Drugs Details

Drugs Info of Vesanoid
Drugs Details
  • Drugs Type  : FDA
  • Date : 29th Jun 2015 03:02 am
  • Brand Name : Vesanoid
  • Generic Name : tretinoin (Pronunciation: TRET i noin)
Descriptions

VESANOID (tretinoin) is a retinoid that induces maturation of acute promyelocytic leukemia (APL) cells in culture. It is available in a 10 mg soft gelatin capsule for oral administration. Each capsule also contains beeswax, butylated hydroxyanisole, edetate disodium, hydrogenated soybean oil flakes, hydrogenated vegetable oils and soybean oil. The gelatin capsule shell contains glycerin, yellow iron oxide, red iron oxide, titanium dioxide, methylparaben and propylparaben.

Chemically, tretinoin is all-trans retinoic acid and is related to retinol (Vitamin A). It is a yellow to light orange crystalline powder with a molecular weight of 300.44.

The structural formula is as follows:

 

VESANOID® (tretinoin) Structural Formula Illustration

 

 

What are the possible side effects of tretinoin (Vesanoid)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • fever, breathing problems, weight gain, swelling of your hands or feet;
  • sudden and severe pain behind your eyes, with nausea, vomiting, and vision problems;
  • black, bloody, or tarry stools; or
  • vomit that looks like blood or coffee grounds.

Less serious side effects may include:

  • feeling tired or...

Read All Potential Side Effects and See Pictures of Vesanoid »

What are the precautions when taking tretinoin (Vesanoid)?

Before taking tretinoin, tell your doctor or pharmacist if you are allergic to it; or to vitamin A-related drugs (other retinoids such as isotretinoin); or if you have any other allergies. This product may contain inactive ingredients (such as soybean, paraben preservatives), which can cause allergic reactions or other problems. Some people who are allergic to peanuts may also be allergic to soy. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high cholesterol/triglycerides (blood fats).

This drug may cause dizziness, severe headaches, or vision changes. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can...

Read All Potential Precautions of Vesanoid »

Indications

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/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated. VESANOID (tretinoin) 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 therapywith VESANOID (tretinoin) .

Dosage Administration

The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first.

If after initiation of treatment of VESANOID (tretinoin) the presence of the t(15;17) translocation is not confirmed by cytogenetics and/or by polymerase chain reaction studies and the patient has not responded to VESANOID (tretinoin) , alternative therapy appropriate for acute myelogenous leukemiashould be considered.

VESANOID (tretinoin) is for the induction of remission only. Optimal consolidation or maintenance regimens have not been determined. All patients should, therefore, receive a standard consolidation and/or maintenance chemotherapy regimen for APL after induction therapy with VESANOID (tretinoin) , unless otherwise contraindicated.

How Supplied

VESANOID (tretinoin) is supplied as 10 mg capsules, two-tone (lengthwise), orange-yellow and reddish-brown and imprinted VESANOID (tretinoin) 10 ROCHE. Supplied in high-density polyethylene, opaque bottles of 100 capsules with child-resistant closure (NDC 0004-0250-01).

Store at 15° to 30°C (59° to 86°F). Protect from light.

Distributed by: Pharmaceuticals Roche Laboratories Inc. 340 kingsland street, Nutley, New Jersey 07110- 1199. Revised: July 2008. FDA Rev date: 7/1/2008

Side Effects

Virtually all patients experience some drug-related toxicity, especially headache, fever, weakness, and fatigue. These adverse effects are seldom permanent or irreversible nor do they usually require interruption of therapy. Some of the adverse events are common in patients with APL, includinghemorrhage, infections, gastrointestinal hemorrhage, disseminated intravascular coagulation, pneumonia, septicemia, and cerebral hemorrhage. The following describes the adverse events, regardless of drug relationship, that were observed in patients treated with VESANOID (tretinoin) .

Typical Retinoid Toxicity

The most frequently reported adverse events were similar to those described in patients taking high doses of vitamin A and included headache (86%), fever (83%), skin/mucous membrane dryness (77%), bone pain (77%), nausea/vomiting (57%), rash (54%), mucositis (26%), pruritus (20%), increased sweating (20%), visual disturbances (17%), ocular disorders (17%), alopecia (14%), skin changes (14%), changed visual acuity (6%), bone inflammation (3%), visual field defects (3%).

