A1, A2, B, C1, C2, D, E, F, G-H, I-K, L, M, N, O, P1, P2, Q-R, S, T, U-V, W-Z

Soriatane Side Effects, and Drug Interactions - Acitretin

SIDE EFFECTS

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 causal 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
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 pai n 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% 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

DRUG INTERACTIONS

Ethanol: Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and ethanol (see boxed CONTRAINDICATIONS AND WARNINGS and CLINICAL PHARMACOLOGY: Pharmacokinetics).

Glibenclamide: In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with Soriatane is recommended (see CLINICAL PHARMACOLOGY: Pharmacokinetics and DOSAGE AND ADMINISTRATION).

Hormonal Contraceptives: It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin "minipill" preparations. Microdosed "minipill" progestin preparations are not recommended for use with Soriatane (see CLINICAL PHARMACOLOGY: Pharmacokinetic Drug Interactions). It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Methotrexate: An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with acitretin is also contraindicated (see CONTRAINDICATIONS).

Phenytoin: If acitretin is given concurrently with phenytoin, the protein binding of phenytoin may be reduced.

Tetracyclines: Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated (see CONTRAINDICATIONS and WARNINGS: Pseudotumor Cerebri).

Vitamin A and oral retinoids: Concomitant administration of vitamin A and/or other oral retinoids with acitretin must be avoided because of the risk of hypervitaminosis A.

Other: There appears to be no pharmacokinetic interaction between acitretin and cimetidine, digoxin, or glyburide. Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.

Laboratory Tests

If significant abnormal laboratory results are obtained, either dosage reduction with careful monitoring or treatment discontinuation is recommended, depending on clinical judgement.

Blood Sugar: Some patients receiving retinoids have experienced problems with blood sugar control. In addition, new cases of diabetes have been diagnosed during retinoid therapy, including diabetic ketoacidosis. In diabetics, blood-sugar levels should be monitored very carefully.

Lipids: In clinical studies, the incidence of hypertriglyceridemia was 66%, hypercholesterolemia was 33% and that of decreased HDL was 40%. Pretreatment and follow-up measurements should be obtained under fasting conditions. It is recommended that these tests be performed weekly or every other week until the lipid response to Soriatane has stabilized (see WARNINGS).

Liver Function Tests: Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 patients treated with Soriatane. It is recommended that these tests be performed prior to initiation of Soriatane therapy, at 1- to 2-week intervals until stable and thereafter at intervals as clinically indicated (see CONTRAINDICATIONS and BOXED WARNINGS).

top

Popular Searches:
weight loss	ultram	penis enlargement	hydrocodone	antibiotic