Soriatane Information
Soriatane (Acitretin) Description:
Soriatane (Acitretin) (acitretin), a retinoid, is available in 10 mg, 17.5 mg, 22.5 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.
Soriatane (Acitretin) Clinical Pharmacology:
The mechanism of action of Soriatane (Acitretin) is unknown.
Soriatane (Acitretin) Clinical Studies:
In two double-blind placebo controlled studies, Soriatane (Acitretin) 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 ) patients treated in Study A with 50 mg Soriatane (Acitretin) 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.
A subset of 141 patients from both pivotal Studies A and B continued to receive Soriatane (Acitretin) in an open fashion for up to 24 weeks. At the end of the treatment period, all efficacy variables, as indicated in , were significantly improved (p ≤ 0.01) from baseline, including extent of psoriasis, mean ratings of psoriasis severity and physician’s global evaluation.
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).
Soriatane (Acitretin) Indications And Usage:
Soriatane (Acitretin) is indicated for the treatment of severe psoriasis in adults. Because of significant adverse effects associated with its use, Soriatane (Acitretin) should be prescribed only by those knowledgeable in the systemic use of retinoids. In females of reproductive potential, Soriatane (Acitretin) 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 — Soriatane (Acitretin) 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.
Soriatane (Acitretin) Warnings:
(see also boxed )
The potential of Soriatane (Acitretin) therapy to induce hepatotoxicity was prospectively evaluated using liver biopsies in an open-label study of 128 patients. Pretreatment and posttreatment biopsies were available for 87 patients. A comparison of liver biopsy findings before and after therapy revealed 49 (58%) patients showed no change, 21 (25%) improved and 14 (17%) patients had a worsening of their liver biopsy status. For 6 patients, the classification changed from class 0 (no pathology) to class I (normal fatty infiltration; nuclear variability and portal inflammation; both mild); for 7 patients, the change was from class I to class II (fatty infiltration, nuclear variability, portal inflammation and focal necrosis; all moderate to severe); and for 1 patient, the change was from class II to class IIIb (fibrosis, moderate to severe). No correlation could be found between liver function test result abnormalities and the change in liver biopsy status, and no cumulative dose relationship was found.
Elevations of AST (SGOT), ALT (SGPT), GGT (GGTP) or LDH have occurred in approximately 1 in 3 patients treated with Soriatane (Acitretin) . Of the 525 patients treated in clinical trials in the US, treatment was discontinued in 20 (3.8%) due to elevated liver function test results. If hepatotoxicity is suspected during treatment with Soriatane (Acitretin) , the drug should be discontinued and the etiology further investigated.
Ten of 652 patients treated in US clinical trials of etretinate, of which acitretin is the active metabolite, had clinical or histologic hepatitis considered to be possibly or probably related to etretinate treatment. There have been reports of hepatitis-related deaths worldwide; a few of these patients had received etretinate for a month or less before presenting with hepatic symptoms or signs.
Blood lipid determinations should be performed before Soriatane (Acitretin) 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 (Acitretin) 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 (Acitretin) 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 (Acitretin) 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 (Acitretin) 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 (Acitretin) should be considered.
The eyes and vision of 329 patients treated with Soriatane (Acitretin) 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 (Acitretin) who is experiencing visual difficulties should discontinue the drug and undergo ophthalmologic evaluation.
Soriatane (Acitretin) Precautions
A description of the 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 booklet includes:
The program also includes a voluntary patient survey for women of childbearing potential to assess the effectiveness of the Soriatane (Acitretin) Pregnancy Prevention Program
Soriatane (Acitretin) Adverse Reactions:
Hypervitaminosis A produces a wide spectrum of signs and symptoms primarily of the mucocutaneous, musculoskeletal, hepatic, neuropsychiatric, and central nervous systems. Many of the clinical adverse reactions reported to date with Soriatane (Acitretin) administration resemble those of the hypervitaminosis A syndrome.
During clinical trials with Soriatane (Acitretin) , 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.
The tables below list by body system and frequency the adverse events reported during clinical trials of 525 patients with psoriasis.
Soriatane (Acitretin) 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 (Acitretin) . 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 (Acitretin) during clinical trials, 66% and 33% experienced elevation in triglycerides and cholesterol, respectively. Decreased high density lipoproteins (HDL) occurred in 40% (see ). Transient, usually reversible elevations of alkaline phosphatase have been observed.
Table 5
Soriatane (Acitretin) Overdosage:
In the event of acute overdosage, Soriatane (Acitretin) must be withdrawn at once. Symptoms of overdose are identical to acute hypervitaminosis A, ie, headache and vertigo. The acute oral toxicity (LD) 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.
1) Have a pregnancy test at the time of overdose; 2) Be counseled as per the boxed and sections regarding birth defects and contraceptive use for at least 3 years’ duration after the overdose.
Soriatane (Acitretin) Dosage And Administration:
There is intersubject variation in the pharmacokinetics, clinical efficacy and incidence of side effects with Soriatane (Acitretin) . 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 (Acitretin) 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 (Acitretin) is used with phototherapy, the prescriber should decrease the phototherapy dose, dependent on the patient’s individual response (see ).
Soriatane (Acitretin) How Supplied:
Brown and white capsules, 10 mg, imprinted "A-10 mg"; bottles of 30 (NDC 0145-0090-25).
Rich yellow capsules, 17.5 mg, imprinted "A-17.5 mg"; bottles of 30 (NDC 0145-3817-03).
Brown capsules, 22.5 mg, imprinted "A-22.5 mg"; bottles of 30 (NDC 0145-3821-03).
Brown and yellow capsules, 25 mg, imprinted "A-25 mg"; bottles of 30 (NDC 0145-0091-25).
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.
Soriatane (Acitretin) References:
Soriatane (Acitretin) Patient Agreement/informed Consent For Female Patients
*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.
_____________________________________________________________
(Patient’s name)
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
INITIAL: ___________
I now authorize my prescriber, ______________________________________________________, to begin my treatment with Soriatane (Acitretin) .
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 (Acitretin) and have answered those questions to the best of my ability.
Prescriber signature: _______________________________________
Date: __________________
March 2011
SRN:1PI
Soriatane (Acitretin) Medication Guide For Patients
[sor-RYE-uh-tane]
(acitretin)
CAPSULES
Read this Medication Guide carefully before you start taking Soriatane (Acitretin) and read it each time you get more Soriatane (Acitretin) . There may be new information.
The first information in this Guide is about birth defects and how to avoid pregnancy. 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.
Soriatane (Acitretin) Principal Display Panel
(acitretin) Capsules
30 Capsules
Store between 15and 25C (59 and 77F).
Protect from light. Avoid exposure to high temperatures and humidity after the bottle is opened.
PHARMACIST: PROVIDE A MEDICATION GUIDE WITH EACH PRESCRIPTION.
DO NOT COVER LOT AND EXPIRY.
Each capsule contains 10 mg acitretin.
Made in Switzerland Manufactured for
Stiefel Laboratories, Inc., RTP, NC 27709
10000000094999
Soriatane (Acitretin) Principal Display Panel
(acitretin) Capsules
30 Capsules
Store between 15and 25C (59 and 77F).
Protect from light. Avoid exposure to high temperatures and humidity after the bottle is opened.
Soriatane (Acitretin) is a registered trademark of Stiefel Laboratories, Inc.
PHARMACIST: PROVIDE A MEDICATION GUIDE WITH EACH PRESCRIPTION.
DO NOT COVER LOT AND EXPIRY.
Each capsule contains 17.5 mg acitretin.
Made in Switzerland Manufactured for
Stiefel Laboratories, Inc., RTP, NC 27709
10000000095054
Soriatane (Acitretin) Principal Display Panel
Soriatane (Acitretin) Principal Display Panel
(acitretin) Capsules
30 Capsules
Store between 15and 25C (59 and 77F).
Protect from light. Avoid exposure to high temperatures and humidity after the bottle is opened.
Soriatane (Acitretin) is a registered trademark of Stiefel Laboratories, Inc.
PHARMACIST: PROVIDE A MEDICATION GUIDE WITH EACH PRESCRIPTION.
DO NOT COVER LOT AND EXPIRY.
Each capsule contains 25 mg acitretin.
Made in Switzerland Manufactured for
Stiefel Laboratories, Inc., RTP, NC 27709
10000000095053
