolac should be used only as continuation after initial intravenous therapy.
• There is insufficient data supporting safe use of multiple-dose parenteral treatment in children; use with caution.
• Ketorolac may cause drowsiness, blurred vision, and dizziness; may impair the ability to drive or operate heavy machinery.