Diclofenac Sodium 30 mg/g Gel — NDC 0115-1483-61 (Billing 00115-1483-61)

WARNINGS Fetal Toxicity Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs, including Diclofenac Sodium Gel, 3%, in pregnant women at about 30 weeks gestation and later. NSAIDs including Diclofenac Sodium Gel, 3%, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including Diclofenac Sodium Gel, 3%, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation.

In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Diclofenac Sodium Gel, 3% use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Diclofenac Sodium Gel, 3% treatment extends beyond 48 hours.

Discontinue Diclofenac Sodium Gel, 3% if oligohydramnios occurs and follow up according to clinical practice [see PRECAUTIONS; Pregnancy]. As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to diclofenac. Diclofenac sodium should be given with caution to patients with the aspirin triad.

The triad typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Serious Skin Reactions, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as Diclofenac Sodium Gel, 3%.

Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis.

Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved.

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue Diclofenac Sodium Gel, 3% and evaluate the patient immediately. Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal.

Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate.

Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treate… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS Of the 423 patients evaluable for safety in adequate and well-controlled trials, 211 were treated with diclofenac sodium gel, 3% drug product and 212 were treated with a vehicle gel. Eighty-seven percent (87%) of the diclofenac sodium gel, 3%-treated patients (183 patients) and 84% of the vehicle-treated patients (178 patients) experienced one or more adverse events (AEs) during the studies. The majority of these reactions were mild to moderate in severity and resolved upon discontinuation of therapy.

Of the 211 patients treated with diclofenac sodium gel, 3%, 172 (82%) experienced AEs involving skin and the application site compared to 160 (75%) vehicle-treated patients. Application site reactions (ASRs) were the most frequent AEs in both diclofenac sodium gel, 3%-and vehicle-treated groups. Of note, four reactions, contact dermatitis, rash, dry skin and exfoliation (scaling) were significantly more prevalent in the diclofenac sodium gel, 3% group than in the vehicle-treated patients.

Eighteen percent of diclofenac sodium gel, 3%-treated patients and 4% of vehicle-treated patients discontinued from the clinical trials due to adverse events (whether considered related to treatment or not). These discontinuations were mainly due to skin irritation or related cutaneous adverse reactions. Table 1 below presents the AEs reported at an incidence of >1% for patients treated with either diclofenac sodium gel, 3% or vehicle (60- and 90-day treatment groups) during the phase 3 studies.

Table 1. Adverse Events Reported (>1% in Any Treatment Group) During Diclofenac Sodium Gel, 3% Phase 3 Clinical Trials Incidences for 60-Day and 90-Day Treatments 60-day Treatment 90-day Treatment Diclofenac Sodium Gel, 3% (%) N=48 Gel Vehicle (%) N=49 Diclofenac Sodium Gel, 3% (%) N=114 Gel Vehicle (%) N=114 BODY AS A WHOLE 21 20 20 18 Abdominal Pain 2 0 1 0 Accidental Injury 0 0 4 2 Allergic Reaction 0 0 1 3 Asthenia 0 0 2 0 Back Pain 4 0 2 2 Chest Pain 2 0 1 0 Chills 0 2 0 0 Flu Syndrome 10 6 1 4 Headache 0 6 7 6 Infection 4 6 4 5 Neck Pain 0 0 2 0 Pain 2 0 2 2 CARDIOVASCULAR SYSTEM 2 4 3 1 Hypertension 2 0 1 0 Migraine 0 2 1 0 Phlebitis 0 2 0 0 DIGESTIVE SYSTEM 4 0 6 8 Constipation 0 0 0 2 Diarrhea 2 0 2 3 Dyspepsia 2 0 3 4 METABOLIC AND NUTRITIONAL DISORDERS 2 8 7 2 Creatine Phosphokinase Increased 0 0 4 1 Creatinine Increased 2 2 0 1 Edema 0 2 0 0 Hypercholesteremia 0 2 1 0 Hyperglycemia 0 2 1 0 SGOT Increased 0 0 3 0 SGPT Increased 0 0 2 0 MUSCULOSKELETAL SYSTEM 4 0 3 4 Arthralgia 2 0 0 2 Arthrosis 2 0 0 0 Myalgia 2 0 3 1 NERVOUS SYSTEM 2 2 2 5 Anxiety 0 2 0 1 Dizziness 0 0 0 4 Hypokinesia 2 0 0 0 RESPIRATORY SYSTEM 8 8 7 6 Asthma 2 0 0 0 Dyspnea 2 0 2 0 Pharyngitis 2 8 2 4 Pneumonia 2 0 0 1 Rhinitis 2 2 2 2 Sinusitis 0 0 2 0 SKIN AND APPENDAGES 75 86 86 71 Acne 0 2 0 1 Application Site Reaction 75 71 84 70 Acne 0 4 1 0 Alopecia 2 0 1 1 Contact Dermatitis 19 4 33 4 Dry Skin 27 12 25 17 Edema 4 0 3 0 Exfoliation 6 4 24 13 Hyperesthesia 0 0 3 1 Pain 15 22 26 30 Paresthesia 8 4 20 20 Photosensitivity Reaction 0 2 3 0 Pruritus 31 59 52 45 Rash 35 20 46 17 Vesiculobullous Rash 0 0 4 1 Contact Dermatitis 2 0 0 0 Dry Skin 0 4 3 0 Herpes Simplex 0 2 0 0 Maculopapular Rash 0 2 0 0 Pain 2 2 1 0 Pruritus 4 6 4 1 Rash 2 10 4 0 Skin Carcinoma 0 6 2 2 Skin Nodule 0 2 0 0 Skin Ulcer 2 0 1 0 SPECIAL SENSES 2 0 4 2 Conjunctivitis 2 0 4 1 Eye Pain 0 2 2 0 UROGENITAL SYSTEM 0 0 4 5 Hematuria 0 0 2 1 OTHER 0 0 0 3 Procedure 0 0 0 3 Skin and Appendages Adverse Events Reported for diclofenac sodium gel, 3% at Less Than 1% Incidence in the Phase 3 Studies: skin hypertrophy, paresthesia, seborrhea, urticaria, application site reactions (skin carcinoma, hypertonia, skin hypertrophy lacrimation disorder, maculopapular rash, purpuric rash, vasodilation).