RA-APL Syndrome

APL patients treated with VESANOID (tretinoin) have experienced a potentially fatal 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 and has been observed with or without concomitant leukocytosis. Some patients have expired due to progressive hypoxemia and multi-organ failure. The syndrome generally occurs during the first month of treatment, with some cases reported following the first dose of VESANOID (tretinoin) . The management of the syndrome has not been defined rigorously, but high-dose steroids given at the first signs of the syndrome appear to reduce morbidity and mortality. Treatment with dexamethasone, 10 mg intravenously administered every 12 hours for 3 days or until resolution of symptoms, should be initiated without delay at the first suspicion of symptoms (one or more of the following: fever, dyspnea, weight gain, abnormal chest auscultatory findings or radiographic abnormalities). Sixty percent or more of patients treated with VESANOID (tretinoin) may require high-dose steroids because of these symptoms. The majority of patients do not require termination of VESANOID (tretinoin) therapy during treatment of the syndrome.

Body as a Whole

General disorders related to VESANOID (tretinoin) administration and/or associated with APL included malaise (66%), shivering (63%), hemorrhage (60%), infections (58%), peripheral edema (52%), pain (37%), chest discomfort (32%), edema (29%), disseminated intravascular coagulation (26%), weight increase (23%), injection site reactions (17%), anorexia (17%), weight decrease (17%), myalgia (14%), flank pain (9%), cellulitis (8%), face edema (6%), fluid imbalance (6%), pallor (6%), lymph disorders (6%),acidosis (3%), hypothermia (3%), ascites (3%).

Respiratory System Disorders

Respiratory system disorders were commonly reported in APL patients administered VESANOID (tretinoin) . The majority of these events are symptoms of the RA-APL syndrome (see boxed WARNINGS). Respiratory system adverse events included upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), expiratory wheezing (14%), lower respiratory tract disorders (9%), pulmonary infiltration (6%), bronchial asthma (3%),pulmonary edema (3%), larynx edema (3%), unspecified pulmonary disease (3%).

Ear Disorders

Ear disorders were consistently reported, with earache or feeling of fullness in the ears reported by 23% of the patients. Hearing loss and other unspecified auricular disorders were observed in 6% of patients, with infrequent (<1%) reports of irreversible hearing loss.

Gastrointestinal Disorders

GI disorders included GI hemorrhage (34%), abdominal pain (31%), other gastrointestinal disorders (26%), diarrhea (23%), constipation (17%),dyspepsia (14%), abdominal distention (11%), hepatosplenomegaly (9%),hepatitis (3%), ulcer (3%), unspecified liver disorder (3%).

Cardiovascular and Heart Rate and Rhythm Disorders

Arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%),phlebitis (11%), cardiac failure (6%) and for 3% of patients: cardiac arrest,myocardial infarction, enlarged heart, heart murmur, ischemia, stroke,myocarditis, pericarditis, pulmonary hypertension, secondarycardiomyopathy.

Central and Peripheral Nervous System Disorders and Psychiatric

Dizziness (20%), paresthesias (17%), anxiety (17%), insomnia (14%),depression (14%), confusion (11%), cerebral hemorrhage (9%), intracranialhypertension (9%), agitation (9%), hallucination (6%) and for 3% of patients: abnormal gait, agnosia, aphasia, asterixis, cerebellar edema, cerebellar disorders, convulsions, coma, CNS depression, dysarthria, encephalopathy, facial paralysis, hemiplegia, hyporeflexia, hypotaxia, no light reflex, neurologic reaction, spinal cord disorder, tremor, leg weakness, unconsciousness,dementia, forgetfulness, somnolence, slow speech.

Urinary System Disorders

Renal insufficiency (11%), dysuria (9%), acute renal failure (3%), micturitionfrequency (3%), renal tubular necrosis (3%), enlarged prostate (3%).

Miscellaneous Adverse Events

Isolated cases of erythema nodosum, basophilia and hyperhistaminemia, Sweet's syndrome, organomegaly, hypercalcemia, pancreatitis and myositishave been reported.

Additional Adverse Reactions Reported With VESANOID (tretinoin)

Cardiovascular

Cases of thrombosis (both venous and arterial) involving various sites (eg,cerebrovascular accident, myocardial infarction, renal infarct) have been reported rarely (see PRECAUTIONS: General).

Hematologic

Rare cases of thrombocytosis have been reported.

Skin

Genital ulceration

Miscellaneous Adverse Events

Rare cases of vasculitis, predominantly involving the skin, have been reported.

Interactions

Limited clinical data on potential drug interactions are available.

Drugs Metabolized By the Hepatic P450 System

As VESANOID (tretinoin) is metabolized by the hepatic P450 system, there is a potential for alteration of pharmacokinetics parameters in patients administered concomitant medications that are also inducers or inhibitors of this system. Medications that generally induce hepatic P450 enzymes include rifampicin, glucocorticoids, phenobarbital and pentobarbital. Medications that generally inhibit hepatic P450 enzymes include ketoconazole, cimetidine,erythromycin, verapamil, diltiazem and cyclosporine. To date there are no data to suggest that co-use with these medications increases or decreases either efficacy or toxicity of VESANOID (tretinoin) .

Agents Known to Cause Pseudotumor Cerebri/Intracranial Hypertension (Such as Tetracyclines)

VESANOID (tretinoin) may cause pseudotumor cerebri/intracranial hypertension. Concomitant administration of VESANOID (tretinoin) and agents known to cause pseudotumor cerebri/intracranial hypertension as well might increase the risk of this condition (see WARNINGS).

Vitamin A

As with other retinoids, VESANOID (tretinoin) must not be administered in combination with vitamin A because symptoms of hypervitaminosis A could be aggravated.

Anti-fibrinolytic Agents (Such as Tranexamic Acid, Aminocaproic Acid, or Aprotinin)

Cases of fatal thrombotic complications have been reported rarely in patients concomitantly treated with VESANOID (tretinoin) and anti-fibrinolytic agents. Therefore, caution should be exercised when administering VESANOID (tretinoin) concomitantly with these agents (see PRECAUTIONS: General).

Effect of Food

No data on the effect of food on the absorption of VESANOID (tretinoin) are available. The absorption of retinoids as a class has been shown to be enhanced when taken together with food.

Warnings

Pregnancy Category D - See Boxed WARNINGS

Tretinoin has teratogenic and embryotoxic effects in mice, rats, hamsters, rabbits and pigtail monkeys, and may be expected to cause fetal harm when administered to a pregnant woman. Tretinoin causes fetal resorptions and a decrease in live fetuses in all animals studied. Gross external, soft tissue and skeletal alterations occurred at doses higher than 0.7 mg/kg/day in mice, 2 mg/kg/day in rats, 7 mg/kg/day in hamsters, and at a dose of 10 mg/kg/day, the only dose tested, in pigtail monkeys (about 1/20, 1/4, and 1/2 and 4 times the human dose, respectively, on a mg/m2 basis).

There are no adequate and well-controlled studies in pregnant women. Although experience with humans administered VESANOID (tretinoin) is extremely limited, increased spontaneous abortions and major human fetal abnormalities related to the use of other retinoids have been documented in humans. Reported defects include abnormalities of the CNS, musculoskeletal system, external ear, eye, thymus and great vessels; and facial dysmorphia,cleft palate, and parathyroid hormone deficiency. Some of these abnormalities were fatal. Cases of IQ scores less than 85, with or without obvious CNS abnormalities, have also been reported. All fetuses exposed during pregnancy can be affected and at the present time there is no antepartum means of determining which fetuses are and are not affected.

Effective contraception must be used by all females during VESANOID (tretinoin) therapy and for 1 month following discontinuation of therapy. Contraception must be used even when there is a history of infertility ormenopause, unless a hysterectomy has been performed. Whenever contraception is required, it is recommended that two reliable forms of contraception be used simultaneously, unless abstinence is the chosen method. If pregnancy does occur during treatment, the physician and patient should discuss the desirability of continuing or terminating the pregnancy.

Patients Without the t(15;17) Translocation

Initiation of therapy with VESANOID (tretinoin) may be based on the morphological diagnosis of acute promyelocytic leukemia. Confirmation of the diagnosis of APL should be sought by detection of the t(15;17) genetic marker by cytogenetic studies. If these are negative, PML/RARα fusion should be sought using molecular diagnostic techniques. The response rate of other AML subtypes to VESANOID (tretinoin) has not been demonstrated; therefore, patients who lack the genetic marker should be considered for alternative treatment.

Retinoic Acid-APL (RA-APL) Syndrome

In up to 25% of patients with APL treated with VESANOID (tretinoin) , a syndrome occurs which can be fatal (see boxed WARNINGS and ADVERSE REACTIONS).

Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During VESANOID Treatment

See boxed WARNINGS.

Pseudotumor Cerebri

Retinoids, including VESANOID (tretinoin) , have been associated with pseudotumor cerebri (benign intracranial hypertension), especially in pediatric patients. The concomitant use of other agents known to cause pseudotumor cerebri/intracranial hypertension, such as tetracyclines, might increase the risk of this condition (see PRECAUTIONS: DRUG INTERACTIONS). Early signs and symptoms of pseudotumor cerebri includepapilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be evaluated for pseudotumor cerebri, and, if present, appropriate care should be instituted in concert with neurological assessment.

Lipids

Up to 60% of patients experienced hypercholesterolemia and/or hypertriglyceridemia, which were reversible upon completion of treatment. The clinical consequences of temporary elevation of triglycerides and cholesterol are unknown, but venous thrombosis and myocardial infarctionhave been reported in patients who ordinarily are at low risk for such complications.

Elevated Liver Function Test Results

Elevated liver function test results occur in 50% to 60% of patients during treatment. Liver function test results should be carefully monitored during treatment and consideration be given to a temporary withdrawal of VESANOID (tretinoin) if test results reach >5 times the upper limit of normal values. However, the majority of these abnormalities resolve without interruption of VESANOID (tretinoin) or after completion of treatment.

Precautions

General

VESANOID (tretinoin) has potentially significant toxic side effects in APL patients. Patients undergoing therapy should be closely observed for signs of respiratory compromise and/or leukocytosis (see boxed WARNINGS). Supportive care appropriate for APL patients, eg, prophylaxis for bleeding, prompt therapy for infection, should be maintained during therapy with VESANOID (tretinoin) .

There is a risk of thrombosis (both venous and arterial) which may involve any organ system, during the first month of treatment (see ADVERSE REACTIONS). Therefore, caution should be exercised when treating patients with the combination of VESANOID (tretinoin) and anti-fibrinolytic agents, such as tranexamic acid, aminocaproic acid or aprotinin (see DRUG INTERACTIONS).

The ability to drive or operate machinery might be impaired in patients treated with VESANOID (tretinoin) , particularly if they are experiencing dizziness or severe headache.

Microdosed progesterone preparations ("minipill") may be an inadequate method of contraception during treatment with VESANOID (tretinoin) .

Laboratory Tests

The patient's hematologic profile, coagulation profile, liver function test results, and triglyceride and cholesterol levels should be monitored frequently.

Carcinogenesis, Mutagenesis and Impairment of Fertility

No long-term carcinogenicity studies with tretinoin have been conducted. In short-term carcinogenicity studies, tretinoin at a dose of 30 mg/kg/day (about 2 times the human dose on a mg/m2 basis) was shown to increase the rate of diethylnitrosamine (DEN)-induced mouse liver adenomas and carcinomas. Tretinoin was negative when tested in the Ames and Chinese hamster V79 cell HGPRT assays for mutagenicity. A twofold increase in the sister chromatid exchange (SCE) has been demonstrated in human diploid fibroblasts, but other chromosome aberration assays, including an in vitroassay in human peripheral lymphocytes and an in vivo mouse micronucleus assay, did not show a clastogenic or aneuploidogenic effect. Adverse effects on fertility and reproductive performance were not observed in studies conducted in rats at doses up to 5 mg/kg/day (about 2/3 the human dose on a mg/m2 basis). In a 6-week toxicology study in dogs, minimal to marked testicular degeneration, with increased numbers of immature spermatozoa, were observed at 10 mg/kg/day (about 4 times the equivalent human dose in mg/m2).

