Soriatane (acitretin), a retinoid, is available in 10 mg and 25 mg gelatin capsules for oral administration. Chemically, acitretin is all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid. It is a metabolite of etretinate and is related to both retinoic acid and retinol (vitamin A). It is a yellow to greenish-yellow powder with a molecular weight of 326.44. The structural formula is:

Each capsule contains acitretin, microcrystalline cellulose, sodium ascorbate, gelatin, black monogramming ink and maltodextrin (a mixture of polysaccharides).

Gelatin capsule shells contain gelatin, iron oxide (yellow, black, and red), and titanium dioxide. They may also contain benzyl alcohol, carboxymethylcellulose sodium, edetate calcium disodium.

REFERENCES

1. Berbis Ph, et al.: Arch Dermatol Res (1988) 280:388-389.

2. Maier H, Honigsmann H: Concentration of etretinate in plasma and subcutaneous fat after long-term acitretin. Lancet 348:1107, 1996.

3. Geiger JM, Walker M: Is there a reproductive safety risk in male patients treated with acitretin (Neotigason®/Soriatane®)? Dermatology 205:105-107, 2002.

Last updated on RxList: 11/16/2007

Soriatane is indicated for the treatment of severe psoriasis in adults. Because of significant adverse effects associated with its use, Soriatane should be prescribed only by those knowledgeable in the systemic use of retinoids. In females of reproductive potential, Soriatane should be reserved for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments (see boxed CONTRAINDICATIONS AND WARNINGS - Soriatane can cause severe birth defects).

Most patients experience relapse of psoriasis after discontinuing therapy. Subsequent courses, when clinically indicated, have produced efficacy results similar to the initial course of therapy.

There is intersubject variation in the pharmacokinetics, clinical efficacy and incidence of side effects with Soriatane. A number of the more common side effects are dose related. Individualization of dosage is required to achieve sufficient therapeutic response while minimizing side effects. Soriatane therapy should be initiated at 25 to 50 mg per day, given as a single dose with the main meal. Maintenance doses of 25 to 50 mg per day may be given dependent upon an individual patient's response to initial treatment. Relapses may be treated as outlined for initial therapy.

When Soriatane is used with phototherapy, the prescriber should decrease the phototherapy dose, dependent on the patient's individual response (see PRECAUTIONS: General).

Females who have taken Tegison (etretinate) must continue to follow the contraceptive recommendations for Tegison.

Information for Pharmacists: A Soriatane Medication Guide must be given to the patient each time Soriatane is dispensed, as required by law.

Brown and white capsules, 10 mg, imprinted SORIATANE 10 mg; bottles of 30 (NDC 63032-090-25).

Brown and yellow capsules, 25 mg, imprinted SORIATANE 25 mg; bottles of 30 (NDC 63032-091-25).

Store between 15° and 25°C (59° and 77°F). Protect from light. Avoid exposure to high temperatures and humidity after the bottle is opened.

PATIENT AGREEMENT/INFORMED CONSENT FOR FEMALE PATIENTS

To be completed by the patient* and signed by her prescriber

CAUSES BIRTH DEFECTS/DO NOT GET PREGNANT

*Must also be initialed by the parent or guardian of a minor patient (under age 18)

Read each item below and initial in the space provided to show that you understand each item. Do not sign this consent and do not take SORIATANE® (acitretin) if there is anything that you do not understand.

_____________________________________________________________

(Patient's name)

1. I understand that there is a very high risk that my unborn baby could have severe birth defects if I am pregnant or become pregnant while taking SORIATANE in any amount even for short periods of time. Birth defects have also happened in babies of women who became pregnant after stopping SORIATANE treatment. INITIAL: ___________
2. I understand that I must not become pregnant while taking SORIATANE and for at least 3 years after the end of my treatment with SORIATANE. INITIAL: ___________
3. I know that I must avoid all alcohol, including drinks, food, medicines, and over-the-counter products that contain alcohol. I understand that the risk of birth defects may last longer than 3 years if I swallow any form of alcohol during SORIATANE therapy, and for 2 months after I stop taking SORIATANE. INITIAL: ___________
4. I understand that I must not have sexual intercourse, or I must use 2 separate, effective forms of birth control at the same time. The only exceptions are if I have had surgery to remove the womb (a hysterectomy) or my prescriber has told me I have gone completely through menopause. INITIAL: ___________
5. I understand that I have to use 2 effective forms of birth control (contraception) at the same time for at least 1 month before starting SORIATANE, for the entire time of SORIATANE therapy, and for at least 3 years after SORIATANE treatment has stopped. INITIAL: ___________
6. I understand that any form of birth control can fail. Therefore, I must use 2 different methods at the same time, every time I have sexual intercourse. INITIAL: ___________
7. I understand that the following are considered effective forms of birth control: Primary: Tubal ligation (having my tubes tied), partner's vasectomy, birth control pills, injectable/implantable/insertable/topical (patch) hormonal birth control products, and IUDs (intrauterine devices). Secondary: Latex condoms (with or without spermicide, which is a special cream or jelly that kills sperm), diaphragms and cervical caps (which must be used with a spermicide). I understand that at least 1 of my 2 methods of birth control must be a primary method. INITIAL: ___________
8. I will talk with my prescriber about any medicines or dietary supplements I plan to take during my SORIATANE treatment because certain birth control methods may not work if I am taking certain medicines or herbal products (for example, Saint John's wort). INITIAL: ___________
9. Unless I have had a hysterectomy or my prescriber says I have gone completely through menopause, I understand that I must have 2 negative pregnancy test results before I can get a prescription to start SORIATANE. I will then have pregnancy tests on a monthly basis during my SORIATANE therapy as instructed by my prescriber. In addition, for at least 3 years after the end of my treatment with SORIATANE, I will have a pregnancy test every 3 months. INITIAL: ___________
10. I understand that I should not start taking SORIATANE until I am sure that I am not pregnant and have negative results from 2 pregnancy tests. INITIAL: ___________
11. I have received information on emergency contraception (birth control). INITIAL: ___________
12. I understand that my prescriber can give me a referral for a free contraceptive (birth control) counseling session and pregnancy testing. INITIAL: ___________
13. I understand that on a monthly basis during SORIATANE therapy and every 3 months for at least 3 years after stopping Soriatane treatment that I should receive counseling from my prescriber about contraception (birth control) and behaviors associated with an increased risk of pregnancy. INITIAL: ___________
14. I understand that I must stop taking SORIATANE right away and call my prescriber if I get pregnant, miss my menstrual period, stop using birth control, or have sexual intercourse without using my 2 birth control methods during and at least 3 years after stopping SORIATANE treatment. INITIAL: ___________
15. If I do become pregnant while on SORIATANE or at any time within 3 years of stopping SORIATANE, I understand that I should report my pregnancy to Stiefel at 1-888-500-DERM (3376) or to the Food and Drug Administration (FDA) MedWatch program at 1-800-FDA-1088. The information I share will be kept confidential (private) and will help the company and the FDA evaluate the pregnancy prevention program to prevent birth defects. INITIAL: ___________

I have received a copy of the Do Your P.A.R.T™ brochure. My prescriber has answered all my questions about SORIATANE. I understand that it is my responsibility to follow my doctor's instructions, and not to get pregnant during SORIATANE treatment or for at least 3 years after I stop taking SORIATANE.

I now authorize my prescriber, _____________________________________________, to begin my treatment with SORIATANE.

Patient signature: ________________________________________

Date: ___________________

Parent/guardian signature (if under age 18): ____________________

Date: ___________________

Please print: Patient name and address: _______________________________________ _______________________________________________________________

Telephone: _____________________________________________________________

I have fully explained to the patient, _________________________________________, the nature and purpose of the treatment described above and the risks to females of childbearing potential. I have asked the patient if she has any questions regarding her treatment with SORIATANE and have answered those questions to the best of my ability.

Prescriber signature: _____________________________ Date: __________________

Manufactured for Stiefel Laboratories, Inc., Coral Gables, FL 33134. October 2007. FDA rev date: 10/18/2007

Last updated on RxList: 11/16/2007

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
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		Alcohol intolerance	Malaise
	Edema		Dizziness	Moniliasis
	Fatigue		Fever	Muscle weakness
	Hot flashes		Influenza-like symptoms	Weight increase
	Increased appetite
Cardiovascular	Flushing		Chest pain	Intermittent
			Cyanosis	claudication
			Increased	Peripheral
			bleeding time	ischemia
CNS (also see Psychiatric)	Headache		Abnormal gait	Pseudotumor
	Pain		Migraine	cerebri
			Neuritis	(intracranial
				hypertension)
Eye Disorders	Abnormal/	Decreased night	Abnormal	Itchy eyes and lids
	blurred vision	vision/night	lacrimation	Papilledema
	Blepharitis	blindness	Chalazion	Recurrent sties
	Conjunctivitis/	Eye abnormality	Conjunctival	Subepithelial
	irritation	Eye pain	hemorrhage	corneal lesions
	Corneal epithelial	Photophobia	Corneal ulceration
	abnormality		Diplopia
			Ectropion
Gastrointestinal	Abdominal pain		Constipation	Glossitis
	Diarrhea		Dyspepsia	Hemorrhoids
	Nausea		Esophagitis	Melena
	Tongue< disorder		Gastritis	Tenesmus
			Gastroenteritis	Tongue ulceration
Liver and Biliary			Hepatic function
			abnormal
			Hepatitis
			Jaundice
Mucous Membranes	Gingival bleeding	Stomatitis	Altered saliva	Hemorrhage
	Gingivitis	Thirst	Anal disorder	Pharyngitis
	Increased saliva	Ulcerative	Gum hyperplasia
		stomatitis
Musculoskeletal	Arthritis	Osteodynia	Bone disorder
	Arthrosis	Peripheral joint	Olecranon bursitis
	Back pain	hyperostosis	Spinal hyperostosis
	Hypertonia	(progression of	(new lesions)
	Myalgia	existing lesions)	Tendonitis
Psychiatric	Depression		Anxiety
	Insomnia		Dysphonia
	Somnolence		Libido decreased
			Nervousness
Reproductive			Atrophic vaginitis
			Leukorrhea
Respiratory	Sinusitis		Coughing
			Increased sputum
			Laryngitis
Skin and Appendages	Abnormal skin	Psoriasiform rash	Acne	Otitis externa
	odor	Purpura	Breast pain	Photosensitivity
	Abnormal hair	Pyogenic	Cyst	reaction
	texture	granuloma	Eczema	Psoriasis aggravated
	Bullous eruption	Rash	Fungal infection	Scleroderma
	Cold/clammy	Seborrhea	Furunculosis	Skin nodule
	skin	Skin fissures	Hair discoloration	Skin hypertrophy
	Dermatitis	Skin ulceration	Herpes simplex	Skin disorder
	Increased	Sunburn	Hyperkeratosis	Skin irritation
	sweating		Hypertrichosis	Sweat gland
	Infection		Hypoesthesia	disorder
			Impaired healing	Urticaria
			Otitis media	Verrucae
Special Senses/ Other	Earache		Ceruminosis
	Taste perversion		Deafness
	Tinnitus		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:	Decreased:
			-Phosphorus	-Phosphorus
			-Potassium	-Potassium
			-Sodium	-Sodium
			Increased and	Increased and
			decreased:	decreased:
			-Magnesium	-Calcium
				-Chloride
Hematologic		Increased:	Decreased:	Increased:
		-Reticulocytes	-Hematocrit	-Bands
			-Hemoglobin	-Basophils
			-WBC	-Eosinophils
			Increased:	-Hematocrit
			-Haptoglobin	-Hemoglobin
			-Neutrophils	-Lymphocytes
			-WBC	-Monocytes
				Decreased:
				-Haptoglobin
				-Lymphocytes
				-Neutrophils
				-Reticulocytes
				Increased or
				decreased:
				-Platelets
				-RBC
Hepatic		Increased:	Increased:	Increased:
		-Cholesterol	-Alkaline	-Globulin
		-LDH	phosphatase	-Total bilirubin
		-SGOT	-Direct bilirubin	-Total protein
		-SGPT	-GGTP	Increased and
		Decreased:		decreased:
		-HDL		-Serum albumin
		cholesterol
Miscellaneous	Increased:	Increased:	Decreased:	Increased and
	-Triglycerides	-CPK	-Fasting blood	decreased:
		-Fasting blood	sugar	-Iron
		sugar	-High occult
			blood
Renal			Increased:	Increased:
			-Uric acid	-BUN
				-Creatinine
Urinary		WBC in urine	Acetonuria	Glycosuria
			Hematuria	Proteinuria
			RBC in urine

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.

Last updated on RxList: 12/13/2007

(see also boxed CONTRAINDICATIONS AND WARNINGS)

Hyperostosis: In adults receiving long-term treatment with Soriatane, appropriate examinations should be periodically performed in view of possible ossification abnormalities (see ADVERSE REACTIONS). Because the frequency and severity of iatrogenic bony abnormality in adults is low, periodic radiography is only warranted in the presence of symptoms or long-term use of Soriatane. If such disorders arise, the continuation of therapy should be discussed with the patient on the basis of a careful risk/benefit analysis. In clinical trials with Soriatane, patients were prospectively evaluated for evidence of development or change in bony abnormalities of the vertebral column, knees and ankles.

Vertebral Results: Of 380 patients treated with Soriatane, 15% had preexisting abnormalities of the spine which showed new changes or progression of preexisting findings. Changes included degenerative spurs, anterior bridging of spinal vertebrae, diffuse idiopathic skeletal hyperostosis, ligament calcification and narrowing and destruction of a cervical disc space. De novo changes (formation of small spurs) were seen in 3 patients after 1½ to 2½ years.

