Ketorolac Tromethamine
FULL PRESCRIBING INFORMATION: CONTENTS*
- WARNING
- KETOROLAC TROMETHAMINE DESCRIPTION
- CLINICAL PHARMACOLOGY
- CLINICAL STUDIES
- INDICATIONS & USAGE
- KETOROLAC TROMETHAMINE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- INFORMATION FOR PATIENTS
- LABORATORY TESTS
- DRUG INTERACTIONS
- CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
- PREGNANCY
- LABOR & DELIVERY
- NURSING MOTHERS
- PEDIATRIC USE
- GERIATRIC USE
- KETOROLAC TROMETHAMINE ADVERSE REACTIONS
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
- STORAGE AND HANDLING
- SPL MEDGUIDE
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
FULL PRESCRIBING INFORMATION
WARNING
Ketorolac tromethamine tablets, a non-steroidal anti-inflammatory drug (NSAID), are indicated for the short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level and only as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total combined duration of use of ketorolac tromethamine tablets and ketorolac tromethamine should not exceed 5 days.Ketorolac tromethamine tablets are not indicated for use in pediatric patients and they are NOT indicated for minor or chronic painful conditions. Increasing the dose of ketorolac tromethamine tablets beyond a daily maximum of 40 mg in adults will not provide better efficacy but will increase the risk of developing serious adverse events.
GASTROINTESTINAL RISK
WARNINGS).
CARDIOVASCULAR RISK
WARNINGSandCLINICAL STUDIES).
WARNINGS).
RENAL RISK
WARNINGS).
RISK OF BLEEDING
WARNINGSandPRECAUTIONS).
Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery.
RISK DURING LABOR AND DELIVERY
CONCOMITANT USE WITH NSAIDs
SPECIAL POPULATIONS
DOSAGE AND ADMINISTRATION) and for patients with moderately elevated serum creatinine (seeWARNINGS).
KETOROLAC TROMETHAMINE DESCRIPTION
CLINICAL PHARMACOLOGY
PharmacodynamicsPharmacokinetics
TABLE 1. In adults, the extent of bioavailability following administration of the ORAL form of ketorolac tromethamine and IM form of ketorolac tromethamine was equal to that following an IV bolus.
TABLE 1). Oral administration of ketorolac tromethamine after a high-fat meal resulted in decreased peak and delayed time-to-peak concentrations of ketorolac tromethamine by about 1 hour. Antacids did not affect the extent of absorption.
PRECAUTIONS, Nursing Mothers).
TABLE 2(seeCLINICAL PHARMACOLOGY, Kinetics in Special Populations).
Kinetics in Special Populations
TABLE 2). There was little difference in the Cmax for the two groups (elderly, 2.52 mcg/mL1.03) (seePRECAUTIONS, Geriatric Use (65 Years of Age)).
TABLE 1). There are no pharmacokinetic data available for administration of ketorolac tromethamine by the IM route in pediatric patients.
WARNINGS, Renal Effects).
PRECAUTIONS, Hepatic EffectandTABLE 2).
TABLE 1: Table of Approximate Average Pharmacokinetic Parameters (MeanSD) Following Oral, Intramuscular and Intravenous Doses of Ketorolac Tromethamine
*
#
*(min)#(mcg/mL) [single-dose](mcg/mL) [steady state qid](mcg/mL) [steady state qid](L/kg)
TABLE 2: The Influence of Age, Liver, and Kidney Function on the Clearance and Terminal Half-Life of Ketorolac Tromethamine (IM *and ORAL ) in Adult Populations
*
IV Administration
Kinetics in Special Populationsfor use of IV dosing of ketorolac tromethamine in pediatric patients).
CLINICAL STUDIES
Adult PatientsPediatric Patients
INDICATIONS & USAGE
Acute Pain in Adult Patients
WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION,andADVERSEREACTIONS). Patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine tablet therapy is not to exceed 5 days.
KETOROLAC TROMETHAMINE CONTRAINDICATIONS
(See also Boxed WARNING.)WARNINGS, Anaphylactoid ReactionsandPRECAUTIONS, Preexisting Asthma).
WARNINGS).
WARNINGSfor correction of volume depletion).
WARNINGSandPRECAUTIONS).
