Ketorolac

Generic Name: Ketorolac tromethamine
Dosage Form: Injection

Ketorolac Description

Ketorolac tromethamine is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs). The chemical name for Ketorolac tromethamine is (±)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1), and the chemical structure is:

Ketorolac tromethamine is a racemic mixture of [-]S and [+]R Ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. Ketorolac tromethamine has a pKa of 3.5 and an n-octanol/water partition coefficient of 0.26. The molecular weight of Ketorolac tromethamine is 376.41. Its molecular formula is C19H24N2O6.

Ketorolac tromethamine is available for intravenous (IV) or intramuscular (IM) administration as: 15 mg in 1 mL (1.5%) and 30 mg in 1 mL (3%) in sterile solution; 60 mg in 2 mL (3%) of Ketorolac tromethamine in sterile solution is available for IM administration only. The solutions contain 0.1% citric acid, 10% (w/v) alcohol, USP, and 6.68 mg, 4.35 mg and 8.70 mg, respectively, of sodium chloride in sterile water. The pH is adjusted with sodium hydroxide or hydrochloric acid, and the solutions are packaged with nitrogen. The sterile solutions are clear and slightly yellow in color.

Ketorolac - Clinical Pharmacology

Pharmacodynamics

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits analgesic activity in animal models. Ketorolac tromethamine inhibits synthesis of prostaglandins and may be considered a peripherally acting analgesic. The biological activity of Ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine possesses no sedative or anxiolytic properties.

The peak analgesic effect of Ketorolac tromethamine occurs within 2 to 3 hours and was not statistically significantly different over the recommended dosage range of Ketorolac tromethamine. The greatest difference between large and small doses of Ketorolac tromethamine by either route was in the duration of analgesia.

Pharmacokinetics

Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic activity.

Comparison of IV, IM and Oral Pharmacokinetics

The pharmacokinetics of Ketorolac tromethamine, following IV, IM and oral doses of Ketorolac tromethamine are compared in Table 1. In adults, the extent of bioavailability following administration of the oral and IM forms of Ketorolac tromethamine was equal to that following an IV bolus.

Linear Kinetics

In adults, following administration of single oral, IM or IV doses of Ketorolac tromethamine in the recommended dosage ranges, the clearance of the racemate does not change. This implies that the pharmacokinetics of Ketorolac tromethamine in adults, following single or multiple IM, IV or recommended oral doses of Ketorolac tromethamine, are linear. At the higher recommended doses, there is a proportional increase in the concentrations of free and bound racemate.

Distribution

The mean apparent volume (Vß) 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.

Ketorolac tromethamine is excreted in human milk (see PRECAUTIONS, Lactation and Nursing).

Metabolism

Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.

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).

The half-life of the Ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD ± 0.4) compared with 5 hours (SD ± 1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours.

Accumulation

Ketorolac tromethamine administered as an IV bolus every 6 hours for 5 days to healthy subjects (n=13), showed no significant difference in Cmax on Day 1 and Day 5. Trough levels averaged 0.29 mcg/mL (SD± 0.13) on Day 1 and 0.55 mcg/mL (SD ± 0.23) on Day 6. Steady state was approached after the fourth dose.

Accumulation of Ketorolac tromethamine has not been studied in special populations (geriatric, pediatric, renal failure or hepatic disease patients).

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

Following a single intravenous bolus dose of 0.5 mg/kg in 10 children 4 to 8 years old, the half-life was 6 hours (range: 3.5 to 10 h), the average clearance was 0.042 L/hr/kg and the Vd was 0.26 L/kg (range: 0.19 to 0.44 L/kg). In a second study, following a single intravenous dose of 0.6 mg/kg in 24 children 3 to 18 years old, Cmax was 4.3 ± 1.7 mcg/mL, Tmax was 10.25 ± 1.15 minutes, half-life was 3.8 ± 2.6 hours, Cl was 0.0678 L/hr/kg and Vd was 0.25 L/kg. The volume of distribution and clearance of Ketorolac in pediatric patients was twice that observed in adult subjects (see Tables 1 and 2). There are no pharmacokinetic data available for Ketorolac tromethamine administration by the IM route in pediatric patients.

Renal Insufficiency

Based on single-dose data only, the mean half-life of Ketorolac tromethamine in renally impaired patients is between 6 and 19 hours and is dependent on the extent of the impairment. There is poor correlation between creatinine clearance and total Ketorolac tromethamine clearance in the elderly and populations with renal impairment (r = 0.5).

In patients with renal disease, the AUC∞of each enantiomer increased by approximately 100% compared with healthy volunteers. The volume of distribution doubles for the S-enantiomer and increases by 1/5th for the R-enantiomer. The increase in volume of distribution of Ketorolac tromethamine implies an increase in unbound fraction.

The AUC∞-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 and Table 2).

Hepatic Insufficiency

There was no significant difference in estimates of half-life, AUC∞and Cmax in 7 patients with liver disease compared to healthy volunteers (seePRECAUTIONS,Hepatic Effectsand Table 2).

Race

Pharmacokinetic differences due to race have not been identified.