Skeletal Appendicular Results: Six of 128 patients treated with Soriatane showed abnormalities in the knees and ankles before treatment that progressed during treatment. In 5, these changes involved the formation of additional spurs or enlargement of existing spurs. The sixth patient had degenerative joint disease which worsened. No patients developed spurs de novo. Clinical complaints did not predict radiographic changes.

Lipids and Possible Cardiovascular Effects: Blood lipid determinations should be performed before Soriatane is administered and again at intervals of 1 to 2 weeks until the lipid response to the drug is established, usually within 4 to 8 weeks. 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% of patients. These effects of Soriatane were generally reversible upon cessation of therapy.

Patients with an increased tendency to develop hypertriglyceridemia included those with disturbances of lipid metabolism, diabetes mellitus, obesity, increased alcohol intake or a familial history of these conditions. Because of the risk of hypertriglyceridemia, serum lipids must be more closely monitored in high-risk patients and during long-term treatment.

Hypertriglyceridemia and lowered HDL may increase a patient's cardiovascular risk status. Although no causal relationship has been established, there have been postmarketing reports of acute myocardial infarction or thromboembolic events in patients on Soriatane therapy. In addition, elevation of serum triglycerides to greater than 800 mg/dL has been associated with fatal fulminant pancreatitis. Therefore, dietary modifications, reduction in Soriatane dose, or drug therapy should be employed to control significant elevations of triglycerides. If, despite these measures, hypertriglyceridemia and low HDL levels persist, the discontinuation of Soriatane should be considered.

Ophthalmologic Effects: The eyes and vision of 329 patients treated with Soriatane were examined by ophthalmologists. The findings included dry eyes (23%), irritation of eyes (9%) and brow and lash loss (5%). The following were reported in less than 5% of patients: Bell's Palsy, blepharitis and/or crusting of lids, blurred vision, conjunctivitis, corneal epithelial abnormality, cortical cataract, decreased night vision, diplopia, itchy eyes or eyelids, nuclear cataract, pannus, papilledema, photophobia, posterior subcapsular cataract, recurrent sties and subepithelial corneal lesions.

Any patient treated with Soriatane who is experiencing visual difficulties should discontinue the drug and undergo ophthalmologic evaluation.

Pancreatitis: Lipid elevations occur in 25% to 50% of patients treated with Soriatane. Triglyceride increases sufficient to be associated with pancreatitis are much less common, although fatal fulminant pancreatitis has been reported. There have been rare reports of pancreatitis during Soriatane therapy in the absence of hypertriglyceridemia.

Pseudotumor Cerebri: Soriatane and other retinoids administered orally have been associated with cases of pseudotumor cerebri (benign intracranial hypertension). Some of these events involved concomitant use of isotretinoin and tetracyclines. However, the event seen in a single Soriatane patient was not associated with tetracycline use. Early signs and symptoms include papilledema, headache, nausea and vomiting and visual disturbances. Patients with these signs and symptoms should be examined for papilledema and, if present, should discontinue Soriatane immediately and be referred for neurological evaluation and care. Since both Soriatane and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated (see CONTRAINDICATIONS).

A description of the Do Your P.A.R.T. materials is provided below. The main goals of the materials are to explain the program requirements, to reinforce the educational messages, and to assess program effectiveness.

The Do Your P.A.R.T. booklet includes:

• The Do Your P.A.R.T. Patient Brochure: information on the program requirements, risks of acitretin, and the types of contraceptive methods
• The Contraceptive Counseling Referral Form for female patients who want to receive free contraception counseling reimbursed by the manufacturer
• The Patient Agreement/Informed Consent Form for female patients
• Medication Guide

The Do Your P.A.R.T. program also includes a voluntary patient survey for women of childbearing potential to assess the effectiveness of the Soriatane Pregnancy Prevention Program Do Your P.A.R.T.

Information for Patients (see Medication Guide for all patients and Patient Agreement/Informed Consent for Female Patients at end of professional labeling)

Patients should be instructed to read the Medication Guide supplied as required by law when Soriatane is dispensed.

Females of reproductive potential: Soriatane can cause severe birth defects. Female patients must not be pregnant when Soriatane therapy is initiated, they must not become pregnant while taking Soriatane, and for at least 3 years after stopping Soriatane, so that the drug can be eliminated to below a blood concentration that would be associated with an increased incidence of birth defects. Because this threshold has not been established for acitretin in humans and because elimination rates vary among patients, the duration of posttherapy contraception to achieve adequate elimination cannot be calculated precisely (see boxed CONTRAINDICATIONS AND WARNINGS).

Females of reproductive potential should also be advised that they must not ingest beverages or products containing ethanol while taking Soriatane and for 2 months after Soriatane treatment has been discontinued. This allows for elimination of the acitretin which can be converted to etretinate in the presence of alcohol.

Female patients should be advised that any method of birth control can fail, including tubal ligation, and that microdosed progestin “minipill” preparations are not recommended for use with Soriatane (see CLINICAL PHARMACOLOGY: Pharmacokinetic Drug Interactions ). Data from one patient who received a very low-dosed progestin contraceptive (levonorgestrel 0.03 mg) had a significant increase of the progesterone level after three menstrual cycles during acitretin treatment.²

Female patients should sign a consent form prior to beginning Soriatane therapy (see boxed CONTRAINDICATIONS AND WARNINGS).

Nursing Mothers: Studies on lactating rats have shown that etretinate is excreted in the milk. There is one prospective case report where acitretin is reported to be excreted in human milk. Therefore, nursing mothers should not receive Soriatane prior to or during nursing because of the potential for serious adverse reactions in nursing infants.

All Patients

Depression and/or other psychiatric symptoms such as aggressive feelings or thoughts of self-harm 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. Patients should be counseled to stop taking Soriatane and notify their prescriber immediately if they experience psychiatric symptoms.

Patients should be advised that a transient worsening of psoriasis is sometimes seen during the initial treatment period. Patients should be advised that they may have to wait 2 to 3 months before they get the full benefit of Soriatane, although some patients may achieve significant improvements within the first 8 weeks of treatment as demonstrated in clinical trials.

Decreased night vision has been reported with Soriatane therapy. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Visual problems should be carefully monitored (see WARNINGS and ADVERSE REACTIONS). Patients should be advised that they may experience decreased tolerance to contact lenses during the treatment period and sometimes after treatment has stopped.

Patients should not donate blood during and for at least 3 years following therapy because Soriatane can cause birth defects and women of childbearing potential must not receive blood from patients being treated with Soriatane.

Because of the relationship of Soriatane to vitamin A, patients should be advised against taking vitamin A supplements in excess of minimum recommended daily allowances to avoid possible additive toxic effects.

Patients should avoid the use of sun lamps and excessive exposure to sunlight (non-medical UV exposure) because the effects of UV light are enhanced by retinoids.

Patients should be advised that they must not give their Soriatane capsules to any other person.

For Prescribers

Soriatane has not been studied in and is not indicated for treatment of acne.

Phototherapy: Significantly lower doses of phototherapy are required when Soriatane is used because Soriatane-induced effects on the stratum corneum can increase the risk of erythema (burning) (see DOSAGE AND ADMINISTRATION).

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

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).

Carcinogenesis, Mutagenesis and Impairment of Fertility: Carcinogenesis: A carcinogenesis study of acitretin in Wistar rats, at doses up to 2 mg/kg/day administered 7 days/week for 104 weeks, has been completed. There were no neoplastic lesions observed that were considered to have been related to treatment with acitretin. An 80-week carcinogenesis study in mice has been completed with etretinate, the ethyl ester of acitretin. Blood level data obtained during this study demonstrated that etretinate was metabolized to acitretin and that blood levels of acitretin exceeded those of etretinate at all times studied. In the etretinate study, an increased incidence of blood vessel tumors (hemangiomas and hemangiosarcomas at several different sites) was noted in male, but not female, mice at doses approximately one-half the maximum recommended human therapeutic dose based on a mg/m² comparison.

Mutagenesis: Acitretin was evaluated for mutagenic potential in the Ames test, in the Chinese hamster (V79/HGPRT) assay, in unscheduled DNA synthesis assays using rat hepatocytes and human fibroblasts and in an in vivo mouse micronucleus assay. No evidence of mutagenicity of acitretin was demonstrated in any of these assays.

Impairment of Fertility: In a fertility study in rats, the fertility of treated animals was not impaired at the highest dosage of acitretin tested, 3 mg/kg/day (approximately one-half the maximum recommended therapeutic dose based on a mg/m² comparison). Chronic toxicity studies in dogs revealed testicular changes (reversible mild to moderate spermatogenic arrest and appearance of multinucleated giant cells) in the highest dosage group (50 then 30 mg/kg/day).

No decreases in sperm count or concentration and no changes in sperm motility or morphology were noted in 31 men (17 psoriatic patients, 8 patients with disorders of keratinization and 6 healthy volunteers) given 30 to 50 mg/day of acitretin for at least 12 weeks. In these studies, no deleterious effects were seen on either testosterone production, LH or FSH in any of the 31 men.^4-6 No deleterious effects were seen on the hypothalamic-pituitary axis in any of the 18 men where it was measured.^4,5

Pregnancy: Teratogenic Effects: Pregnancy Category X (see boxed CONTRAINDICATIONS AND WARNINGS).

In a study in which acitretin was administered to male rats only at a dosage of 5 mg/kg/day for 10 weeks (approximate duration of one spermatogenic cycle) prior to and during mating with untreated female rats, no teratogenic effects were observed in the progeny (see boxed CONTRAINDICATIONS AND WARNINGS for information about male use of Soriatane).

Nonteratogenic Effects: In rats dosed at 3 mg/kg/day (approximately one-half the maximum recommended therapeutic dose based on a mg/m² comparison), slightly decreased pup survival and delayed incisor eruption were noted. At the next lowest dose tested, 1 mg/kg/day, no treatment-related adverse effects were observed.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established. No clinical studies have been conducted in pediatric patients. Ossification of interosseous ligaments and tendons of the extremities, skeletal hyperostoses, decreases in bone mineral density, and premature epiphyseal closure have been reported in children taking other systemic retinoids, including etretinate, a metabolite of Soriatane. A causal relationship between these effects and Soriatane has not been established. While it is not known that these occurrences are more severe or more frequent in children, there is special concern in pediatric patients because of the implications for growth potential (see WARNINGS: Hyperostosis).

Geriatric Use: Clinical studies of Soriatane did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A twofold increase in acitretin plasma concentrations was seen in healthy elderly subjects compared with young subjects, although the elimination half-life did not change (see CLINICAL PHARMACOLOGY: Special Populations).

REFERENCES

4. Sigg C, et al.: Andrological investigations in patients treated with etretin. Dermatologica 175:48-49, 1987.

5. Parsch EM, et al.: Andrological investigation in men treated with acitretin (Ro 10-1670). Andrologia 22:479-482, 1990.

6. Kadar L, et al.: Spermatological investigations in psoriatic patients treated with acitretin. In: Pharmacology of Retinoids in the Skin; Reichert U. et al., ed, KARGER, Basel, vol. 3, pp 253-254, 1988.

Last updated on RxList: 11/16/2007

In the event of acute overdosage, Soriatane must be withdrawn at once. Symptoms of overdose are identical to acute hypervitaminosis A, ie, headache and vertigo. The acute oral toxicity (LD₅₀) of acitretin in both mice and rats was greater than 4000 mg/kg.

In one reported case of overdose, a 32-year-old male with Darier's disease took 21 x 25 mg capsules (525 mg single dose). He vomited several hours later but experienced no other ill effects.

All female patients of childbearing potential who have taken an overdose of Soriatane must:

1) Have a pregnancy test at the time of overdose; 2) Be counseled as per the boxed CONTRAINDICATIONS AND WARNINGS and PRECAUTIONS sections regarding birth defects and contraceptive use for at least 3 years' duration after the overdose.

Pregnancy Category X (see boxed CONTRAINDICATIONS AND WARNINGS).

Soriatane is contraindicated in patients with severely impaired liver or kidney function and in patients with chronic abnormally elevated blood lipid values (see boxed WARNINGS: Hepatoxicity, WARNINGS: Lipids and Possible Cardiovascular Effects, and PRECAUTIONS).

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

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

Soriatane is contraindicated in cases of hypersensitivity to the preparation (acitretin or excipients) or to other retinoids.

Last updated on RxList: 11/16/2007

The mechanism of action of Soriatane is unknown.

Pharmacokinetics

Absorption:Oral absorption of acitretin is optimal when given with food. For this reason, acitretin was given with food in all of the following studies. After administration of a single 50 mg oral dose of acitretin to 18 healthy subjects, maximum plasma concentrations ranged from 196 to 728 ng/mL (mean 416 ng/mL) and were achieved in 2 to 5 hours (mean 2.7 hours). The oral absorption of acitretin is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.

Distribution: Acitretin is more than 99.9% bound to plasma proteins, primarily albumin.

Metabolism : (see Pharmacokinetic Drug Interactions: Ethanol): Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). The formation of cis-acitretin relative to parent compound is not altered by dose or fed/fast conditions of oral administration of acitretin. Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted. Following multiple-dose administration of acitretin, steady-state concentrations of acitretin and cis-acitretin in plasma are achieved within approximately 3 weeks.

Elimination: The chain-shortened metabolites and conjugates of acitretin and cis-acitretin are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%). The terminal elimination half-life of acitretin following multiple-dose administration is 49 hours (range 33 to 96 hours), and that of cis-acitretin under the same conditions is 63 hours (range 28 to 157 hours). The accumulation ratio of the parent compound is 1.2; that of cis-acitretin is 6.6.

