Twice-Dailyside effects

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events GI Bleeding, Ulceration and Perforation Hepatotoxicity Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylactic Reactions Serious Skin Reactions Hematologic Toxicity The most common adverse reactions in FLECTOR and placebo-treated adult patients were pruritus (5% and 8%, respectively) and nausea (3% and 2%, respectively). The most common adverse reactions in FLECTOR treated pediatric patients were headache (9%) and application site pruritus (7%). To report SUSPECTED ADVERSE REACTIONS, contact IBSA Pharma Inc at 1-800-587-3513 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Clinical Trials Experience In controlled trials during the premarketing development of FLECTOR, approximately 600 patients with minor strains, sprains, and contusions were treated with FLECTOR for up to two weeks. Adverse Events Leading to Discontinuation of Treatment In the controlled trials, 3% of patients in both the FLECTOR and placebo groups discontinued treatment due to an adverse event. The most common adverse events leading to discontinuation were application site reactions, occurring in 2% of both the FLECTOR and placebo groups. Application site reactions leading to dropout included pruritus, dermatitis, and burning. Common Adverse Events Overall, the most common adverse events associated with FLECTOR treatment were skin reactions at the site of treatment. Table 1 lists all adverse events, regardless of causality, occurring in ≥ 1% of patients in controlled trials of FLECTOR. A majority of patients treated with FLECTOR had adverse events with a maximum intensity of "mild" or "moderate." Table 1. Common Adverse Events (by body system and preferred term) in ≥ 1% of Patients treated with FLECTOR or Placebo The table lists adverse events occurring in placebo-treated patients because the placebo was comprised of the same ingredients as FLECTOR except for diclofenac. Adverse events in the placebo group may therefore reflect effects of the non-active ingredients. Category Diclofenac N=572 Placebo N=564 N Percent N Percent Application Site Conditions 64 11 70 12 Pruritus 31 5 44 8 Dermatitis 9 2 3 <1 Burning 2 <1 8 1 Other Includes: application site dryness, irritation, erythema, atrophy, discoloration, hyperhidriosis, and vesicles. 22 4 15 3 Gastrointestinal Disorders 49 9 33 6 Nausea 17 3 11 2 Dysgeusia 10 2 3 <1 Dyspepsia 7 1 8 1 Other Includes: gastritis, vomiting, diarrhea, constipation, upper abdominal pain, and dry mouth. 15 3 11 2 Nervous System Disorders 13 2 18 3 Headache 7 1 10 2 Paresthesia 6 1 8 1 Somnolence 4 1 6 1 Other Includes: hypoesthesia, dizziness, and hyperkinesias. 4 1 3 <1 Foreign labeling describes that dermal allergic reactions may occur with FLECTOR treatment. Additionally, the treated area may become irritated or develop itching, erythema, edema, vesicles, or abnormal sensation. Pediatric Clinical Trials Experience In one open-label trial, 104 male and female pediatric patients 6 years and older presenting with minor strains, sprains, and contusions received FLECTOR twice a day for as many as 16 days. The most commonly reported adverse events (incidence ≥ 2%) were headache (9%), application site pruritus (7%), nausea (3%), and dyspepsia (3%). No adverse events led to discontinuation of treatment.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of diclofenac. 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.

Skin and Appendages: Exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of diclofenac. 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.

Skin and Appendages: Exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).