ADVERSE REACTIONS
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 SORIATANE Capsules administration 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 Capsules. 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 casual relationship to drug exposure.
Cardiovascular
Acute myocardial infarction, thromboembolism (see WARNINGS), stroke.
Nervous System
Myopathy with peripheral neuropathy has been reported during SORIATANE Capsules therapy. Both conditions improved with discontinuation of the drug.
Psychiatric
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 Capsules. Since other factors may have contributed to these events, it is not known if they are related to SORIATANE Capsules (see PRECAUTIONS).
Reproductive
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.
Clinical Trials
During clinical trials with SORIATANE Capsules, 513/525 (98%) of patients reported a total of 3545 adverse events. One-hundred sixteen patients (22%) left studies prematurely, primarily because of adverse experiences involving the mucous membranes and skin. Three patients died. Two of the deaths were not drug related (pancreatic adenocarcinoma and lung cancer); the other patient died of an acute myocardial infarction, considered remotely related to drug therapy. In clinical trials, SORIATANE Capsules 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 patients with psoriasis.
Table 3. Adverse Events Frequently Reported During Clinical Trials - Percent of Patients Reporting (N=525) | BODY SYSTEM | > 75% | 50% to 75% | 25% to 50% | 10% to 25% |
| CNS | | | | Rigors |
| Eye Disorders | | | | Xerophthalmia |
| Mucous Membranes | Cheilitis | | Rhinitis |
Dry mouth
Epistaxis |
| Musculoskeletal | | | |
Arthralgia
Spinal hyperostosis
(progression of existing lesions) |
| Skin and Appendages | |
Alopecia
Skin peeling |
Dry skin
Nail disorder
Pruritus |
Erythematous rash
Hyperesthesia
Paresthesia
Paronychia
Skin atrophy
Sticky skin |
Table 4. Adverse Events Less Frequently Reported During Clinical Trials (Some of Which May Bear No Relationship to Therapy) - Percent of Patients Reporting (N=525) | BODY SYSTEM | 1% to 10% | < 1% |
| Body as a Whole |
Anorexia
Edema
Fatigue
Hot flashes
Increased
appetite | |
Alcohol
intolerance
Dizziness
Fever
Influenza-like
symptoms |
Malaise
Moniliasis
Muscle weakness
Weight increase |
| Cardiovascular | Flushing | |
Chest pain
Cyanosis
Increased
bleeding time |
Intermittent
claudication
Peripheral
ischemia |
| CNS (also see Psychiatric) |
Headache
Pain | |
Abnormal gait
Migraine
Neuritis |
Pseudotumor
cerebri
(intracranial
hypertension) |
| Eye Disorders |
Abnormal/
blurred vision
Blepharitis
Conjunctivitis/
irritation
Corneal epithelial
abnormality |
Decreased night
vision/night
blindness
Eye abnormality
Eye pain
Photophobia |
Abnormal
lacrimation
Chalazion
Conjunctival
hemorrhage
Corneal ulceration
Diplopia
Ectropion |
Itchy eyes and lids
Papilledema
Recurrent sties
Subepithelial
corneal lesions |
| Gastrointestinal |
Abdominal pain
Diarrhea
Nausea
Tongue disorder | | Constipation
Dyspepsia
Esophagitis
Gastritis
Gastroenteritis | Glossitis
Hemorrhoids
Melena
Tenesmus
Tongue ulceration |
| Liver and Biliary | | |
Hepatic function
abnormal
Hepatitis
Jaundice | |
| Mucous Membranes |
Gingival bleeding
Gingivitis
Increased saliva |
Stomatitis
Thirst
Ulcerative
stomatitis | Altered saliva
Anal disorder
Gum hyperplasia | Hemorrhage
Pharyngitis |
| Musculoskeletal |
Arthritis
Arthrosis
Back pain
Hypertonia
Myalgia |
Osteodynia
Peripheral joint
hyperostosis
(progression of
existing lesions) |
Bone disorder
Olecranon bursitis
Spinal hyperostosis
(new lesions)
Tendonitis | |
| Psychiatric |
Depression Insomnia
Somnolence | |
Anxiety
Dysphonia
Libido decreased Nervousness | |
| Reproductive | | | Atrophic vaginitis Leukorrhea | |
| Respiratory | Sinusitis | |
Coughing
Increased sputum
Laryngitis | |
| Skin and Appendages |
Abnormal skin
odor
Abnormal hair
texture
Bullous eruption
Cold/clammy
skin
Dermatitis
Increased
sweating
Infection |
Psoriasiform rash
Purpura
Pyogenic
granuloma
Rash
Seborrhea
Skin fissures
Skin ulceration
Sunburn | Acne
Breast pain
Cyst
Eczema
Fungal infection
Furunculosis
Hair discoloration
Herpes simplex
Hyperkeratosis
Hypertrichosis
Hypoesthesia
Impaired healing
Otitis media |
Otitis externa
Photosensitivity
reaction
Psoriasis aggravated
Scleroderma
Skin nodule
Skin hypertrophy
Skin disorder
Skin irritation
Sweat gland
disorder
Urticaria
Verrucae |
| Special Senses/ Other |
Earache
Taste perversion
Tinnitus | | Ceruminosis
Deafness
Taste loss | |
| Urinary | | | Abnormal urine
Dysuria
Penis disorder | |
Laboratory
SORIATANE Capsules therapy 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 patients treated with SORIATANE Capsules. In most patients, elevations were slight to moderate and returned to normal either during continuation of therapy or after cessation of treatment. In patients receiving SORIATANE Capsules 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 Patients Reporting | BODY SYSTEM | 50% to 75% | 25% to 50% | 10% to 25% | 1% to 10% |
| Electrolytes | | | Increased:
–Phosphorus
–Potassium
–Sodium | Decreased:
–Phosphorus
–Potassium
–Sodium |
| | |
Increased and
decreased:
–Magnesium |
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 |
|