* Derived from PO pharmacokinetic studies in 77 normal fasted volunteers † Derived from IM pharmacokinetic studies in 54 normal volunteers ‡ Derived from IV pharmacokinetic studies in 24 normal volunteers § Time-to-peak plasma concentration ¶ Mean value was simulated from observed plasma concentration data and standard deviation was simulated from percent coefficient of variation for observed Cmax and Tmax data # Peak plasma concentration Þ Not applicable because 60 mg is only recommended as a single dose ß Trough plasma concentration à Average plasma concentration è Volume of distribution
	Table 1 Table of Approximate Average Pharmacokinetic Parameters (Mean±SD)Following Oral, Intramuscular and Intravenous Doses of Ketorolac Tromethamine
PharmacokineticParameters (units)	Oral*	Intramuscular†			Intravenous Bolus‡
	10 mg	15 mg	30 mg	60 mg	15 mg	30 mg
Bioavailability (extent)	100%
Tmax§ (min)	44 ± 34	33 ± 21¶	44 ± 29	33 ± 21¶	1.1 ± 0.7¶	2.9 ± 1.8
Cmax# (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) [stead state qid]	1.05 ± 0.26¶	1.56 ± 0.44¶	3.11 ± 0.87¶	N/AÞ	3.09 ± 1.17¶	6.85 ± 2.61
Cminß (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
Cavgà (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
Vβè (L/kg)	------0.175 ± 0.039------				0.210 ± 0.044

% Dose metabolized = <50

% Dose excreted in feces = 6

% Dose excreted in urine = 91

% Plasma protein binding = 99

* estimated from 30 mg single IM doses of Ketorolac tromethamine † estimated from 10 mg single oral doses of Ketorolac tromethamine ‡ Liters/hour/kilogram
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)
	Total Clearance [in L/h/kg]‡		Terminal Half-life [in hours]
Type Of Subjects	IM Mean (range)	ORAL Mean (range)	IM Mean (range)	ORAL 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)	--

IV Administration: In normal adult subjects (n=37), the total clearance of 30 mg IV-administered Ketorolac tromethamine was 0.030 (0.017-0.051) L/h/kg. The terminal half-life was 5.6 (4.0-7.9) hours. (See Kinetics in Special Populations for use of Ketorolac tromethamine IV in pediatric patients.)

Clinical Studies

Adult Patients

The analgesic efficacy of intramuscularly, intravenously and orally administered Ketorolac tromethamine was investigated in two postoperative pain models: general surgery (orthopedic, gynecologic and abdominal) and oral surgery (removal of impacted third molars). The studies were double-blind, single- and multiple-dose, parallel trial designs in patients with moderate to severe pain at baseline. Ketorolac Tromethamine Injection was compared as follows: IM to meperidine or morphine administered intramuscularly and IV to morphine administered either directly IV or through a PCA (Patient-Controlled Analgesia) pump.

Short-Term Use (Up to 5 Days) Studies

In adults, the comparisons of intramuscular administration during the first hour, the onset of analgesic action was similar for Ketorolac tromethamine and the narcotics, but the duration of analgesia was longer with Ketorolac tromethamine than with the opioid comparators meperidine or morphine.

In a multi-dose, postoperative (general surgery) double-blind trial of Ketorolac tromethamine 30 mg IM versus morphine 6 and 12 mg IM, each drug given on an as needed basis for up to 5 days, the overall analgesic effect of Ketorolac tromethamine 30 mg IM was between that of morphine 6 and 12 mg. The majority of patients treated with either Ketorolac tromethamine or morphine were dosed for up to 3 days; a small percentage of patients received 5 days of dosing.

In clinical settings where perioperative morphine was allowed, Ketorolac tromethamine 30 mg IV, given once or twice as needed, provided analgesia comparable to morphine 4 mg IV once or twice as needed.

There was relatively limited experience with 5 consecutive days of Ketorolac tromethamine IV use in controlled clinical trials, as most patients were given the drug for 3 days or less. The adverse events seen with IV-administered Ketorolac tromethamine were similar to those observed with IM-administered Ketorolac tromethamine, as would be expected based on the similar pharmacokinetics and bioequivalence (AUC, clearance, plasma half-life) of IV and IM routes of Ketorolac tromethamine administration.

Pediatric Patients

The analgesic efficacy of single doses of Ketorolac Tromethamine Injection has been demonstrated by showing a decrease in the need for supplemental narcotic in pediatric patients receiving Ketorolac as compared to placebo. See discussion of these results under Clinical Studies With Concomitant Use of Opioids below.

Clinical Studies With Concomitant Use of Opioids

Adult Patients

Clinical studies in postoperative pain management have demonstrated that Ketorolac Tromethamine Injection, when used in combination with opioids, significantly reduced opioid consumption. This combination may be useful in the subpopulation of patients especially prone to opioid-related complications. Ketorolac tromethamine and narcotics should not be administered in the same syringe.

In a postoperative study, where all patients received morphine by a PCA device, patients treated with Ketorolac tromethamine IV as fixed intermittent boluses (e.g., 30 mg initial dose followed by 15 mg q3h), required significantly less morphine (26%) than the placebo group. Analgesia was significantly superior, at various postdosing pain assessment times, in the patients receiving Ketorolac tromethamine IV plus PCA morphine as compared to patients receiving PCA-administered morphine alone.

