Ketorolac (Toradol) is a non-selective COX inhibitor that is available as tablets and injections for the treatment of pain, fever, and inflammation.

Ketorolac (Toradol) Uses:

• Acute moderately severe pain:

  • Management of moderate to severe acute pain for a short period (5 days)

Ketorolac (Toradol) Dose in Adults:

Ketorolac (Toradol) Dose in acute moderately severe pain in patients ≥50 kg:

Note:

• • The maximum parenteral and oral treatment duration is five days.
  • Increases in dose or frequency are not recommended.
  • If necessary, supplement with low-dose opioids for pain that won't go away.
  • Never administer an oral formulation as a first dose.
• IM:
  • 30 mg QID or 60 mg as a single dose
  • As an alternative, it has been suggested to provide the medication as needed in increments of 10 to 30 mg (stat dosage) every 4 to 6 hours.
  • Maximum daily dose: 120 mg
• IV:
  • 30 mg as a single dose or 30 mg every two hours (up to 120 mg per day).

• Oral:
  • 20 mg, then 10 mg every four to six hours as necessary
  • 40 mg maximum per day
  • Only IM or IV therapy is meant to be continued with oral dosage.

Patient population-specific Ketorolac dosing:

• Critically ill patients (off-label dose):

  • IM, IV: 15 to 30 mg QID for up to 5 days (maximum: 120 mg/day), then 30 mg stat dosage.

• Perioperative patients (off-label dose):

  • IV: Use a multimodal pain management approach during surgery.
  • The daily dosing cap is 120 mg.
  • A bolus dosage of 10 to 30 mg, followed by a continuous infusion of 2 to 5 mg/hour for 24 hours, has been mentioned in the
  • literature as a perioperative dosing strategy.
  • Note:
    • May be more likely to get GI bleeding, ulcers, and perforations.
    • Parenteral and oral treatments may not last more than five days in total.
    • Never administer an oral formulation as a first dose.

• Dosage adjustment for low body weight (<50 kg):

Note:

• • IM: (Maximum: 60 mg/day) 30 mg as a single dose or 15 mg once daily.
  • IV: 15 mg as a single dosage or 15 mg every two hours (up to 60 mg per day).
  • Orally: 10 mg, then 10 mg every 4 to 6 hours as necessary (40 mg daily maximum). Only IM or IV therapy is meant to be continued with oral dosage.

Ketorolac (Toradol) Dose in Children:

Note:

• To lessen the risk of negative cardiovascular and Gastrointestinal effects, use the smallest effective dose for the shortest amount of time.

Ketorolac (Toradol) Dose in the treatment of acute moderately severe pain:

• Infants and Children <2 years: Limited data available:

  • Multiple-dose treatment:

    • IV:

      • 0.5 mg/kg/dose given every 6 to 8 hours, with a maximum treatment time of 48 to 72 hours
      • has mostly been used postoperatively following abdominal and heart surgery.

• Children ≥2 years and Adolescents ≤16 years: Limited data available:

  • IM, IV:

    • A dosage of 0.5 mg/kg QID
    • Maximum dose is 30 mg/dose, with reported reported durations of 48 to 72 hours and no longer than 5 days.

  • Oral:

    • A standard dose of 1 mg/kg
    • Prior to surgery, children have been reported to receive a maximum dose of 10 mg/dose (eg, bilateral myringotomy).

• Adolescents ≥17 years:

Note:

• Parenteral and oral treatments may not last longer than five days in total.
• There should be no increase in dosage or frequency.
• If additional low-dose opioids are required to treat pain, do so.

  • <50 kg:

    • IM: With a daily dose cap of 60 mg, the recommended dose is 30 mg as a stat dose or 15 mg qid.
    • With a daily dose cap of 60 mg, administer 15 mg IV as a stat dose or 15 mg qid.
    • Oral: 10 mg at first, followed by 10 mg every 4 to 6 hours, with a daily dose cap of 40 mg.

  • ≥50 kg:

    • IM: Maximum daily dose is 120 mg, either as a single dose of 60 mg or as 30 mg twice daily.
    • With a daily dose cap of 120 mg, administer 30 mg IV as a stat dose or 30 mg qid.
    • Oral: Initial dosage is 20 mg, followed by 10 mg every 4 to 6 hours, with a daily dose cap of 40 mg.

