Vesanoid

Vesanoid is a prescription medication used to treat acute promyelocytic leukemia (APL).

Vesanoid belongs to a group of drugs called retinoids. These work to slows or stops the growth of cancer cells by causing immature blood cells to develop into normal blood cells.

Vesanoid comes as a capsule to take by mouth. It is usually taken twice a day for up to 90 days. Take Vesanoid at around the same times every day.

Common side effects of Vesanoid include headache, fever, weakness, and fatigue. Do not drive or operate heavy machinery until you know how this medication affects you.

Vesanoid is used to treat acute promyelocytic leukemia (APL) in people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. APL is a type of cancer in which there are too many immature blood cells in the blood and bone marrow. Vesanoid is used to produce remission (a decrease or disappearance of signs and symptoms of cancer) of APL, but other medications must be used after treatment with Vesanoid to prevent the cancer from returning.

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

Common side effects of Vesanoid include the following:

• headache
• fever
• fatigue
• weakness
• extreme tiredness
• shivering
• pain
• earache
• feeling of fullness in the ears
• dry skin
• rash
• hair loss
• constipation
• diarrhea
• stomach pain
• heartburn
• loss of appetite
• weight loss
• bone pain
• dizziness
• numbness, burning, or tingling in the hands or feet
• nervousness
• depression
• difficulty falling asleep or staying asleep
• confusion
• agitation
• hallucinating (seeing things or hearing voices that do not exist)
• difficulty urinating
• flushing

This is not a complete list of Vesanoid side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• thiazide diuretics
• tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Monodox, Vibramycin, others), minocycline (Minocin), oxytetracycline (Terramycin), and tetracycline (Sumycin, Tetrex, others)
• fluoroquinolone antibiotics
• ketoconazole (Nizoral)
• phenothiazine medications
• sulfonamide-containing medications
• aminocaproic acid (Amicar)
• certain calcium channel blockers such as diltiazem (Cardizem, Dilacor, Tiazac, others) and verapamil (Calan, Covera, Isoptin, Verelan)
• cimetidine (Tagamet)
• cyclosporine (Sandimmune, Gengraf, Neoral)
• erythromycin (E.E.S., Erythrocin, E-Mycin)
• hydroxyurea (Droxia)
• pentobarbital
• phenobarbital
• rifampin (Rifadin, Rimactane)
• oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone)
• tranexamic acid (Cyklokapron)
• vitamin A

This is not a complete list of all drug interactions. Ask your doctor or pharmacist for more information.

Do not use Vesanoid if:

• you are pregnant or plan to become pregnant
• you are sunburned or your skin is irritated
• you are highly sensitive to sunlight
• have eczema or other skin conditions
• you are allergic to any of the ingredients in Vesanoid

Vesanoid may cause severe side effects.

• Vesanoid may increase the levels of cholesterol and other fats in your blood and may stop your liver from working normally. Your doctor will monitor you carefully to see whether you are experiencing either of these side effects.
• Vesanoid should be given only under the supervision of a doctor who has experience in treating people who have leukemia (cancer of the white blood cells) and in a hospital where patients can be monitored for severe side effects and treated if these side effects occur.
• Vesanoid may cause a serious or life-threatening group of symptoms called retinoic acid-APL (RA-APL) syndrome. Your doctor will monitor you carefully to see whether you are developing this syndrome. If you experience any of the following symptoms, call your doctor immediately: fever; weight gain; swelling of the arms, hands, feet, ankles, or lower legs; shortness of breath; labored breathing; wheezing; chest pain; or cough. At the first sign that you are developing RA-APL syndrome, your doctor will prescribe one or more medications to treat the syndrome.
• Vesanoid may cause a rapid increase in the number of white blood cells in the body. This is associated with a higher risk of life-threatening side effects. If you have a very high number of white blood cells before you begin Vesanoid treatment, or if you have an increase in the number of white blood cells during your treatment with Vesanoid, especially if you experience any of the symptoms of RA-APL syndrome, your doctor may prescribe one or more medications to treat or prevent the increase in white blood cells.
• For female patients:
  • Vesanoid must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that Vesanoid will cause the baby to be born with birth defects (physical problems that are present at birth).
  • If you can become pregnant, you will need to avoid pregnancy during your treatment with Vesanoid. You must use two acceptable forms of birth control during your treatment and for 1 month after your treatment, even if you have infertility (difficulty becoming pregnant) or have experienced menopause ('change of life'; end of monthly menstrual periods). You must use these two forms of birth control at all times unless you can promise that you will not have any sexual contact with a male for 1 month after your treatment. Your doctor will tell you which forms of birth control are acceptable, and will give you full information about birth control.
  • If you plan to use oral contraceptives (birth control pills) while taking Vesanoid, tell your doctor the name of the pill you will use. Microdosed progestin ('minipill') oral contraceptives (Ovrette, Micronor, Nor-D) may not be an effective form of birth control for people who are taking Vesanoid.
  • You must have a negative pregnancy test within 1 week before you begin to take Vesanoid. You will also need to be tested for pregnancy in a laboratory each month during your treatment.
• Do not drive or operate heavy machinery until you know how this medication affects you.

