Sprix
Generic: KETOROLAC TROMETHAMINE
Basic Information
Manufacturer
Zyla Life Sciences US LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
NASAL
FDA Set ID
97005a1c-167e-4676-bae7-e49b38c36f9e
Indications & Usage
1 INDICATIONS AND USAGE SPRIX is indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.
Limitations of Use Sprix is not for use in pediatric patients less than 2 years of age.
SPRIX is a nonsteroidal anti-inflammatory drug indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.
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Limitations of Use Sprix is not for use in pediatric patients less than 2 years of age.
SPRIX is a nonsteroidal anti-inflammatory drug indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.
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Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [ see Warnings and Precautions ( 5.1 ) ] GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions ( 5.2 ) ] Hepatotoxicity [ see Warnings and Precautions ( 5.3 ) ] Hypertension [ see Warnings and Precautions ( 5.4 ) ] Heart Failure and Edema [ see Warnings and Precautions ( 5.5 ) ] Renal Toxicity and Hyperkalemia [ see Warnings and Precautions ( 5.6 ) ] Anaphylactic Reactions [ see Warnings and Precautions ( 5.7 ) ] Serious Skin Reactions [ see Warnings and Precautions ( 5.9 ) ] Hematologic Toxicity [ see Warnings and Precautions ( 5.12 ) ] 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.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zyla Life Sciences US Inc.
at 1-800-518-1084 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to SPRIX in patients enrolled in placebo-controlled efficacy studies of acute pain following major surgery.
The studies enrolled 828 patients (183 men, 645 women) ranging from 18 years to over 75 years of age.
The patients in the postoperative pain studies had undergone major abdominal, orthopedic, gynecologic, or other surgery; 455 patients received SPRIX (31.5 mg) three or four times a day for up to 5 days, and 245 patients received placebo.
Most patients were receiving concomitant opioids, primarily PCA morphine.
The most frequently reported adverse reactions were related to local symptoms, i.e., nasal discomfort or irritation.
These reactions were generally mild and transient in nature.
The most common drug-related adverse events leading to premature discontinuation were nasal discomfort or nasal pain (rhinalgia).
Table 1: Post-Operative Patients with Adverse Reactions Observed at a Rate of 2% or More and at Least Twice the Incidence of the Placebo Group.
SPRIX (N = 455) Placebo (N = 245) Nasal discomfort 15% 2% Rhinalgia 13% <1% Lacrimation increased 5% 0% Throat irritation 4% <1% Oliguria 3% 1% Rash 3% <1% Bradycardia 2% <1% Urine output decreased 2% <1% ALT and/or AST increased 2% 1% Hypertension 2% 1% Rhinitis 2% <1% In controlled clinical trials in major surgery, primarily knee and hip replacements and abdominal hysterectomies, seven patients (N=455, 1.5%) treated with SPRIX experienced serious adverse events of bleeding (4 patients) or hematoma (3 patients) at the operative site versus one patient (N=245, 0.4%) treated with placebo (hematoma).
Six of the seven patients treated with SPRIX underwent a surgical procedure and/or blood transfusion and the placebo patient subsequently required a blood transfusion.
Adverse Reactions Reported in Clinical Trials with Other Dosage Forms of Ketorolac or Other NSAIDs Adverse reaction rates increase with higher doses of ketorolac.
It is necessary to remain alert for the severe complications of treatment with ketorolac, such as GI ulceration, bleeding, and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, and liver failure.
These complications can be serious in certain patients for whom ketorolac is indicated, especially when the drug is used inappropriately.
In patients taking ketorolac or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are: * Incidence greater than 10% Gastrointestinal (GI) experiences including: abdominal pain flatulence gross bleeding/perforation stomatitis constipation/diarrhea GI fullness heartburn vomiting dyspepsia GI ulcers (gastric/duodenal) nausea* Other experiences: abnormal renal function drowsiness headache* injection site pain rash anemia edema hypertension pruritus tinnitus dizziness elevated liver enzymes increased bleeding time purpura sweating Additional adverse experiences reported occasionally (<1% in patients taking ketorolac or other NSAIDs in clinical trials) include: Body as a Whole: fever, infection, sepsis Cardiovascular System: congestive heart failure, palpitation, pallor, tachycardia, syncope Digestive System: anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding Hemic and Lymphatic: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia Metabolic and Nutritional: weight change Nervous System: abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise Respiratory: asthma, dyspnea, pulmonary edema, rhinitis Special Senses: abnormal taste, abnormal vision, blurred vision, hearing loss Urogenital: cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of ketorolac or other NSAIDs.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Other observed reactions (reported from postmarketing experience in patients taking ketorolac or other NSAIDs) are: Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema, myalgia Cardiovascular: arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis Dermatologic: exfoliative dermatitis, erythema multiforme, Lyell's syndrome, bullous reactions including Stevens-Johnson syndrome, fixed drug eruption (FDE), and toxic epidermal necrolysis Gastrointestinal: acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative wound hemorrhage (rarely requiring blood transfusion) Metabolic and Nutritional: hyperglycemia, hyperkalemia, hyponatremia Nervous System: aseptic meningitis, convulsions, coma, psychosis Respiratory: bronchospasm, respiratory depression, pneumonia Special Senses: conjunctivitis Urogenital: flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zyla Life Sciences US Inc.
