(see also Boxed WARNING)

► The combined use of ketorolac tromethamine injection and ketorolac tromethamine tablets is 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 G.I. 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 G.I. 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 ketorolac tromethamine injection to parenteral opioids, higher rates of clinically serious G.I. bleeding were seen in 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 IM administered ketorolac tromethamine (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 associationwith 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 injection 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 receiving opioids. The postoperative hemorrhage rate in patients 12 years and younger was 6.5% and 3.3% with and without ketorolac tromethamine injection, respectively. In a prospective study of ketorolac tromethamine injection 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 injection 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, interstitial 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.