Ketorolac (Toradol) Pregnancy Risk Factor C

• [US Boxed Warning]
  • Pregnancy and delivery are not recommended. It may inhibit uterine contractions, and negatively affect fetal circulation.
• Ketorolac crosses over the placenta.
• Some studies have shown that birth defects can be caused by in utero NSAID use. However, the data is inconsistent.
• Following in utero NSAID administration, nonteratogenic effects such as prenatal constriction, persistent pulmonary hypertension, oligohydramnios and necrotizing enterocolitis have been seen in the fetus/neonate.
• Avoid using NSAIDs during pregnancy as they can cause premature closure of ductus arteriosus.
• After cesarean delivery, NSAIDs can be used in multimodal pain management.
• Consider your breastfeeding status before you use a particular agent.
• Women of reproductive age who have been using NSAIDs for a long time may experience infertility. This can be reversed by stopping the medication.
• Women who are having trouble conceiving or who are undergoing fertility treatment should stop using this medication.
• There is a higher chance of miscarriage if you use NSAIDs near your conception.

Ketorolac use during breastfeeding:

• Breast milk contains Ketorolac.
• When derived from the greatest breastmilk concentration and compared to a mother weight-adjusted dose of 40 mg/day, the relative infant dose (RID) of ketorolac is 0.2%.
• When the RID is less than 10%, breastfeeding is considered acceptable.
• The highest possible milk concentration (7.9ng/mL) is used to estimate the daily infant dose via breastmilk at 1.185 mg/kg/day.
• This was achieved by maternal administration of oral ketorolac QID 10 mg for 2 days to women who gave birth between 2 and 6 days after giving birth.
• NSAIDs can be used by postpartum mothers who want to breastfeed. However, if a mother has platelet dysfunction or thrombocytopenia, they should avoid using ketorolac.
• If breastfeeding women are being given the medication, it is important to be cautious.

Ketorolac (Toradol) Dose in Kidney Disease:

• Dosage adjustment recommendations:

  • Manufacturer’s labeling:

    • Renally impaired patients:

Note:

• The product labelling does not specify the precise level of renal impairment where use is allowed.
• However, it should not be used by people who have significant renal impairment or those who are at risk of developing renal failure as a result of volume depletion.
  • • • IM:(Maximum: 60 mg/day) 30 mg as a single dose or 15 mg once daily.
      • IV: 15 mg as a single dosage or 15 mg every two hours (up to 60 mg per day).
      • Orally: 10 mg, then 10 mg every 4 to 6 hours as necessary (up to 40 mg per day). & oral dose is only meant to be a supplement to IM or IV therapy
    • Advanced impairment or those at risk for renal failure as a result of volume depletion are contraindicated for use.

  • Alternative recommendations:

    • GFR >50 mL/minute/1.73 m :
      • 15 to 30 mg IM or IV QID
    • GFR 10 to 50 mL/minute/1.73 m :
      • Preferably avoid or administer 7.5 to 15 mg IM or IV QID
    • GFR <10 mL/minute/1.73 m :
      • Preferably avoid
    • Hemodialysis:
      • Preferably avoid
    • CAPD:
      • Preferably avoid
    • CRRT:
      • 5 to 15 mg IM or IV QID

Ketorolac (Toradol) Dose in Liver disease:

• The manufacturer's labelling does not mention dosage modifications.
• Take with caution as it may elevate liver enzyme levels.
• If you experience any clinical symptoms or indicators of liver damage, stop immediately.