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from VESANOID (tretinoin) in nursing infants, mothers should discontinue nursing prior to taking this drug.

Pediatric Use

There are limited clinical data on the pediatric use of VESANOID (tretinoin) . Of 15 pediatric patients (age range: 1 to 16 years) treated with VESANOID (tretinoin) , the incidence of complete remission was 67%. Safety and effectiveness in pediatric patients below the age of 1 year have not been established. Some pediatric patients experience severe headache and pseudotumor cerebri, requiring analgesic treatment and lumbar puncture for relief. Increased caution is recommended in the treatment of pediatric patients. Dose reduction may be considered for pediatric patients experiencing serious and/or intolerable toxicity; however, the efficacy and safety of VESANOID (tretinoin) at doses lower than 45 mg/m2/day have not been evaluated in the pediatric population.

Geriatric Use

Of the total number of subjects in clinical studies of VESANOID (tretinoin) , 21.4% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

OverDose

In case of overdose with VESANOID (tretinoin) , reversible signs of hypervitaminosis A (headache, nausea, vomiting, mucocutaneous symptoms) can appear. The maximal tolerated dose in patients with myelodysplastic syndrome or solid tumors was 195 mg/m2/day. The maximal tolerated dose inpediatric patients was lower at 60 mg/m2/day. Overdosage with other retinoids has been associated with transient headache, facial flushing, cheilosis, abdominal pain, dizziness and ataxia. These symptoms have quickly resolved without apparent residual effects.

There is no specific treatment in the case of an overdose; however, it is important that the patient be treated in a special hematological unit.

ContrainDications

VESANOID (tretinoin) is contraindicated in patients with a known hypersensitivity to VESANOID (tretinoin) , any of its components, or other retinoids. VESANOID (tretinoin) should not be given to patients who are sensitive to parabens, which are used as preservatives in the gelatin capsule.

Clinical Pharamacology

Mechanism of Action

Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. In APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

Pharmacokinetics

Tretinoin activity is primarily due to the parent drug. In human pharmacokinetics studies, orally administered drug was well absorbed into the systemic circulation, with approximately two-thirds of the administered radiolabel recovered in the urine. The terminal elimination half-life of tretinoin following initial dosing is 0.5 to 2 hours in patients with APL. There is evidence that tretinoin induces its own metabolism. Plasma tretinoin concentrations decrease on average to one-third of their day 1 values during 1 week of continuous therapy. Mean ± SD peak tretinoin concentrations decreased from 394 89 to 138 ± 139 ng/mL, while area under the curve (AUC) values decreased from 537 ± 191 ng·h/mL to 249 ± 185 ng·h/mL during 45 mg/m2 daily dosing in 7 APL patients. Increasing the dose to "correct" for this change has not increased response.

Absorption

A single 45 mg/m2 (~80 mg) oral dose to APL patients resulted in a mean SD peak tretinoin concentration of 347 ± 266 ng/mL. Time to reach peak concentration was between 1 and 2 hours.

Distribution

The apparent volume of distribution of tretinoin has not been determined. Tretinoin is greater than 95% bound in plasma, predominately to albumin. Plasma protein binding remains constant over the concentration range of 10 to 500 ng/mL.

Metabolism

Tretinoin metabolites have been identified in plasma and urine. Cytochrome P450 enzymes have been implicated in the oxidative metabolism of tretinoin. Metabolites include 13-cis retinoic acid, 4-oxo trans retinoic acid, 4-oxo cis retinoic acid, and 4-oxo trans retinoic acid glucuronide. In APL patients, daily administration of a 45 mg/m2 dose of tretinoin resulted in an approximately tenfold increase in the urinary excretion of 4-oxo trans retinoic acid glucuronide after 2 to 6 weeks of continuous dosing, when compared to baseline values.

Excretion

Studies with radiolabeled drug have demonstrated that after the oral administration of 2.75 and 50 mg doses of tretinoin, greater than 90% of the radioactivity was recovered in the urine and feces. Based upon data from 3 subjects, approximately 63% of radioactivity was recovered in the urine within 72 hours and 31% appeared in the feces within 6 days.