at 1-800-518-1084 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to SPRIX in patients enrolled in placebo-controlled efficacy studies of acute pain following major surgery.
The studies enrolled 828 patients (183 men, 645 women) ranging from 18 years to over 75 years of age.
The patients in the postoperative pain studies had undergone major abdominal, orthopedic, gynecologic, or other surgery; 455 patients received SPRIX (31.5 mg) three or four times a day for up to 5 days, and 245 patients received placebo.
Most patients were receiving concomitant opioids, primarily PCA morphine.
The most frequently reported adverse reactions were related to local symptoms, i.e., nasal discomfort or irritation.
These reactions were generally mild and transient in nature.
The most common drug-related adverse events leading to premature discontinuation were nasal discomfort or nasal pain (rhinalgia).
Table 1: Post-Operative Patients with Adverse Reactions Observed at a Rate of 2% or More and at Least Twice the Incidence of the Placebo Group.
SPRIX (N = 455) Placebo (N = 245) Nasal discomfort 15% 2% Rhinalgia 13% <1% Lacrimation increased 5% 0% Throat irritation 4% <1% Oliguria 3% 1% Rash 3% <1% Bradycardia 2% <1% Urine output decreased 2% <1% ALT and/or AST increased 2% 1% Hypertension 2% 1% Rhinitis 2% <1% In controlled clinical trials in major surgery, primarily knee and hip replacements and abdominal hysterectomies, seven patients (N=455, 1.5%) treated with SPRIX experienced serious adverse events of bleeding (4 patients) or hematoma (3 patients) at the operative site versus one patient (N=245, 0.4%) treated with placebo (hematoma).
Six of the seven patients treated with SPRIX underwent a surgical procedure and/or blood transfusion and the placebo patient subsequently required a blood transfusion.
Adverse Reactions Reported in Clinical Trials with Other Dosage Forms of Ketorolac or Other NSAIDs Adverse reaction rates increase with higher doses of ketorolac.
It is necessary to remain alert for the severe complications of treatment with ketorolac, such as GI ulceration, bleeding, and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, and liver failure.
These complications can be serious in certain patients for whom ketorolac is indicated, especially when the drug is used inappropriately.
In patients taking ketorolac or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are: * Incidence greater than 10% Gastrointestinal (GI) experiences including: abdominal pain flatulence gross bleeding/perforation stomatitis constipation/diarrhea GI fullness heartburn vomiting dyspepsia GI ulcers (gastric/duodenal) nausea* Other experiences: abnormal renal function drowsiness headache* injection site pain rash anemia edema hypertension pruritus tinnitus dizziness elevated liver enzymes increased bleeding time purpura sweating Additional adverse experiences reported occasionally (<1% in patients taking ketorolac or other NSAIDs in clinical trials) include: Body as a Whole: fever, infection, sepsis Cardiovascular System: congestive heart failure, palpitation, pallor, tachycardia, syncope Digestive System: anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding Hemic and Lymphatic: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia Metabolic and Nutritional: weight change Nervous System: abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise Respiratory: asthma, dyspnea, pulmonary edema, rhinitis Special Senses: abnormal taste, abnormal vision, blurred vision, hearing loss Urogenital: cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of ketorolac or other NSAIDs.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Other observed reactions (reported from postmarketing experience in patients taking ketorolac or other NSAIDs) are: Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema, myalgia Cardiovascular: arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis Dermatologic: exfoliative dermatitis, erythema multiforme, Lyell's syndrome, bullous reactions including Stevens-Johnson syndrome, fixed drug eruption (FDE), and toxic epidermal necrolysis Gastrointestinal: acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative wound hemorrhage (rarely requiring blood transfusion) Metabolic and Nutritional: hyperglycemia, hyperkalemia, hyponatremia Nervous System: aseptic meningitis, convulsions, coma, psychosis Respiratory: bronchospasm, respiratory depression, pneumonia Special Senses: conjunctivitis Urogenital: flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome