Arsenic Trioxide

(ar-se-nik tri-OX-side)

Trade Name(s): Trisenox®

Arsenic trioxide is the generic name for the trade name drug Trisenox®. In some cases, health care professionals may use the trade name Trisenox® when referring to the generic drug name Arsenic Trioxide.

Drug type: Arsenic Trioxide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is classified as a "natural product." (For more detail, see "How Arsenic Trioxide works" section below).

What Arsenic Trioxide Is Used For:

• Acute promyelocytic leukemia (APL)

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 may be helpful.

How Arsenic Trioxide Is Given:

• Arsenic trioxide is administered via an intravenous (IV) injection over the course of one or two hours. This may be extended up to four hours if the patient has a vasomotor reaction (lightheadedness, change in blood pressure).

The amount of arsenic trioxide that you will receive depends on many factors, including: your height and weight, your general health or other health problems and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.

Side Effects of Arsenic Trioxide:

Important things to remember about the side effects of Arsenic Trioxide:

• Most people do not experience all of the side effects listed.
• Arsenic Trioxide's side effects are often predictable in terms of their onset and duration.
• Arsenic Trioxide's 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 arsenic trioxide:

• Nausea and vomiting
• Cough
• Fatigue
• Fever
• Headache
• Rapid heartbeat (tachycardia) (see heart problems)
• Abdominal pain
• Diarrhea
• Shortness of breath
• Blurred vision and eye irritation (see eye problems
• Blood test abnormalities (low potassium and magnesium) (elevated blood sugar level)
• Swelling of the face, hands, feet or legs (edema
• Sore throat (see cold symptoms)
• Difficulty sleeping (Insomnia)
• Rash (see skin reactions)
• Heart rhythm changes (seen on EKG tests) (see heart problems)
• Joint pain
• Itching
• Numbness or tingling of hands or feet
• Chills (see flu-like symptoms)
• Anxiety
• Shivering or a sudden feeling of cold
• Increase in the number of white blood cells in the blood

These side effects are less common side effects (occurring in about 10-29%) of patients receiving arsenic trioxide:

• Constipation
• Chest pain
• High blood pressure
• Low blood pressure
• Heart palpitations
• Decreased breath sounds and crackling or rattling breath sounds (see breathing problems)
• Pain/redness at the injection site
• Poor appetite
• Nosebleeds or Bruising (see bleeding problems)
• Depression
• Dyspepsia
• Muscle, bone or generalized pains
• Dizziness
• Post nasal drip or sinusitis (see cold symptoms)
• Altered blood liver enzyme levels (see liver problems)
• Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding.
• Blood count abnormalities (high potassium level) (low calcium level)
• Weight gain
• Vaginal bleeding (see bleeding problems)
• Dry skin (see skin reactions)
• A possible, but rare 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 and lung and heart problems. It is generally treated with high-dose steroids. In most cases, treatment with arsenic trioxide will continue. Be sure to let your health care professional know if you experience fever of 100.4°F or 38°C, difficulty breathing, or sudden weight gain.
• Another possible, but rare serious side effect that is preventable with proper monitoring is a condition called torsade de pointes. This condition is a result of worsening abnormal heart rhythm. A health care provider will need to do some tests to determine your risk and may have to stop some of your medications that may increase your chances of developing this condition. Be sure to let your health care provider know if you have a history of abnormal heart rhythm and seek care if you feel your heartbeat has changed in some way (heart beating faster or slower).

