Diclofenac sodium
Generic: DICLOFENAC SODIUM
Basic Information
Manufacturer
NuCare Pharmaceuticals,Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
TOPICAL
FDA Set ID
22f4b8aa-902f-a860-e063-6394a90ada26
Indications & Usage
1 INDICATIONS AND USAGE Diclofenac sodium topical gel is indicated for the topical treatment of actinic keratoses (AK).
Diclofenac sodium topical gel is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the topical treatment of actinic keratoses (AK).
( 1 )
Diclofenac sodium topical gel is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the topical treatment of actinic keratoses (AK).
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Anaphylactic Reactions [ see Warnings and Precautions (5.1) ] Exacerbation of Asthma Related to Aspirin Sensitivity [ see Warnings and Precautions (5.2) ] Serious Skin Reactions [ see Warnings and Precautions (5.3) ] Cardiovascular Thrombotic Events [ see Warnings and Precautions (5.4) ] GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions (5.5) ] Hepatotoxicity [ see Warnings and Precautions (5.6) ] Hypertension [ see Warnings and Precautions (5.7) ] Heart Failure and Edema [ see Warnings and Precautions (5.8) ] Renal Toxicity and Hyperkalemia [ see Warnings and Precautions (5.9) ] DRESS [ see Warnings and Precautions (5.10) ] Hematologic Toxicity [ see Warnings and Precautions (5.12) ] Photosensitivity [ see Warnings and Precautions (5.15) ] Most common adverse reactions with diclofenac sodium topical gel are application site reactions, including dermatitis.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc.
at 1-866-923-4914 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Of the 423 subjects evaluable for safety in adequate and well-controlled trials, 211 were treated with diclofenac sodium topical gel drug product and 212 were treated with a vehicle gel.
Eighty-seven percent (87%) of the diclofenac sodium topical gel-treated subjects (183 subjects) and 84% of the vehicle-treated subjects (178 subjects) experienced one or more adverse events (AEs) during the trials.
The majority of these reactions were mild to moderate in severity and resolved upon discontinuation of therapy.
Of the 211 subjects treated with diclofenac sodium topical gel, 172 (82%) experienced AEs involving skin and the application site compared to 160 (75%) vehicle-treated subjects.
Application site reactions (ASRs) were the most frequent AEs in both diclofenac sodium topical 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 topical gel group than in the vehicle-treated subjects.
Eighteen percent of diclofenac sodium topical gel-treated subjects and 4% of vehicle-treated subjects 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 subjects treated with either diclofenac sodium topical gel or vehicle (60- and 90-day treatment groups) during the phase 3 trials.
Table 1.
Adverse Events Reported (>1% in Any Treatment Group) During Diclofenac Sodium Topical Gel Phase 3 Clinical Trials Incidences for 60-Day and 90-Day Treatments 60-day Treatment 90-day Treatment Diclofenac Sodium Topical Gel (%) N=48 Gel Vehicle (%) N=49 Diclofenac Sodium Topical Gel (%) 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 Topical 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.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of diclofenac sodium topical gel and other topical diclofenac products.
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.
Adverse reactions from diclofenac sodium topical gel: burning sensation, hypersensitivity.
Adverse reactions from other topical diclofenac products: hypoesthesia, gait disturbance, musculoskeletal stiffness.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc.
at 1-866-923-4914 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Of the 423 subjects evaluable for safety in adequate and well-controlled trials, 211 were treated with diclofenac sodium topical gel drug product and 212 were treated with a vehicle gel.
Eighty-seven percent (87%) of the diclofenac sodium topical gel-treated subjects (183 subjects) and 84% of the vehicle-treated subjects (178 subjects) experienced one or more adverse events (AEs) during the trials.
The majority of these reactions were mild to moderate in severity and resolved upon discontinuation of therapy.
Of the 211 subjects treated with diclofenac sodium topical gel, 172 (82%) experienced AEs involving skin and the application site compared to 160 (75%) vehicle-treated subjects.
Application site reactions (ASRs) were the most frequent AEs in both diclofenac sodium topical 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 topical gel group than in the vehicle-treated subjects.
Eighteen percent of diclofenac sodium topical gel-treated subjects and 4% of vehicle-treated subjects 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 subjects treated with either diclofenac sodium topical gel or vehicle (60- and 90-day treatment groups) during the phase 3 trials.
Table 1.
Adverse Events Reported (>1% in Any Treatment Group) During Diclofenac Sodium Topical Gel Phase 3 Clinical Trials Incidences for 60-Day and 90-Day Treatments 60-day Treatment 90-day Treatment Diclofenac Sodium Topical Gel (%) N=48 Gel Vehicle (%) N=49 Diclofenac Sodium Topical Gel (%) 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 Topical 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.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of diclofenac sodium topical gel and other topical diclofenac products.
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.
Adverse reactions from diclofenac sodium topical gel: burning sensation, hypersensitivity.
Adverse reactions from other topical diclofenac products: hypoesthesia, gait disturbance, musculoskeletal stiffness.