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Drug Information on KETOROLAC TROMETHAMINE - WOCKHARDT USA LLC | Pharmaguru.com
KETOROLAC TROMETHAMINE (WOCKHARDT USA LLC)
INJECTION 25 VIAL, SINGLE-DOSE in 1 CARTON (64679-757-01) > 1 mL in 1 VIAL, SINGLE-DOSE Label Information
INJECTION 1 VIAL, SINGLE-DOSE in 1 CARTON (64679-757-03) > 1 mL in 1 VIAL, SINGLE-DOSE Label Information
INJECTION 10 VIAL, SINGLE-DOSE in 1 CARTON (64679-757-02) > 1 mL in 1 VIAL, SINGLE-DOSE Label Information
Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, ketorolac tromethamine is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).
Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS ).
Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of ketorolac tromethamine injection (see CONTRAINDICATIONS and WARNINGS ). Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs.) of body weight (see DOSAGE AND ADMINISTRATION ) and for patients with moderately elevated serum creatinine (see WARNINGS ). Doses of ketorolac tromethamine injection are not to exceed 60 mg (total dose per day) in these patients.
The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for ketorolac tromethamine injection (maximum 120 mg) (see DOSAGE AND ADMINISTRATION ).
â€ Derived from IM pharmacokinetic studies in 54 normal volunteers
â€¡ Derived from IV pharmacokinetic studies in 24 normal volunteers
33 ± 21§
1.1 ± 0.7§
1.14 ± 0.32§
4.55 ± 1.27§
2.47 ± 0.51§
1.05 ± 0.26§
1.56 ± 0.44§
3.11 ± 0.87§
3.09 ± 1.17§
Cmax3 (mcg/mL)
0.29 ± 0.07§
0.47 ± 0.13§
0.93 ± 0.26§
0.61 ± 0.21§
0.59 ± 0.2§
0.94 ± 0.29§
1.88 ± 0.59§
1.09 ± 0.3§
Distribution: The mean apparent volume (VÎ²) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data. The ketorolac tromethamine racemate has been shown to be highly protein-bound (99%). Nevertheless, even plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations.
Excretion: The principal route of elimination of ketorolac and its metabolites is renal. About 92% of a given dose is found in the urine, approximately 40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of a dose is excreted in the feces. A single-dose study with 10 mg ketorolac tromethamine (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. There is little or no inversion of the R- to S- form in humans. The clearance of the racemate in normal subjects, elderly individuals and in hepatically and renally impaired patients is outlined in Table 2 (see CLINICAL PHARMACOLOGY - Kinetics in Special Populations).
Geriatric Patients: Based on single-dose data only, the half-life of the ketorolac tromethamine racemate increased from 5 to 7 hours in the elderly (65 to 78 years) compared with young healthy volunteers (24 to 35 years) (see Table 2>). There was little difference in the Cmax for the two groups (elderly, 2.52 mcg/mL ± 0.77; young, 2.99 mcg/mL ± 1.03) (see PRECAUTIONS - Geriatric Use).
Pediatric Patients: Limited information is available regarding the pharmacokinetics of dosing of ketorolac tromethamine in the pediatric population. Following a single intravenous bolus dose of 0.5 mg/kg in 10 children 4 to 8 years old, the half-life was 5.8 ± 1.6 hours, the average clearance was 0.042 ± 0.01 L/hr/kg, the volume of distribution during the terminal phase (VÎ²) was 0.34 ± 0.12 L/kg and the volume of distribution at steady state (Vss) was 0.26± 0.08 L/kg. The volume of distribution and clearance of ketorolac in pediatric patients was higher than those observed in adult subjects (see Table 1). There are no pharmacokinetic data available for administration of ketorolac tromethamine by the IM route in pediatric patients.
The AUCâˆž-ratio of the ketorolac tromethamine enantiomers in healthy subjects and patients remained similar, indicating there was no selective excretion of either enantiomer in patients compared to healthy subjects (see WARNINGS - Renal Effects).
Hepatic Insufficiency: There was no significant difference in estimates of half-life, AUCâˆž and Cmax in 7 patients with liver disease compared to healthy volunteers (see PRECAUTIONS - Hepatic Effects and Table 2).