Special Populations

Psoriasis: In an 8-week study of acitretin pharmacokinetics in patients with psoriasis, mean steady-state trough concentrations of acitretin increased in a dose proportional manner with dosages ranging from 10 to 50 mg daily. Acitretin plasma concentrations were nonmeasurable ( < 4 ng/mL) in all patients 3 weeks after cessation of therapy.

Elderly: In a multiple-dose study in healthy young (n=6) and elderly (n=8) subjects, a two-fold increase in acitretin plasma concentrations were seen in elderly subjects, although the elimination half-life did not change.

Renal Failure: Plasma concentrations of acitretin were significantly (59.3%) lower in end-stage renal failure subjects (n=6) when compared to age-matched controls, following single 50 mg oral doses. Acitretin was not removed by hemodialysis in these subjects.

Pharmacokinetic Drug Interactions (see also boxed CONTRAINDICATIONS AND WARNINGS and PRECAUTIONS: DRUG INTERACTIONS): In studies of in vivo pharmacokinetic drug interactions, no interaction was seen between acitretin and cimetidine, digoxin, phenprocoumon or glyburide.

Ethanol: Clinical evidence has shown that etretinate (a retinoid with a much longer half-life, see below) can be formed with concurrent ingestion of acitretin and ethanol. In a two-way crossover study, all 10 subjects formed etretinate with concurrent ingestion of a single 100 mg oral dose of acitretin during a 3-hour period of ethanol ingestion (total ethanol, approximately 1.4 g/kg body weight). A mean peak etretinate concentration of 59 ng/mL (range 22 to 105 ng/mL) was observed, and extrapolation of AUC values indicated that the formation of etretinate in this study was comparable to a single 5 mg oral dose of etretinate. There was no detectable formation of etretinate when a single 100 mg oral dose of acitretin was administered without concurrent ethanol ingestion, although the formation of etretinate without concurrent ethanol ingestion cannot be excluded (see boxed CONTRAINDICATIONS AND WARNINGS). Of 93 evaluable psoriatic patients on acitretin therapy in several foreign studies (10 to 80 mg/day), 16% had measurable etretinate levels ( > 5 ng/mL).

Etretinate has a much longer elimination half-life compared to that of acitretin. In one study the apparent mean terminal half-life after 6 months of therapy was approximately 120 days (range 84 to 168 days). In another study of 47 patients treated chronically with etretinate, 5 had detectable serum drug levels (in the range of 0.5 to 12 ng/mL) 2.1 to 2.9 years after therapy was discontinued. The long half-life appears to be due to storage of etretinate in adipose tissue.

Progestin-only 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 preparations.¹ Microdosed “minipill” progestin preparations are not recommended for use with Soriatane. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Clinical Studies

In two double-blind placebo controlled studies, Soriatane was administered once daily to patients with severe psoriasis (ie, covering at least 10% to 20% of the body surface area). At 8 weeks (see Table 1) patients treated in Study A with 50 mg Soriatane per day showed significant improvements (p ≤ 0.05) relative to baseline and to placebo in the physician's global evaluation and in the mean ratings of severity of psoriasis (scaling, thickness, and erythema). In study B, differences from baseline and from placebo were statistically significant (p ≤ 0.05) for all variables at both the 25 mg and 50 mg doses; it should be noted for Study B that no statistical adjustment for multiplicity was carried out.

Table 1. Summary of the Soriatane Efficacy Results of the 8-Week Double-Blind Phase of Studies A and B

	StudyA		Study B
	Total daily dose		Total daily dose
Efficacy Variables	Placebo (N=29)	50 mg (N=29)	Placebo (N=72)	25 mg (N=74)	50 mg (N=71)
Physician's Global Evaluation
Baseline	4.62	4.55	4.43	4.37	4.49
Mean Change After 8 Weeks	- 0.29	- 2.00*	- 0.06	- 1.06*	- 1.57*
Scaling
Baseline	4.10	3.76	3.97	4.11	4.10
Mean Change
After 8 Weeks	- 0.22	- 1.62*	- 0.21	- 1.50*	- 1.78*
Thickness
Baseline	4.10	4.10	4.03	4.11	4.20
Mean Change
After 8 Weeks	- 0.39	- 2.10*	- 0.18	- 1.43*	- 2.11*
Erythema
Baseline	4.21	4.59	4.42	4.24	4.45
Mean Change After 8 Weeks	- 0.33	- 2.10*	- 0.37	- 1.12*	- 1.65*
*Values were statistically significantly different from placebo and from baseline (p ≤ 0.05). No adjustment for multiplicity was done for Study B.

The efficacy variables consisted of: the mean severity rating of scale, lesion thickness, erythema, and the physician's global evaluation of the current status of the disease. Ratings of scaling, erythema, and lesion thickness, and the ratings of the global assessments were made using a seven-point scale (0=none, 1=trace, 2=mild, 3=mild-moderate, 4=moderate, 5=moderate-severe, 6=severe).

A subset of 141 patients from both pivotal studies A and B continued to receive Soriatane in an open fashion for up to 24 weeks. At the end of the treatment period, all efficacy variables, as indicated in Table 2, were significantly improved (p ≤ 0.01) from baseline, including extent of psoriasis, mean ratings of psoriasis severity and physician's global evaluation.

Table 2. Summary of the First Course of Soriatane Therapy (24 Weeks)

Variables	Study A	Study B
Mean Total Daily Soriatane Dose (mg)	42.8	43.1
Mean Duration of Therapy (Weeks)	21.1	22.6
Physician's Global Evaluation	N=39	N=98
Baseline	4.51	4.43
Mean Change From Baseline	- 2.26*	- 2.60*
Scaling	N=59	N=132
Baseline	3.97	4.07
Mean Change From Baseline	- 2.15*	- 2.42*
Thickness	N=59	N=132
Baseline	4.00	4.12
Mean Change From Baseline	- 2.44*	- 2.66*
Erythema	N=59	N=132
Baseline	4.35	4.33
Mean Change From Baseline	- 2.31*	- 2.29*
* Indicates that the difference from baseline was statistically significant (p ≤ 0.01).

The efficacy variables consisted of: the mean severity rating of scale, lesion thickness, erythema, and the physician's global evaluation of the current status of the disease. Ratings of scaling, erythema, and lesion thickness, and the ratings of the global assessments were made using a seven-point scale (0=none, 1=trace, 2=mild, 3=mild-moderate, 4=moderate, 5=moderate-severe, 6=severe).

All efficacy variables improved significantly in a subset of 55 patients from Study A treated for a second, 6-month maintenance course of therapy (for a total of 12 months of treatment); a small subset of patients (n=4) from Study A continued to improve after a third 6-month course of therapy (for a total of 18 months of treatment).