Grapefruit and grapefruit juice may interact with this medication and can lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before taking Vesanoid, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Vesanoid or to any of its ingredients
• have eczema or other skin conditions
• have heart problems
• have elevated cholesterol levels
• have liver problems
• are pregnant or breastfeeding
• are using any other medicines to treat your acne. Do not use other medicines unless they are recommended by your doctor.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.
 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D.

• YOU MUST NOT BECOME PREGNANT DURING TREATMENT. There is an extremely high risk that a deformed baby will result if you become pregnant while taking Vesanoid, in any amount, for even short periods of time. Potentially any exposed fetus (unborn baby) can be affected. There is also an increased risk of miscarriage. Premature births may also occur.
• Effective contraception (birth control) should be discussed with your doctor. Two forms of reliable contraception must be used during therapy, and must be continued for one month after Vesanoid treatment has stopped. If directed by your doctor, two forms of reliable contraception must also be used simultaneously for at least one month before beginning therapy. It is recommended that you either abstain from sexual intercourse or use two reliable kinds of birth control at the same time. Birth control must be used even if you think you cannot become pregnant, unless you have had a hysterectomy.
• If you are pregnant or become pregnant while on Vesanoid therapy or during the month after treatment has stopped, immediately contact your doctor to discuss the desirability of continuing the pregnancy.

YOU MUST NOT TAKE  VESANOID IF YOU ARE A NURSING MOTHER.

Vesanoid should not be taken by nursing mothers since it is not known whether it is excreted in human milk. Since many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Vesanoid, mothers should discontinue nursing prior to taking this drug.

Vesanoid comes as a capsule to take by mouth. It is usually taken twice a day for up to 90 days. Take Vesanoid at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Vesanoid exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take Vesanoid even if you feel well. Do not stop taking Vesanoid without talking to your doctor.

The recommended dose is 45 mg/m2/day given as two evenly divided doses until complete remission is documented.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Vesanoid capsules: store at room temperature

Oral:

1.Experienced Physician and Institution

Patients with acute promyelocytic leukemia (APL) are at high risk in general and can have severe adverse reactions to tretinoin. Tretinoin 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 tretinoin 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 tretinoin 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 tretinoin.

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 tretinoin therapy during treatment of the RA-APL syndrome. However, in cases of moderate and severe RA-APL syndrome, temporary interruption of tretinoin therapy should be considered. 1

3.Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During Tretinoin Treatment

During tretinoin treatment about 40% of patients will develop rapidly evolving leukocytosis. Patients who present with high WBC at diagnosis (> 5x109/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 tretinoin treatment in the case of patients presenting with a WBC count of > 5x109/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 tretinoin therapy on day 1 or 2 for patients presenting with a WBC count of > 5x109/L, or immediately, for patients presenting with a WBC count of < 5x109/L, if the WBC count reaches ≥ 6x109/L by day 5, or ≥ 10x109/L by day 10, or ≥ 15x109/L by day 28.

4.Teratogenic Effects. Pregnancy Category D

There is a high risk that a severely deformed infant will result if tretinoin is administered during pregnancy. If, nonetheless, it is determined that tretinoin 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 tretinoin 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, tretinoin 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 tretinoin treatment.