"The U.S. Food and Drug Administration today approved Hysingla ER (hydrocodone bitartrate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternat"...
The following serious adverse reactions are discussed elsewhere in the labeling:
- Cardiovascular thrombotic events [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Gastrointestinal effects [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Hepatic effects [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Congestive heart failure and edema [see WARNINGS AND PRECAUTIONS]
- Renal effects [see WARNINGS AND PRECAUTIONS]
- Anaphylactoid reactions [see WARNINGS AND PRECAUTIONS]
- Serious skin reactions [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions reported in clinical studies are nausea, flatulence, vomiting, and headache.
The most common reason for discontinuation due to adverse events in controlled trials of Caldolor is pruritus ( < 1%).
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
During clinical development, 560 patients were exposed to Caldolor, 438 in pain and 122 with fever. In the pain studies, Caldolor was started intra-operatively and administered at a dose of 400 mg or 800 mg every six hours for up to three days. In the fever studies, Caldolor was administered at doses of 100 mg, 200 mg, or 400 mg every four or six hours for up to 3 days.
The most frequent type of adverse reaction occurring with oral ibuprofen is gastrointestinal.
The incidence rates of adverse reactions listed in the following table were derived from multi-center, controlled clinical studies in post-operative patients comparing Caldolor to placebo in patients also receiving morphine as needed for postoperative pain.
Table 1: Post-operative Patients with Adverse
Reactions Observed in ≥ 3% of Patients in any Caldolor Treatment Group in
|Any Reaction||118 (88%)||260 (86%)||258 (90%)|
|Nausea||77 (57%)||161 (53%)||179 (62%)|
|Vomiting||30 (22%)||46 (15%)||50 (17%)|
|Flatulence||10 (7%)||49 (16%)||44 (15%)|
|Headache||12 (9%)||35 (12%)||31 (11%)|
|Hemorrhage||13 (10%)||13 (4%)||16 (6%)|
|Dizziness||8 (6%)||13 (4%)||5 (2%)|
|Edema peripheral||1 (<1%)||9 (3%)||4 (1%)|
|Urinary retention||7 (5%)||10 (3%)||10 (3%)|
|Anemia||5 (4%)||7 (2%)||6 (2%)|
|Decreased hemoglobin||4 (3%)||6 (2%)||3 (1%)|
|Dyspepsia||6 (4%)||4 (1%)||2 (<1%)|
|Wound hemorrhage||4 (3%)||4 (1%)||4 (1%)|
|Abdominal discomfort||4 (3%)||2 (<1%)||0|
|Cough||4 (3%)||2 (<1%)||1 ( < 1%)|
|Hypokalemia||5 (4%)||3 (<1%)||8 (3%)|
|* All patients received concomitant morphine during these studies.|
Fever studies were conducted in febrile hospitalized patients with malaria and febrile hospitalized patients with varying causes of fever. In hospitalized febrile patients with malaria, the adverse reactions observed in at least two Caldolortreated patients included abdominal pain and nasal congestion.
In hospitalized febrile patients (all causes), adverse reactions observed in more than two patients in any given treatment group are presented in the table below.
Table 2: Patients with Adverse Reactions Observed in ≥
3% of Patients in any Caldolor Treatment Group in All- Cause Fever Study
|Any Reaction||27 (87%)||25 (83%)||23 (74%)||25 (89%)|
|Anemia||5 (17%)||6 (20%)||11 (36%)||4 (14%)|
|Eosinophilia||7 (23%)||7 (23%)||8 (26%)||7 (25%)|
|Hypokalemia||4 (13%)||4 (13%)||6 (19%)||5 (18%)|
|Hypoproteinemia||3 (10%)||0||4 (13%)||2 (7%)|
|Neutropenia||2 (7%)||2 (7%)||4 (13%)||2 (7%)|
|Blood urea increased||0||0||3 (10%)||0|
|Hypernatremia||2 (7%)||0||3 (10%)||0|
|Hypoalbuminemia||3 (10%)||1 (3%)||3 (10%)||1 (4%)|
|Hypotension||0||2 (7%)||3 (10%)||1 (4%)|
|Diarrhea||3 (10%)||3 (10%)||2 (7%)||2 (7%)|
|Pneumonia bacterial||3 (10%)||1 (3%)||2 (7%)||0|
|Blood LDH increased||3 (10%)||2 (7%)||1 (3%)||1 (4%)|
|Thrombocythemia||3 (10%)||2 (7%)||1 (3%)||0|
Read the Caldolor (ibuprofen in water for injection) Side Effects Center for a complete guide to possible side effects
When ibuprofen is administered with aspirin, ibuprofen's protein binding is reduced, although the clearance of free ibuprofen is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Caldolor and aspirin is not generally recommended because of the potential for increased adverse effects.
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a higher risk of serious GI bleeding than users of either drug alone [see WARNINGS AND PRECAUTIONS].
NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.
Clinical studies and postmarketing observations have shown that ibuprofen can reduce the natriuretic effects of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, observe patients closely for signs of renal failure, as well as to assure diuretic efficacy [see WARNINGS AND PRECAUTIONS].
NSAIDs have produced elevations of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance of lithium decreased by 20%. This effect has been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity.
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This indicates that NSAIDs may enhance the toxicity of methotrexate. Use caution when NSAIDs are administered concomitantly with methotrexate.
In studies of human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/29/2014
Additional Caldolor Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Chronic Pain/Back Pain
Find tips and advances in treatment.