Dosing and uses of Ketorolac (Toradol)
Adult dosage forms and strengths
tablet
- 10mg
injectable solution
- 15mg/mL
- 30mg/mL
prefilled syringe
- 15mg/mL
- 30mg/mL
- 60mg/2mL
Moderately Severe Acute Pain
Short-term (≤5 days) management of moderately severe acute pain that requires analgesia at opioid level; not indicated for minor or chronic painful conditions
IV: 30 mg as single dose or 30 mg q6hr; not to exceed 120 mg/day
IM: 60 mg as single dose or 30 mg q6hr; not to exceed 120 mg/day
PO: 20 mg once after IV or IM therapy, THEN 10 mg q4-6hr; not to exceed 40 mg/day
Dosing Considerations
Always begin with parenteral therapy; oral administration indicated only as continuation of IV/IM dosing, if necessary
Duration of therapy should not exceed 5 days
Dosage beyond maximum or labeled doses will not provide better efficacy but will increase risk of serious adverse events
Decrease daily dose in patients >65 years, <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 IM/IV
Hepatic impairment
- Not studied; use caution; discontinue if symptoms of liver toxicity develop
Pediatric dosage forms and strengths
Moderately Severe Acute Pain (Off-label)
<2 years
- Safety and efficacy not established
2-16 years
- Single dose: 0.5 mg/kg IV/IM once; not to exceed 15 mg
- Multiple dose: 0.5 mg/kg IV/IM q6hr; not to exceed 5 days
>16 years, <50 kg
- IV: 15 mg as single dose or 15 mg q6hr; not to exceed 60 mg/day
- IM: 30 mg as single dose or 15 mg q6hr; not to exceed 60 mg/day
- PO: 10 mg once after IV/IM therapy, THEN 10 mg q4-6hr; not to exceed 40 mg/day
>16 years, >50 kg
- IV: 30 mg as single dose or 30 mg q6hr; not to exceed 120 mg/day
- IM: 60 mg as single dose or 30 mg q6hr; not to exceed 120 mg/day
- PO: 20 mg once after IV/IM therapy, THEN 10 mg q4-6hr; not to exceed 40 mg/day
Dosing Considerations
Not approved for use in pediatric patients
Duration of therapy should not exceed 5 days
Geriatric dosage forms and strengths
Moderately Severe Acute Pain
Short-term (≤5 days) management of moderately severe acute pain that requires analgesia at opioid level; not indicated for minor or chronic painful conditions
IV: 15 mg as single dose or 15 mg q6hr; not to exceed 60 mg/day
IM: 30 mg as single dose or 15 mg q6hr; not to exceed 60 mg/day
PO: 10 mg once after IV or IM therapy, THEN 10 mg q4-6hr; 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 >65 years or <50 kg (see Black box warnings)
Ketorolac (Toradol) adverse (side) effects
>10%
Headache (17%)
Somnolence (3-14%)
Dyspepsia (12-13%)
GI pain (12-13%)
Nausea (12-13%)
1-10%
Diarrhea (3-9%)
Dizziness (3-9%)
Pruritus (3-9%)
Edema (1-3%)
Increased blood urea nitrogen (BUN) (3%)
Constipation (<3%)
Purpura (<3%)
Increased serum creatinine (2%)
Drowsiness (6%)
Hypertension (4%)
<1%
Abnormal thinking
Anaphylaxis
Blurred vision
Bronchospasm
Cholestatic jaundice
Depression
Difficulty in concentration
Dysgeusia
Euphoria
Hemolytic-uremic syndrome
Hepatitis
Hyperkalemia
Hyponatremia
Hypotension
Increased liver function test values
Insomnia
Laryngeal/lingual edema
Liver failure
Melena
Nervousness
Oliguria
Pallor
Peptic ulcer
Rash
Rectal bleeding
Stomatitis
Urinary frequency
Urinary retention
Vasodilation
Warnings
Black box warnings
Cardiovascular risk
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery
- Patients treated with NSAIDs following heart attack reported to be more likely to die in first yearof heart attack compared to patients not treated with NSAIDs after first heart attack
Gastrointestinal risk
- NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
Additional Warnings
- Major surgery: Contraindicated for prophylactic analgesic
- CABG: Contraindicated for treatment of perioperative pain in the setting of CABG surgery
- Labor and delivery: Contraindicated because it may adversely affect fetal circulation and inhibit uterine contractions
- Breastfeeding women: Contraindicated because of potential adverse effects of prostaglandin-inhibiting drugs on neonates
- Use with other NSAIDs: Contraindicated in patients currently receiving aspirin or other NSAIDs, because of a cumulative risk of inducing serious NSAID-related adverse effects
- Renal risk: Contraindicated with advanced renal impairment and in patients at risk for renal failure due to volume depletion
- Gastrointestinal: Contraindicated with active peptic ulcer disease, recent GI bleeding or perforation, or history of peptic ulcer disease or GI bleeding
- Bleeding risk: Inhibits platelet function; contraindicated with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and high risk of bleeding
- Demonstrated hypersensitivity: Contraindicated with previously demonstrated hypersensitivity to ketorolac or allergic manifestations to aspirin or other NSAIDs
- Injectable: Contraindicated for intrathecal or epidural administration, due to its alcohol content.
- Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred, and appropriate counteractive measures must be available when administering the first dose of ketorolac injection
Contraindications
Duration of therapy >5 days
Not for chronic or minor pain
Demonstrated hypersensitivity to ketorolac or allergic manifestations to aspirin or other NSAIDs; appropriate counteractive measures must be available when first ketorolac injection is given
Major surgery: Contraindicated for prophylactic analgesia; contraindicated for treatment of perioperative pain in setting of CABG surgery
OB/GYN: Contraindicated during labor and delivery because it may adversely affect fetal circulation and inhibit uterine contractions; contraindicated in breastfeeding women because of potential adverse effects of prostaglandin-inhibiting drugs on neonates
Renal: Contraindicated with advanced renal impairment and in patients at risk for renal failure due to volume depletion
GI: Contraindicated with previous or currently active peptic ulcer disease, previous or current GI bleeding or perforation
Bleeding risk: Because of inhibition of platelet function; contraindicated with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and high risk of bleeding
Use with other NSAIDs: Contraindicated in patients currently receiving aspirin or other NSAIDs, because of a cumulative risk of inducing serious NSAID-related adverse effects
Contraindicated for intrathecal or epidural administration because of alcohol content
Cautions
Use with caution in perioperative setting, tonsillectomy in children (may interfere with hemostasis), gastric perforation, hepatic/renal impairment, history of hepatic/renal disease, concomitant anticoagulant therapy, hypertension (may cause new onset of hypertension or worsening of existing hypertension)
PO therapy should be used only as continuation after initial parenteral therapy
Limited data supporting safe use of multiple-dose parenteral treatment in children
Potential risk of cardiovascular damage
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals; those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion; and those taking diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers
Risk of severe skin reactions
May cause drowsiness, blurred vision, and dizziness; may impair ability to operate heavy machinery
May increase risk of hyperkalemia, especially in renal disease, patients with diabetes, the elderly, and when used concomitantly with other agents capable of inducing hyperkalemia
Not for use in patients with aspirin-sensitive asthma (severe bronchospasm may occur)
Heart Failure(HF) risk
- NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
- NSAIDS should be avoided or withdrawn whenever possible
- AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
Pregnancy and lactation
Pregnancy category: C; D in third trimester (may cause premature closure of ductus arteriosus)
Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and approximately 2.6% of controls
Lactation: Drug excreted in breast milk with multiple doses; use contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ketorolac (Toradol)
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2
May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity
Absorption
Bioavailability: 80-100%
Onset: IM, 10 min; PO, 30-60 min
Duration: 4-6 hr (analgesia)
Peak serum time: 1-3 min (IV); 30-60 min (IM); ~1 hr (PO)
Peak plasma concentration: Varies with dose and route
Distribution
Protein bound: >99%
Vd: ~13 L
Metabolism
Metabolized in liver
Metabolites: p-hydroxyketorolac, unidentified polar metabolites
Elimination
Half-life: 2-6 hr
Dialyzable: Yes, with unknown effect
Excretion: Urine (91%), feces (6%)
Administration
IV Incompatibilities
Additive: Hydroxyzine, meperidine, morphine, promethazine
Syringe: Haloperidol, hydroxyzine, nalbuphine, prochlorperazine, promethazine, thiethylperazine
Y-site: Azithromycin, fenoldopam
IV Compatibilities
Solution: D5/NS, D5W, Ringer solution, LR, Ns
Syringe: Hydromorphone, sufentaniL
Y-site: Cisatracurium, dexmedetomidine, fentanyl, hydromorphone, methadone, morphine sulfate, remifentanil, sufentaniL
IV/IM Administration
IM: Inject slowly and deeply into muscle
IV: Inject over ≥15 seconds
60 mg/2 mL preparation for IM administration only
Storage
Store at controlled room temperature
Protect from light