Frequencies noted for parenteral administration:

Common Side Effects of Ketorolac (Toradol):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Gastrointestinal pain
  • Dyspepsia
  • Nausea

Less Common Side Effects of Ketorolac (Toradol):

• Cardiovascular:

  • Edema
  • Hypertension

• Central Nervous System:

  • Dizziness
  • Drowsiness

• Dermatologic:

  • Diaphoresis
  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Diarrhea
  • Constipation
  • Flatulence
  • Gastrointestinal Fullness
  • Gastrointestinal Hemorrhage
  • Gastrointestinal Perforation
  • Gastrointestinal Ulcer
  • Heartburn
  • Stomatitis
  • Vomiting

• Hematologic & Oncologic:

  • Anemia
  • Prolonged Bleeding Time
  • Purpura

• Hepatic:

  • Increased Liver Enzymes

• Local:

  • Pain At Injection Site

• Otic:

  • Tinnitus

• Renal:

  • Renal Function Abnormality

Contraindications to Ketorolac (Toradol):

• Hypersensitivity to aspirin, ketorolac, and other NSAIDs or any component of this formulation
• Peptic ulcer disease: History or active
• Perforation or GI bleeding in the past or recent
• History of asthma, urticaria or allergic-type reactions following aspirin use or any other NSAIDs
• Patients at high risk of developing advanced renal disease or renal failure from volume depletion
• Before any major surgery, prophylactic analgesia
• High risk of bleeding: Suspected or confirmed hemorhagic diathesis or hemorhagic bleeding.
• Use aspirin, NSAIDs, pentoxifylline, and probenecid concurrently
• Injections only, or intramuscular administration
• Use for the placement of coronary bypass graft surgery (CABG).
• Delivery and labor

Canadian labeling: Additional contraindications:

• Intraoperative use
• Coagulation disorders
• Active GI bleeding
• Patients with high-bleeding risks after surgery
• Uncontrolled severe heart failure
• Inflammatory bowel disease
• Active hepatic disease or severe hepatic impairment
• Moderate to severe renal impairment (serum creatinine >442 micromol/L, and/or creatinine clearance = 30 mg/minute) or deteriorating kidney disease
• Hyperkalemia is a well-known condition
• The third trimester is the most important.
• Breastfeeding
• Use in children and adolescents under 18 years old

Warnings and precautions

• Bleeding and hematologic reactions: [US Boxed Warn]

  • Platelet function is inhibited
  • It is not advised for patients with hemorrhagic diathesis, suspected or proven cerebrovascular haemorrhage, or individuals at high risk for bleeding to use this medicine.
  • The possibility of platelet adhesion or aggregation being reduced and bleeding time being prolonged may be possible.
  • Patients with coagulation problems or those who are taking anticoagulants need to be closely monitored.
  • Anemia may occur.
  • Anemia should be checked in patients on long-term nonsteroidal, anti-inflammatory drug (NSAID), therapy.
  • Rarely, NSAIDs have been linked to potentially severe blood disorders (eg, agranulocytosis or thrombocytopenia and anemia).

• Cardiovascular events: [US Boxed Warn]

  • The increased risk of severe (and possibly fatal) adverse cardiovascular events due to NSAIDs, such as stroke and MI, can be caused by NSAIDs.
  • This risk can occur during treatment and may increase as the duration of use is prolonged.
  • The relative risk of developing cardiovascular disease is similar for those with and without known risk factors.
  • Patients with known cardiovascular disease and risk factors were more likely to experience serious cardiovascular thrombotic episodes (which can occur earlier during treatment).
  • Exacerbation or new-onset hypertension can occur. NSAIDs could also affect the response to ACE inhibitors, thiazide or loop diuretics; may cause cardiovascular events. Monitor BP.
  • Patients with edema may experience sodium and fluid retention.
  • Avoid heart failure
  • Patients with a recent MI should not have any treatment unless the benefits are greater than the risk of developing cardiovascular thrombotic complications.
  • For patients at high risk, it is best to reduce the effective dose and use it for the shortest time possible. Alternate therapies should also be considered.

• CNS effects

  • This can cause blurred vision, drowsiness, dizziness and other neurologic effects that may lead to impairment of mental or physical abilities.
  • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.