WARNINGS
(See also Boxed WARNING.)Gastrointestinal EffectsRisk of Ulceration, Bleeding, and Perforation
To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration.Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of ketorolac tromethamine until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Hemorrhage
Because prostaglandins play an important role in hemostasis and NSAIDs affect platelet aggregation as well, use of ketorolac tromethamine in patients who have coagulation disorders shoul dbe undertaken very cautiously, and those patients should be carefully monitored. Patients on therapeutic doses of anticoagulants (e.g., heparine or dicumarol derivatives) have increased risk of bleeding complications if given ketorolac tromethamine concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously. The concurrent use of ketorolac tromethamine and therapy that affects hemostasis, including prophylactic low-dose heparin (2500 to 5000 units q12h), warfarin and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding. Until data from such studies are available, physicians should carefully weight the benefits against the risks and use such concomitant therapy in these patients only extremely cautiously. Patients receiving therapy that affects hemostasis should be monitored closely.
PRECAUTIONS).
Renal Effects
CLINICAL PHARMACOLOGY). Therefore, ketorolac tromethamine should be used with caution in patients with impaired renal function (seeDOSAGE AND ADMINISTRATION) and such patients should be followed closely. With the use of ketorolac tromethamine, there have been reports of acute renal failure, interstitial nephritis and nephrotic syndrome.
Impaired Renal Function
Anaphylactoid Reactions
CONTRAINDICATIONSandPRECAUTIONS, Preexisting Asthma). Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Emergency help should be sought in cases where an anaphylactoid reaction occurs.
Cardiovascular Effects
Gastrointestinal EffectsRiskofUlceration, Bleeding, and Perforation). Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (seeCONTRAINDICATIONS).
Congestive Heart Failure and Edema
Skin Reactions
Pregnancy
PRECAUTIONS
GeneralPreexisting Asthma
INFORMATION FOR PATIENTS
Boxed WARNING, WARNINGS, PRECAUTIONS,andADVERSE REACTIONS), instruct patients to seek medical advice if they develop treatment-related adverse events, andadvise patients not to giveketorolac tromethamine tablets to other family members and to discard any unused drug.
WARNINGS, Cardiovascular Effects).
WARNINGS, Gastrointestinal EffectsRisk of Ulceration, Bleeding, and Perforation).
WARNINGS).
LABORATORY TESTS
DRUG INTERACTIONS
warfarinto plasma proteins is only slightly reduced by ketorolac tromethamine (99.5% control vs 99.3%) when ketorolac plasma concentrations reach 5 to 10 mcg/mL. Ketorolac does not alterdigoxinprotein binding. In vitro studies indicate that, at therapeutic concentrations ofsalicylate(300 mcg/mL), the binding of ketorolac was reduced from approximately 99.2% to 97.5%, representing a potential twofold increase in unbound ketorolac plasma levels. Therapeutic concentrations ofdigoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoinandtolbutamidedid not alter ketorolac tromethamine protein binding.
warfarin, causing no significant changes in pharmacokinetics or pharmacodynamics of warfarin. In another study, ketorolac tromethamine dosed IV or IM was given with two doses of 5000 U ofheparinto 11 healthy volunteers, resulting in a mean template bleeding time of 6.4 minutes (3.2 to 11.4 min) compared to a mean of 6.0 minutes (3.4 to 7.5 min) for heparin alone and 5.1 minutes (3.5 to 8.5 min) for placebo. Although these results do not indicate a significant interaction between ketorolac tromethamine and warfarin or heparin, the administration of ketorolac tromethamine to patients taking anticoagulants should be done extremely cautiously, and patients should be closely monitored (seeWARNINGSandPRECAUTIONS, Hematologic Effect).
WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
probenecidresulted in decreased clearance and volume of distribution of ketorolac and significant increases in ketorolac plasma levels (total AUC increased approximately threefold from 5.4 to 17.8 mcg/h/mL) and terminal half-life increased approximately twofold from 6.6 to 15.1 hours. Therefore, concomitant use of ketorolac tromethamine and probenecid is contraindicated.
ACE inhibitors and/or angiotensin II receptor antagonistsmay increase the risk of renal impairment, particularly in volume-depleted patients.
antiepileptic drugs(phenytoin, carbamazepine).
psychoactive drugs(fluoxetine, thiothixene, alprazolam).
nondepolarizing muscle relaxantsthat resulted in apnea. The concurrent use of ketorolac tromethamine with muscle relaxants has not been formally studied.
CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
PREGNANCY
LABOR & DELIVERY
CONTRAINDICATIONS).NURSING MOTHERS
PEDIATRIC USE
GERIATRIC USE
CLINICALPHARMACOLOGY) who are also more sensitive to the dose-related adverse effects of NSAIDs (seeWARNINGS, Gastrointestinal EffectsRisk of Ulceration, Bleeding, and Perforation), extreme caution, reduced dosages (seeDOSAGE AND ADMINISTRATION), and careful clinical monitoring must be used when treating the elderly with ketorolac tromethamine.KETOROLAC TROMETHAMINE ADVERSE REACTIONS
Boxed WARNING, WARNINGS, PRECAUTIONS,andDOSAGE AND ADMINISTRATION). These NSAID-related complications can be serious in certain patients for whom ketorolac tromethamine is indicated, especially when the drug is used inappropriately.Body as a Whole:fever, infections, sepsis
Cardiovascular:congestive heart failure, palpitation, pallor, tachycardia, syncope
Dermatologic:alopecia, photosensitivity, urticaria
Gastrointestinal:anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding
Hemic and Lymphatic:ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia
Metabolic and Nutritional:weight change
Nervous System:abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise
Reproductive, female:infertility
Respiratory:asthma, cough, dyspnea, pulmonary edema, rhinitis
Special Senses:abnormal taste, abnormal vision, blurred vision, hearing loss
Urogenital:cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention
Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema (see WARNINGS), myalgia
Cardiovascular:arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis
Dermatologic:exfoliative dermatitis, erythema multiforme, Lyellsyndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrosis
Gastrointestinal:acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease)
Hemic and Lymphatic:agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative wound hemorrhage (rarely requiring blood transfusionBoxedWARNING, WARNINGS,andPRECAUTIONS)
Metabolic and Nutritional:hyperglycemia, hyperkalemia, hyponatremia
Nervous System:aseptic meningitis, convulsions, coma, psychosis
Respiratory:bronchospasm, respiratory depression, pneumonia
Special Senses:conjunctivitis
Urogenital:flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome
Postmarketing Surveillance Study
TABLES 3Aand3B). This was particularly true in elderly patients who received an average daily dose greater than 60 mg/day of ketorolac tromethamineIV/IM (seeTABLE 3A).
TABLE 3: Incidence of Clinically Serious GI Bleeding as Related to Age, Total Daily Dose, and History of GI Perforation, Ulcer, Bleeding (PUB) After up to 5 Days of Treatment With KetorolacTromethamineIV/IM
A. Adult Patients Without History of PUB
B. Adult Patients With History of PUB
OVERDOSAGE
Symptoms and SignsTreatment
DOSAGE & ADMINISTRATION
Carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac tromethamine. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. In adults, the combined duration of use of IV or IM dosing of ketorolac tromethamine and ketorolac tromethamine tablets is not to exceed 5 days. In adults, the use of ketorolac tromethamine tablets is only indicated as continuation therapy to IV or IM dosing of ketorolac tromethamine.Transition from IV or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose ketorolac tromethamine tablets:
not > 40 mg/day
Note:
Oral formulationshouldnotbe givenas an initial dose
Use minimum effective dosefor the individual patient
not shorten dosing intervalof 4 to 6 hours
Total duration of treatment in adult patients:the combined duration of use of IV or IM dosing of ketorolac tromethamine and ketorolac tromethamine tablets is not to exceed 5 days.
TABLE 4: Summary of Dosing Instructions
Patient Population Ketorolac Tromethamine Tablets (following IV or IM dosing of ketorolac tromethamine)
HOW SUPPLIED
STORAGE AND HANDLING
SPL MEDGUIDE
Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)Rx only
What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines may increase the chance of a heart attack or stroke that can lead to death.This chance increases:
NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)."
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
The chance of a person getting an ulcer or bleeding increases with:
NSAID medicines should only be used:
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:
Tell your healthcare provider:
Keep a list of your medicines to show to your healthcare provider and pharmacist.
NSAID medicines should not be used by pregnant women late in their pregnancy.
Talk to your doctor.
What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Serious Side effects include: Other side effects include: Get emergency help right away if you have any of the following symptoms:
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
NSAID medicines that need a prescription
*
Generic Name Tradename *(combined with hydrocodone), Combunox (combined with oxycodone)Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
Ketorolac TromethamineKETOROLAC TROMETHAMINE TABLET
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PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