Normal Subjects Intramuscular (n=54) mean age=32,
range=18 to 60 Oral (n=77)
mean age=32, range=20 to 60
Intramuscular (n=13),
Oral (n=12) mean age=72,
range=65 to 78
Dysfunction Intramuscular
and Oral (n=7) mean age=51,
range=43 to 64
Patients with Renal Impairment Intramuscular (n=25),
Oral (n=9) serum
creatinine=1.9 to 5 mg/dL,
mean age (Intramuscular)=54,
range=35 to 71 mean age
(Oral)=57, range=39 to 70
mean age=40, range=27 to 63
Ketorolac tromethamine is indicated for the short-term (â‰¤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Therapy should always be initiated with IV or IM dosing of ketorolac tromethamine, and oral ketorolac tromethamine is to be used only as continuation treatment, if necessary.
Ketorolac tromethamine should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS - Anaphylactoid Reactions, and PRECAUTIONS - Pre-existing Asthma).
Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation: Ketorolac tromethamine is contraindicated in patients with previously documented peptic ulcers and/or GI bleeding. Ketorolac tromethamine can cause serious gastrointestinal (GI) adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with ketorolac tromethamine.
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).
In a study involving 12 adult volunteers, oral ketorolac tromethamine was coadministered with a single dose of 25 mg 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 of heparin to 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 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 (see WARNINGS and PRECAUTIONS - Hematological Effects).
Diuretics: Clinical studies, as well as postmarketing observations, have shown that ketorolac tromethamine can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS - Renal Effects), as well as to assure diuretic efficacy.
ACE Inhibitors/Angiotensin II Receptor Antagonists: Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal impairment, particularly in volume-depleted patients.
(â‰¥65 Years of Age)
Because ketorolac tromethamine may be cleared more slowly by the elderly (see CLINICAL PHARMACOLOGY) who are also more sensitive to the dose-related adverse effects of NSAIDs (see WARNINGS - Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation), extreme caution, reduced dosages (see DOSAGE AND ADMINISTRATION), and careful clinical monitoring must be used when treating the elderly with ketorolac tromethamine.
Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, post operative wound hemorrhage (rarely requiring blood transfusion - see Boxed WARNING, WARNINGS, and PRECAUTIONS)
Ketorolac tromethamine injection may be used as a single or multiple dose on a regular or "prn" schedule for the management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Hypovolemia should be corrected prior to the administration of ketorolac tromethamine (see WARNINGS - Renal Effects). Patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed 5 days.
When administering ketorolac tromethamine injection, the intravenous bolus must be given over no less than 15 seconds. The intramuscular administration should be given slowly and deeply into the muscle. The analgesic effect begins in ~30 minutes with maximum effect in 1 to 2 hours after dosing IV or IM. Duration of analgesic effect is usually 4 to 6 hours.
For patients â‰¥ 65 years of age, renally impaired patients (see WARNINGS ), and patients less than 50 kg (110 lbs): The recommended dose is 15 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations should not exceed 60 mg.
*FOR INTRAMUSCULAR USE ONLY.
Rev.100715
â— Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
â— Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:
Tell your healthcare provider about all of the medicines you take, including prescription or over-the counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.
Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea,vomiting, and dizziness.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information call 1-800-346-6854.
NDC: 64679-757-04
STRENGTH: 15 mg/mL
QTY: 15 mg/mL SDV Label
NDC: 64679-758-11
QTY: 30 mg/mL SDV Label
NDC: 64679-758-10
STRENGTH: 60 mg/2 mL (30 mg/mL)
QTY: 60 mg/2 mL (30 mg/mL) SDV Label
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64679-757
NDC:64679-757-01 25 in 1 CARTON 03/27/2007
NDC:64679-757-04 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
NDC:64679-757-02 10 in 1 CARTON 03/27/2007
NDC:64679-757-03 1 in 1 CARTON 03/27/2007
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64679-758
NDC:64679-758-01 25 in 1 CARTON 03/27/2007
NDC:64679-758-11 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
NDC:64679-758-04 10 in 1 CARTON 03/27/2007
NDC:64679-758-02 25 in 1 CARTON 03/27/2007
NDC:64679-758-10 2 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
NDC:64679-758-06 10 in 1 CARTON 03/27/2007
NDC:64679-758-05 1 in 1 CARTON 03/27/2007
NDC:64679-758-03 15 in 1 CARTON 03/27/2007
Wockhardt Limited 676257570 ANALYSIS(64679-757, 64679-758) , MANUFACTURE(64679-757, 64679-758) , LABEL(64679-757, 64679-758) , PACK(64679-757, 64679-758)