• GI events: [US Boxed Warning]

  • The risk of severe GI inflammation, bleeding, ulceration, and perforation is increased by NSAID use (may even be fatal).
  • Individuals over 65 and those with a history of peptic ulcer disease or GI bleeding are particularly vulnerable to major GI events.
  • These events can occur without warning and at any time during therapy.
  • Patients with active GI bleeding should be avoided
  • Avoid non-aspirin NSAIDs in patients who have had a history or experience of severe lower GI bleeding.
  • Use cautiously in patients with a history of GI ulcers, inflammatory bowel disease, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in the elderly or debilitated patients.
  • To reduce the risk of GI adverse reactions, use the lowest effective dose for the shortest time. Consider alternative therapies for high-risk patients.
  • Concomitant gastroprotective medication, such as proton pump inhibitors, is advised because using aspirin concurrently increases the risk of GI problems (such as ulcers) significantly.

• Hepatic effects

  • Use has been associated with transaminase elevations. It is therefore recommended that patients suffering from abnormal LFT be closely monitored.
  • Rare but sometimes fatal hepatic reactions have been linked to the use of NSAIDs.
  • If you notice any signs or symptoms of hepatic diseases, or if there are systemic manifestations, stop taking the medication immediately.

• Hyperkalemia:

  • NSAIDs may raise the risk of hyperkalemia, particularly in aged, diabetic, and renally ill individuals.
  • Potassium should always be monitored closely

• Hypersensitivity reactions: [US Boxed Warning]

  • Ketorolac injection is not recommended for patients who have a history of aspirin or NSAID hypersensitivity.
  • Patients may experience hypersensitivity even if they have never been exposed to the drug. Patients with the "aspirin trifecta" (bronchial asthma and aspirin intolerance, rhinitis, or both) could be at greater risk.
  • Patients who have rhinitis or NSAID therapy and bronchospasm are not recommended to use this medication.

• Effects on the renal system:

  • NSAIDs can cause kidney damage. Dose-dependent decreases of prostaglandin synthesis could be caused by NSAIDs, which reduce renal blood flow.
  • This may lead to renal decompensation, usually reversible.
  • Patients with impaired renal function, hypovolemia and heart failure, as well as those who take diuretics or ACE inhibitors, are at greater risk for renal toxicity.
  • Before starting treatment, patients should be properly hydrated.
  • Pay attention to your renal function.
  • Ketorolac use has been linked to nephrotic syndrome, interstitial nephritis, and acute renal failure.
  • Papillary necrosis and renal damage have been linked to long-term NSAID use.

• Reactions to skin:

  • NSAIDs can cause severe skin adverse reactions that could prove fatal, including exfoliative dermatitis (SJS), Stevens-Johnson syndrome and toxic epidermal necrolysis.
  • It may happen without notice.
  • Stop using it immediately if you notice any skin rash or hypersensitivity.

• Aseptic meningitis

  • Aseptic meningitis can be more common in patients with SLE (systemic lupus, erythematosus) and mixed connective tissue disorders.

• Asthma

  • Patients with asthma that is aspirin-sensitive should not use this product. Bronchospasm can be severe and potentially fatal.
  • Patients with other forms or asthma should be cautious.

• Bariatric surgery

  • Gastric ulceration: Use of oral nonselective NSAIDs after bariatric surgery should be avoided; it may result in the development of anastomotic ulcerations/perforations.
  • As part of a multimodal pain management strategy, short-term celecoxib and IV ketorolac are recommended.

• Coronary artery bypass surgery or major surgery: [US-Boxed Warning]

  • It is not recommended to be used as a prophylactic analgesic prior to major surgery or in the setting up of coronary bypass graft surgery (CABG).
  • After CABG surgery, the risk of stroke and MI may increase.
  • Ketorolac usage in the perioperative setting has been linked to wound bleeding and postoperative hemorhages.

• Hepatic impairment

  • Individuals who have a history of the hepatic disease or who have hepatic impairment should exercise caution. Advanced hepatic disease patients are more likely to get GI bleeding from NSAIDs.

• Renal impairment: [US-Boxed Warning]

  • It is not recommended for patients with advanced renal impairment or those who are at a high risk of developing renal failure as a result of volume depletion.
  • Patients with a history or renal impairment should be cautious.
  • Patients with moderately elevated serum creatinine levels will need to adjust their dosage.

