WARNINGS
1. Experienced Physician and Institution
Patients with acute promyelocytic leukemia (APL) are at high risk in general and can have severe adverse reactions to VESANOID (tretinoin). VESANOID should therefore be administered only to patients with APL under the strict supervision of a physician who is experienced in the management of patients with acute leukemia and in a facility with laboratory and supportive services sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity, including respiratory compromise. Use of VESANOID requires that the physician concludes that the possible benefit to the patient outweighs the following known adverse effects of the therapy.
2. Retinoic Acid-APL Syndrome
About 25% of patients with APL treated with VESANOID have experienced a syndrome called the retinoic acid-APL (RA-APL) syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural and pericardial effusions, edema, and hepatic, renal, and multi-organ failure. This syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multi-organ failure. The syndrome generally occurs during the first month of treatment, with some cases reported following the first dose of VESANOID.
The management of the syndrome has not been defined rigorously, but high-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality. At the first signs suggestive of the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg intravenously administered every 12 hours for 3 days or until the resolution of symptoms) should be immediately initiated, irrespective of the leukocyte count. The majority of patients do not require termination of VESANOID therapy during treatment of the RA-APL syndrome. However, in cases of moderate and severe RA-APL syndrome, temporary interruption of VESANOID therapy should be considered.
3. Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During VESANOID Treatment
During VESANOID treatment about 40% of patients will develop rapidly evolving leukocytosis. Patients who present with high WBC at diagnosis (>5×109/L) have an increased risk of a further rapid increase in WBC counts. Rapidly evolving leukocytosis is associated with a higher risk of life-threatening complications.
If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately. Some investigators routinely add chemotherapy to VESANOID treatment in the case of patients presenting with a WBC count of >5×109/L or in the case of a rapid increase in WBC count for patients leukopenic at start of treatment, and have reported a lower incidence of the RA-APL syndrome. Consideration could be given to adding full-dose chemotherapy (including an anthracycline if not contraindicated) to the VESANOID therapy on day 1 or 2 for patients presenting with a WBC count of >5×109/L, or immediately, for patients presenting with a WBC count of <5×109/L, if the WBC count reaches ≥6×109/L by day 5, or ≥10×109/L by day 10, or ≥15×109/L by day 28.
4. Teratogenic Effects.
Pregnancy Category D – see WARNINGS
There is a high risk that a severely deformed infant will result if VESANOID is administered during pregnancy. If, nonetheless, it is determined that VESANOID represents the best available treatment for a pregnant woman or a woman of childbearing potential, it must be assured that the patient has received full information and warnings of the risk to the fetus if she were to be pregnant and of the risk of possible contraception failure and has been instructed in the need to use two reliable forms of contraception simultaneously during therapy and for 1 month following discontinuation of therapy, and has acknowledged her understanding of the need for using dual contraception, unless abstinence is the chosen method
Within 1 week prior to the institution of VESANOID therapy, the patient should have blood or urine collected for a serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL. When possible, VESANOID therapy should be delayed until a negative result from this test is obtained. When a delay is not possible, the patient should be placed on two reliable forms of contraception. Pregnancy testing and contraception counseling should be repeated monthly throughout the period of VESANOID treatment.
|
| |
VESANOID SUMMARY
VESANOID®
(tretinoin)
CAPSULES
VESANOID (tretinoin) is a retinoid that induces maturation of acute promyelocytic leukemia (APL) cells in culture.
VESANOID (tretinoin) capsules are indicated for the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RAR(alpha) gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated. VESANOID is for the induction of remission only. The optimal consolidation or maintenance regimens have not been defined, but all patients should receive an accepted form of remission consolidation and/or maintenance therapy for APL after completion of induction therapy with VESANOID.
|
|
NEWS HIGHLIGHTS
Published Studies Related to Vesanoid (Tretinoin Oral)
Tretinoin cyclodextrin complex (RA/CyD) causes less irritation with an equal
antiwrinkle effect compared with conventional tretinoin: clinical and histologic
studies of photoaged skin. [2012]
the side effects compared with RA treatment alone... CONCLUSION: The findings show that RA and RA/CyD result in the equivalent
A randomized, double-blind, placebo-controlled, pilot study to assess the
efficacy and safety of clindamycin 1.2% and tretinoin 0.025% combination gel for
the treatment of acne rosacea over 12 weeks. [2012]
rosacea after 12 weeks of usage... CONCLUSIONS: A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025%
A randomized, double-blind, controlled comparative trial of the anti-aging
properties of non-prescription tri-retinol 1.1% vs. prescription tretinoin
0.025%. [2012]
Vitamin A and its derivatives (commonly termed retinoids) are widely used in
topical anti-aging products. Certain retinoids such as retinol and its esters are
available without a prescription, while others such as tretinoin are available
only via prescription... Subjects reported >93 percent overall satisfaction with
both products at weeks 8 and 12.