Adverse Reactions Reported for Oral Diclofenac Dosage Form (not topical diclofenac sodium gel, 3%): *Incidence Greater than 1% marked with asterisk. Body as a Whole: abdominal pain or cramps*, headache*, f… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS General Diclofenac sodium gel, 3% should be used with caution in patients with active gastrointestinal ulceration or bleeding and severe renal or hepatic impairments. Diclofenac sodium gel, 3% should not be applied to open skin wounds, infections, or exfoliative dermatitis. It should not be allowed to come in contact with the eyes.

The safety of the concomitant use of sunscreens, cosmetics or other topical medications and diclofenac sodium gel, 3% is unknown. Information for Patients Fetal Toxicity If treatment with Diclofenac Sodium Gel, 3% is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours. Inform pregnant women to avoid use of Diclofenac Sodium Gel, 3% and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus [see WARNINGS; Fetal Toxicity, PRECAUTIONS; Pregnancy].

In clinical studies, localized dermal side effects such as contact dermatitis, exfoliation, dry skin and rash were found in patients treated with diclofenac sodium gel, 3% at a higher incidence than in those with placebo. Patients should understand the importance of monitoring and follow-up evaluation, the signs and symptoms of dermal adverse reactions, and the possibility of irritant or allergic contact dermatitis. If severe dermal reactions occur, treatment with diclofenac sodium gel, 3% may be interrupted until the condition subsides.

Exposure to sunlight and the use of sunlamps should be avoided. Safety and efficacy of the use of diclofenac sodium gel, 3% together with other dermal products, including cosmetics, sunscreens, and other topical medications on the area being treated, have not been studied. Serious Skin Reactions, including DRESS Advise patients to stop taking Diclofenac Sodium Gel, 3% immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see WARNINGS, Serious Skin Reactions].

Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately. Heart Failure and Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur. Drug Interactions Specific interaction studies between diclofenac sodium gel, 3% and other topical or oral agents were not performed.

Oral Nonsteroidal Anti-Inflammatory Drugs Although low, there is systemic exposure to diclofenac following labeled use of diclofenac sodium gel, 3%. Therefore, concomitant administration of diclofenac sodium gel, 3% with oral NSAIDS or aspirin may result in increased NSAID adverse effects. Carcinogenesis, Mutagenesis, Impairment of Fertility There did not appear to be any increase in drug-related neoplasms following daily topical applications of diclofenac sodium gel for 2 years at concentrations up to 0.035% diclofenac sodium and 2.5% hyaluronate sodium in albino mice.

(Note: diclofenac sodium gel, 3% contains 3% diclofenac sodium.) When administered orally for 2 years, diclofenac showed no evidence of carcinogenic potential in rats given diclofenac sodium at up to 2 mg/kg/day (3 times the estimated systemic human exposure*), or in mice given diclofenac sodium at up to 0.3 mg/kg/day in males and 1 mg/kg/day in females (25% and 83%, respectively, of the estimated systemic human exposure). A photococarcinogenicity study with up to 0.035% diclofenac in the diclofenac sodium gel, 3% vehicle gel was conducted in hairless mice at topical doses up to 2.8 mg/kg/day.

Median tumor onset was earlier in the 0.035% group (diclofenac sodium gel, 3% contains 3% diclofenac sodium). Diclofenac was not ge… [Excerpted — this section continues on DailyMed.]