Pediatric Patients

Ketorolac tromethamine IM reduced the need for supplemental opioid (fentanyl) when a 1 mg/kg dose was administered immediately following tonsillectomy compared to saline controls (see WARNINGS, Hemorrhage). In another study, when a single bolus dose of 0.9 mg/kg of Ketorolac tromethamine IV was given to pediatric patients ages 5 to 12 years, compared to saline, a reduction in supplemental opioid was needed following various surgical procedures. In a third study less supplemental morphine was needed in pediatric patients ages 8 to 16 years, who received a 0.8 mg/kg IV injection of Ketorolac tromethamine in conjunction with morphine following orthopedic surgical procedures, compared to morphine alone. In a study in pediatric patients ages 3 to 12 years, Ketorolac tromethamine IV demonstrated a slower onset of analgesia, but a longer duration of action compared to morphine. There is limited data available to support the use of multiple doses of Ketorolac Tromethamine Injection in pediatric patients.

Postmarketing Surveillance Study

A large postmarketing observational, non-randomized study, involving approximately 10,000 patients receiving Ketorolac tromethamine, demonstrated that the risk of clinically serious gastrointestinal (GI) bleeding was dose-dependent (see Tables 3A and 3B). This was particularly true in elderly patients who received an average daily dose greater than 60 mg/day of Ketorolac tromethamine (Table 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 Ketorolac Tromethamine Injection
A. Adult Patients Without 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	0.4%	0.4%	0.9%	4.6%
≥65 years of age	1.2%	2.8%	2.2%	7.7%
B. Adult 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%

Indications and Usage for Ketorolac

Adult Patients

Ketorolac tromethamine is indicated for the short-term (≤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 Ketorolac Tromethamine Injection and Ketorolac tromethamine tablets are to be used only as continuation treatment, if necessary. Combined use of Ketorolac Tromethamine Injection and Ketorolac tromethamine tablets is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS). Patients should be switched to alternative analgesics as soon as possible, but Ketorolac tromethamine therapy is not to exceed 5 days.

Pediatric Patients

The safety and effectiveness of single doses of Ketorolac Tromethamine Injection have been established in pediatric patients between the ages of 2 and 16 years. Ketorolac tromethamine, as a single injectable dose, has been shown to be effective in the management of moderately severe acute pain that requires analgesia at the opioid level, usually in the postoperative setting. There is limited data available to support the use of multiple doses of Ketorolac tromethamine in pediatric patients. Safety and effectiveness have not been established in pediatric patients below the age of 2 years. Use of Ketorolac tromethamine in pediatric patients is supported by evidence from adequate and well-controlled studies of Ketorolac tromethamine in adults with additional pharmacokinetic, efficacy and safety data on its use in pediatric patients available in the published literature (see CLINICAL PHARMACOLOGY, Clinical Studies, WARNINGS, and PRECAUTIONS).

Ketorolac Tromethamine Injection has been used concomitantly with morphine and meperidine and has shown an opioid-sparing effect. For breakthrough pain, it is recommended to supplement the lower end of the Ketorolac Tromethamine Injection dosage range with low doses of narcotics prn, unless otherwise contraindicated. Ketorolac Tromethamine Injection and narcotics should not be administered in the same syringe (see DOSAGE AND ADMINISTRATION - Pharmaceutical Information for Ketorolac Tromethamine Injection).

Contraindications

(see also Boxed WARNING)

• 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.
• Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion (see WARNINGS for correction of volume depletion).
• Ketorolac tromethamine is CONTRAINDICATED in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage.
• The use of Ketorolac tromethamine is CONTRAINDICATED in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.
• 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).
• Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery and is CONTRAINDICATED intraoperatively when hemostasis is critical because of the increased risk of bleeding.
• Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS).
• Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving ASA or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events.
• Ketorolac Tromethamine Injection is CONTRAINDICATED for neuraxial (epidural or intrathecal) administration due to its alcohol content.
• The concomitant use of Ketorolac tromethamine and probenecid is CONTRAINDICATED.

Warnings

(see also Boxed WARNING)

The combined use of Ketorolac Tromethamine Injection and Ketorolac tromethamine tablets are not to exceed 5 days in adults. Only single doses of Ketorolac Tromethamine Injection are recommended for use in pediatric patients.

The most serious risks associated with Ketorolac tromethamine are:

Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding and Perforation

Ketorolac tromethamine is CONTRAINDICATED in patients with previously documented peptic ulcers and/or GI bleeding. Serious gastrointestinal toxicity, such as bleeding, ulceration and perforation, can occur at any time, with or without warning symptoms, in patients treated with Ketorolac tromethamine. Studies to date with NSAIDs have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population. Postmarketing experience with parenterally administered Ketorolac tromethamine suggests that there may be a greater risk of gastrointestinal ulcerations, bleeding and perforation in the elderly.

The incidence and severity of gastrointestinal complications increases with increasing dose of, and duration of treatment with, Ketorolac tromethamine. In a non-randomized, in-hospital postmarketing surveillance study comparing parenteral Ketorolac tromethamine to parenteral opioids, higher rates of clinically serious GI bleeding were seen in adult patients <65 years of age who received an average total daily dose of more than 90 mg of Ketorolac Tromethamine Injection per day (see CLINICAL PHARMACOLOGY, Postmarketing Surveillance Study).