Special Populations

The pharmacokinetics of tretinoin have not been separately evaluated in women, in members of different ethnic groups, or in individuals with renal or hepatic insufficiency.

Drug-Drug Interactions

In 13 patients who had received daily doses of tretinoin for 4 consecutive weeks, administration of ketoconazole (400 to 1200 mg oral dose) 1 hour prior to the administration of the tretinoin dose on day 29 led to a 72% increase (218 224 vs 375 ± 285 ng·h/mL) in tretinoin mean plasma AUC. The precise cytochrome P450 enzymes involved in these interactions have not been specified; CYP 3A4, 2C8 and 2E have been implicated in various preliminary reports.

Clinical Studies

VESANOID (tretinoin) has been investigated in 114 previously treated APL patients and in 67 previously untreated ("de novo") patients in one open-label, uncontrolled single investigator clinical study (Memorial Sloan-Kettering Cancer Center [MSKCC]) and in two cohorts of compassionate cases treated by multiple investigators under the auspices of the National Cancer Institute(NCI). All patients received 45 mg/m2/day as a divided oral dose for up to 90 days or 30 days beyond the day that CR was reached. Results are shown in the following table:

 

  MSKCC NCI COHORT 1 NCI COHORT 2
RELAPSED
N=20
DE NOVO
N=15
RELAPSED*
N=48
DE NOVO
N=14
RELAPSED
N=46
DE NOVO†
N=38
Complete Remission 16 (80%) 11 (73%) 24 (50%) 5 (36%) 24 (52%) 26 (68%)
Median Survival (Mo) 10.8 NR 5.8 0.5 8.8 NR
Median Follow-up (Mo) 9.9 42.9 5.6 1.2 8.0 13.1
RA-APL Syndrome 4 (20%) 5 (33%) 10 (21%) 6 (43%) NA NA
NR = Not Reached
NA = Not Available 
*Including 9 chemorefractory patients 
†Including 8 patients who received chemotherapy but failed to enter remission

 

The median time to CR was between 40 and 50 days (range: 2 to 120 days). Most patients in these studies received cytotoxic chemotherapy during the remission phase. These results compare to the 30% to 50% CR rate and ≤ 6 month median survival reported for cytotoxic chemotherapy of APL in the treatment of relapse.

Ten of 15 pediatric cases achieved CR (8 of 10 males and 2 of 5 females). There were insufficient patients of black, Hispanic or Asian derivation to estimate relative response rates in these groups, but responses were seen in each category.

Responses were seen in 3 of 4 patients for whom cytogenetic analysis failed to detect the t(15;17) translocation typically seen in APL. The t(15;17) translocation results in the PML/RARα gene, which appears necessary for this disease. Molecular genetic studies were not conducted in these cases, but it is likely they represent cases with a masked translocation giving rise to PML/RARα. Responses to tretinoin have not been observed in cases in which PML/RARα fusion has been shown to be absent.

Patient Information

No information provided. Please refer to the WARNINGS and PRECAUTIONSsections.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

TRETINOIN - ORAL

 

(TRET-i-noyn)

 

COMMON BRAND NAME(S): Vesanoid

 

WARNING: Tretinoin may cause serious (sometimes fatal) side effects. Therefore, it must be used only under close medical supervision. Some patients may develop a life-threatening syndrome, usually during the first month of treatment with this medication. Tell your doctor immediately if you experience any of the following symptoms: fever, trouble breathing, unusual tiredness, weight gain, swelling of the arms/legs/ankles/feet, dizziness, or fainting. You may be given other medications (e.g., corticosteroids such as dexamethasone) to treat these side effects. Your doctor will also monitor your white blood cell count.

This medication can cause severe birth defects if used during pregnancy. Therefore, this medication is not recommended for use during pregnancy. Also, it is important to prevent pregnancy while taking this drug. Pregnancy tests should be done one week before you start treatment with tretinoin. When possible, do not start tretinoin treatment until you have a negative pregnancy test result. As soon as treatment begins, you must immediately start using two effective forms of birth control together (or completely avoid sexual intercourse). However, do not use "mini-pills" (progesterone birth control pills that do not contain estrogen) because they may not work as well while you are taking tretinoin. You must also have monthly pregnancy testing and birth control counseling from your doctor while taking this medication. Continue using birth control as directed until one month after tretinoin use has been stopped.

