Ketorolac (Toradol®) vs Diclofenac (Voltaren®)

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD

Difference between Ketorolac and Diclofenac chart

Ketorolac	Diclofenac
• Toradol ®	• Cataflam® • Cambia ® • Dyloject ® • Voltaren® • Voltaren-XR® • Zipsor ®
Drug class
• Nonsteroidal anti-inflammatory drugs
• Member of the pyrrolo-pyrrole group	• Member of phenylacetic acid derivatives
Dose formulations
• Tablets • Solution for injection (for intramuscular and intravenous routes) • Nasal spray • Ophthalmic solution	• Tablets • Capsules • Topical gel • Transdermal patch • Ophthalmic solution • Powder for oral solution • Solution for intramuscular injection • Solution for intravenous injection • Suppositories
Legal status
• Non-controlled substance • Prescription only
FDA-approved indications
• Short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level. Maximum duration of ketorolac therapy should not exceed 5 days for tablets, or 2 days for continuous daily dosing with parenteral formulations.	• Mild to moderate pain • Rheumatoid arthritis • Osteoarthritis • Ankylosing spondylitis • Primary dysmenorrhea • Migraine attacks
"Off-label" uses
• Renal colic • Athletic injuries • Injection administration into the intra-articular space • Subcutaneous route	• Multimodal analgesic regimen • Dental surgical procedures • Acute pain in children • Biliary colic
Potency
• While the analgesic potency of ketorolac is about 5 times that of diclofenac, the anti-inflammatory potency of ketorolac is only twice that of diclofenac1.
Mechanism of action
• Peripherally acting analgesics. • Both drugs inhibit prostaglandin synthesis via non-selective inhibition of COX-1 and COX-2.
• Inhibition of prostaglandin synthesis through blocking cyclooxygenase enzymes COX-1 and COX-2.	• Diclofenac inhibits COX-2 enzyme with greater potency than it does COX-1. • Diclofenac appears to inhibit the lipoxygenase pathways, reducing inflammation by decreasing production of leukotrienes. • Diclofenac also inhibits arachidonic acid release and stimulates its reuptake.
Half-life
• 5-6 hours	• 1-4 hours •Duration of therapeutic effect of diclofenac is considerably longer than its half-life because the drug accumulates in synovial fluid
Oral bioavailability
• 80-100%	• 50-60%
Metabolism, Elimination
• Ketorolac undergoes hepatic metabolism. The metabolic products and unchanged drug are excreted in the urine.	• Diclofenac undergoes first-pass or presystemic metabolism. First pass metabolism causes bioavailability of 50% despite almost complete oral bioavailability. • The drug is extensively metabolized by the cytochrome P450 3A4 and 2C8. • About 65% of diclofenac dose is excreted in the urine and about 35% through bile in the feces as conjugates of unchanged diclofenac and its metabolites.
Contraindications
• Hypersensitivity to ketorolac • Active peptic ulcer disease • Recent gastrointestinal bleeding • Perforation • History of peptic ulcer disease or gastrointestinal bleeding. • Ketorolac should not be used as prophylactic analgesic before any major surgery • Advanced renal impairment or in patients at risk for renal failure due to volume depletion • Labor and delivery patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding	• Hypersensitivity to diclofenac
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. • Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery. • Third trimester of pregnancy.
Side effects
• The main differences between NSAIDs are the incidence and type of side effects, mainly gastric irritation and ulceration, cardiovascular effects, and nephrotoxicity.
• One of the main problems with ketorolac is the inhibition of platelet function and the potential for post-surgical bleeding. Dyspepsia • Nausea • Headache • Fluid retention • Hyperkalemia • Elevations of ALT or AST • Gastrointestinal damage - ketorolac makes stomach lining susceptible to damage, promotes ulcers in the stomach and bleeding. • Renal injury (including renal failure, interstitial nephritis and nephrotic syndrome)	• Nausea • Constipation • Dyspepsia • Headache • Dizziness • Vomiting • Modest elevation of hepatic transaminases
Pregnancy category
• C • Use during late pregnancy should be avoided	• C (prior to 30 weeks gestation) • D (after 30 weeks gestation, may cause premature closure of the ductus arteriosus)

Renal Colic

Renal colic is an acute pain caused by urinary stones. Ketorolac seems to be as effective as diclofenac in the treatment of renal colic.

