Acitretin

Name: Acitretin

Acitretin Side Effects

Common Side Effects of Acitretin

Tell your doctor if any of the following side effects become severe or don't go away:

  • Dry or irritated eyes
  • Dry mouth, lips, or nose
  • Swelling of the mouth, tongue, gums, or lips
  • Blisters in the tongue or mouth
  • Chapped lips
  • Excessive saliva
  • Runny nose
  • Nosebleed
  • Change in taste
  • Sinus infection
  • Hair loss
  • Dandruff
  • Thinning of the eyelashes or eyebrows
  • Brittle or weak nails
  • Sweating
  • Hot flashes or flushing
  • Thinning, peeling, or scaling of the skin
  • Mild diarrhea or stomach pain

Serious Side Effects of Acitretin

Tell your doctor right away if you experience any of the symptoms listed in the Acitretin Warnings section above, or any of the following serious side effects:

  • Blurred vision or other vision changes
  • Eye pain
  • Joint or back pain or stiffness
  • Bone pain
  • Chest pain
  • Leg or calf pain or swelling
  • Pale-colored stools
  • Fever
  • Severe dizziness or fainting
  • Mental or mood changes
  • Suicidal thoughts or actions
  • Slow, fast, or irregular heartbeat
  • Muscle weakness, pain, or stiffness
  • Tingling or numbness in the hands or feet
  • One-sided weakness
  • Cold, gray, or pale skin
  • Severe or persistent headache
  • Ear pain or ringing
  • Severe stomach pain
  • Shortness of breath
  • Slurred speech
  • Frequent hunger, thirst, or urination
  • Swelling or weight gain
  • Vaginal itching, odor, or discharge
  • Signs of a severe allergic reaction, which may include hives, itching, rash, difficulty breathing, tightness in the chest, or swelling of the face, mouth, lips, or tongue

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What is acitretin?

Acitretin is a retinoid, which is a form of vitamin A.

Acitretin is used to treat severe psoriasis in adults. Acitretin is not a cure for psoriasis, and you may relapse after you stop taking this medication.

Acitretin may also be used for purposes not listed in this medication guide.

Acitretin dosing information

Usual Adult Dose for Psoriasis:

Initial dose: 25 to 50 mg orally once a day, administered as a single dose with main meal
Maintenance dose: 25 to 50 mg orally once a day, administered upon an individual patient's response to initial treatment

Comments: When used with phototherapy, the healthcare provider should decrease the phototherapy dose, dependent on the patient's individual response.

Use: Treatment of severe psoriasis in adults

What other drugs will affect acitretin?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with acitretin, especially:

  • etretinate;

  • glyburide;

  • methotrexate;

  • phenytoin;

  • St. John's wort; or

  • hormone replacement therapy or birth control pills (especially "minipills").

This list is not complete. Other drugs may interact with acitretin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Advice to Patients

  • Provide all patients with a copy of the medication guide upon initial and subsequent dispensing of drug.1

  • Describe risk of birth defects.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions and also see Teratogenicity in Boxed Warning.)

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Necessity of advising women of childbearing potential to avoid pregnancy by using 2 methods of contraception simultaneously for ≥1 month prior to, throughout, and for ≥3 years after acitretin therapy.1 2 At least one method of contraception must be a primary form (e.g., tubal sterilization; vasectomized partner; intrauterine device; oral, injectable, inserted, transdermal, or implanted hormonal contraceptive) unless patient practices abstinence, has undergone a hysterectomy, or is postmenopausal.1 23 (See Do Your PART Program under Cautions.)

  • Importance of discontinuing therapy and immediately notifying clinician if pregnancy, unprotected intercourse, or a missed menstrual cycle occurs during or within 3 years after drug discontinuance.1 (See Pregnancy under Cautions.)

  • Importance of warning both male and female patients not to share acitretin with anyone else and not to donate blood while receiving acitretin and for at least 3 years after cessation of therapy.1

  • Importance of women avoiding alcohol from any source (e.g., OTC preparations, foods) during therapy and for 2 months following drug discontinuance.1 2 23 (See Alcohol in Boxed Warning and Specific Drugs under Interactions.)

  • Importance of discontinuing acitretin therapy and promptly reporting symptoms of depression or other psychiatric symptoms (e.g., aggression, self-injurious behaviors, suicidal thoughts) to clinician.1

  • Importance of informing clinicians if acute abdominal pain or emesis occurs; may be early indicators of pancreatitis.3

  • Risk of decreased night vision; importance of being cautious when driving or operating any vehicle at night.1

  • Importance of advising patients who wear contact lenses that they may experience decreased tolerance to the lenses during or after therapy with the drug; lubricating ophthalmic ointments or artificial tears may be needed.1 9 15

  • Importance of informing clinicians if concomitant phototherapy is being received.1 (See Phototherapy under Cautions.)

