Diclofenac, Sodium Gel, 3%

/Diclofenac, Sodium Gel, 3%
Diclofenac, Sodium Gel, 3%2018-09-06T09:12:40+00:00

Prescription Drug Name:

Diclofenac, Sodium Gel, 3%

ID:

cc352589-8d6a-4b2b-b225-fbba5a2a4555

Code:

34391-3

DESCRIPTION


id: 1ae5118b-1ee9-424c-9273-b0c5cf582771
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Diclofenac Sodium Gel, 3%, contains the active ingredient, diclofenac sodium, in a clear, transparent, colorless to slightly yellow gel base. Diclofenac sodium is a white to slightly yellow crystalline powder. It is freely soluble in methanol, soluble in ethanol, sparingly soluble in water, slightly soluble in acetone, and partially insoluble in ether. The chemical name for diclofenac sodium is: Sodium [o-(2,6-dichloranilino) phenyl] acetate Diclofenac sodium has a molecular weight of 318.13. The CAS number is CAS-15307-79-6. The structural formula is represented below: Diclofenac Sodium Gel, 3% also contains benzyl alcohol, hyaluronate sodium, polyethylene glycol monomethyl ether, and purified water. 1 g of Diclofenac Sodium Gel contains 30 mg of the active substance, diclofenac sodium.

CLINICAL PHARMACOLOGY


id: 150fcc9f-008b-4813-a5ec-b2ed36dd7c3f
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

The mechanism of action of diclofenac sodium in the treatment of actinic keratoses (AK) is unknown. The contribution to efficacy of individual components of the vehicle has not been established.

INDICATIONS AND USAGE


id: 782d56f3-d4aa-47d4-8f0e-85e2e841a20d
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Diclofenac Sodium Gel is indicated for the topical treatment of actinic keratoses (AK). Sun avoidance is indicated during therapy.

CLINICAL STUDIES


id: 93682360-2264-4097-a481-7e9bade8a912
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

Clinical trials were conducted involving a total of 427 patients (213 treated with diclofenac sodium gel and 214 with a gel vehicle). Each patient had no fewer than five AK lesions in a major body area, which was defined as one of five 5 cm × 5 cm regions: scalp, forehead, face, forearm and hand. Up to three major body areas were studied in any patient. All patients were 18 years of age or older (male and female) with no clinically significant medical problems outside of the AK lesions and had undergone a 60-day washout period from disallowed medications (masoprocol, 5-fluorouracil, cyclosporine, retinoids, trichloroacetic acid/lactic acid/peel, 50% glycolic acid peel) and hyaluronan-containing cosmetics. Patients were excluded from participation for reasons of known or suspected hypersensitivity to any diclofenac sodium gel ingredient, pregnancy, allergies to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), or other dermatological conditions which might affect the absorption of the study medication. Application of dermatologic products such as sunscreens, cosmetics, and other drug products was not permitted. Patients were instructed to apply a small amount of diclofenac sodium gel (approximately 0.5 g) onto the affected skin, using their fingers, and gently smoothing the gel over the lesion. In addition, all patients were instructed to avoid sun exposure. Complete clearing of the AK lesions 30 days after completion of treatment was the primary efficacy variable. No long-term patient follow-ups, after the 30-day assessments, were performed for the detection of recurrence.

Complete Clearance of Actinic Keratosis Lesions 30 Days Post-Treatment (all locations)
Diclofenac Sodium Gel Vehicle p-value
Study 1 90 days treatment 27/58 (47%) 11/59 (19%) <0.001
Study 2 90 days treatment 18/53 (34%) 10/55 (18%) 0.061
Study 3 60 days treatment 15/48 (31%) 5/49 (10%) 0.021
30 days treatment 7/49 (14%) 2/49 (4%) 0.221
Complete Clearance of Actinic Keratosis Lesions 30 Days Post-Treatment (by location)
Scalp Forehead Face Arm/Forearm Back of Hand
Study 1 90 days treatment
Diclofenac Sodium Gel 1/4 (25%) 17/30 (57%) 9/17 (53%) 4/12 (33%) 6/16 (38%)
Vehicle 3/9 (33%) 8/24 (33%) 5/17 (29%) 4/12 (33%) 0/14 (0)
p-value 0.7646 0.0908 0.1682 1.000 0.0650
Study 2 90 days treatment
Diclofenac Sodium Gel 2/6 (33%) 9/19 (47%) 4/5 (80%) 5/8 (63%) 1/17 (6%)
Vehicle 0/4 (0) 6/22 (27%) 2/8 (25%) 0/5 (0) 3/16 (19%)
p-value 0.4235 0.1870 0.0727 0.0888 0.2818
Study 3 60 days treatment
Diclofenac Sodium Gel 3/7 (43%) 13/31 (42%) 10/19 (53%) 0/1 (0) 2/8 (25%)
Vehicle 0/6 (0) 5/36 (14%) 2/13 (15%) 0/2 (0) 1/9 (11%)
p-value 0.2271 0.0153 0.0433 -0.4637
30 days treatment
Diclofenac Sodium Gel 2/5 (40%) 4/29 (14%) 3/14 (21%) 0/0 (0) 0/9 (0)
Vehicle 0/5 (0) 2/29 (7%) 2/18 (11%) 0/1 (0) 1/9 (11%)
p-value 0.2299 0.3748 0.4322 -0.6521
All data combined
Diclofenac Sodium Gel 8/22 (36%) 43/109 (39%) 26/55 (47%) 9/21 (43%) 9/50 (18%)
Vehicle 3/24 (13%) 21/111 (19%) 11/56 (20%) 4/20 (20%) 5/48 (10%)
p-value 0.0903 0.0013 0.0016 0.2043 0.3662

CONTRAINDICATIONS


id: f5955cc4-d382-4cb9-b08a-29f4af5232bc
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Diclofenac Sodium Gel is contraindicated in patients with a known hypersensitivity to diclofenac, benzyl alcohol, polyethylene glycol monomethyl ether 350 and/or hyaluronate sodium.