Ketorolac (ophthalmic): Drug Interaction

Monitoring parameters:

• Monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation
• Observe for weight gain
• Edema
• Monitor Kidney function (serum creatinine, BUN, urine output)
• CBC &platelets
• Liver function tests
• Chemistry profile
• Blood pressure
• Observe for bleeding, bruising
• Evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia)
• Mental confusion & disorientation

How to administer Ketorolac (Toradol)?

Oral:

• To minimise Gastrointestinal distress, you could administer with food.

IM:

• Give to the muscle slowly and deeply.

IV:

• Give the IV bolus over at least 15 seconds.
• In the perioperative environment, the use of a continuous infusion (off-label) has been discussed.

Mechanism of action of Ketorolac (Toradol):

• Reversible inhibition of cyclooxygenase-1 (COX-1) enzymes results in decreased production of prostaglandin precursors.
• Antipyretic, analgesic and anti-inflammatory properties.
• The inhibition of chemotaxis, modification of lymphocyte activity, inhibition of neutrophil aggregation/activation, and a decrease in proinflammatory cytokine levels are additional proposed mechanisms that have not yet been fully elucidated but may contribute to the anti-inflammatory effect to varying degrees.

The onset of action:

• Analgesic:
  • Oral: 30 to 60 minutes
  • IM, IV: ~30 minutes

Peak effect:

• Analgesic:
  • Oral: 2 to 3 hours
  • IM, IV: ≤2 to 3 hours

Duration:

• Analgesic: 4 to 6 hours

Absorption:

• Oral: Well absorbed (100%)
• IM: Rapid and complete

Distribution:

• Poor penetration into CSF

Protein binding:

• 99%

Metabolism:

• Hepatic; hydroxylation and glucuronide conjugation occur; plasma and V clearance in children 4 to 8 years old was twice that of adults.

Bioavailability:

• Oral, IM: 100%

Half-life elimination:

• Infants 6 to 18 months of age (n=25): S-enantiomer: 0.83 ± 0.7 hours; R-enantiomer: 4 ± 0.8 hours (Lynn 2007)
• Children:
  • • 1 to 16 years (n=36): Mean: 3 ± 1.1 hours (Dsida 2002)
    • 3 to 18 years (n=24): Mean: 3.8 ± 2.6 hours
    • 4 to 8 years (n=10): Mean: ~6 hours; Range: 3.5 to 10 hours
• Adults:
  • Mean:
    • ~5 hours
    • Range: 2 to 9 hours [S-enantiomer ~2.5 hours (biologically active)
    • Renantiomer ~5 hours]
    • Prolonged 30% to 50% in elderly
  • With renal impairment: S 1.9 to 5 mg/dL:
    • Mean: ~11 hours
    • Range: 4 to 19 hours
  • Renal dialysis patients:
    • Mean: ~14 hours
    • Range: 8 to 40 hours

Time to peak, serum:

• Oral: ~45 minutes
• IM: 30 to 60 minutes
• IV: 1 to 3 minutes

Excretion:

• Urine (92%, ~60% as unchanged drug)
• feces ~6%

International Brands of Ketorolac:

• ReadySharp Ketorolac
• ALTI-Ketorolac
• APO-Ketorolac
• Mar-Ketorolac
• MINT-Ketorolac
• Toradol
• Acuvail
• Adolor
• Altrom
• Analac
• Arolak
• Arvolac
• Bedoral
• Dilox
• Dolac
• Dolorex
• Dolorex Gel
• Dolten
• Eleadol
• Erphapain
• Eurolac
• Fam
• Farpain
• Inco
• Kelac
• Kenalgesic
• Keromin
• Ketanov
• Keto
• Ketobet
• Ketogesic
• Ketolac
• Ketolong
• Ketomed
• Ketoracin
• Ketoral
• Ketoro
• Ketorol
• Ketron
• Kine
• Korac
• Kortezor
• Minolac
• Ni Song
• Nomadol
• Notolac
• Ocudol
• Oradol
• Painoff
• Poenkerat
• Remopain
• Rolac
• Rolesen
• Scelto
• Supradol
• Tabel
• Taradyl
• Teromac
• Tora-Dol
• Toradol
• Toramed
• Toramine
• Torpain
• Tral
• Trolac
• Winop
• Xevolac
• Zerodol

Ketorolac Brand Names in Pakistan: