Hypervitaminosis A produces a wide spectrum of signs and symptoms primarily of the mucocutaneous, musculoskeletal, hepatic, neuropsychiatric, and central nervous systems. Many of the clinical adverse reactions reported to date with administration of SORIATANE resemble those of the hypervitaminosis A syndrome.
Adverse Events/Postmarketing Reports
In addition to the events listed in the tables for the clinical trials, the following adverse events have been identified during postapproval use of SORIATANE. Because these events 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.
Acute myocardial infarction, thromboembolism (see WARNINGS), stroke.
Immune System Disorders
Hypersensitivity, including angioedema and urticaria (see CONTRAINDICATIONS).
Myopathy with peripheral neuropathy has been reported during therapy with SORIATANE. Both conditions improved with discontinuation of the drug.
Aggressive feelings and/or suicidal thoughts have been reported. These events, including self-injurious behavior, have been reported in patients taking other systemically administered retinoids, as well as in patients taking SORIATANE. Since other factors may have contributed to these events, it is not known if they are related to SORIATANE (see PRECAUTIONS).
Vulvo-vaginitis due to Candida albicans.
Skin and Appendages
Thinning of the skin, skin fragility, and scaling may occur all over the body, particularly on the palms and soles; nail fragility is frequently observed. Madarosis and exfoliative dermatitis/erythroderma have been reported (see WARNINGS).
Capillary leak syndrome (see WARNINGS).
During clinical trials with SORIATANE, 513/525 (98%) of subjects reported a total of 3,545 adverse events. One-hundred sixteen subjects (22%) left trials prematurely, primarily because of adverse experiences involving the mucous membranes and skin. Three subjects died. Two of the deaths were not drug-related (pancreatic adenocarcinoma and lung cancer); the other subject died of an acute myocardial infarction, considered remotely related to drug therapy. In clinical trials, SORIATANE was associated with elevations in liver function test results or triglyceride levels and hepatitis.
The tables below list by body system and frequency the adverse events reported during clinical trials of 525 subjects with psoriasis.
Table 3: Adverse Events Frequently Reported During Clinical Trials Percent of Subjects Reporting (N = 525)
|Body System||> 75%||50% to 75%||25% to 50%||10% to 25%|
|Mucous Membranes||Cheilitis||Rhinitis||Dry mouth
Spinal hyperostosis (progression of existing lesions)
|Skin and Appendages||Alopecia Skin peeling||Dry skin
Table 4: Adverse Events Less Frequently Reported During Clinical Trials (Some of Which May Bear No Relationship to Therapy) Percent of Subjects Reporting (N = 525)
|Body System||1% to10%||< 1%|
|Body as a Whole||Anorexia
Increased bleeding time
|CNS (also see Psychiatric)||Headache
|Pseudotumor cerebri (intracranial hypertension)|
|Eye Disorders||Abnormal/ blurred vision
Corneal epithelial abnormality
|Decreased night vision/night blindness
|Itchy eyes and lids
Subepithelial corneal lesions
|Liver and Biliary||Hepatic function abnormal
|Mucous Membranes||Gingival bleeding Gingivitis Increased saliva||Stomatitis Thirst Ulcerative stomatitis||Altered saliva
|Osteodynia Peripheral joint hyperostosis (progression of existing lesions)||Bone disorder
Spinal hyperostosis (new lesions)
|Skin and Appendages||Abnormal skin odor
Abnormal hair texture
Increased sweating Infection
Furunculosis Hair discoloration
Sweat gland disorder
|Special Senses/ Other||Earache
Therapy with SORIATANE induces changes in liver function tests in a significant number of patients. Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 subjects treated with SORIATANE. In most subjects, elevations were slight to moderate and returned to normal either during continuation of therapy or after cessation of treatment. In subjects receiving SORIATANE during clinical trials, 66% and 33% experienced elevation in triglycerides and cholesterol, respectively. Decreased high density lipoproteins (HDL) occurred in 40% (see WARNINGS). Transient, usually reversible elevations of alkaline phosphatase have been observed.
Table 5 lists the laboratory abnormalities reported during clinical trials.
Table 5: Abnormal Laboratory Test Results Reported During Clinical Trials Percent of Subjects Reporting
|Body System||50% to 75%||25% to 50%||10% to 25%||1% to 10%|
|Electrolytes||Increased: -Phosphorus -Potassium -Sodium Increased and decreased: -Magnesium||Decreased: -Phosphorus -Potassium -Sodium Increased and decreased: -Calcium -Chloride|
|Hematologic||Increased: -Reticulocytes||Decreased: -Hematocrit -Hemoglobin -WBC Increased: -Haptoglobin -Neutrophils -WBC||Increased: -Bands -Basophils -Eosinophils -Hematocrit -Hemoglobin -Lymphocytes -Monocytes Decreased: -Haptoglobin -Lymphocytes -Neutrophils -Reticulocytes Increased or decreased: -Platelets -RBC|
|Hepatic||Increased: -Cholesterol -LDH -SGOT -SGPT Decreased: -HDL cholesterol||Increased: -Alkaline phosphatase -Direct bilirubin -GGTP||Increased: -Globulin -Total bilirubin -Total protein Increased and decreased: -Serum albumin|
|Miscellaneous||Increased: -Triglycerides||Increased: -CPK -Fasting blood sugar||Decreased: -Fasting blood sugar -High occult blood||Increased and decreased: -Iron|
|Renal||Increased: -Uric acid||Increased: -BUN -Creatinine|
|Urinary||WBC in urine||Acetonuria Hematuria RBC in urine||Glycosuria Proteinuria|