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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]
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 clinical practice.
Adverse Reactions in Patients with Acute Pain
Two-hundred sixteen (216) patients received ZORVOLEX in the completed, 48-hour, double-blind, placebo-controlled, clinical trial of acute pain following bunionectomy. The most frequent adverse reactions in this study are summarized in Table 1.
Table 1 : Summary of Adverse Reactions ( ≥ 2% in
ZORVOLEX 18 mg or 35 mg group) – Phase 3 Study in Patients With Postsurgical
|Adverse Reactions||ZORVOLEX 18 mg or 35 mg three times daily*
N = 216
N = 106
|Pain in Extremity||3%||1%|
|*One tablet of hydrocodone/acetaminophen 10 mg/325 mg was permitted every 4 to 6 hours as rescue medication for pain management. There was a greater use of concomitant opioid rescue medication in placebo-treated patients than in ZORVOLEX-treated patients. About 82% of patients in the ZORVOLEX 35 mg group, 85% of the patients in the ZORVOLEX 18 mg group, and 97% of patients in the placebo group took rescue medication for pain management during the study.|
Adverse Reactions in Patients with Osteoarthritis Pain
Two-hundred two (202) patients received ZORVOLEX in the completed, 12-week, double-blind, placebo-controlled, clinical trial of osteoarthritis pain of the knee or hip. The most frequent adverse reactions in this study are summarized in Table 2.
Table 2 : Summary of Adverse
Reactions ( ≥ 2%) – 12-week Phase 3 Study in Patients With Osteoarthritis
|Adverse Reactions||ZORVOLEX 35 mg
|Abdominal Pain Upper||3%||1%|
|Alanine Aminotransferase Increased||2%||0|
|Blood Creatinine Increased||2%||0|
|* Adverse reactions that occurred in ≥ 2% of patients treated with ZORVOLEX and occurred more frequently than in patients treated with placebo|
Six-hundred one (601) patients received ZORVOLEX 35 mg either twice or three times daily in a 52-week, open-label, clinical trial in osteoarthritis pain of the knee or hip. Of those, 360 (60%) patients completed the trial. The most frequent adverse reactions in this study are summarized in Table 3.
Table 3 : Summary of Adverse
Reactions ( ≥ 2%) – 52-week Open-label Study in Patients with
|Adverse Reactions||ZORVOLEX 35 mg
|Upper respiratory tract infection||8%|
|Urinary tract infection||7%|
|Alanine aminotransferase increased||4%|
|Abdominal pain upper||3%|
|Aspartate aminotransferase increased||2%|
Adverse Reactions Reported For Diclofenac And Other NSAIDs:
In patients taking other NSAIDs, the most frequently reported adverse reactions occurring in approximately 1%-10% of patients are:
Additional adverse reactions reported occasionally include:
Body as a Whole: fever, infection, sepsis
Metabolic and Nutritional: weight changes
Special Senses: blurred vision
Other adverse reactions, which occur rarely are:
Body as a Whole: anaphylactic reactions, appetite changes, death
Metabolic and Nutritional: hyperglycemia
Nervous System: convulsions, coma, hallucinations, meningitis
Respiratory System: respiratory depression, pneumonia
Special Senses: conjunctivitis, hearing impairment
Read the Zorvolex (diclofenac capsules) Side Effects Center for a complete guide to possible side effects
When administered with aspirin, the protein binding of ZORVOLEX is reduced. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of ZORVOLEX and aspirin is not generally recommended because of the potential of increased GI adverse reactions [see WARNINGS AND PRECAUTIONS].
The effects of anticoagulants, such as warfarin and NSAIDs on GI bleeding, are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that with use of either drug alone [see WARNINGS AND PRECAUTIONS].
This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients [see WARNINGS AND PRECAUTIONS]. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with ZORVOLEX and these diuretics, observe patients closely for signs of renal failure, as well as to assure diuretic efficacy [see WARNINGS AND PRECAUTIONS].
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have 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.
NSAIDs may affect renal prostaglandins and increase the toxicity of cyclosporine. Therefore, concomitant therapy with NSAIDs may increase cyclosporine's nephrotoxicity. Use caution when NSAIDs are administered concomitantly with cyclosporine.
Inhibitors Or Substrates Of Cytochrome P450 2C9 Other Considerations
Diclofenac is metabolized predominantly by cytochrome P450 2C9. Co-administration of diclofenac with another drug known to be metabolized by, or which inhibits, cytochrome P450 2C9 may unpredictably affect the pharmacokinetics of diclofenac or the coadministered drug. Caution should be used to evaluate each patient's medical history when consideration is given to prescribing diclofenac [see CLINICAL PHARMACOLOGY].
Last reviewed on RxList: 9/4/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Zorvolex Information
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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.
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