A-Z Drug Facts > Ketorolac Tromethamine

Ketorolac Tromethamine

Pronunciation: (KEY-TOR-oh-lak tro-METH-uh-meen)
Class: Analgesic

Trade Names:
Acular
- Solution 0.5%

Trade Names:
Acular LS
- Solution 0.4%

Trade Names:
Acular PF
- Solution 0.5%

Trade Names:
Ketorolac Tromethamine
- Tablets 10 mg
- Injection 15 mg/mL
- Injection 30 mg/mL

Apo-Ketorolac (Canada)
Apo-Ketorolac Ophthalmic Solution (Canada)
ratio-Ketorolac (Canada)
Toradol (Canada)
Toradol IM (Canada)

Pharmacology

Decreases inflammation, pain, and fever through inhibition of prostaglandin synthesis.

Pharmacokinetics

Absorption

Bioavailability is 100%. T _max is approximately 44 min for oral single dose (10 mg), 33 min for IM, and 1.1 min for IV (15 mg). C _max is approximately 0.87 mcg/mL for oral single dose (10 mg), 1.14 mcg/mL for IM, and 2.47 mcg/mL for IV (15 mg).

Distribution

Ketorolac is 99% protein bound. Nevertheless, plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. A decrease in serum albumin will lead to an increase in free drug concentrations. Vd is approximately 13 L.

Metabolism

Largely metabolized in the liver via hydroxylation and conjugation. Ketorolac is a racemic mixture of S- and R-enantiometric forms, with the S form having analgesic activity.

Elimination

S-enantiomer is cleared 2 times faster than R-enantiomer. The t _{1/ 2} of S-enantiomer is approximately 2.5 h and the t _½ of R-enantiomer is approximately 5 h. 92% of dose excreted in the urine; 6% excreted in feces.

Onset

30 min for injection (IM).

Peak

2 to 3 h for injection (IM, PO).

Duration

4 to 6 h (IV, IM).

Special Populations

Renal Function Impairment

Ketorolac is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure because of volume depletion. Adjust dose for patients with moderately elevated serum creatinine.

Elderly

Adjust dosage for patients 65 yr of age and older.

Patients weighing less than 50 kg

Adjust dosage.

Indications and Usage

Oral, IM, IV Adults

Short-term management of moderately severe, acute pain.

IM, IV Children 2 yr of age and older

Moderately severe, acute pain.

Ophthalmic forms Adults and children 3 yr of age and older Acular

Temporary relief of ocular itching caused by seasonal allergic conjunctivitis and treatment of postoperative inflammation in patients who have undergone cataract extraction.

Acular LS

Reduction of ocular pain and burning/stinging following corneal refractive surgery.

Acular PF

Reduction of ocular pain and photophobia following incisional refractive surgery.

Contraindications

Patients in whom ketorolac, aspirin, or any NSAID have caused hypersensitivity or allergic-type or reactions; active peptic ulcer disease; recent GI bleeding or perforation; advanced renal impairment and in patients at risk for renal failure because of volume depletion; suspected or confirmed cerebrovascular bleeding; hemorrhagic diathesis, incomplete hemostasis, and those at high risk of bleeding; history of peptic ulcer disease or GI bleeding; as prophylactic analgesia before any major surgery and intraoperatively when hemostasis is critical; for intrathecal or epidural administration; labor and delivery; lactation; concomitant use with aspirin or other NSAIDs; concomitant use with probenecid.

Dosage and Administration

Multiple Dose
Adults

IM Younger than 65 yr of age: 30 mg every 6 h. Do not exceed 120 mg/day. Older than 65 yr of age, renal impairment, or weight less than 50 kg (110 lbs): 15 mg every 6 h. Do not exceed 60 mg/day.

Single Dose
Adults

IM, IV Younger than 65 yr of age: 60 mg. Older than 65 yr of age, renal impairment, or weight less than 50 kg (110 lbs): 30 mg. IV Younger than 65 yr of age: 30 mg. Older than 65 yr of age, renal impairment, or weight less than 50 kg (110 lbs): 15 mg.

Children 2 to 16 yr of age

IM 1 mg/kg up to 30 mg max. IV 0.5 mg/kg up to 15 mg max.