Further enhancement of facial appearance with a hydroquinone skin care system plus tretinoin in patients previously treated with botulinum toxin Type A. [2011.07]
BACKGROUND: A hydroquinone (HQ) skin care system has been designed for use in conjunction with nonsurgical procedures. OBJECTIVE: The authors evaluate the efficacy of this system plus tretinoin for improving facial appearance in comparison to a standard skin care regimen in users of botulinum toxin Type A (BoNT-A)... CONCLUSIONS: Adjunctive use of the HQ system plus tretinoin can further enhance the improvements in facial appearance attained with BoNT-A. Applying the HQ system plus tretinoin offers multiple clinical benefits over standard skin care, including significantly greater improvements in fine lines/wrinkles and hyperpigmentation.
Cortexolone 17alpha-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0.05% cream. [2011.07]
BACKGROUND: Acne vulgaris is a disorder of the pilosebaceous unit in which the androgens contribute to its onset and persistence. The use of antiandrogens is therefore potentially effective; however, antiandrogens for topical use are not available on the market. Cortexolone 17alpha-propionate (CB-03-01; Cosmo S.p.A, Lainate, Italy) is a new potent topical antiandrogen potentially useful in acne vulgaris. OBJECTIVES: To evaluate the safety and the topical efficacy of CB-03-01 1% cream in acne vulgaris as compared with placebo and with tretinoin 0.05% cream (Retin-A(R) ; Janssen-Cilag)... CONCLUSIONS: This pilot study supports the rationale for the use of topical antiandrogens in the treatment of acne vulgaris. CB-03-01 1% cream seems to fit with the profile of an ideal antiandrogen for topical use. (c) 2011 The Authors. BJD (c) 2011 British Association of Dermatologists 2011.
Clinical Trials Related to Vesanoid (Tretinoin Oral)
Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy [Recruiting]
The purpose of this study is to find what effects, good and/or bad, treatment with two drugs
has on leukemia. The first medicine is tretinoin (also called all-trans retinoic acid,
ATRA, or Vesanoid). It is an approved medicine that causes the leukemia cells in APL to
mature. It is related to vitamin A. The second is arsenic trioxide (Trisenox). It is an
approved medicine for APL that comes back after earlier treatment.
APL is most often treated with tretinoin and standard chemotherapy drugs. These
chemotherapy drugs can cause infection and bleeding. They can also damage the heart and
normal bone marrow cells. This can lead to a second leukemia years later.
In this study, the investigators are using tretinoin and arsenic trioxide together. Both
drugs work to treat APL. They have been used together in only a limited number of people.
The investigators want to use these drugs together to reduce the amount of standard
chemotherapy and decrease side effects. The patient will receive standard chemotherapy with
a drug called idarubicin only if they have a higher chance of the leukemia coming back or a
higher risk of side effects.
Comparison of Retinol 1.0% and Tretinoin 0.02% in the Treatment of Moderate to Severe Photodamage and Wrinkles [Recruiting]
The purpose of this study is to assess the comparative efficacy of retinol 1. 0% and
tretinoin 0. 02% in minimizing wrinkles, discoloration, roughness, and other signs of
moderate to severe photodamage. Our hypothesis is that both products will be of comparable
benefit.
A Study Comparing Combination Clindamycin Phosphate/Tretinoin Gel Alone Versus With Benzoyl Peroxide Foaming Cloths for Facial Acne [Recruiting]
There are many different factors that cause acne. So combination treatment using different
medications that can address these different factors is commonly used to treat acne.
Fixed-dose combination clindamycin phosphate 1. 2% and tretinoin 0. 025% gel and benzoyl
peroxide 6% foaming cloths are both used to treat acne. This study will evaluate the use of
the medications when used together.
A Comparative Study of Adapalene Gel,0.3% Versus Tretinoin Emollient Cream, 0.05% for the Treatment of Photoaging [Recruiting]
The purpose of this study is to:
1. Evaluate the efficacy of Adapalene gel 0. 3% compared to Tretinoin Emollient cream
0. 05%, reducing signs of cutaneous photoageing, measured trough photonumeric scale
evaluation, investigator evaluation of global response to treatment and subject's
evaluation of improvement.
2. Evaluate the safety and tolerability of Adapalene Gel 0. 3%, compared to Tretinoin
Emollient cream 0. 05% during 24 weeks of treatment.
The study has the clinical hypothesis that Adapalene Gel 0. 3% is as effective as Tretinoin
Emollient cream 0. 05% in the treatment of cutaneous photoaging.
Atralin Gel for the Treatment of Rosacea [Recruiting]
Erythematotelangiectatic rosacea is a type of rosacea that causes a red face often with
frequent flushing, topical sensitivity and prominent blood vessels. We think that long term
damage to skin from the sun (photodamage) may play a role in causing this type of rosacea.
Tretinoin is a topical medication that is known to improve photodamage. We want to find out
if Atralin (tretinoin 0. 05%) Gel used for up to 46 weeks will improve
erythematotelangiectatic rosacea (ETR).
Reports of Suspected Vesanoid (Tretinoin Oral) Side Effects
Retinoic Acid Syndrome (8),
Acute Promyelocytic Leukaemia Differentiation Syndrome (6),
Pyrexia (6),
Myositis (6),
Haemorrhage (5),
Infection (5),
Death (5),
Benign Intracranial Hypertension (5),
Myocardial Infarction (5),
Renal Failure (5), more >>
|
|
|
|
Page last updated: 2013-02-10
|
