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]
- Renal effects [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
- Hepatic effects [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Congestive heart failure and edema [see WARNINGS AND PRECAUTIONS]
- Anaphylactoid reactions [see WARNINGS AND PRECAUTIONS]
- Serious skin reactions [see WARNINGS AND PRECAUTIONS]
Adverse reactions from clinical studies of Dyloject
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
During clinical development, 1,156 patients were exposed to Dyloject in multiple-dose, controlled and open-label studies. Dyloject was administered post-surgically every 6 hours for up to 5 days. The incidence rates of adverse reactions listed in the following table are derived from multicenter, controlled clinical studies in post-operative patients comparing Dyloject to placebo in patients who may have also received morphine rescue medication.
Table 1: Proportion of Patients Experiencing Common Adverse Reactions in Placebo-Controlled Clinical Studies in Patients with Acute Moderate-to-Severe Postoperative Pain occurring in greater than or equal to 3% in patients treated with Dyloject*
| MedDRA Preferred Term | Placebo N=126 |
Dyloject N=187 |
| Any Reaction | 104 (83%) | 146 (78%) |
| Nausea | 50 (40%) | 45 (24%) |
| Constipation | 14 (11%) | 25 (13%) |
| Headache | 20 (16%) | 19 (10%) |
| Infusion Site Pain | 10 (8%) | 19 (10%) |
| Dizziness | 2 (2%) | 15 (8%) |
| Flatulence | 20 (16%) | 15 (8%) |
| Vomiting | 23 (18%) | 12 (6%) |
| Insomnia | 12 (10%) | 11 (6%) |
| Pruritus | 10 (8%) | 9 (5%) |
| Hypotension | 6 (5%) | 9 (5%) |
| Pyrexia | 13 (10%) | 8 (4%) |
| Anemia | 9 (7%) | 8 (4%) |
| Infusion Site Extravasation | 1 (1%) | 6 (3%) |
| *Intravenous morphine was permitted as rescue medication for pain management. | ||
Adverse Reactions From Clinical Studies Or Spontaneous Reports For Other Formulations Of Diclofenac And Other NSAIDs
In patients taking diclofenac or 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: 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
Adverse Reactions of Special Interest
Based on the analysis of the pooled data from the multi-dose, controlled clinical trials, postoperative patients treated with Dyloject had more adverse reactions related to wound healing (7.5%) compared to patients treated with placebo (4%).