Transition from IV or IM to Oral
Adults

Younger than 65 yr of age: 20 mg as a first oral dose for patients who received 60 mg IM single dose, 30 mg IV single dose, or 30 mg multiple dose IV/IM, followed by 10 mg every 4 to 6 h, not to exceed 40 mg per 24 h. Older than 65 yr of age, renal impairment, or weight less than 50 kg (110 lbs): 10 mg as a first oral dose for patients who received a 30 mg IM single dose, 15 mg IV single dose, or 15 mg multiple dose IV/IM, followed by 10 mg every 4 to 6 h, not to exceed 40 mg per 24 h.

Ophthalmic
Adults and children 3 yr of age and older

Acular : 1 drop (0.25 mg) 4 times daily for relief of ocular itching caused by seasonal allergic conjunctivitis. For patients undergoing cataract extraction, 1 drop to affected eye(s) 4 times daily beginning 24 h after cataract surgery and continuing through the first 2 wk of the postoperative period. Acular LS : 1 drop 4 times daily in operated eye as needed for pain and burning/stinging for up to 4 days following corneal refractive surgery. Acular PF : 1 drop (0.25 mg) 4 times daily in operated eye as needed for pain and photophobia for up to 3 days postincisional refractive surgery.

General Advice

• Injection
• The combined duration of ketorolac IV/IM and oral is not to exceed 5 days. Oral use is only indicated as continuation therapy to IV/IM.
• Do not mix IV/IM ketorolac in a small volume (eg, in a syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride, or hydroxyzine hydrochloride; this will result in precipitation of ketorolac from solution.
• When administering IM/IV, the IV bolus must be given over no less than 15 sec. Give IM administration slowly and deeply into the muscle. Rotate injection sites.

• Ophthalmic Solution
• For ophthalmic use only. Not for use on the skin or for injection into eye.
• Have patient tilt head back and instill prescribed number of drops into affected eye(s) as ordered. Have patient close eye(s) for 2 to 3 min and apply light finger pressure to bridge of nose (nasolacrimal duct) for 1 to 2 min after instillation. Do not touch top of dropper bottle to eye, fingers, or other surface.
• Because Acular PF does not contain a preservative, discard any unused Acular PF solution immediately after each instillation.
• If using other topical ophthalmic drugs, separate each medication by at least 5 min. Instill ophthalmic ointment last.

Storage/Stability

Store tablets and injection at controlled room temperature (59° to 86°F). Protect from light. Store ophthalmic solution at controlled room temperature. Keep tightly capped and protect from light.

Drug Interactions

Aminoglycosides

Serum aminoglycoside levels may be increased.

Anticoagulants

May increase risk of gastric erosion and bleeding.

Aspirin, NSAIDs

Risk of inducing serious NSAID-related side effects. Concomitant use is contraindicated.

Furosemide

IM/IV may reduce the diuretic response about 20%.

Lithium

Serum lithium levels may be increased.

Methotrexate

May increase methotrexate levels.

Probenecid

May increase ketorolac plasma levels. Concomitant use is contraindicated.

SSRIs (fluoxetine, paroxetine)

Risk of GI adverse reactions may be increased.

Laboratory Test Interactions

Drug may prolong bleeding time.

Adverse Reactions

Cardiovascular

Edema (4%); hypertension (greater than 1%); flushing, hypotension (postmarketing).

CNS

Headache (17%); dizziness (7%); drowsiness (6%); sweating (greater than 1%); aseptic meningitis, convulsions, psychosis (postmarketing).

Dermatologic

Pruritus, rash (greater than 1%); exfoliative dermatitis, Lyell syndrome, maculopapular rash, Stevens-Johnson syndrome, urticaria (postmarketing).

EENT

Stomatitis (greater than 1%).

Ophthalmic

Burning/stinging (40%); corneal edema, iritis, ocular inflammation/irritation, superficial keratitis, superficial ocular infections (1% to 10%); corneal erosion, corneal perforation, corneal thinning, epithelial breakdown (postmarketing).

GI

GI pain (13%); dyspepsia, nausea (12%); diarrhea (7%); constipation, flatulence, GI fullness, vomiting (greater than 1%); acute pancreatitis, esophagitis; GI hemorrhage/perforation, hematemesis, melena, peptic ulceration (postmarketing).

Genitourinary

Acute renal failure, hemolytic uremic syndrome, interstitial nephritis (postmarketing).

Hematologic

Leukopenia, postoperative wound hemorrhage, thrombocytopenia (postmarketing).

Hepatic

Abnormal LFTs, cholestatic jaundice, hepatitis, liver failure (postmarketing).

Metabolic

Hyperkalemia, hyponatremia (postmarketing).

