SOLARAZE SIDE EFFECTS

Last updated on MDtodate: 10/11/2022

SIDE EFFECTS

Of the 423 patients evaluable for safety in adequate and well-controlled trials, 211 were treated with Solaraze® drug product and 212 were treated with a vehicle gel. Eighty-seven percent (87%) of the Solaraze®-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 Solaraze®, 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 Solaraze®-and vehicle-treated groups. Of note, four reactions, contact dermatitis, rash, dry skin and exfoliation (scaling) were significantly more prevalent in the Solaraze® group than in the vehicle-treated patients.

Eighteen percent of Solaraze®-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 Solaraze® 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 Solaraze®Phase 3 Clinical Trials Incidences for 60-Day and 90-Day Treatments

	60-day Treatment		90-day Treatment
	Solaraze® (%) N=48	Gel Vehicle (%) N=49	Solaraze® (%) 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
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 Solaraze® 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 Solaraze® 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.