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) or higher, chills (possible signs of infection)
• Difficulty breathing or shortness of breath
• Sudden weight gain

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

• Nausea (interferes with ability to eat and unrelieved with prescribed medication)
• Vomiting (vomiting more than 4-5 times in a 24-hour period)
• Rapid heartbeat (recurrent or persistent - does not go away)
• Diarrhea (4-6 episodes in a 24-hour period)
• Unusual bleeding or bruising
• Black or tarry stools, or blood in your stools
• Extreme fatigue (unable to carry on self-care activities)

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

Precautions:

• Before starting arsenic trioxide treatment, make sure you tell your doctor about any other medications you are taking (including prescriptions, over-the-counter, vitamins, herbal remedies, etc.).
• Avoid seafood and homeopathic remedies as these may contain arsenic.
• Do not receive any kind of immunization or vaccination without your doctor's approval while taking arsenic trioxide.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (arsenic trioxide may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
• For both men and women: Do not conceive a child (get pregnant) while taking arsenic trioxide. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
• Do not breast feed while taking arsenic trioxide.
• Decreased sensation, numbness and tingling in fingers and toes may become progressively worse with repeated doses of arsenic trioxide. It is important to report this to your doctor.

Self-Care Tips:

• Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your health care provider.
• Wash your hands often.
• Tell dentists, surgeons and other doctors you use Arsenic Trioxide.
• 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.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sport or activities that could cause injury.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• Avoid sun exposure. Wear SPF 30 (or higher) sunblock and protective clothing.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition.
• 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.
• Use birth control that you trust to avoid pregnancy while taking Arsenic Trioxide.
• If you are male, use birth control to protect a female you are having sex with from becoming pregnant while you are using Arsenic Trioxide and for some time after stopping. Talk with your doctor about how long to use birth control after stopping Arsenic Trioxide.
• For flu-like symptoms, keep warm with blankets and drink plenty or liquids. There are medications that can help reduce the discomfort caused by chills.
• Acetaminophen or ibuprofen may help relieve discomfort from fever, headache and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.

Monitoring and testing while taking Arsenic Trioxide:

You will be checked regularly by your doctor while you are taking arsenic trioxide, to monitor effects and check your response to therapy. Periodic blood work to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) and your blood electrolytes will also be ordered by your doctor. The manufacturer recommends a baseline electrocardiogram (EKG) before starting this medication.

How Arsenic Trioxide Works:

Arsenic is a naturally occurring element widely distributed in the earth's crust. In the environment, arsenic is combined with oxygen, chlorine, and sulfur to form inorganic arsenic compounds. Arsenic in animals and plants combines with carbon and hydrogen to form organic arsenic compounds. Inorganic arsenic compounds are mainly used to preserve wood. Organic arsenic compounds are used as pesticides, primarily on cotton plants.

Arsenic cannot be destroyed in the environment; it can only change its form. Arsenic in the air will settle to the ground or is washed out of the air by rain. Many arsenic compounds can dissolve in water. Fish and shellfish can accumulate arsenic, but this arsenic is mostly in a form that is not harmful.

Exposure to arsenic can occur from eating food, drinking water, or breathing air containing arsenic. Breathing sawdust from wood treated with arsenic or breathing smoke from burning wood treated with arsenic is another way to be exposed to arsenic. Some areas of the world have high levels of arsenic in rock that can increase exposure to those living nearby.

Breathing high levels of inorganic arsenic can give you a sore throat or irritated lungs. Ingesting (swallowing) high levels of inorganic arsenic can result in death. Lower levels of arsenic can cause nausea and vomiting, decreased red and white blood cells, abnormal heart rhythm, and numbness and tingling in the hands and feet. Organic arsenic compounds are less toxic than inorganic arsenic. Exposure to high levels of organic arsenic may cause similar effects as inorganic arsenic.

Arsenic-containing preparations have been in medical use for more than 2000 years. Arsenic-based therapy was used in the United States and Europe more than 100 years ago to treat leukemia and infections, but modern chemotherapy and antibiotics replaced these treatments. More recently, interest in arsenic-based therapy was revived by reports of the anti-leukemic activity of some traditional Chinese preparations. Chinese scientists subsequently found out that the active ingredient was arsenic trioxide.

The mechanism of action of arsenic trioxide is not well understood. There is speculation that it causes death of leukemia cells via morphological changes and DNA fragmentation. Arsenic Trioxide also damages or degrades the fusion protein promyelocytic leukemia (PML) - retinoic acid receptor (RAR) alpha.

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.