  • Importance of advising patients to avoid excessive exposure to natural or artificial sunlight (e.g., sun lamps).1 3 (See Photosensitivity under Cautions.)

  • Importance of informing patients that a transient worsening of psoriasis may occur initially and that full clinical benefit may not be evident for 2–3 months.1 6 23

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs and herbal supplements, as well as any concomitant illnesses.1 Importance of avoiding vitamin A supplements in excess of the minimum recommended daily allowance.1 3 (See Contraindications under Cautions and also see Specific Drugs under Interactions.)

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Before Using acitretin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For acitretin, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to acitretin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of acitretin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of acitretin in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving acitretin.

Pregnancy

Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking acitretin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using acitretin with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Chlortetracycline
  • Demeclocycline
  • Doxycycline
  • Lymecycline
  • Meclocycline
  • Methacycline
  • Minocycline
  • Oxytetracycline
  • Rolitetracycline
  • Tetracycline

Using acitretin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Levonorgestrel

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using acitretin with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use acitretin, or give you special instructions about the use of food, alcohol, or tobacco.

  • Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of acitretin. Make sure you tell your doctor if you have any other medical problems, especially:

  • Depression, history of or
  • Eye or vision problems or
  • Heart disease or
  • Hypercholesterolemia (high cholesterol in the blood) or
  • Hyperostosis (bone growth that is not normal) or
  • Hypertriglyceridemia (high triglycerides or fats in the blood) or
  • Hypervitaminosis A (too much vitamin A in the body), or history of or
  • Pancreatitis (inflammation of the pancreas) or
  • Pseudotumor cerebri (brain problem) or
  • Psychosis, history of—Use with caution. May make these conditions worse.
  • Diabetes mellitus, or a family history of or
  • Obesity—Use with caution. May increase risk for side effects.
  • Hyperlipidemia, severe (high fats in the blood) or
  • Kidney disease, severe or
  • Liver disease, severe—Should not be used in patients with these conditions.

How is this medicine (Acitretin) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take acitretin with food.
  • Take this medicine at the same time of day.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Special Populations Renal Function Impairment

Plasma concentrations are lower in end-stage renal failure. Acitretin is not removed by dialysis.

Storage

Store between 15°C to 25°C (59°F to 77°F). Avoid high temperatures and humidity. Protect from light.

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 administration of SORIATANE resemble those of the hypervitaminosis A syndrome.

Adverse Events/Postmarketing Reports

In addition to the events listed in the tables for the clinical trials, the following adverse events have been identified during postapproval use of SORIATANE. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular

Acute myocardial infarction, thromboembolism (see WARNINGS), stroke.

Immune System Disorders

Hypersensitivity, including angioedema and urticaria (see CONTRAINDICATIONS).

Nervous System

Myopathy with peripheral neuropathy has been reported during therapy with SORIATANE. 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. Madarosis and exfoliative dermatitis/erythroderma have been reported (see WARNINGS).

Vascular Disorders

Capillary leak syndrome (see WARNINGS).

Clinical Trials

During clinical trials with SORIATANE, 513 of 525 (98%) subjects reported a total of 3,545 adverse events. One-hundred sixteen subjects (22%) left trials prematurely, primarily because of adverse experiences involving the mucous membranes and skin. Three subjects died. Two of the deaths were not drug-related (pancreatic adenocarcinoma and lung cancer); the other subject died of an acute myocardial infarction, considered remotely related to drug therapy. In clinical trials, SORIATANE was associated with elevations in liver function test results or triglyceride levels and hepatitis.

The tables below list by body system and frequency the adverse events reported during clinical trials of 525 subjects with psoriasis.

Table 3: Adverse Events Frequently Reported during Clinical Trials Percent of Subjects Reporting (N = 525)

Body System > 75% 50% to 75% 25% to 50% 10% to 25%
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 Subjects Reporting (N = 525)

Body System 1% to 10%   < 1%
Body as a Whole Anorexia Edema Fatigue Hot flashes Increased appetite   Alcohol intolerance Dizziness Fever Influenza-like symptoms Malaise Moniliasis Muscle weakness Weight increase
Cardiovascular Flushing   Chest pain Cyanosis Increased bleeding time Intermittent claudication Peripheral ischemia
CNS (also see Psychiatric) Headache Pain   Abnormal gait Migraine Neuritis Pseudotumor cerebri (intracranial hypertension)
Eye Disorders Abnormal/ blurred vision Blepharitis Conjunctivitis/ irritation Corneal epithelial abnormality Decreased night vision/night blindness Eye abnormality Eye pain Photophobia Abnormal lacrimation Chalazion Conjunctival hemorrhage Corneal ulceration Diplopia Ectropion Itchy eyes and lids Papilledema Recurrent sties Subepithelial corneal lesions
Gastrointestinal Abdominal pain Diarrhea Nausea Tongue disorder   Constipation Dyspepsia Esophagitis Gastritis Gastroenteritis Glossitis Hemorrhoids Melena Tenesmus Tongue ulceration
Liver and Biliary     Hepatic function abnormal Hepatitis Jaundice  
Mucous Membranes Gingival bleeding Gingivitis Increased saliva Stomatitis Thirst Ulcerative stomatitis Altered saliva Anal disorder Gum hyperplasia Hemorrhage Pharyngitis
Musculoskeletal Arthritis Arthrosis Back pain Hypertonia Myalgia Osteodynia Peripheral joint hyperostosis (progression of existing lesions) Bone disorder Olecranon bursitis Spinal hyperostosis (new lesions) Tendonitis  
Psychiatric Depression Insomnia Somnolence   Anxiety Dysphonia Libido decreased Nervousness  
Reproductive     Atrophic vaginitis Leukorrhea  
Respiratory Sinusitis   Coughing Increased sputum Laryngitis  
Skin and Appendages Abnormal skin odor Abnormal hair texture Bullous eruption Cold/clammy skin Dermatitis Increased sweating Infection Psoriasiform rash Purpura Pyogenic granuloma Rash Seborrhea Skin fissures Skin ulceration Sunburn Acne Breast pain Cyst Eczema Fungal infection Furunculosis Hair discoloration Herpes simplex Hyperkeratosis Hypertrichosis Hypoesthesia Impaired healing Otitis media Otitis externa Photosensitivity reaction Psoriasis aggravated Scleroderma Skin nodule Skin hypertrophy Skin disorder Skin irritation Sweat gland disorder Urticaria Verrucae
Special Senses/ Other Earache Taste perversion Tinnitus   Ceruminosis Deafness Taste loss  
Urinary     Abnormal urine Dysuria Penis disorder  

Laboratory

Therapy with SORIATANE induces changes in liver function tests in a significant number of patients. Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 subjects treated with SORIATANE. In most subjects, elevations were slight to moderate and returned to normal either during continuation of therapy or after cessation of treatment. In subjects receiving SORIATANE during clinical trials, 66% and 33% experienced elevation in triglycerides and cholesterol, respectively. Decreased high density lipoproteins (HDL) occurred in 40% (see WARNINGS). Transient, usually reversible elevations of alkaline phosphatase have been observed.

Table 5 lists the laboratory abnormalities reported during clinical trials.

Table 5: Abnormal Laboratory Test Results Reported during Clinical Trials Percent of Subjects Reporting

Body System 50% to 75% 25% to 50% 10% to 25% 1% to 10%
Electrolytes     Increased: -Phosphorus -Potassium -Sodium Increased and decreased: -Magnesium Decreased: -Phosphorus -Potassium -Sodium Increased and decreased: -Calcium -Chloride
Hematologic   Increased: -Reticulocytes Decreased: -Hematocrit -Hemoglobin -WBC Increased: -Haptoglobin -Neutrophils -WBC Increased: -Bands -Basophils -Eosinophils -Hematocrit -Hemoglobin -Lymphocytes -Monocytes Decreased: -Haptoglobin -Lymphocytes -Neutrophils -Reticulocytes Increased or decreased: -Platelets -RBC
Hepatic   Increased: -Cholesterol -LDH -SGOT -SGPT Decreased: -HDL cholesterol Increased: -Alkaline phosphatase -Direct bilirubin -GGTP Increased: -Globulin -Total bilirubin -Total protein Increased and decreased: -Serum albumin
Miscellaneous Increased: -Triglycerides Increased: -CPK -Fasting blood sugar Decreased: -Fasting blood sugar -High occult blood Increased and decreased: -Iron
1
Renal     Increased: -Uric acid Increased: -BUN -Creatinine
Urinary   WBC in urine Acetonuria Hematuria RBC in urine Glycosuria Proteinuria

Clinical pharmacology

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 trials. After administration of a single 50-mg oral dose of acitretin to 18 healthy subjects, maximum plasma concentrations ranged from 196 to 728 ng per mL (mean: 416 ng per 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 trial of acitretin pharmacokinetics in subjects 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 per mL) in all subjects 3 weeks after cessation of therapy.

