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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 Pain

Adverse Reactions ZORVOLEX 18 mg or 35 mg three times daily*
N = 216
Placebo*
N = 106
Edema 33% 32%
Nausea 27% 37%
Headache 13% 15%
Dizziness 10% 16%
Vomiting 9% 12%
Constipation 8% 4%
Pruritus 7% 6%
Flatulence 3% 2%
Pain in Extremity 3% 1%
Dyspepsia 2% 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 Pain*

Adverse Reactions ZORVOLEX 35 mg
N=202
Placebo
N=103
Nausea 7% 2%
Diarrhea 6% 3%
Headache 4% 3%
Abdominal Pain Upper 3% 1%
Sinusitis 3% 1%
Vomiting 3% 1%
Alanine Aminotransferase Increased 2% 0
Blood Creatinine Increased 2% 0
Dyspepsia 2% 1%
Flatulence 2% 0
Hypertension 2% 1%
* 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 Osteoarthritis Pain

Adverse Reactions ZORVOLEX 35 mg
N=601
Upper respiratory tract infection 8%
Headache 8%
Urinary tract infection 7%
Diarrhea 6%
Nasopharyngitis 6%
Nausea 6%
Constipation 5%
Sinusitis 5%
Osteoarthritis 5%
Cough 4%
Alanine aminotransferase increased 4%
Back pain 3%
Dyspepsia 3%
Procedural pain 3%
Bronchitis 3%
Hypertension 3%
Abdominal pain upper 3%
Influenza 3%
Arthralgia 3%
Contusion 3%
Vomiting 3%
Abdominal discomfort 2%
Aspartate aminotransferase increased 2%
Dizziness 2%
Fall 2%
Abdominal pain 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:

Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal) and vomiting.

Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes and tinnitus.

Additional adverse reactions reported occasionally include:

Body as a Whole: fever, infection, sepsis

Cardiovascular System: congestive heart failure, hypertension, tachycardia, syncope

Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice

Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and Nutritional: weight changes

Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory System: asthma, dyspnea

Skin and Appendages: alopecia, photosensitivity, sweating increased

Special Senses: blurred vision

Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

Other adverse reactions, which occur rarely are:

Body as a Whole: anaphylactic reactions, appetite changes, death

Cardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive System: colitis, eructation, fulminant hepatitis with and without jaundice, liver failure, liver necrosis, pancreatitis

Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

Metabolic and Nutritional: hyperglycemia

Nervous System: convulsions, coma, hallucinations, meningitis

Respiratory System: respiratory depression, pneumonia

Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria

Special Senses: conjunctivitis, hearing impairment