Last updated on RxList: 11/16/2007

MEDICATION GUIDE FOR PATIENTS

SORIATANE®
[sor-RYE-uh-tane]
(acitretin) CAPSULES

Read this Medication Guide carefully before you start taking Soriatane and read it each time you get more Soriatane. There may be new information.

The first information in this Guide is about birth defects and how to avoid pregnancy. After this section there is important safety information about possible effects for any patient taking Soriatane. ALL patients should read this entire Medication Guide carefully.

This information does not take the place of talking with your prescriber about your medical condition or treatment.

What is the most important information I should know about Soriatane?

Soriatane can cause severe birth defects. If you are a female who can get pregnant, you should use Soriatane only if you are not pregnant now, can avoid becoming pregnant for at least 3 years, and other medicines do not work for your severe psoriasis or you cannot use other psoriasis medicines. Information about effects on unborn babies and about how to avoid pregnancy is found in the next section: “What are the important warnings and instructions for females taking Soriatane?”.

CAUSES BIRTH DEFECTS
DO NOT GET PREGNANT

What are the important warnings and instructions for females taking Soriatane?

• Before you receive your Soriatane prescription, you should have discussed and signed a Patient Information/Consent form with your prescriber. This is to help make sure you understand the risk of birth defects and how to avoid getting pregnant. If you did not talk to your prescriber about this and sign the form, contact your prescriber.
• You must not take Soriatane if you are pregnant or might become pregnant during treatment or at any time for at least 3 years after you stop treatment because Soriatane can cause severe birth defects.
• During Soriatane treatment and for 2 months after you stop Soriatane treatment, you must avoid drinks, foods, and all medicines that contain alcohol. This includes over-the-counter products that contain alcohol. Avoiding alcohol is very important, because alcohol changes Soriatane into a drug that may take longer than 3 years to leave your body. The chance of birth defects may last longer than 3 years if you swallow any form of alcohol during Soriatane therapy and for 2 months after you stop taking Soriatane.
• You and your prescriber must be sure you are not pregnant before you start Soriatane therapy. You must have negative results from 2 pregnancy tests before you start Soriatane treatment. A negative result shows you are not pregnant. Because it takes a few days after pregnancy begins for a test to show that you are pregnant, the first negative test may not ensure you are not pregnant. Do not start Soriatane until you have negative results from 2 pregnancy tests.
  • The first pregnancy test will be done at the time you and your prescriber decide if Soriatane might be right for you.
  • The second pregnancy test will usually be done during the first 5 days of your menstrual period, right before you plan to start Soriatane. Your prescriber may suggest another time.
• After you start Soriatane therapy, you must have a pregnancy test repeated each month that you are taking Soriatane. This is to be sure that you are not pregnant during treatment because Soriatane can cause birth defects.
• For at least 3 years after stopping Soriatane treatment, you must have a pregnancy test repeated every three months to make sure that you are not pregnant.
• Discuss effective birth control (contraception) with your prescriber. You must use 2 effective forms of birth control (contraception) at the same time during all of the following:
  • for at least 1 month before beginning Soriatane treatment
  • during treatment with Soriatane
  • for at least 3 years after stopping Soriatane treatment
• If you are sexually active, you must use 2 effective forms of birth control (contraception) at the same time even if you think you cannot become pregnant, unless 1 of the following is true for you:
  • You had your womb (uterus) removed during an operation (a hysterectomy).
  • Your prescriber said you have gone completely through menopause (the “change of life”).
• You can get a free birth control counseling session and pregnancy testing from a prescriber or family planning expert. Your prescriber can give you a Soriatane Patient Referral Form for this free session.
• You must use 2 effective forms of birth control (contraception) at the same time while you are on Soriatane treatment. You must use birth control for at least 1 month before you start Soriatane, during treatment, and at least 3 years after you stop Soriatane treatment.

The following are considered effective forms of birth control:

Primary Forms:

• having your tubes tied (tubal ligation)
• partner's vasectomy
• IUD (intrauterine device)
• birth control pills that contain both estrogen and progestin (combination oral contraceptives)
• hormonal birth control products that are injected, implanted, or inserted in your body
• birth control patch

Secondary Forms (use with a Primary Form):

• diaphragms with spermicide
• latex condoms (with or without spermicide)
• cervical caps with spermicide

At least 1 of your 2 methods of birth control must be a primary form.

• If you have sex at any time without using 2 effective forms of birth control (contraception) at the same time, or if you get pregnant or miss your period, stop using Soriatane and call your prescriber right away.
• Consider “Emergency Contraception” (EC) if you have sex with a male without correctly using 2 effective forms of birth control (contraception) at the same time. EC is also called “emergency birth control” or the “morning after” pill. Contact your prescriber as soon as possible if you have sex without using 2 effective forms of birth control (contraception) at the same time, because EC works best if it is used within 1 or 2 days after sex. EC is not a replacement for your usual 2 effective forms of birth control (contraception) because it is not as effective as regular birth control methods.

  You can get EC from private doctors or nurse practitioners, women's health centers, or hospital emergency rooms. You can get the name and phone number of EC providers nearest you by calling the free Emergency Contraception Hotline at 1-888-NOT-2-LATE (1-888-668-2528).

• Stop taking Soriatane right away and contact your prescriber if you get pregnant while taking Soriatane or at any time for at least 3 years after treatment has stopped. You need to discuss the possible effects on the unborn baby with your prescriber.
• If you do become pregnant while taking Soriatane or at any time for at least 3 years after stopping Soriatane, you should report your pregnancy to Stiefel Laboratories, Inc. at 1-888-500-DERM (3376) or directly to the Food and Drug Administration (FDA) MedWatch program (1-800-FDA-1088). Your name will be kept in private (confidential). The information you share will help the FDA and the manufacturer evaluate the Pregnancy Prevention Program for Soriatane.
• Do not take Soriatane if you are breast feeding. Soriatane can pass into your milk and may harm your baby. You will need to choose either to breast feed or take Soriatane, but not both.

What should males know before taking Soriatane?

Small amounts of Soriatane are found in the semen of males taking Soriatane. Based upon available information, it appears that these small amounts of Soriatane in semen pose little, if any, risk to an unborn child while a male patient is taking the drug or after it is discontinued. Discuss any concerns you have about this with your prescriber.

All patients should read the rest of this Medication Guide.

What is Soriatane?

Soriatane is a medicine used to treat severe forms of psoriasis in adults. Psoriasis is a skin disease that causes cells in the outer layer of the skin to grow faster than normal and pile up on the skin's surface. In the most common type of psoriasis, the skin becomes inflamed and produces red, thickened areas, often with silvery scales. Because Soriatane can have serious side effects, you should talk with your prescriber about whether Soriatane's possible benefits outweigh its possible risks.

Soriatane may not work right away. You may have to wait 2 to 3 months before you get the full benefit of Soriatane. Psoriasis gets worse for some patients when they first start Soriatane treatment.

Soriatane has not been studied in children.

Who should not take Soriatane?

• Do NOT take Soriatane if you can get pregnant. Do not take Soriatane if you are pregnant or might get pregnant during Soriatane treatment or at any time for at least 3 years after you stop Soriatane treatment (see “What are the important warnings and instructions for females taking Soriatane?”).
• Do NOT take Soriatane if you are breast feeding. Soriatane can pass into your milk and may harm your baby. You will need to choose either to breast feed or take Soriatane, but not both.
• Do NOT take Soriatane if you have severe liver or kidney disease.
• Do NOT take Soriatane if you have repeated high blood lipids (fat in the blood).
• Do NOT take Soriatane if you take these medicines:
  • methotrexate
  • tetracyclines

  The use of these medicines with Soriatane may cause serious side effects.

• Do NOT take Soriatane if you are allergic to acitretin, the active ingredient in Soriatane, to any of the other ingredients (see the end of this Medication Guide for a list of all the ingredients in Soriatane), or to any similar drugs (ask your prescriber or pharmacist whether any drugs you are allergic to are related to Soriatane).

Tell your prescriber if you have or ever had:

• diabetes or high blood sugar
• liver problems
• kidney problems
• high cholesterol or high triglycerides (fat in the blood)
• heart disease
• depression
• alcoholism
• an allergic reaction to a medication

Your prescriber needs this information to decide if Soriatane is right for you and to know what dose is best for you.

Tell your prescriber about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines can cause serious side effects if taken while you also take Soriatane. Some medicines may affect how Soriatane works, or Soriatane may affect how your other medicines work. Be especially sure to tell your prescriber if you are taking the following medicines:

• methotrexate
• tetracyclines
• phenytoin
• vitamin A supplements
• progestin-only oral contraceptives (“minipills”)
• Tegison® or Tigason (etretinate). Tell your prescriber if you have ever taken this medicine in the past.
• St. John's Wort herbal supplement

Tell your prescriber if you are getting phototherapy treatment. Your doses of phototherapy may need to be changed to prevent a burn.

How should I take Soriatane?

• Take Soriatane with food.
• Be sure to take your medicine as prescribed by your prescriber. The dose of Soriatane varies from patient to patient. The number of capsules you must take is chosen specially for you by your prescriber. This dose may change during treatment.
• If you miss a dose, do not double the next dose. Skip the missed dose and resume your normal schedule.
• If you take too much Soriatane (overdose), call your local poison control center or emergency room.

You should have blood tests for liver function, cholesterol and triglycerides before starting treatment and during treatment to check your body's response to Soriatane. Your prescriber may also do other tests.

Once you stop taking Soriatane, your psoriasis may return. Do not treat this new psoriasis with leftover Soriatane. It is important to see your prescriber again for treatment recommendations because your situation may have changed.

What should I avoid while taking Soriatane?

• Avoid pregnancy. See “What is the most important information I should know about Soriatane?”, and “What are the important warnings and instructions for females taking Soriatane?”.
• Avoid breast feeding. See “What are the important warnings and instructions for females taking Soriatane?”
• Avoid alcohol. Females must avoid drinks, foods, medicines, and over-the-counter products that contain alcohol. The risk of birth defects may continue for longer than 3 years if you swallow any form of alcohol during Soriatane treatment and for 2 months after stopping Soriatane (see “What are the important warnings and instructions for females taking Soriatane?”).
• Avoid giving blood. Do not donate blood while you are taking Soriatane and for at least 3 years after stopping Soriatane treatment. Soriatane in your blood can harm an unborn baby if your blood is given to a pregnant woman. Soriatane does not affect your ability to receive a blood transfusion.
• Avoid progestin-only birth control pills (“minipills”). This type of birth control pill may not work while you take Soriatane. Ask your prescriber if you are not sure what type of pills you are using.
• Avoid night driving if you develop any sudden vision problems. Stop taking Soriatane and call your prescriber if this occurs (see “Serious side effects”).
• Avoid non-medical ultraviolet (UV) light. Soriatane can make your skin more sensitive to UV light. Do not use sunlamps, and avoid sunlight as much as possible. If you are taking light treatment (phototherapy), your prescriber may need to change your light dosages to avoid burns.
• Avoid dietary supplements containing vitamin A. Soriatane is related to vitamin A. Therefore, do not take supplements containing vitamin A, because they may add to the unwanted effects of Soriatane. Check with your prescriber or pharmacist if you have any questions about vitamin supplements.
• DO NOT SHARE Soriatane with anyone else, even if they have the same symptoms. Your medicine may harm them or their unborn child.

What are the possible side effects of Soriatane?

• Soriatane can cause birth defects. See “What is the most important information I should know about Soriatane?” and “What are the important warnings and instructions for females taking Soriatane?”
• Psoriasis gets worse for some patients when they first start Soriatane treatment. Some patients have more redness or itching. If this happens, tell your prescriber. These symptoms usually get better as treatment continues, but your prescriber may need to change the amount of your medicine.
• Serious side effects. These do not happen often, but they can lead to permanent harm, or rarely, to death. Stop taking Soriatane and call your prescriber right away if you get the following signs or symptoms:
• Bad headaches, nausea, vomiting, blurred vision. These symptoms can be signs of increased brain pressure that can lead to blindness or even death.
• Decreased vision in the dark (night blindness). Since this can start suddenly, you should be very careful when driving at night. This problem usually goes away when Soriatane treatment stops. If you develop any vision problems or eye pain stop taking Soriatane and call your prescriber.
• Depression. There have been some reports of patients developing mental problems including a depressed mood, aggressive feelings, or thoughts of ending their own life (suicide). These events, including suicidal behavior, have been reported in patients taking other drugs similar to Soriatane as well as patients taking Soriatane. Since other things may have contributed to these problems, it is not known if they are related to Soriatane. It is very important to stop taking Soriatane and call your prescriber right away if you develop such problems.
• Yellowing of your skin or the whites of your eyes, nausea and vomiting, loss of appetite, or dark urine. These can be signs of serious liver damage.
• Aches or pains in your bones, joints, muscles, or back; trouble moving; loss of feeling in your hands or feet. These can be signs of abnormal changes to your bones or muscles.
• Frequent urination, great thirst or hunger. Soriatane can affect blood sugar control, even if you do not already have diabetes. These are some of the signs of high blood sugar.
• Shortness of breath, dizziness, nausea, chest pain, weakness, trouble speaking, or swelling of a leg. These may be signs of a heart attack, blood clots, or stroke. Soriatane can cause serious changes in blood fats (lipids). It is possible for these changes to cause blood vessel blockages that lead to heart attacks, strokes, or blood clots.

Common side effects. If you develop any of these side effects or any unusual reaction, check with your prescriber to find out if you need to change the amount of Soriatane you take. These side effects usually get better if the Soriatane dose is reduced or Soriatane is stopped.