Respiratory

Asthma, bronchospasm (postmarketing).

Miscellaneous

Injection site pain, purpura (greater than 1%); anaphylaxis/anaphylactoid reaction, angioedema, flank pain, laryngeal edema, myalgia, tongue edema (postmarketing).

Ophthalmic

Allergic reactions (1% to 10%).

Precautions

Warnings Tablets, injection Limit therapy to 5 days. Oral therapy is indicated only as continuation therapy to IV/IM, and the combined use is not to exceed 5 days because of the increased risk of serious adverse reactions. GI effects Peptic ulcers, GI bleeding, and/or perforation can occur. Contraindicated in patients with active or history of these states. Renal effects Contraindicated in patients with advanced renal impairment or at risk of renal failure caused by volume depletion. Bleeding risk is caused by platelet inhibition. Contraindicated as preoperative analgesic or as intra-operative analgesic when hemostasis is critical or in patients at high risk of bleeding. Intrathecal/epidural administration is contraindicated because of alcohol content.

Pregnancy

Category C . Avoid use in late pregnancy because it may cause premature closure of the ductus arteriosus.

Lactation

Excreted in breast milk. Contraindicated.

Children

IM/IV

Safety and efficacy not established in patients younger than 2 yr of age.

Ophthalmic

Safety and efficacy not established in patients younger than 3 yr of age.

Elderly

Increased risk of adverse reactions.

Hypersensitivity

Hypersensitivity may occur; use drug with caution in aspirin-sensitive individuals because of possible cross-sensitivity.

Renal Function

Assess function before and during therapy because NSAID metabolites are eliminated renally. Dosage adjustments may be necessary.

Hepatic Function

May lead to liver enzyme elevations.

Anaphylactoid reactions

May occur without known hypersensitivity to aspirin, ketorolac, or other NSAIDs, or in patients with a history of angioedema, bronchospastic activity, and nasal polyps.

Cardiac effects

Fluid retention and edema have been reported with ketorolac. Use cautiously in patients with cardiac decompensation, hypertension, or other similar conditions.

Chronic use

Not intended for long-term use. Limit to short-term therapy (no longer than 5 days).

Healing

All topical NSAIDs and corticosteroids may slow or delay healing. Thus, concomitant use of ketorolac and corticosteroids may increase the risk of healing problems.

Hemorrhage

Use cautiously in patients with coagulation disorders.

Ophthalmic use

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These reaction may be sight-threatening. Patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases, rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse reactions. Use with caution in patients with known bleeding tendencies or who are receiving medications that may prolong bleeding time. Topical use of NSAIDs more than 24 h prior to surgery or for use beyond 14 days postsurgery may increase risk for occurrence and severity of corneal adverse reaction.

Overdosage

Symptoms

Abdominal pain, anaphylactoid reaction, drowsiness, lethargy, vomiting, nausea, renal dysfunction, erosive gastritis, hyperventilation, peptic ulcers, GI bleeding (hypertension, acute renal failure, respiratory depression, coma [rare]).

Patient Information

• Instruct patient to take drug with food, milk, or antacid if GI upset occurs.
• Inform patient that drug is an NSAID and can cause serious side effects, such as GI bleeding.
• Instruct patient to avoid alcohol, aspirin, and other NSAIDs.
• Advise patient to inform dentist and other health care providers of drug therapy before any treatment or surgery.
• Instruct patient to report the following symptoms to health care provider: black stools, edema, itching, persistent headache, skin rash, visual disturbances, or weight gain.
• Advise patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other tasks requiring mental alertness.

• Ophthalmic Solution
• Remind patient that eye drops are for use in the eye only.
• Teach patient proper technique for instilling eye drops: wash hands; do not allow dropper to touch eye. Tilt head back and look up; pull lower eyelid down; instill prescribed number of drops. Close eye for 1 to 2 min and apply gentle pressure to bridge of nose for 1 to 3 min. Do not rub eye.
• Advise patient not to touch top of dropper bottle to eye, fingers, or other surface.
• Advise patient that if more than 1 topical ophthalmic drug is being used, administer the drugs at least 5 min apart. Administer ointment last.
• Inform patient that temporary stinging or burning are the most common side effects and to contact health care provider if they occur and are bothersome.
• Advise patient to contact eye doctor if eye or eyelid inflammation is noted or if eye symptoms do not improve or worsen.
• Instruct patient wearing contact lenses to remove them when instilling eye drops.

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