KETOROLAC TROMETHAMINE
KETOROLAC TROMETHAMINE INJECTION USP
FULL PRESCRIBING INFORMATION: CONTENTS*
- KETOROLAC TROMETHAMINE DESCRIPTION
- CLINICAL PHARMACOLOGY
- Clinical Studies
- KETOROLAC TROMETHAMINE INDICATIONS AND USAGE
- KETOROLAC TROMETHAMINE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- KETOROLAC TROMETHAMINE ADVERSE REACTIONS
- OVERDOSAGE
- KETOROLAC TROMETHAMINE DOSAGE AND ADMINISTRATION
- HOW SUPPLIED
FULL PRESCRIBING INFORMATION
Rx ONLY
WARNING
Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level. Oral ketorolac tromethamine is indicated only as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total combined duration of use of oral ketorolac tromethamine and ketorolac tromethamine injection should not exceed 5 days. Ketorolac tromethamine is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will increase the risk of developing serious adverse events. GASTROINTESTINAL RISK
CARDIOVASCULAR RISK
RENAL RISK
RISK OF BLEEDING
Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery. HYPERSENSITIVITY
INTRATHECAL OR EPIDURAL ADMINISTRATION
RISK DURING LABOR AND DELIVERY
CONCOMITANT USE WITH NSAIDs
SPECIAL POPULATIONS
DOSAGE AND ADMINISTRATION Ketorolac Tromethamine Tablets
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KETOROLAC TROMETHAMINE DESCRIPTION
CLINICAL PHARMACOLOGY
Pharmacodynamics
Pharmacokinetics
Comparison of IV, IM and Oral Pharmacokinetics:
Pharmacokinetic Parameters (units) | Oral* | Intramuscular† | Intravenous Bolus‡ | |||
---|---|---|---|---|---|---|
10 mg | 15 mg | 30 mg | 60 mg | 15 mg | 30 mg | |
Bioavailability (extent) | 100% | |||||
Tmax 1 (min) | 44 ± 34 | 33 ± 21§ | 44 ± 29 | 33 ± 21§ | 1.1 ± 0.7§ | 2.9 ± 1.8 |
Cmax
2 (mcg/mL) [single-dose] |
0.87 ± 0.22 | 1.14 ± 0.32§ | 2.42 ± 0.68 | 4.55 ± 1.27§ | 2.47 ± 0.51§ | 4.65 ± 0.96 |
Cmax (mcg/mL) [steady state qid] |
1.05 ± 0.26§ | 1.56 ± 0.44§ | 3.11 ± 0.87§ | N/A|| | 3.09 ± 1.17§ | 6.85 ± 2.61 |
Cmin
3 (mcg/mL) [steady state qid] |
0.29 ± 0.07§ | 0.47 ± 0.13§ | 0.93 ± 0.26§ | N/A | 0.61 ± 0.21§ | 1.04 ± 0.35 |
Cavg
4 (mcg/mL) [steady state qid] |
0.59 ± 0.20§ | 0.94 ± 0.29§ | 1.88 ± 0.59§ | N/A | 1.09 ± 0.30§ | 2.17 ± 0.59 |
Vβ5 (L/kg) | 0.175 ± 0.039 | 0.210 ± 0.044 |
2
3
4
5
maxmax
Linear Kinetics:
Distribution: β
PRECAUTIONS: Nursing mothers
Metabolism:
Excretion: CLINICAL PHARMACOLOGY: Kinetics in Special Populations
Accumulation: max
Kinetics in Special Populations: Geriatric Patients:max PRECAUTIONS - Geriatric Use
Pediatric Patients:β
Renally Insufficiency:
WARNINGS- Renal Effects
Hepatic Insufficiency:max PRECAUTIONS: Hepatic EffectsTable 2
Race:
Total Clearance [in L/h/kg]3 | Terminal Half-life [in hours] | |||
---|---|---|---|---|
Type of Subjects | IM | ORAL | IM | ORAL |
Mean (range) | Mean (range) | Mean (range) | Mean (range) | |
Normal Subjects IM (n=54) mean age=32, range=18–60 Oral (n=77) mean age=32, range=20–60 |
0.023 (0.010–0.046) |
0.025 (0.013–0.050) |
5.3 (3.5–9.2) |
5.3 (2.4–9.0) |
Healthy Elderly Subjects IM (n=13), Oral (n=12) mean age=72, range=65–78 |
0.019 (0.013–0.034) |
0.024 (0.018–0.034) |
7.0 (4.7–8.6) |
6.1 (4.3–7.6) |
Patients with Hepatic Dysfunction IM and Oral (n=7) mean age=51, range=43–64 |
0.029 (0.013–0.066) |
0.033 (0.019–0.051) |
5.4 (2.2–6.9) |
4.5 (1.6–7.6) |
Patients with Renal Impairment IM (n=25), Oral (n=9) serum creatinine=1.9–5.0 mg/dL, mean age (IM)=54, range=35–71 mean age (Oral)=57, range=39–70 |
0.015 (0.005–0.043) |
0.016 (0.007–0.052) |
10.3 (5.9–19.2) |
10.8 (3.4–18.9) |
Renal Dialysis Patients IM and Oral (n=9) mean age=40, range=27–63 |
0.016 (0.003–0.036) |
— | 13.6 (8.0–39.1) |
— |
2
3
IV Administration:Kinetics in Special Populations
Clinical Studies
Adult Patients:KETOROLAC TROMETHAMINE INDICATIONS AND USAGE
WARNINGSAcute Pain in Adult Patients
WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION,ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION -Pharmaceutical Information for Ketorolac Tromethamine Injection
KETOROLAC TROMETHAMINE CONTRAINDICATIONS
WARNINGS Anaphylactoid Reactions,PRECAUTIONS Preexisting Asthma
WARNINGS
WARNINGS for correction of volume depletion
WARNINGS PRECAUTIONS
WARNINGS
Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation
o minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration.
Hemorrhage
PRECAUTIONS
Renal Effects
CLINICAL PHARMACOLOGYDOSAGE ADMINISTRATION
Impaired Renal Function
CONTRAINDICATIONS
Anaphylactoid Reactions
CONTRAINDICATIONS and PRECAUTIONS- Preexisting Asthma
Cardiovascular Effects
Cardiovascular Thrombotic Events:
Gastrointestinal Effects- Risk of Ulceration, Bleeding, and PerforationCONTRAINDICATIONS
Hypertension
Congestive Heart Failure and Edema
Skin Reactions
Pregnancy
PRECAUTIONS
General
Hepatic Effects
Hematological Effects
Preexisting Asthma
Information for patients
Boxed WARNING, WARNINGS, PRECAUTIONS, ADVERSE REACTIONSadvise patients not to give oral ketorolac tromethamine to other family members and to discard any unused drug.
- Ketorolac tromethamine, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS: Cardiovascular Effects).
- Ketorolac tromethamine, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation).
- Ketorolac tromethamine, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
- Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
- Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
- Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
- In late pregnancy, as with other NSAIDs, ketorolac tromethamine should be avoided because it will cause premature closure of the ductus arteriosus.
Laboratory tests
Drug interactions
Warfarin, Digoxin, Salicylate, and Heparin: in vitro warfarin digoxin In vitro salicylate digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin tolbutamide
warfarin heparin WARNINGSPRECAUTIONS: Hematological Effects
Aspirin:
Diuretics:WARNINGS: Renal Effects
Probenecid: probenecid
Lithium:
Methotrexate:
ACE Inhibitors/Angiotensin II Receptor Antagonists: ACE inhibitors and/or angiotensin II receptor antagonists
Antiepileptic Drugs: antiepileptic drugs
Psychoactive Drugs: psychoactive drugs
Pentoxifylline: pentoxifylline
Nondepolarizing Muscle Relaxants: nondepolarizing muscle relaxants
Selective Serotonin Reuptake Inhibitors (SSRIs): selective serotonin reuptake inhibitors
Carcinogenesis, mutagenesis, impairment of fertility
Pregnancy
Teratogenic effects: Pregnancy Category CNonteratogenic effects
Labor and delivery
CONTRAINDICATIONS
Effects on Fertility
Nursing mothers
Pediatric use
Geriatric use (≥65 years of age)
CLINICAL PHARMACOLOGYWARNINGS: Gastrointestinal Effects- Risk of Ulceration, Bleeding, and PerforationDOSAGE AND ADMINISTRATION
KETOROLAC TROMETHAMINE ADVERSE REACTIONS
Boxed WARNING, WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATIONBody as a Whole:
Cardiovascular:
Dermatologic:
Gastrointestinal:
Hemic and Lymphatic:
Metabolic and Nutritional:
Nervous System:
Reproductive, female:
Respiratory:
Special Senses:
Urogenital:
Body as a Whole:WARNINGS
Cardiovascular:
Dermatologic:
Gastrointestinal:
Hemic and Lymphatic: Boxed WARNING, WARNINGS, PRECAUTIONS
Metabolic and Nutritional:
Nervous System:
Respiratory:
Special Senses:
Urogenital:
Postmarketing Surveillance Study
Table 3 Incidence of Clinically Serious G.I. Bleeding as Related to Age, Total Daily Dose, and History of G.I. Perforation, Ulcer, Bleeding (PUB) after up to 5 Days of Treatment with Ketorolac Tromethamine Injection |
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A. Patients without History of PUB |
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Age of Patients |
Total Daily Dose of Ketorolac Tromethamine Injection |
|||
≤60 mg |
>60 to 90 mg |
>90 to 120 mg |
>120 mg |
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<65 years of age |
0.4% |
0.4% |
0.9% |
4.6% |
≥65 years of age |
1.2% |
2.8% |
2.2% |
7.7% |
B. Patients with History of PUB |
||||
Age of Patients |
Total Daily Dose of Ketorolac Tromethamine Injection |
|||
≤60 mg |
>60 to 90 mg |
>90 to 120 mg |
>120 mg |
|
<65 years of age |
2.1% |
4.6% |
7.8% |
15.4% |
≥65 years of age |
4.7% |
3.7% |
2.8% |
25.0% |
OVERDOSAGE
Symptoms and SignsTreatment