The same study showed that elderly (≥65 years of age) and debilitated patients are more susceptible to gastrointestinal complications. A history of peptic ulcer disease was revealed as another risk factor that increases the possibility of developing serious gastrointestinal complications during Ketorolac tromethamine therapy (see Tables 3A and 3B).

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 should be undertaken very cautiously, and those patients should be carefully monitored. Patients on therapeutic doses of anticoagulants (e.g., heparin or dicumarol derivatives) have an 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 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 weigh the benefits against the risks and use such concomitant therapy in these patients only extremely cautiously. In patients who receive anticoagulants for any reason, there is an increased risk of intramuscular hematoma formation from administered Ketorolac tromethamine IM (see PRECAUTIONS - Drug Interactions). Patients receiving therapy that affects hemostasis should be monitored closely.

In postmarketing experience, postoperative hematomas and other signs of wound bleeding have been reported in association with the perioperative use of Ketorolac Tromethamine Injection. Therefore, perioperative use of Ketorolac tromethamine should be avoided and postoperative use be undertaken with caution when hemostasis is critical (see WARNINGS and PRECAUTIONS).

Pediatrics and Tonsillectomy

Physicians should consider the increased risk of bleeding before deciding to administer Ketorolac tromethamine in patients following tonsillectomy. Ketorolac Tromethamine Injection is not recommended for use in pediatric patients below the age of 2 years. In a retrospective analysis of patients having undergone tonsillectomy with or without adenoidectomy, the risk of bleeding was 10.1% in patients administered Ketorolac Tromethamine Injection compared to 2.2% in those receving opioids. The postoperative hemorrhage rate in patients 12 years and younger was 6.5% and 3.3% with and without Ketorolac tromethamine, respectively. In a prospective study of Ketorolac tromethamine in pediatric patients (ages 3 to 9 years) undergoing tonsillectomy with or without adenoidectomy, the overall incidence of bleeding was similar between the patients receiving Ketorolac tromethamine and morphine (16.3% versus 17%, respectively). However, during the first 24 hours after surgery, a higher incidence of bleeding was observed in the Ketorolac Tromethamine Injection group (14.3%) versus the morphine group (4.2%).

Anaphylactoid Reactions

Anaphylactoid reactions may occur in patients without a known previous exposure or hypersensitivity to aspirin, Ketorolac tromethamine or other NSAIDs, or in individuals with a history of angioedema, bronchospastic reactivity (e.g., asthma) and nasal polyps. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.

Impaired Renal Function

Ketorolac tromethamine should be used with caution in patients with impaired renal function or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis. Renal toxicity with Ketorolac tromethamine has been seen in patients with conditions leading to a reduction in blood volume and/or renal blood flow where renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients administration of Ketorolac tromethamine may cause a dose-dependent reduction in renal prostaglandin formation and may precipitate acute renal failure. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics and the elderly. Discontinuation of Ketorolac tromethamine therapy is usually followed by recovery to the pretreatment state.

Renal Effects

Ketorolac tromethamine and its metabolites are eliminated primarily by the kidneys, which, in patients with reduced creatinine clearance, will result in diminished clearance of the drug (see CLINICAL PHARMACOLOGY). Therefore, Ketorolac tromethamine should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION) and such patients should be followed closely. With the use of Ketorolac tromethamine, there have been reports of acute renal failure, nephritis and nephrotic syndrome.

Because patients with underlying renal insufficiency are at increased risk of developing acute renal failure, the risks and benefits should be assessed prior to giving Ketorolac tromethamine to these patients. Hence, in patients with moderately elevated serum creatinine, it is recommended that the daily dose of Ketorolac Tromethamine Injection be reduced by half, not to exceed 60 mg/day. Ketorolac TROMETHAMINE IS CONTRAINDICATED IN PATIENTS WITH SERUM CREATININE CONCENTRATIONS INDICATING ADVANCED RENAL IMPAIRMENT (see CONTRAINDICATIONS).

Hypovolemia should be corrected before treatment with Ketorolac tromethamine is initiated.

Fluid Retention and Edema

Fluid retention, edema, retention of NaCl, oliguria, elevations of serum urea nitrogen and creatinine have been reported in clinical trials with Ketorolac tromethamine. Therefore, Ketorolac tromethamine should be used only very cautiously in patients with cardiac decompensation, hypertension or similar conditions.

Pregnancy

In late pregnancy, as with other NSAIDs, Ketorolac tromethamine should be avoided because it may cause premature closure of the ductus arteriosus.

Precautions

General

Hepatic Effects

Ketorolac tromethamine should be used with caution in patients with impaired hepatic function or a history of liver disease. Treatment with Ketorolac tromethamine may cause elevations of liver enzymes, and, in patients with pre-existing liver dysfunction, it may lead to the development of a more severe hepatic reaction. The administration of Ketorolac tromethamine should be discontinued in patients in whom an abnormal liver test has occurred as a result of Ketorolac tromethamine therapy.

Hematologic Effects

Ketorolac tromethamine inhibits platelet aggregation and may prolong bleeding time; therefore, it is contraindicated as a preoperative medication, and caution should be used when hemostasis is critical. Unlike aspirin, the inhibition of platelet function by Ketorolac tromethamine disappears within 24 to 48 hours after the drug is discontinued. Ketorolac tromethamine does not appear to affect platelet count, prothrombin time (PT) or partial thromboplastin time (PTT). In controlled clinical studies, where Ketorolac tromethamine was administered intramuscularly or intravenously postoperatively, the incidence of clinically significant postoperative bleeding was 0.4% for Ketorolac tromethamine compared to 0.2% in the control groups receiving narcotic analgesics.