• Chapped lips; peeling fingertips, palms, and soles; itching; scaly skin all over; weak nails; sticky or fragile (weak) skin; runny or dry nose, or nosebleeds. Your prescriber or pharmacist can recommend a lotion or cream to help treat drying or chapping.
• Dry mouth
• Joint pain
• Tight muscles
• Hair loss. Most patients have some hair loss, but this condition varies among patients. No one can tell if you will lose hair, how much hair you may lose or if and when it may grow back.
• Dry eyes. Soriatane may dry your eyes. Wearing contact lenses may be uncomfortable during and after treatment with Soriatane because of the dry feeling in your eyes. If this happens, remove your contact lenses and call your prescriber. Also read the section about vision under “Serious side effects”.
• Rise in blood fats (lipids). Soriatane can cause your blood fats (lipids) to rise. Most of the time this is not serious. But sometimes the increase can become a serious problem (see information under “Serious side effects”). You should have blood tests as directed by your prescriber.

These are not all the possible side effects of Soriatane. For more information, ask your prescriber or pharmacist.

How should I store Soriatane?

Keep Soriatane away from sunlight, high temperature, and humidity. Keep Soriatane away from children.

What are the ingredients in Soriatane?

Active ingredient: acitretin

Inactive ingredients: microcrystalline cellulose, sodium ascorbate, gelatin, black monogramming ink and maltodextrin (a mixture of polysaccharides). Gelatin capsule shells contain gelatin, iron oxide (yellow, black, and red), and titanium dioxide. They may also contain benzyl alcohol, carboxymethylcellulose sodium, edetate calcium disodium.

General information about the safe and effective use of Soriatane

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Soriatane for a condition for which it was not prescribed. Do not give Soriatane to other people, even if they have the same symptoms that you have.

This Medication Guide summarizes the most important information about Soriatane. If you would like more information, talk with your prescriber. You can ask your pharmacist or prescriber for information about Soriatane that is written for health professionals.

This Medication Guide has been approved by the U.S. Food and Drug Administration.
Tegison® is a registered trademark of Hoffmann-La Roche Inc.
Do Your P.A.R.T. is a trademark, and SORIATANE and Stiefel are registered trademarks, owned by Stiefel Laboratories, Inc.

Last updated on RxList: 11/16/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ACITRETIN - ORAL

(A-si-TRE-tin)

COMMON BRAND NAME(S): Soriatane

WARNING: Do not use this medication if you are pregnant or planning to become pregnant within 3 years of stopping this drug because it has caused serious birth defects.

Use 2 effective birth control methods starting 1 month before taking this medication and at least 3 years after treatment has stopped. Do not use "minipills" (non-estrogen-containing pills) for birth control because they may not work as well with this drug.

Females who are able to have children must not use this medication unless the following requirements are met: test negative on 2 pregnancy tests (they should be taken 1 week before starting this drug or at least 11 days after the last act of unprotected sexual intercourse); start therapy on the second or third day of the next normal menstrual period; present severe psoriasis and other treatments cannot be used; receive oral and written information on using 2 methods of birth control while taking this drug and for 3 years after stopping it; aware of the dangers of birth control failure and use during pregnancy; understand and correctly follow all birth control requirements and instructions including monthly pregnancy tests during treatment and every 3 months for 3 years after treatment has stopped.

Do not drink alcohol while using acitretin and for 2 months after stopping it because alcohol causes this drug to stay in the body longer.

It is not known if traces of this drug found in semen of male patients pose a risk to the unborn baby during use or after treatment has stopped.

Acitretin has been rarely linked to serious (sometimes fatal) liver problems (hepatitis) and increased fluid pressure on the brain (pseudotumor cerebri). Notify your doctor immediately if you develop any of these symptoms: yellowing eyes or skin, dark urine, stomach pain, unusual fatigue, headache, nausea and vomiting, or vision changes. Your doctor will decide whether to continue using acitretin.

Acitretin has also been linked to pancreatitis (inflammation of the pancreas). Notify your doctor immediately if you develop persistent, lower abdominal pain.

USES: This medication is a retinoid used in the treatment of severe psoriasis and other skin disorders in adults.

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using acitretin and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Read and complete the Patient Agreement and Informed Consent document before taking this drug.

Take this medication by mouth exactly as prescribed, usually once a day with your main meal.

The dosage is based on your medical condition and response to therapy. Do not take this more often or increase your dose without consulting your doctor. Your condition will not improve any faster but the risk of side effects may increase.

It may take 2 to 3 months before the full benefit of this medication is seen.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day.

SIDE EFFECTS: You may experience more redness, itching, skin scaling, peeling and dry skin the first several weeks as your body adjusts to the medication. Dry eyes, eye irritation, crusting of the eye lids, increased sensitivity to sunlight, dry mouth, peeling of the skin of fingertips, palms or soles of feet, chapped lips, runny nose, thirst, taste changes and hair loss may also occur. If any of these effects persist or worsen, inform your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these serious side effects occur: decreased night vision, other vision changes, fever, chills.

Tell your doctor immediately if any of these unlikely but serious side effects occur: aches and pain in the bones or joints, difficulty moving.

Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: severe headache, nausea, vomiting, mood changes (e.g., depression, aggressive or violent behavior, and in rare cases thoughts of suicide), yellowing of the skin or eyes, dark urine, stomach pain.

Contact lens wearers may be uncomfortable while taking this drug because it causes dry eyes.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking acitretin, tell your doctor or pharmacist if you are allergic to it; or to other retinoids; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe liver disease, severe kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, heart disease, diabetes, receive phototherapy.

Do not donate blood while taking this drug and for at least 3 years after stopping therapy. This will prevent the possibility of your blood being given to a pregnant woman.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Acitretin can affect your night vision. Be cautious when driving or operating machinery after dark.

Avoid drinking alcohol while taking this medication and for 2 months after stopping it.

This drug must not be used during pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately. This drug should not be used if you are planning to become pregnant during treatment or within 3 years after use has stopped.

Use 2 effective forms of birth control starting 1 month before and during treatment and at least 3 years after use has stopped. If you are unsure which types of birth control are effective, consult your doctor, pharmacist, or Medication Guide.

Semen may pose a risk to a pregnant woman if a male is using this drug. Consult your doctor.

It is not known if this drug is excreted into breast milk. Breast-feeding is not recommended while using this medication and for at least three years after the medication has been stopped.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: methotrexate, St. John's wort, tetracycline antibiotics, vitamin A.

If you are currently using any of these medications, tell your doctor or pharmacist before starting acitretin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "minipills" (progestin-only contraceptive pills).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include severe headache, nausea, vomiting, drowsiness, irritability, loss of balance, and itching.

NOTES: Do not share this medication with others.

Laboratory tests (e.g., monthly pregnancy tests, liver function tests, X-rays, and lipid tests) will be done frequently while taking this medication to monitor the effects and prevent side effects. See your doctor regularly.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of your next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store this medication at room temperature between 59-77 degrees F (15-25 degrees C) away from heat and light. Do not store in the bathroom. Keep this and all medications out of the reach of children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.