IV Dilution &
Medication Reference

Ketorolac tromethamine - Toradol®

Usual Diluents

Standard Dilution [Amount of drug] [Infusion volume] [Infusion rate]

Not approved for IVPB administration.
IV Bolus: When administering Ketorolac Tromethamine Injection, the IV bolus must be given over no less than 15 seconds.

Stability / Miscellaneous

CLINICAL PHARMACOLOGY

Pharmacodynamics
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID). 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.

Pain relief was statistically different after ketorolac tromethamine dosing from that of placebo at 1/2 hour (the first time point at which it was measured) following the largest recommended doses of ketorolac tromethamine and by 1 hour following the smallest recommended doses. The peak analgesic effect occurred 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. 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
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 humans, 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.

Binding and Distribution
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.

The mean apparent volume (Vß) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data.

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.

Clearance and Excretion
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. 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.

DOSAGE AND ADMINISTRATION
THE COMBINED DURATION OF USE OF KETOROLAC TROMETHAMINE INJECTION AND KETOROLAC TROMETHAMINE TABLETS IS NOT TO EXCEED FIVE (5) DAYS. THE USE OF KETOROLAC TROMETHAMINE TABLETS IS ONLY INDICATED AS CONTINUATION THERAPY TO KETOROLAC TROMETHAMINE INJECTION.

Ketorolac Tromethamine Injection
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 five (5) days.

When administering Ketorolac Tromethamine Injection, the IV bolus must be given over no less than 15 seconds. The IM 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.

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.

IV Dosing:
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.

Multiple-Dose Treatment (IV or IM)

Patients< 65 Years of Age:
The recommended dose is 30 mg Ketorolac Tromethamine Injection every 6 hours. The maximum daily dose should not exceed 120 mg.

For Patients ≥ 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 breakthrough pain do not increase the dose or the frequency of ketorolac tromethamine. Consideration should be given to supplementing these regimens with low doses of opioids "prn" unless otherwise contraindicated.

Pharmaceutical Information for Ketorolac Tromethamine Injection
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Ketorolac Tromethamine Injection should not be mixed in a small volume (e.g., in a syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride; this will result in precipitation of ketorolac from solution.

HOW SUPPLIED
Ketorolac Tromethamine Injection, USP is available in pre-filled syringes as follows:

For IV or IM Single-Dose use:
A syringe containing 1 mL of 15 mg/mL Ketorolac Tromethamine, USP, NDC 10019-021-09, available in boxes of 10.

A syringe containing 1 mL of 30 mg/mL Ketorolac Tromethamine, USP, NDC 10019-022-09, available in boxes of 10.

For IM Single-Dose use only:
A syringe containing 2 mL of 30 mg/mL Ketorolac Tromethamine, USP, (60 mg), NDC 10019-022-32, available in boxes of 10.

Each disposable syringe is supplied with an individually wrapped 22gauge, 1 1/2 inch needle.

Vials:
Ketorolac Tromethamine Injection, USP for intramuscular and intravenous use is available as:
15 mg: 15 mg/mL, 1 mL Vial box of 25, List 3793.
30 mg: 30 mg/mL, 1 mL Vial box of 25, List 3795.
Ketorolac Tromethamine Injection, USP for intramuscular use only is available as:
60 mg: 30 mg/mL, 2 mL Vial box of 25, List 3796.

Store at controlled room temperature 15°-30°C (59°-86°F).
PROTECT FROM LIGHT
Retain in carton until time of use.

Reference(s)

Drug Tables and Calculators

---Medical Articles / News / Other---