Information for Patients

Ketorolac tromethamine is a potent NSAID and may cause serious side effects such as gastrointestinal bleeding or kidney failure, which may result in hospitalization and even fatal outcome.

Physicians, when prescribing Ketorolac tromethamine, should inform their patients or their guardians of the potential risks of Ketorolac tromethamine treatment (see Boxed WARNING, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections). Advise patients not to give Ketorolac tromethamine tablets to other family members and to discard any unused drug.

Remember that the total duration of Ketorolac tromethamine therapy is not to exceed five (5) days in adults or a single dose in pediatric patients ages 2 to 16 years.

Drug Interactions

Ketorolac is highly bound to human plasma protein (mean 99.2%).

Warfarin, Digoxin, Salicylate, and Heparin

Thein vitro binding of warfarin to 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 alter digoxin protein binding. In vitrostudies indicate that, at therapeutic concentrations of salicylate (300 mcg/mL), the binding of Ketorolac was reduced from approximately 99.2% to 97.5%, representing a potential two-fold increase in unbound Ketorolac plasma levels. Therapeutic concentrations ofdigoxin,warfarin, ibuprofen, naproxen,piroxicam, acetaminophen, phenytoin andtolbutamide did not alter Ketorolac tromethamine protein binding.

In a study involving 12 adult volunteers, Ketorolac tromethamine tablets were coadministered with a single dose of 25 mg warfarin, causing no significant changes in pharmacokinetics or pharmacodynamics of warfarin. In another study, Ketorolac Tromethamine Injection 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 6.0 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 (see WARNINGS and PRECAUTIONS).

Furosemide

Ketorolac Tromethamine Injection reduced the diuretic response to furosemide in normovolemic healthy subjects by approximately 20% (mean sodium and urinary output decreased 17%).

Probenecid

Concomitant administration of Ketorolac tromethamine tablets and probenecid resulted in decreased clearance of Ketorolac and significant increases in Ketorolac plasma levels (total AUC increased approximately three-fold from 5.4 to 17.8 mcg/h/mL) and terminal half-life increased approximately two-fold from 6.6 to 15.1 hours. Therefore, concomitant use of Ketorolac tromethamine and probenecid is contraindicated.

Lithium

Inhibition of renal lithium clearance, leading to an increase in plasma lithium concentration, has been reported with some prostaglandin synthesis-inhibiting drugs. The effect of Ketorolac tromethamine on plasma lithium has not been studied, but cases of increased lithium plasma levels during Ketorolac tromethamine therapy have been reported.

Methotrexate

Concomitant administration of methotrexate and some NSAIDs has been reported to reduce the clearance of methotrexate, enhancing the toxicity of methotrexate. The effect of Ketorolac tromethamine on methotrexate clearance has not been studied.

Nondepolarizing Muscle Relaxants

In postmarketing experience there have been reports of a possible interaction between Ketorolac Tromethamine Injection and nondepolarizing muscle relaxants that resulted in apnea. The concurrent use of Ketorolac tromethamine with muscle relaxants has not been formally studied.

ACE Inhibitors

Concomitant use of ACE inhibitors may increase the risk of renal impairment, particularly in volume-depleted patients.

Antiepileptic Drugs

Sporadic cases of seizures have been reported during concomitant use of Ketorolac tromethamine and antiepileptic drugs (phenytoin, carbamazepine).

Psychoactive Drugs

Hallucinations have been reported when Ketorolac tromethamine was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam).

Morphine

Ketorolac Tromethamine Injection has been administered concurrently with morphine in several clinical trials of postoperative pain without evidence of adverse interactions. Do not mix Ketorolac tromethamine and morphine in the same syringe.

There is no evidence in animal or human studies that Ketorolac tromethamine induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs.

Carcinogenesis and Mutagenesis and Impairment of Fertility

An 18-month study in mice with oral doses of Ketorolac tromethamine at 2 mg/kg/day (0.9 times the human systemic exposure at the recommended IM or IV dose of 30 mg qid, based on area-under-the-plasma-concentration curve [AUC]), and a 24-month study in rats at 5 mg/kg/day (0.5 times the human AUC) showed no evidence of tumorigenicity.

Ketorolac tromethamine was not mutagenic in the Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays. Ketorolac tromethamine did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 mcg/mL and at higher concentrations, Ketorolac tromethamine increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells.

Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg (0.9 times the human AUC) and 16 mg/kg (1.6 times the human AUC) of Ketorolac tromethamine, respectively.

Pregnancy

Pregnancy Category C

Reproduction studies have been performed during organogenesis using daily oral doses of Ketorolac tromethamine at 3.6 mg/kg (0.37 times the human AUC) in rabbits and at 10 mg/kg (1.0 times the human AUC) in rats. Results of these studies did not reveal evidence of teratogenicity to the fetus. Oral doses of Ketorolac tromethamine at 1.5 mg/kg (0.14 times the human AUC), administered after gestation day 17, caused dystocia and higher pup mortality in rats. There are no adequate and well-controlled studies of Ketorolac tromethamine in pregnant women. Ketorolac tromethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The use of Ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage (see CONTRAINDICATIONS).

Lactation and Nursing

After a single administration of 10 mg of Ketorolac tromethamine tablets to humans, the maximum milk concentration observed was 7.3 ng/mL, and the maximum milk-to-plasma ratio was 0.037. After 1 day of dosing (qid), the maximum milk concentration was 7.9 ng/mL, and the maximum milk-to-plasma ratio was 0.025. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers is CONTRAINDICATED.

Pediatric Use

The safety and effectiveness of single doses of Ketorolac Tromethamine Injection have been established in pediatric patients between the ages of 2 and 16 years. Ketorolac Tromethamine Injection has been shown to be effective in the management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Safety and efficacy in pediatric patients below the age of 2 have not been established. Therefore, Ketorolac Tromethamine Injection is not recommended in pediatric patients below the age of 2.



Where can I get more information about Ketorolac injection Ketorolac injection USP ? We recommend to use www.Drugs.com

---

Typical mistypes for Ketorolac injection Ketorolac injection USP
jetorolac injection ketorolac injection usp, metorolac injection ketorolac injection usp, letorolac injection ketorolac injection usp, oetorolac injection ketorolac injection usp, ietorolac injection ketorolac injection usp, kwtorolac injection ketorolac injection usp, kstorolac injection ketorolac injection usp, kdtorolac injection ketorolac injection usp, krtorolac injection ketorolac injection usp, k4torolac injection ketorolac injection usp, k3torolac injection ketorolac injection usp, kerorolac injection ketorolac injection usp, keforolac injection ketorolac injection usp, kegorolac injection ketorolac injection usp, keyorolac injection ketorolac injection usp, ke6orolac injection ketorolac injection usp, ke5orolac injection ketorolac injection usp, ketirolac injection ketorolac injection usp, ketkrolac injection ketorolac injection usp, ketlrolac injection ketorolac injection usp, ketprolac injection ketorolac injection usp, ket0rolac injection ketorolac injection usp, ket9rolac injection ketorolac injection usp, ketoeolac injection ketorolac injection usp, ketodolac injection ketorolac injection usp, ketofolac injection ketorolac injection usp, ketotolac injection ketorolac injection usp, keto5olac injection ketorolac injection usp, keto4olac injection ketorolac injection usp, ketorilac injection ketorolac injection usp, ketorklac injection ketorolac injection usp, ketorllac injection ketorolac injection usp, ketorplac injection ketorolac injection usp, ketor0lac injection ketorolac injection usp, ketor9lac injection ketorolac injection usp, ketorokac injection ketorolac injection usp, ketoropac injection ketorolac injection usp, ketorooac injection ketorolac injection usp, ketorolzc injection ketorolac injection usp, ketorolsc injection ketorolac injection usp, ketorolwc injection ketorolac injection usp, ketorolqc injection ketorolac injection usp, ketorolax injection ketorolac injection usp, ketorolav injection ketorolac injection usp, ketorolaf injection ketorolac injection usp, ketorolad injection ketorolac injection usp, ketorolac unjection ketorolac injection usp, ketorolac jnjection ketorolac injection usp, ketorolac knjection ketorolac injection usp, ketorolac onjection ketorolac injection usp, ketorolac 9njection ketorolac injection usp, ketorolac 8njection ketorolac injection usp, ketorolac ibjection ketorolac injection usp, ketorolac imjection ketorolac injection usp, ketorolac ijjection ketorolac injection usp, ketorolac ihjection ketorolac injection usp, ketorolac inhection ketorolac injection usp, ketorolac innection ketorolac injection usp, ketorolac inmection ketorolac injection usp, ketorolac inkection ketorolac injection usp, ketorolac iniection ketorolac injection usp, ketorolac inuection ketorolac injection usp, ketorolac injwction ketorolac injection usp, ketorolac injsction ketorolac injection usp, ketorolac injdction ketorolac injection usp, ketorolac injrction ketorolac injection usp, ketorolac inj4ction ketorolac injection usp, ketorolac inj3ction ketorolac injection usp, ketorolac injextion ketorolac injection usp, ketorolac injevtion ketorolac injection usp, ketorolac injeftion ketorolac injection usp, ketorolac injedtion ketorolac injection usp, ketorolac injecrion ketorolac injection usp, ketorolac injecfion ketorolac injection usp, ketorolac injecgion ketorolac injection usp, ketorolac injecyion ketorolac injection usp, ketorolac injec6ion ketorolac injection usp, ketorolac injec5ion ketorolac injection usp, ketorolac injectuon ketorolac injection usp, ketorolac injectjon ketorolac injection usp, ketorolac injectkon ketorolac injection usp, ketorolac injectoon ketorolac injection usp, ketorolac inject9on ketorolac injection usp, ketorolac inject8on ketorolac injection usp, ketorolac injectiin ketorolac injection usp, ketorolac injectikn ketorolac injection usp, ketorolac injectiln ketorolac injection usp, ketorolac injectipn ketorolac injection usp, ketorolac injecti0n ketorolac injection usp, ketorolac injecti9n ketorolac injection usp, ketorolac injectiob ketorolac injection usp, ketorolac injectiom ketorolac injection usp, ketorolac injectioj ketorolac injection usp, ketorolac injectioh ketorolac injection usp, ketorolac injection jetorolac