Important Safety Information
WARNING: LIMITATIONS OF USE, GASTROINTESTINAL, BLEEDING, CARDIOVASCULAR, and RENAL RISK
Limitations of Use
SPRIX® (ketorolac tromethamine) Nasal Spray, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for short-term (up to 5 days in adults) management of moderate to moderately severe pain that requires analgesia at the opioid level. Do not exceed a total combined duration of use of SPRIX® and other ketorolac formulations (IM/IV or oral) of 5 days.
SPRIX® is not indicated for use in pediatric patients and it is not indicated for minor or chronic painful conditions.
Ketorolac tromethamine, including SPRIX®, 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, SPRIX® 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.
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.
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
SPRIX® is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
SPRIX® is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.
SPRIX® (ketorolac tromethamine) Nasal Spray is also contraindicated:
- in patients with known hypersensitivity or history of asthma, urticaria, or other allergic-type reactions to aspirin, ketorolac, other NSAIDs or EDTA
- as a prophylactic analgesic prior to major surgery
- in labor and delivery
Additional Warnings and Precautions:
- SPRIX® should not be used concomitantly with IM/IV or oral ketorolac,
aspirin, or other NSAIDs, or with probenecid or pentoxifylline.
- Risk of GI Ulceration, Bleeding, and Perforation: Ketorolac can cause
serious adverse events including bleeding, ulceration, and perforation
which can be fatal. Elderly patients are at increased risk for serious GI
events. Treat patients for the shortest duration possible, and do not
exceed 5 days of therapy with SPRIX® alone or sequentially with
other forms of ketorolac.
- Hematological Effects: NSAIDs affect platelet aggregation and may
cause bleeding complications. SPRIX® should be used with caution in
patients who have coagulation disorders or are on therapy that affects
hemostasis. Do not use SPRIX® in patients for whom hemostasis is
- Renal Effects: Ketorolac can cause renal injury. SPRIX® should not
be used in patients with advanced renal disease or patients at risk for
renal failure due to volume depletion, and should be used with caution
in patients taking diuretics or ACE inhibitors. Long-term administration
of NSAIDs has resulted in renal papillary necrosis and other renal injury
such as interstitial nephritis and nephrotic syndrome.
- Anaphylactoid Reactions: Anaphylactoid reactions may occur in
patients with or without a history of allergic reactions to aspirin or
- CV Effects: CV Thrombotic Events, Hypertension, Congestive Heart
Failure (CHF) and Edema: NSAIDs can lead to onset of new hypertension
or worsening of preexisting hypertension, either of which may contribute
to the increased incidence of CV events. Patients taking thiazides or
loop diuretics may have impaired response when taking NSAIDs. Fluid
retention, edema, retention of NaCl, oliguria, and elevations of serum
urea nitrogen and creatinine have been reported in clinical trials of
ketorolac. SPRIX® should be used with caution in patients with cardiac
decompensation or similar conditions.
- Skin Reactions: NSAIDs, including ketorolac, can cause serious
dermatologic adverse reactions such as exfoliative dermatitis, Stevens-
Johnson syndrome, and toxic epidermal necrolysis, which can be
fatal. These serious events may occur without warning. SPRIX® should
be discontinued immediately with skin reactions or other signs of
- Pregnancy: During pregnancy, use of SPRIX® beyond 30 weeks gestation
can cause premature closure of the ductus arteriosus, resulting in fetal
harm (Pregnancy Category D). Prior to 30 weeks gestation, SPRIX®
should be used during pregnancy only if potential benefit justifies the
potential risk to the fetus (Pregnancy Category C).
- Hepatic Effects: Use SPRIX® with caution in patients with impaired
hepatic function or history of liver disease.
- Inflammation and Fever: The pharmacologic activity of SPRIX® in
reducing inflammation and fever may diminish the utility of these
diagnostic signs in detecting infections.
- Preexisting Asthma: Patients with asthma may have aspirin-sensitive
asthma. The use of aspirin in patients with aspirin-sensitive asthma has
been associated with severe bronchospasm which can be fatal.
- Eye Exposure: Avoid contact of SPRIX® with the eyes. If eye contact
occurs, wash out the eye with water or saline, and consult a physician if
irritation persists for more than an hour.
Additional Drug Interactions:
- Aspirin: Protein binding is reduced when ketorolac is administered
with aspirin although the clearance of free ketorolac is not altered. The
clinical significance of this interaction is not known; however, as with
other NSAIDs, concomitant administration of SPRIX® and aspirin is not
generally recommended because of the potential of increased adverse
- Diuretics: Ketorolac can reduce the natriuretic effect of furosemide and
thiazides in some patients.
- 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. NSAIDs may diminish the antihypertensive effect of ACE
inhibitors and/or angiotensin II receptor antagonists. Consider this
interaction in patients taking SPRIX® concomitantly with ACE inhibitors
and/or angiotensin II receptor antagonists.
Most Common Adverse Reactions:
The most common adverse reactions (incidence ≥ 2%) in patients treated
with SPRIX® and occurring at a rate at least twice that of placebo are nasal
discomfort, rhinalgia, increased lacrimation, throat irritation, oliguria,
rash, bradycardia, decreased urine output, increased ALT and/or AST,
hypertension, and rhinitis.
SPRIX® is not an inhaled product. Patients should be instructed not to inhale when using the product.
Please see Important Safety Information and complete Prescribing
Information, including Boxed Warning at www.sprix.com.