KETOROLAC TROMETHAMINE DOSAGE AND 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 oral ketorolac tromethamine is not to exceed 5 days. In adults, the use of oral ketorolac tromethamine is only indicated as continuation therapy to IV or IM dosing of ketorolac tromethamine. See package insert for ketorolac tromethamine tablets for transition from IV or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose oral ketorolac tromethamine.Note:
Oral formulationnotas an initial dose
Use minimum effective dose
Total duration of treatment in adult patients:
Ketorolac Tromethamine Injection
WARNINGS -
Single-Dose Treatment: The Following Regimen Should Be Limited To Single Administration Use Only IM Dosing:
- Patients < 65 years of age: One dose of 60 mg.
- Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.
- Patients < 65 years of age: One dose of 30 mg.
- Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.
- Patients < 65 years of age: The recommended dose is 30 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations should not exceed 120 mg.
- For patients ≥ 65 years of age, renally impaired patients (see WARNINGS), and patients less than 50 kg (110 lbs):
Pharmaceutical Information for Ketorolac Tromethamine Injection:
HOW SUPPLIED
Ketorolac Tromethamine Injection USPFOR IM USE ONLY
Protect from light.
Manufactured by:
Distributed by:
Medication Guide for
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a list of prescription NSAID medicines.)
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.
- with longer use of NSAID medicines
- in people who have heart disease
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
- can happen without warning symptoms
- may cause death
- taking medicines called "corticosteroids" and “anticoagulants"
- longer use
- smoking
- drinking alcohol
- older age
- having poor health
- exactly as prescribed
- at the lowest dose possible for your treatment
- for the shortest time needed
- different types of arthritis
- menstrual cramps and other types of short-term pain
Do not take an NSAID medicine:
- if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
- for pain right before or after heart bypass surgery
- about all of your medical conditions.
- about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.
- if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
- if you are breastfeeding. Talk to your doctor.
Serious side
effects include:
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Other side effects
include:
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- shortness of breath or trouble breathing
- chest pain
- weakness in one part or side of your body
- slurred speech
- swelling of the face or throat
- nausea
- more tired or weaker than usual
- itching
- your skin or eyes look yellow
- stomach pain
- flu-like symptoms
- vomit blood
- there is blood in your bowel movement or it is black and sticky like tar
- unusual weight gain
- skin rash or blisters with fever
- swelling of the arms and legs, hands and feet
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
- Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
- Some of these NSAID medicines are sold in lower doses without a prescription (over -the -counter). Talk to your healthcare provider before using over -the -counter NSAIDs for more than 10 days.
Generic Name | Tradename |
---|---|
Celecoxib | Celebrex |
Diclofenac | Cataflam, Voltaren, Arthrotec (combined with misoprostol) |
Diflunisal | Dolobid |
Etodolac | Lodine, Lodine XL |
Fenoprofen | Nalfon, Nalfon 200 |
Flurbirofen | Ansaid |
Ibuprofen | Motrin, Tab-Profen, Vicoprofen* (combined with hydrocodone), Combunox (combined with oxycodone) |
Indomethacin | Indocin, Indocin SR, Indo-Lemmon, Indomethagan |
Ketoprofen | Oruvail |
Ketorolac | Toradol |
Mefenamic Acid | Ponstel |
Meloxicam | Mobic |
Nabumetone | Relafen |
Naproxen | Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole) |
Oxaprozin | Daypro |
Piroxicam | Feldene |
Sulindac | Clinoril |
Tolmetin | Tolectin, Tolectin DS, Tolectin 600 |
KETOROLAC TROMETHAMINEKETOROLAC TROMETHAMINE INJECTION
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