Pronunciation:

TRET-i-noin

Brand Names:

• Vesanoid

Dosage Forms:

• Capsule, Liquid Filled

Warnings:

Patients with acute promyelocytic leukemia (APL) 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 a favorable risk benefit profile.Retinoic Acid-APL Syndrome: Patients treated with tretinoin have experienced 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. RA-APL has 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. RA-APL may occur during the first month of treatment, with some cases reported following the first dose of tretinoin. High-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality. At the first signs of RA-APL (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg IV 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, consider temporary interruption of therapy.Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During Tretinoin Treatment: Rapidly evolving leukocytosis may occur with therapy. Patients who present with high WBC at diagnosis (greater than 5x10(9)/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 greater than 5x10(9)/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 greater than 5x10(9)/L, or immediately, for patients presenting with a WBC count of less than 5x10(9)/L, if the WBC count reaches greater than or equal to 6x10(9)/L by day 5, or greater than or equal to 10x10(9)/L by day 10, or greater than or equal to 15x10(9)/L by day 28.Teratogenic Effects. 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 in 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 million international units/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 2 reliable forms of contraception. Pregnancy testing and contraception counseling should be repeated monthly throughout treatment .

Classifications:

Therapeutic—

Antineoplastic Agent

Chemical—

Retinoid

Uses of This Medicine:

Tretinoin belongs to the group of medicines known as retinoids (RET-i-noyds). It is used to treat a form of leukemia (acute promyelocytic leukemia [APL]).

Tretinoin has side effects that can be very serious. Be sure that you discuss with your doctor the good that this medicine can do as well as the risks of taking it.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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.

Children—

Studies in a limited number of children between 1 and 16 years of age have shown that children may be especially sensitive to the effects of this medicine, and may be more likely than adults to experience severe headaches and some other side effects during treatment.

Older adults—

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of tretinoin in the elderly with use in other age groups.

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.

Other 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 this medicine, 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 this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminocaproic Acid
• Aprotinin
• Carbamazepine
• Chlortetracycline
• Clarithromycin
• Demeclocycline
• Doxycycline
• Eravacycline
• Itraconazole
• Lymecycline
• Meclocycline
• Methacycline
• Minocycline
• Omadacycline
• Oxytetracycline
• Paclitaxel
• Paclitaxel Protein-Bound
• Palovarotene
• Rolitetracycline
• Sarecycline
• Tetracycline
• Tigecycline
• Tranexamic Acid

Using this medicine 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.

• Fluconazole
• Ketoconazole
• Voriconazole

Other interactions—

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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of This Medicine:

It is very important that you take tretinoin only as directed by your doctor . Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For acute promyelocytic leukemia (APL):
    • Adults—Dose is based on body size and must be determined by your doctor. The usual dose is 45 milligrams (mg) for each square meter of body surface area a day, given in two equally divided doses.
    • Children—The dose will be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If it is almost time for your next dose, check with your health care professional to find out how much medicine to take for the next dose.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine:

Your doctor should check your progress at regular visits to make sure that the medicine is working properly and to check for unwanted effects.

Tretinoin causes fever, headache, tiredness, and weakness in most people who take it. It is very important that you continue taking the medicine even if it makes you feel ill. Your health care professional may be able to suggest ways to relieve some of these effects. However, if you develop a very severe headache or a headache that occurs together with nausea, vomiting, or vision problems, check with your doctor right away.

Tretinoin sometimes causes a severe reaction that affects the lungs at first, but can later spread to other parts of the body. Signs of this reaction include breathing problems, bone pain, chest pain, and fever. Check with your doctor right away if any of these effects occur during treatment .

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Black, tarry stools

bleeding

blistering

bloody stools

bone pain

burning

coldness

difficulty in moving

discomfort or pain in chest

enlarged heart

feeling of pressure

fever

hives

infection

inflammation

joint pain

lumps

numbness

paleness of skin

rash

redness

scaring

seizures

shortness of breath, troubled breathing, tightness in chest, or wheezing

soreness

stinging

sweating increased

swelling

swollen joints

tenderness

tingling

ulceration

unusual tiredness or weakness

vomiting of blood or material that looks like coffee grounds

warmness at site

weight gain (occurring together with any of the other symptoms listed before)

Less common

Blue lips and fingernails

convulsions (seizures)

difficulty in speaking, slow speech, or inability to speak

faintness

feeling of heaviness in chest

headache (severe)

inability to move arms, legs, or muscles of the face

nausea and vomiting (occurring together with a headache)

no blood pressure or pulse

pain in back or left arm

painful, red lumps under the skin, mostly on the legs

prominent superficial veins over affected area

stopping of heart

unconsciousness

vision problems (occurring together with a headache)

warmth

Check with your doctor as soon as possible if any of the following side effects occur:

More common

Any change in vision (not occurring with a headache)

coughing, sneezing, sore throat, and stuffy or runny nose

cracked lips

crusting, redness, pain, or sores in mouth or nose

decreased urination

earache or feeling of fullness in the ear

increase or decrease in blood pressure

irregular heartbeat

mental depression

pain in stomach, side, abdomen or back

pain and swelling in leg or foot

skin rash

swelling of abdomen (stomach area)

swelling of face, fingers, hands, feet, or lower legs

Less common

Bone swelling

cramping or pain in stomach (severe)

difficult or painful urination

drowsiness (very severe and continuing)

hallucinations (seeing, hearing, or feeling things that are not there)

hearing loss

heartburn, indigestion, or nausea (severe and continuing)

mood, mental, or personality changes

pain in lower back or side

swollen area that feels sore and tender

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Acid or sour stomach

agitation

anxiety

belching

blurred vision

bloating

burning, crawling, or tingling feeling in the skin

chills

confusion

constipation

darkened urine

diarrhea

dizziness

dryness of skin, mouth, or nose

fast heartbeat

flushing

general feeling of discomfort or illness

hair loss

headache (mild and not occurring together with other side effects)

indigestion

irritability

itching of skin

loss of appetite

mood or mental changes

muscle pain

nausea and vomiting (not occurring together with a headache)

shivering

trouble sleeping

weakness

weight loss

Less common

Anxiety and restlessness (occurring together)

clumsiness or unsteadiness when walking

difficulty sleeping

disorientation

forgetfulness

frequent urination

lethargy

lightheadedness

low body temperature

redness, soreness or itching skin

sores, welting or blisters

sores on genitals

swelling of feet or lower legs

thirst

trembling, sometimes with a flapping movement

weak or feeble pulse

weakness in legs

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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