Elderly

In a multiple-dose trial in healthy young (n = 6) and elderly (n = 8) subjects, a 2fold 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 subjects with end-stage renal failure (n = 6) when compared with 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 2-way crossover trial, 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 per kg body weight). A mean peak etretinate concentration of 59 ng per mL (range: 22 to 105 ng per mL) was observed, and extrapolation of AUC values indicated that the formation of etretinate in this trial 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 subjects on acitretin therapy in several foreign trials (10 to 80 mg per day), 16% had measurable etretinate levels ( > 5 ng per mL).

Etretinate has a much longer elimination half-life compared with that of acitretin. In one trial the apparent mean terminal half-life after 6 months of therapy was approximately 120 days (range: 84 to 168 days). In another trial of 47 subjects treated chronically with etretinate, 5 had detectable serum drug levels (in the range of 0.5 to 12 ng per 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 progestin-only contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Clinical Studies

In 2 double-blind, placebo-controlled trials, SORIATANE was administered once daily to subjects with severe psoriasis (e.g., covering at least 10% to 20% of the body surface area). At 8 weeks (see Table 1) subjects treated in Trial A with 50 mg of 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 Trial 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 Trial B that no statistical adjustment for multiplicity was carried out.

Table 1: Summary of the Efficacy Results of the 8-Week Double-Blind Phase of Trials A and B of SORIATANE

Efficacy Variables Trial A Trial B
Total Daily Dose Total Daily Dose
Placebo
(N = 29)
50 mg
(N = 29)
Placebo
(N = 72)
25 mg
(N = 74)
50 m
g (N = 71)
Physician’s Global Evaluation
Baseline 4.62 4.55 4.43 4.37 4.49
Mean Change After 8 Weeks -0.29 -2.00a -0.06 -1.06a -1.57a
Scaling
Baseline 4.10 3.76 3.97 4.11 4.10
Mean Change After 8 Weeks -0.22 -1.62a -0.21 -1.50a -1.78a
Thickness
Baseline 4.10 4.10 4.03 4.11 4.20
Mean Change After 8 Weeks -0.39 -2.10 a -0.18 -1.43 a -2.11 a
Erythema
Baseline 4.21 4.59 4.42 4.24 4.45
Mean Change After 8 Weeks -0.33 -2.10a -0.37 -1.12a -1.65a
a Values were statistically significantly different from placebo and from baseline (P ≤ 0.05). No adjustment for multiplicity was done for Trial 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 7-point scale (0 = none, 1 = trace, 2 = mild, 3 = mild-moderate, 4 = moderate, 5 = moderate-severe, 6 = severe).

A subset of 141 subjects from both pivotal Trials 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 Therapy with SORIATANE (24 Weeks)

Variables Trial A Trial B
Mean Total Daily Dose of SORIATANE (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 -2.26a -2.60a
Scaling N = 59 N = 132
Baseline 3.97 4.07
Mean Change From Baseline -2.15a -2.42a
Thickness N = 59 N = 132
Baseline 4.00 4.12
Mean Change From Baseline -2.44 a -2.66 a
Erythema N = 59 N = 132
Baseline 4.35 4.33
Mean Change From Baseline -2.31a -2.29a
a 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 7-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 subjects from Trial A treated for a second, 6-month maintenance course of therapy (for a total of 12 months of treatment); a small subset of subjects (n = 4) from Trial A continued to improve after a third 6-month course of therapy (for a total of 18 months of treatment).

REFERENCES

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

Acitretin Overview

Acitretin is a prescription medication used to treat severe psoriasis. This medication belongs to a group of drugs called retinoids. The exact way it works is unknown.

Acitretin comes in capsule form. It is usually taken once daily with food.

Common side effects include dry skin, chapped lips, and hair loss.

Do not take acitretin if you are pregnant or plan to become pregnant within the next 3 years. This medication may harm the fetus. You should not begin taking acitretin until you have taken two pregnancy tests with negative results.

Your doctor will give you a Patient Agreement/Informed Consent to read and sign before you begin treatment. Be sure to read this carefully and ask your doctor if you have any questions.

