Soriatane (Acitretin) - Side Effects and Adverse Reactions

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 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. 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 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. Since other factors may have contributed to these events, it is not known if they are related to Soriatane (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, 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 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
Musculosketal				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% to10%	<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 epithealial 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 Subepitheal 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 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. 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 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% to10%
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