WARNINGS


id: 84246be1-4a29-426e-96f5-c7ad750a988a
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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.

ADVERSE REACTIONS


id: f980ce79-185e-4a67-89ca-7e83a3cbe10e
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Of the 423 patients evaluable for safety in adequate and well-controlled trials, 211 were treated with diclofenac sodium gel drug product and 212 were treated with a vehicle gel. Eighty-seven percent (87%) of the diclofenac sodium gel-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, 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-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 group than in the vehicle-treated patients. Eighteen percent of diclofenac sodium gel-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 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 Phase 3 Clinical Trials Incidences for 60-Day and 90-Day Treatments
60-day Treatment 90-day Treatment
Diclofenac Sodium
(%) Gel
Vehicle
(%)
Diclofenac Sodium
(%) Gel
Vehicle
(%)
N=48 N=49 N=114 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 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): Body as a Whole: abdominal pain or crampsIncidence greater than 1% marked with asterisk., headache, fluid retention, abdominal distention, malaise, swelling of lips and tongue, photosensitivity, anaphylaxis, anaphylactoid reactions, chest pain. Cardiovascular: hypertension, congestive heart failure, palpitations, flushing, tachycardia, premature ventricular contractions, myocardial infarction, hypotension. Digestive: diarrhea, indigestion, nausea, constipation, flatulence, liver test abnormalities, PUB, i.e., peptic ulcer, with or without bleeding and/or perforation, or bleeding without ulcer, vomiting, jaundice, melena, esophageal lesions, aphthous stomatitis, dry mouth and mucous membranes, bloody diarrhea, hepatitis, hepatic necrosis, cirrhosis, hepatorenal syndrome, appetite change, pancreatitis with or without concomitant hepatitis, colitis, intestinal perforation. Hemic and Lymphatic: hemoglobin decrease, leukopenia, thrombocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, agranulocytosis, purpura, allergic purpura, bruising. Metabolic and Nutritional Disorders: azotemia, hypoglycemia, weight loss. Nervous System: dizziness, insomnia, drowsiness, depression, diplopia, anxiety, irritability, aseptic meningitis, convulsions, paresthesia, memory disturbance, nightmares, tremor, tic, abnormal coordination, disorientation, psychotic reaction. Respiratory: epistaxis, asthma, laryngeal edema, dyspnea, hyperventilation, edema of pharynx. Skin and Appendages: rash, pruritus, alopecia, urticaria, eczema, dermatitis, bullous eruption, erythema multiforme major, angioedema, Stevens-Johnson syndrome, excess perspiration, exfoliative dermatitis. Special Senses: tinnitus, blurred vision, taste disorder, reversible and irreversible hearing loss, scotoma, vitreous floaters, night blindness, amblyopia. Urogenital: nephrotic syndrome, proteinuria, oliguria, interstitial nephritis, papillary necrosis, acute renal failure, urinary frequency, nocturia, hematuria, impotence, vaginal bleeding.

OVERDOSAGE


id: f9d2819a-3e89-4da9-bd6f-25a30a6273e0
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Due to the low systemic absorption of topically-applied diclofenac sodium gel, overdosage is unlikely. There have been no reports of ingestion of diclofenac sodium gel. In the event of oral ingestion, resulting in significant systemic side effects, it is recommended that the stomach be emptied by vomiting or lavage. Forced diuresis may theoretically be beneficial because the drug is excreted in the urine. The effect of dialysis or hemoperfusion in the elimination of diclofenac (99% protein-bound) remains unproven. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption of diclofenac. Supportive and symptomatic treatment should be given for complications such as renal failure, convulsions, gastrointestinal irritation and respiratory depression.

DOSAGE AND ADMINISTRATION


id: dc45b5d7-15c7-49bb-8045-d64d56711289
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Diclofenac sodium gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough diclofenac sodium gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm × 5 cm lesion site. The recommended duration of therapy is from 60 days to 90 days. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to 30 days following cessation of therapy. Lesions that do not respond to therapy should be carefully re-evaluated and management reconsidered.

HOW SUPPLIED


id: 7f33c316-1e11-49e5-a66e-846616f3dcbf
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Diclofenac Sodium Gel, 3% is available in 100 g (NDC 45861-063-01) tubes. Each gram of gel contains 30 mg of diclofenac sodium.

PRINCIPAL DISPLAY PANEL – 100 g Tube Carton


id: 0dc7a3dd-32e4-4c93-befb-7e48a746d9c7
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 45861-063-01 100 g Diclofenac Sodium
Gel 3%
FOR EXTERNAL USE ONLY.
NOT FOR OPHTHALMIC USE.
Keep this and all medications out of the reach of children. Rx only