Generic Name: Tretinoin
Trade Name: Vesanoid ^®
Other Name: All-trans retinoic acid

Drug Type:

ATRA is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug.  ATRA is classified as a "retinoid."  (For more detail, see "How ATRA Works" section below).

What ATRA Is Used For:

• ATRA is used to treat acute promyelocytic leukemia (APL, APML).

Note:  If a drug has been approved for one use, physicians sometimes elect to use this same drug for other problems if they believe it might be helpful.

How ATRA Is Given:

• ATRA is given by mouth (in capsule form).  
• One size capsule - 10mg, do not crush chew or dissolve capsules. Protect from light.
• Take ATRA with food. 
• It also is used as a lotion (topical) for patients with acne and certain rashes.
• The amount of ATRA you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer you have.  Your doctor will determine your dosage and schedule.

Side Effects of ATRA:

Important things to remember about the side effects of ATRA:

• Most people do not experience all of the side effects listed.
• Side effects are often predictable in terms of their onset and duration. 
• Side effects are almost always reversible and will go away after treatment is complete.
• There are many options to help minimize or prevent side effects.
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication.

The following side effects are common (occurring in greater than 30%) for patients taking ATRA:

• Typical retinoid toxicity (symptoms that are similar to those found in patients taking high doses of vitamin A): Headache, fever, dry skin, dry mucous membranes (mouth, nose), bone pain, nausea and vomiting, rash, mouth sores, itching, sweating, eyesight changes
• Flu-like symptoms: malaise, chills
• Bleeding problems
• Infections
• Swelling of feet or ankles
• Pain (bone and joint pain, chest discomfort)
• Abdominal pain

The following are less common side effects (occurring in 10-29%) for patients receiving ATRA:

• Weight increase
• Heart rate irregularities (arrhythmias - see heart problems)
• Flushing 
• Poor appetite
• Weight loss 
• Earache or feeling of fullness in the ears
• Diarrhea
• Dizziness
• Constipation
• Numbness and tingling in hands and feet
• Anxiety 
• Heartburn
• Low blood pressure 
• Insomnia
• Depression
• High blood pressure 
• Confusion 

A very serious side effect that is preventable with proper monitoring and immediate treatment is APL differentiation syndrome.  This syndrome is a reaction between the drug and the leukemia.  This syndrome produces fever, difficulty breathing, weight gain, lung and heart problems.  It is generally treated with high-dose steroids.  In most cases, treatment with ATRA will continue.  Be sure to let your health care professional know if you experience fever of 100.4F or 38C, difficulty breathing, or sudden weight gain.  The syndrome usually occurs during the first month of treatment, with some cases reported following the first dose.

Not all side effects are listed above, some that are rare (occurring in less than 10% of patients) are not listed here.  However, you should always inform your health care provider if you experience any unusual symptoms.

When To Contact Your Doctor or Health Care Provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.4° F (38° C), chills (possible signs of infection)
• Difficulty breathing, sudden weight gain, swelling, vision changes
• Any signs of bleeding, including black or tarry stools, or blood in your stools or urine
• Severe abdominal pain

The following symptoms require medical attention, but are not emergency situations.  Contact your health care provider within 24 hours of noticing any of the following:

• Nausea (interferes with ability to eat and unrelieved with prescribed medications)
• Vomiting (vomiting more than 4-5 times in a 24-hour period)
• Mouth sores (painful redness, swelling or ulcers)
• Diarrhea (4-6 episodes in a 24-hour period)
• Constipation unrelieved by laxative use
• Signs of infection such as redness or swelling, pain on swallowing, coughing up mucous, or painful urination.
• Swelling of the feet or ankles.
• Sudden weight gain
• Bone or joint pain
• Yellowing of the skin or eyes

Always inform your health care provider if you experience any unusual symptoms.

ATRA Precautions:

• Before starting ATRA treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).   
• Do not receive any kind of immunization or vaccination without your doctor's approval while taking ATRA.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment.  Pregnancy category D (ATRA may be hazardous to the fetus.  Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
• Because of the extremely high risk that a deformed infant can result if pregnancy occurs while taking ATRA in any amount even for short periods of time, for both men and women: Do not conceive a child (get pregnant) while taking ATRA. Two methods of effective contraception are recommended for women of childbearing potential, unless absolute abstinence is the chosen method.  Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
• Do not breast feed while taking ATRA.

ATRA Self Care Tips:

• Drink 2 to 3 quarts of fluid every 24 hours, unless you were told to restrict your fluid intake, and maintain good nutrition. This will decrease your chances of being constipated, and prevent dehydration.
• When you start taking ATRA, you may become dizzy, confused, anxious, or extremely tired. Do not attempt to drive or operate heavy machinery, unless you know how you will respond to ATRA.
• Avoid wearing contact lenses if you have dry or irritated eyes.
• Avoid sun exposure.  Wear SPF 15 (or higher) sun block and protective clothing.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water.
• Keep your bowels moving. Your health care provider may prescribe a stool softener to help prevent constipation that may be caused by ATRA. 
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely.  You should discuss this with your doctor.
• Do not share your medicines with anyone. Keep out of reach of children.
• If you experience symptoms or side effects, be sure to discuss them with your health care team.  They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing While Taking ATRA:

You will be monitored regularly by your health care professional while you are taking ATRA to monitor side effects and check your response to therapy.  For women of childbearing age, a pregnancy test is required one week prior to beginning this therapy and every month during treatment.  Blood counts and lipid (fats, cholesterol) levels and liver function all need to be analyzed before treatment begins and regularly during treatment.  These are measured through blood tests. 

How ATRA Works:

Retinoids are drugs that are relatives of vitamin A.  Retinoids control normal cell growth, cell differentiation (the normal process of making cells different from each other), and cell death during embryonic development and in certain tissues later in life.  Retinoids effects on the cells are controlled by receptors on the nucleus of each cell (nuclear receptors). 

There are two major classes of retinoid nuclear receptors:  retinoic acid receptors (RAR) and retinoid-X-receptors (RXR).  There are also subtypes within each class.  Each of these types of receptors has different functions in different tissues.  The different retinoid drugs work by binding to different receptors; which, in turn, affect cell growth and differentiation.

Retinoids are relatively new types of anti-cancer drugs.  They have been used alone or in combination to treat a variety of cancers such as skin cancers, cutaneous T-cell lymphoma, acute promyelocytic leukemia, lung cancer, breast cancer, ovarian cancer, bladder cancer, kidney cancer, and head and neck cancers.  Retinoids have also been used experimentally in an attempt to prevent certain types of cancer.  There is ongoing research to determine their role in both cancer treatment and prevention.

Retinoids have been associated with side effects such as skin problems (dryness, peeling, itching, sun sensitivity), reversible elevation in liver enzymes, temporary abnormal lipid levels, low thyroid levels (hypothyroidism), and headaches.  Taking supplemental doses of vitamin A may increase the side effects.  Vitamin supplementation should be discussed with your physician.

Note:  We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

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