 

USES: Tretinoin is used with other medications (e.g., chemotherapy) to treat a certain type of cancer of the white blood cells (APL-acute promyelocytic leukemia). APL is a disease of too many white blood cells that do not mature or function properly. This medication is used to lessen the signs and severity of this disease (induce remission). Further treatment after remission will be determined by your doctor. Tretinoin works by promoting the growth of normal, mature cells in the bone marrow and blood. This medication helps to reverse symptoms of APL such as infections, tiredness, and bleeding. Tretinoin belongs to a class of drugs known as retinoids, which are related to vitamin A.

 

HOW TO USE: Take this medication by mouth, usually twice a day or as directed by your doctor. It may be taken with food.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day. The dosage is based on your medical condition, body size, and response to therapy. Follow your doctor's directions for how long to take this medication.

Do not increase your dose or take this medication more often without your doctor's approval. Your condition will not improve any faster and the risk of serious side effects may be increased.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning section.

Headache, dizziness, fever, weakness, tiredness, dry mouth, dry skin, other skin changes, thinning hair, nausea, vomiting, itching, bone pain, mouth sores, increased sweating, and earache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Headache may occur several hours after taking a dose. Mild pain medications (e.g., acetaminophen) usually help relieve these headaches, which tend to go away as your body gets used to tretinoin. Talk with your doctor about which pain relievers are right for you.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

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 unlikely but serious side effects occur: stomach/abdominal pain, yellowing eyes/skin, dark urine, hearing problems (e.g., hearing loss), change in the amount of urine, mental/mood changes, fast/slow/irregular heartbeat.

Seek immediate medical attention if any of these rare but very serious side effects occur: severe headache, persistent nausea/vomiting, vision changes, chest pain, jaw/left arm pain, trouble breathing, weakness on one side of the body, slurred speech, confusion, pain/redness/swelling of arms/legs.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe 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.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Vesanoid (tretinoin) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking tretinoin, tell your doctor or pharmacist if you are allergic to it; or to vitamin A-related drugs (other retinoids such as isotretinoin); or if you have any other allergies. This product may contain inactive ingredients (such as soybean, paraben preservatives), which can cause allergic reactions or other problems. Some people who are allergic to peanuts may also be allergic to soy. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high cholesterol/triglycerides (blood fats).

This drug may cause dizziness, severe headaches, or vision changes. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

Children may be more sensitive to the effects of this drug, especially if they are also taking tetracycline medication. Tell your doctor immediately if your child experiences severe headache, nausea/vomiting, or vision problems.

Do not donate blood while you are taking this medication and for at least 1 month after you stop taking it. This will prevent the possibility of your blood being given to a pregnant woman.

This medication is not recommended for use during pregnancy due to the risk of birth defects and harm to an unborn baby. If you become pregnant or think you may be pregnant, inform your doctor immediately. Use two effective forms of birth control together to prevent pregnancy. Talk to your doctor about reliable birth control options. (See also Warning section.)

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

It is not known if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. 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 medication because very serious interactions may occur: vitamin A.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting tretinoin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that prevent bleeding (anti-fibrinolytic drugs such as aminocaproic acid, aprotinin, tranexamic acid), hydroxyurea, ketoconazole, "mini-pill" (progesterone birth control pills that do not contain estrogen), tetracyclines, sulfisoxazole containing drugs.

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 a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood counts, liver function, blood cholesterol and triglyceride levels, pregnancy tests) should be performed to monitor your progress or check for side effects. Consult your doctor for more details.

 

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

 

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from 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 September 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Vesanoid

Generic Name: tretinoin (Pronunciation: TRET i noin)

  • What is tretinoin (Vesanoid)?
  • What are the possible side effects of tretinoin (Vesanoid)?
  • What is the most important information I should know about tretinoin (Vesanoid)?
  • What should I discuss with my healthcare provider before taking tretinoin (Vesanoid)?
  • How should I use tretinoin (Vesanoid)?
  • What happens if I miss a dose (Vesanoid)?
  • What happens if I overdose (Vesanoid)?
  • What should I avoid while using tretinoin (Vesanoid)?
  • What other drugs will affect tretinoin (Vesanoid)?
  • Where can I get more information?