injection usp, ketorolac injection metorolac injection usp, ketorolac injection letorolac injection usp, ketorolac injection oetorolac injection usp, ketorolac injection ietorolac injection usp, ketorolac injection kwtorolac injection usp, ketorolac injection kstorolac injection usp, ketorolac injection kdtorolac injection usp, ketorolac injection krtorolac injection usp, ketorolac injection k4torolac injection usp, ketorolac injection k3torolac injection usp, ketorolac injection kerorolac injection usp, ketorolac injection keforolac injection usp, ketorolac injection kegorolac injection usp, ketorolac injection keyorolac injection usp, ketorolac injection ke6orolac injection usp, ketorolac injection ke5orolac injection usp, ketorolac injection ketirolac injection usp, ketorolac injection ketkrolac injection usp, ketorolac injection ketlrolac injection usp, ketorolac injection ketprolac injection usp, ketorolac injection ket0rolac injection usp, ketorolac injection ket9rolac injection usp, ketorolac injection ketoeolac injection usp, ketorolac injection ketodolac injection usp, ketorolac injection ketofolac injection usp, ketorolac injection ketotolac injection usp, ketorolac injection keto5olac injection usp, ketorolac injection keto4olac injection usp, ketorolac injection ketorilac injection usp, ketorolac injection ketorklac injection usp, ketorolac injection ketorllac injection usp, ketorolac injection ketorplac injection usp, ketorolac injection ketor0lac injection usp, ketorolac injection ketor9lac injection usp, ketorolac injection ketorokac injection usp, ketorolac injection ketoropac injection usp, ketorolac injection ketorooac injection usp, ketorolac injection ketorolzc injection usp, ketorolac injection ketorolsc injection usp, ketorolac injection ketorolwc injection usp, ketorolac injection ketorolqc injection usp, ketorolac injection ketorolax injection usp, ketorolac injection ketorolav injection usp, ketorolac injection ketorolaf injection usp, ketorolac injection ketorolad injection usp, ketorolac injection ketorolac unjection usp, ketorolac injection ketorolac jnjection usp, ketorolac injection ketorolac knjection usp, ketorolac injection ketorolac onjection usp, ketorolac injection ketorolac 9njection usp, ketorolac injection ketorolac 8njection usp, ketorolac injection ketorolac ibjection usp, ketorolac injection ketorolac imjection usp, ketorolac injection ketorolac ijjection usp, ketorolac injection ketorolac ihjection usp, ketorolac injection ketorolac inhection usp, ketorolac injection ketorolac innection usp, ketorolac injection ketorolac inmection usp, ketorolac injection ketorolac inkection usp, ketorolac injection ketorolac iniection usp, ketorolac injection ketorolac inuection usp, ketorolac injection ketorolac injwction usp, ketorolac injection ketorolac injsction usp, ketorolac injection ketorolac injdction usp, ketorolac injection ketorolac injrction usp, ketorolac injection ketorolac inj4ction usp, ketorolac injection ketorolac inj3ction usp, ketorolac injection ketorolac injextion usp, ketorolac injection ketorolac injevtion usp, ketorolac injection ketorolac injeftion usp, ketorolac injection ketorolac injedtion usp, ketorolac injection ketorolac injecrion usp, ketorolac injection ketorolac injecfion usp, ketorolac injection ketorolac injecgion usp, ketorolac injection ketorolac injecyion usp, ketorolac injection ketorolac injec6ion usp, ketorolac injection ketorolac injec5ion usp, ketorolac injection ketorolac injectuon usp, ketorolac injection ketorolac injectjon usp, ketorolac injection ketorolac injectkon usp, ketorolac injection ketorolac injectoon usp, ketorolac injection ketorolac inject9on usp, ketorolac injection ketorolac inject8on usp, ketorolac injection ketorolac injectiin usp, ketorolac injection ketorolac injectikn usp, ketorolac injection ketorolac injectiln usp, ketorolac injection ketorolac injectipn usp, ketorolac injection ketorolac injecti0n usp, ketorolac injection ketorolac injecti9n usp, ketorolac injection ketorolac injectiob usp, ketorolac injection ketorolac injectiom usp, ketorolac injection ketorolac injectioj usp, ketorolac injection ketorolac injectioh usp, ketorolac injection ketorolac injection ysp, ketorolac injection ketorolac injection hsp, ketorolac injection ketorolac injection jsp, ketorolac injection ketorolac injection isp, ketorolac injection ketorolac injection 8sp, ketorolac injection ketorolac injection 7sp, ketorolac injection ketorolac injection uap, ketorolac injection ketorolac injection uzp, ketorolac injection ketorolac injection uxp, ketorolac injection ketorolac injection udp, ketorolac injection ketorolac injection uep, ketorolac injection ketorolac injection uwp, ketorolac injection ketorolac injection uso, ketorolac injection ketorolac injection usl, ketorolac injection ketorolac injection us-, ketorolac injection ketorolac injection us0, etorolac injection ketorolac injection usp, ktorolac injection ketorolac injection usp, keorolac injection ketorolac injection usp, ketrolac injection ketorolac injection usp, ketoolac injection ketorolac injection usp, ketorlac injection ketorolac injection usp, ketoroac injection ketorolac injection usp, ketorolc injection ketorolac injection usp, ketorola injection ketorolac injection usp, ketorolacinjection ketorolac injection usp, ketorolac