Acitretin FDA Warning

Warning:

For female patients:

Do not take acitretin if you are pregnant or plan to become pregnant within the next 3 years. Acitretin may harm the fetus. You should not begin taking acitretin until you have taken two pregnancy tests with negative results. You must use two acceptable forms of birth control for 1 month before you begin taking acitretin, during your treatment with acitretin, and for 3 years after treatment. Your doctor will tell you which methods of birth control are acceptable. You do not need to use two methods of birth control if you have had a hysterectomy (surgery to remove the womb), if your doctor tells you that you have finished menopause (change of life), or if you practice total sexual abstinence.

If you plan to use oral contraceptives (birth control pills) while taking acitretin, tell your doctor the name of the pill you will use. Acitretin interferes with the action of microdosed progestin ('minipill') oral contraceptives. Do not use this type of birth control while taking acitretin. If you plan to use hormonal contraceptives (birth control pills, patches, implants, injections, and intrauterine devices), be sure to tell your doctor about all the medications, vitamins, and herbal supplements you are taking. Many medications interfere with the action of hormonal contraceptives. Do not take St. John's wort if you are using any type of hormonal contraceptive.

You will need to take pregnancy tests regularly during your treatment with acitretin and for at least 3 years after taking acitretin. Stop taking acitretin and call your doctor immediately if you become pregnant, miss a menstrual period, or have sex without using two forms of birth control. In some cases, your doctor can prescribe emergency contraception ('the morning after pill') to prevent pregnancy.

Do not consume foods, drinks, or prescription or nonprescription medications that contain alcohol while taking acitretin and for 2 months after treatment. Alcohol and acitretin combine to form a substance that remains in the blood for a long time and can harm the fetus. Read medication and food labels carefully and ask your doctor or pharmacist if you are not sure whether a medication contains alcohol.

Your doctor will give you a Patient Agreement/Informed Consent to read and sign before you begin treatment. Be sure to read this carefully and ask your doctor if you have any questions.

For male patients:

A small amount of acitretin is present in the semen of male patients who take this medication. It is not known whether this small amount of medication can harm the fetus. Talk to your doctor about the risks of taking this medication if your partner is pregnant or plans to become pregnant.

For male and female patients:

Do not donate blood while taking acitretin and for 3 years after treatment.

Acitretin may cause liver damage. Tell your doctor if you have or have ever had liver disease. If you experience any of the following symptoms, call your doctor immediately: nausea, vomiting, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, or dark urine.

Liver Dose Adjustments

Severe liver impairment: Contraindicated

Other Comments

Administration advice:
-This drug should be administered with meals.

Storage requirements:
-Protect from light
-Exposure to high temperatures and humidity should be avoided after the bottle is opened.

General:
-A medication guide must be given to the patient each time acitretin is dispensed, as required by law.

Monitoring:
-Hepatic: Liver function (prior to and during therapy)
-Metabolic: Lipid levels (baseline and every 1 to 2 weeks)
-Neurologic: Signs and symptoms of pseudotumor cerebri
-Women of child-bearing potential: Pregnancy tests prior to starting therapy, during treatment, and every 1 to 3 months for 2 years after therapy discontinuation.

Acitretin Pregnancy Warnings

Animal studies have shown this drug to be embryotoxic and/or teratogenic. There are no controlled data in human pregnancy. Major human fetal abnormalities associated with acitretin and/or etretinate administration have been reported including meningomyelocele; meningoencephalocele; multiple synostoses; facial dysmorphia; syndactyly; absence of terminal phalanges; malformations of hip, ankle, and forearm; low-set ears; high palate; decreased cranial volume; cardiovascular malformation; and alterations of the skull and cervical vertebrae. Female patients should not be pregnant when therapy is initiated, they should not become pregnant while taking this drug, and for at least 3 years after therapy termination. Additionally, females of reproductive potential should be advised that they should not consume beverages or products containing ethanol while on therapy and for 2 months after drug has been discontinued. 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 this drug. Samples of seminal fluid from male patients treated with this drug have been assayed for the presence of acitretin. The maximum concentration of acitretin observed in the seminal fluid of these men was 12.5 ng/mL. Although it appears that residual acitretin in seminal fluid poses little, if any, risk to a fetus while a male patient is taking the drug or after it is discontinued, the no-effect limit for teratogenicity is unknown and there is no registry for birth defects associated with acitretin. AU TGA pregnancy category X: Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy. US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

This drug is contraindicated in women of reproductive potential. AU TGA pregnancy category: X US FDA pregnancy category: X

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