What is tretinoin (Vesanoid)?

 

Tretinoin is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.

Tretinoin is used to treat acute promyelocytic leukemia (a type of blood cancer).

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

What are the possible side effects of tretinoin (Vesanoid)?

 

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • fever, breathing problems, weight gain, swelling of your hands or feet;
  • sudden and severe pain behind your eyes, with nausea, vomiting, and vision problems;
  • black, bloody, or tarry stools; or
  • vomit that looks like blood or coffee grounds.

Less serious side effects may include:

  • feeling tired or weak;
  • headache;
  • fever;
  • dry skin, mouth, or nose;
  • bone pain;
  • nausea and vomiting;
  • rash or itching;
  • white patches or sores inside your mouth or on your lips;
  • increased sweating;
  • vision problems; or
  • hair loss or skin changes.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Vesanoid (tretinoin) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about tretinoin (Vesanoid)?

 

Do not use vitamin A supplements or multivitamins that contain vitamin A while you are taking tretinoin.

Do not use this medication without your doctor's consent if you are pregnant. It could cause harm to the unborn baby. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment.

Tretinoin can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Patient Detailed How Take

What should I discuss with my healthcare provider before taking tretinoin (Vesanoid)?

 

Before using tretinoin, tell your doctor if you have high cholesterol, or if you have ever had a reaction to another retinoid (such as Accutane, Retin-A, Renova).

If you have any of these conditions, you may not be able to use tretinoin, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category D. This medication can cause birth defects, miscarriage, premature birth, or death of a baby. Do not use tretinoin if you are pregnant. Tell your doctor right away if you miss a period or become pregnant during treatment. Use an effective form of birth control while you are using this medication and for at least 1 month after your treatment ends.

You may need to have a pregnancy test every month during your treatment. You must use effective birth control while you are taking tretinoin unless you have had a hysterectomy and no longer have a uterus. Use birth control even if you have been infertile (unable to have children) in the past, or if you have gone through menopause.

It is not known whether tretinoin passes into breast milk or if it could harm a nursing baby. Do not take tretinoin without telling your doctor if you are breast-feeding a baby.

How should I use tretinoin (Vesanoid)?

 

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor.

Take each dose with a full glass of water.

You may need to continue taking tretinoin for up to 90 days. Follow your doctor's instructions.

Store tretinoin at room temperature away from moisture, heat, and light.

Patient Detailed Avoid Taking

What happens if I miss a dose (Vesanoid)?

 

Contact your doctor if you miss a dose of tretinoin.

What happens if I overdose (Vesanoid)?

 

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include headache, dizziness, weakness, facial flushing, stomach pain, or dry, cracked lips.

What should I avoid while using tretinoin (Vesanoid)?

 

Do not use vitamin A supplements or multivitamins that contain vitamin A while you are taking tretinoin.

Tretinoin can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

What other drugs will affect tretinoin (Vesanoid)?

 

Before taking tretinoin, tell your doctor if you are using any of the following drugs:

  • cimetidine (Tagamet);
  • cyclosporine (Neoral, Sandimmune, Gengraf);
  • troleandomycin (Tao);
  • rifampin (Rifadin, Rimactane, Rifater);
  • phenobarbital (Luminal);
  • fluoxetine (Prozac), fluvoxamine (Luvox);
  • steroids (prednisone and others);
  • itraconazole (Sporanox), ketoconazole (Nizoral);
  • clarithromycin (Biaxin), erythromycin (Erythrocin, Ery-Tab, E.E.S.);
  • a tetracycline antibiotic such as minocycline (Dynocin, Minocin, Vectrin), doxycycline (Doryx, Vibramycin), demeclocycline (Declomycin);
  • amiodarone (Cordarone), mibefradil (Posicor), diltiazem (Tiazac, Cardizem), verapamil (Covera, Calan); or
  • HIV medicines such as indinavir (Crixivan), saquinavir (Invirase), ritonavir (Norvir), saquinavir (Invirase), or nelfinavir (Viracept).

This list is not complete and there may be other drugs that can interact with tretinoin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about tretinoin.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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