njection ketorolac injection usp, ketorolac ijection ketorolac injection usp, ketorolac inection ketorolac injection usp, ketorolac injction ketorolac injection usp, ketorolac injetion ketorolac injection usp, ketorolac injecion ketorolac injection usp, ketorolac injecton ketorolac injection usp, ketorolac injectin ketorolac injection usp, ketorolac injectio ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac injection etorolac injection usp, ketorolac injection ktorolac injection usp, ketorolac injection keorolac injection usp, ketorolac injection ketrolac injection usp, ketorolac injection ketoolac injection usp, ketorolac injection ketorlac injection usp, ketorolac injection ketoroac injection usp, ketorolac injection ketorolc injection usp, ketorolac injection ketorola injection usp, ketorolac injection ketorolacinjection usp, ketorolac injection ketorolac njection usp, ketorolac injection ketorolac ijection usp, ketorolac injection ketorolac inection usp, ketorolac injection ketorolac injction usp, ketorolac injection ketorolac injetion usp, ketorolac injection ketorolac injecion usp, ketorolac injection ketorolac injecton usp, ketorolac injection ketorolac injectin usp, ketorolac injection ketorolac injectio usp, ketorolac injection ketorolac injectionusp, ketorolac injection ketorolac injection sp, ketorolac injection ketorolac injection up, ketorolac injection ketorolac injection us, ektorolac injection ketorolac injection usp, kteorolac injection ketorolac injection usp, keotrolac injection ketorolac injection usp, ketroolac injection ketorolac injection usp, ketoorlac injection ketorolac injection usp, ketorloac injection ketorolac injection usp, ketoroalc injection ketorolac injection usp, ketorolca injection ketorolac injection usp, ketorola cinjection ketorolac injection usp, ketorolaci njection ketorolac injection usp, ketorolac nijection ketorolac injection usp, ketorolac ijnection ketorolac injection usp, ketorolac inejction ketorolac injection usp, ketorolac injcetion ketorolac injection usp, ketorolac injetcion ketorolac injection usp, ketorolac injeciton ketorolac injection usp, ketorolac injectoin ketorolac injection usp, ketorolac injectino ketorolac injection usp, ketorolac injectio n ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac injection k etorolac injection usp, ketorolac injection ektorolac injection usp, ketorolac injection kteorolac injection usp, ketorolac injection keotrolac injection usp, ketorolac injection ketroolac injection usp, ketorolac injection ketoorlac injection usp, ketorolac injection ketorloac injection usp, ketorolac injection ketoroalc injection usp, ketorolac injection ketorolca injection usp, ketorolac injection ketorola cinjection usp, ketorolac injection ketorolaci njection usp, ketorolac injection ketorolac nijection usp, ketorolac injection ketorolac ijnection usp, ketorolac injection ketorolac inejction usp, ketorolac injection ketorolac injcetion usp, ketorolac injection ketorolac injetcion usp, ketorolac injection ketorolac injeciton usp, ketorolac injection ketorolac injectoin usp, ketorolac injection ketorolac injectino usp, ketorolac injection ketorolac injectio nusp, ketorolac injection ketorolac injectionu sp, ketorolac injection ketorolac injection sup, ketorolac injection ketorolac injection ups, kketorolac injection ketorolac injection usp, keetorolac injection ketorolac injection usp, kettorolac injection ketorolac injection usp, ketoorolac injection ketorolac injection usp, ketorrolac injection ketorolac injection usp, ketoroolac injection ketorolac injection usp, ketorollac injection ketorolac injection usp, ketorolaac injection ketorolac injection usp, ketorolacc injection ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac iinjection ketorolac injection usp, ketorolac innjection ketorolac injection usp, ketorolac injjection ketorolac injection usp, ketorolac injeection ketorolac injection usp, ketorolac injecction ketorolac injection usp, ketorolac injecttion ketorolac injection usp, ketorolac injectiion ketorolac injection usp, ketorolac injectioon ketorolac injection usp, ketorolac injectionn ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac injection ketorolac injection usp, ketorolac injection kketorolac injection usp, ketorolac injection keetorolac injection usp, ketorolac injection kettorolac injection usp, ketorolac injection ketoorolac injection usp, ketorolac injection ketorrolac injection usp, ketorolac injection ketoroolac injection usp, ketorolac injection ketorollac injection usp, ketorolac injection ketorolaac injection usp, ketorolac injection ketorolacc injection usp, ketorolac injection ketorolac injection usp, ketorolac injection ketorolac iinjection usp, ketorolac injection ketorolac innjection usp, ketorolac injection ketorolac injjection usp, ketorolac injection ketorolac injeection usp, ketorolac injection ketorolac injecction usp, ketorolac injection ketorolac injecttion usp, ketorolac injection ketorolac injectiion usp, ketorolac injection ketorolac injectioon usp, ketorolac injection ketorolac injectionn usp, ketorolac injection ketorolac injection usp, ketorolac injection ketorolac injection uusp, ketorolac injection ketorolac injection ussp, ketorolac injection ketorolac injection uspp, etc.

© Copyright by drug-information.ru 2001-2019. All rights reserved