Results of double-blind controlled study 2	Ketorolac	Diclofenac
Dosage regimen	60 mg single intramuscular dose	75 mg single intramuscular dose
Significant pain relief at 60 minutes	77.8% of patients	86.6% of patients
Significant pain relief at 120 minutes	81.5% of patients	96.6% of patients

Pain after Photorefractive Keratectomy

Both diclofenac and ketorolac are effective in reducing pain and ocular discomfort after photorefractive keratectomy3. Ketorolac may provide better control of tearing and photophobia during the first 24 hours after surgery.

Pain after Surgery

Both NSAIDs significantly reduce pain intensity and the need for rescue opioid analgesics 4.

Seasonal Allergic Conjunctivitis

Currently, ketorolac tromethamine 0.5% ophthalmic solution is the only NSAID approved for ocular itching due to seasonal allergic conjunctivitis. Diclofenac sodium 0.1% ophthalmic solution is approved for the relief of ocular inflammation following cataract surgery.

Both medications relieve ocular inflammation, lid edema, conjunctival mucous, keratitis, ocular itching, burning, discharge, and photophobia5. The relief of signs and symptoms of seasonal allergic conjunctivitis occurres as rapidly as 3 days after starting of a single drop of either NSAIDs.

Diclofenac sodium 0.1% better reduces ocular itching, inflammation, and pain than ketorolac tromethamine 0.5%.

Tooth Extraction Pain

Tooth extraction in most cases leads to moderate to severe pain.

Both diclofenac and ketorolac IV injectable formulations are effective for pain after tooth extraction6. However, diclofenac provide more rapid onset of analgesic action.

References

1. Chui PT, Gin T.A comparison between ketorolac and diclofenac in laparoscopic sterilization.Eur J Anaesthesiol. 1995 Nov;12(6):597-601.
2. Stein A, Ben Dov D, Finkel B, Mecz Y, Kitzes R, Lurie A. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic. Am J Emerg Med. 1996 Jul;14(4):385-7.
3. Mohammadpour M, Heidari Z, Molani R. Comparison BetweenDiclofenac and Ketorolac Ophthalmic Drops for Pain Management After Photorefractive Keratectomy: A Randomized Clinical Study. Eye Contact Lens. 2018 Jun 25.
4. Gan TJ, Daniels SE, Singla N, Hamilton DA, Carr DB. A novel injectable formulation of diclofenac compared with intravenous ketorolac or placebo for acute moderate-to-severe pain after abdominal or pelvic surgery: a multicenter, double-blind, randomized, multiple-dose study. AnesthAnalg. 2012 Nov;115(5):1212-20.
5. Dehar N, Gupta A, Singh G. Comparative study of the ocular efficacy and safety of diclofenac sodium (0.1%) ophthalmic solution with that of ketorolac tromethamine (0.5%) ophthalmic solution in patients with acute seasonal allergic conjunctivitis. Int J Appl Basic Med Res. 2012 Jan;2(1):25-30.
6. Christensen K, Daniels S, Bandy D, Ernst CC, Hamilton DA, Mermelstein FH, Wang J, Carr DB. A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar extraction pain. AnesthProg. 2011 Summer; 58(2):73-81

Published: February 17, 2019
Last updated: February 17, 2019

Quick facts

Ketorolac is snot indicated for minor or chronic painful conditions.
Dyloject® is IV formulation of diclofenac that is ready to use as a rapid, small-volume bolus.