DESCRIPTION
id: c47133db-80ed-43c6-9087-6a3afe8fa71e
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: 2fb9574d-f79b-4ebe-a2f9-cca5c1ea03dd
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: 2bb919dc-ae95-45d5-9fce-fa59e26cb9e0
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: 81fb32c4-3085-4abe-ab55-f13f2ef5fe2c
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: 2e06f4dd-65ad-4f9e-b924-e3208819f157
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.
Diclofenac Sodium Gel is contraindicated in the following patients:
- In the setting of coronary artery bypass graft (CABG) surgery.
WARNINGS
id: cbd1a695-85d6-4155-ab29-7adcf0cf677b
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: 9c08bc28-46c8-4b55-9dca-0593910c3005
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 |
|
METABOLICS 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):
*Incidence greater than 1% marked with asterisk.
Body as a Whole: abdominal pain or cramps*, 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: 229d34b1-0c91-4508-b9c6-e610878e5a49
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: fe14f7f1-068d-4c90-89e0-bfce31a74eef
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: 163541ce-77ca-4cf4-9624-d59b5dd8c65f
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Diclofenac Sodium Gel, 3% is available in 50 g (NDC 51672-1363-3) and 100 g (NDC 51672-1363-7) tubes. Each gram of gel contains 30 mg of diclofenac sodium.
PRINCIPAL DISPLAY PANEL – 100 g Tube Carton
id: 9487cd43-7e52-4d2c-af44-c8ec019820bd
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 51672-1363-7
100 g
Dispense the Enclosed Medication Guide to each patient.
Diclofenac Sodium
Gel 3%
FOR EXTERNAL USE ONLY.
NOT FOR OPHTHALMIC USE.
Rx only
Keep this and all medications out of the reach of children.
TARO
