Arsenic Trioxide for Injection (Marcan Pharmaceuticals): Uses, Side Effects and Dosage

Arsenic Trioxide for Injection may cause:

• A serious health problem called APL differentiation syndrome. This may cause blood cells problems and may lead to death. Get medical help right away if you have any symptoms of APL differentiation syndrome: fever, cough, difficulty in breathing, swelling in the arms or legs, sudden weight gain (of more than 5 kg), chest pain, signs of kidney problems like unable to pass urine, change in amount of urine passed; or signs of low blood pressure like dizziness or passing out. At the first sign that you are having APL differentiation syndrome, your healthcare professional will prescribe medication (such as dexamethasone) to treat the condition.

• serious heart problems (QT prolongation, torsades de pointes and complete atrioventricular block). These may lead to death.

  • Get medical help right away if you have an irregular or fast heartbeat or if you faint during your treatment with Arsenic Trioxide for Injection.
  • Before you begin treatment with Arsenic Trioxide for Injection, your healthcare professional will order tests: These tests may check:
  • the electrical activity of the heart (electrocardiogram also called ECG)

  • the level of:

    • essential minerals (electrolytes) like potassium, calcium, and magnesium
    • creatinine (a waste product made by your muscles as part of regular, everyday activity).
  • Talk with your healthcare professional if you are taking any drugs that may cause heart problems (prolonged QT). There are many drugs that can do this. See the Serious drugs interactions table below.
  • serious brain problems (encephalopathy) which may be more common if you do not have enough vitamin B1 in your body. These may lead to death.
  • For more information on these and other serious side effects, see the Serious side effects and what to do about them table, below.
  • You will receive Arsenic Trioxide for Injection under the care of a healthcare professional who has experience in treating people who have leukemia (cancer of the white blood cells).

• you are allergic or hypersensitive to arsenic or any of the nonmedicinal ingredients in Arsenic Trioxide for Injection (See What are the ingredients in Arsenic Trioxide for Injection?).
• you are pregnant or breastfeeding.

• have kidney problems
• have liver problems

• have or had any heart problems including irregular heartbeat. Arsenic Trioxide for Injection may cause a deadly type of heartbeat problems (QT prolongation, torsades de pointes). The chance of having heartbeat problems may be raised if you:

  • have a heart disease. These includes:

    • heart failure
    • QT/QTc prolongation or a family history of QT/QTc prolongation
    • a family history of sudden cardiac death at less than 50 years of age
  • are taking other medicines which are known to cause serious problems in heart rhythm
  • have low levels of potassium, calcium or magnesium in your blood
  • have diabetes

• Do NOT receive Arsenic Trioxide for Injection during pregnancy. Arsenic Trioxide for Injection may cause miscarriage and harm your unborn baby if received during pregnancy.

• If you are of an age where you could become pregnant:

  • your healthcare professional will have you take a pregnancy test before starting Arsenic Trioxide for Injection.
  • you must use an effective birth control during treatment with Arsenic Trioxide for Injection and for at least 6 months after the last dose.
  • ask your healthcare professional about options of effective birth control.
• If you become pregnant while receiving Arsenic Trioxide for Injection tell your healthcare professional right away. You and your healthcare professional will decide what is best for you and your baby.

• Arsenic can pass into your breastmilk and may harm your baby.
• Do NOT breast-feed while on Arsenic Trioxide for Injection and for 3 months after your last dose.

• arsenic may be present in your semen.
• if your sex partner is pregnant or may become pregnant, use a condom during your treatment with Arsenic Trioxide for Injection and for 3 months after receiving your last dose.

• the level of blood cells in your body.
• that your heart, liver, kidneys or lungs are working properly.
• your blood sugar level.
• your blood's ability to clot, and how long it takes to clot.
• the level of calcium, potassium, magnesium and other essential minerals (electrolytes) —like sodium in your blood.

Serious Drug Interactions

Do not receive Arsenic Trioxide for Injection with any medicine that may:

• have an unwanted effect on how well your heart works (QT prolongation).
• cause imbalance in essential minerals (electrolyte) in your body:

See the list of medicines below. There are many other medicines that may cause heart or electrolytes problems. Ask your healthcare professional.

• medicines that may have an unwanted effect on how well your heart works (QT prolongation). These may include.

  • antiarrhythmic medicines (used to treat irregular heart rhythm) such as: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dronedarone, flecainide, propafenone

  • medicines used to treat mood swings and other type of mental problems including schizophrenia, and depression. These include:

    • a class of medicine called antipsychotics such as: chlorpromazine, pimozide, haloperidol, droperidol, ziprasidone
    • a class of medicine called antidepressants such as: fluoxetine, citalopram, venlafaxine, amitriptyline, imipramine, maprotiline
  • opioid medicines (used to treat addiction or relieve severe pain) such as: methadone
  • antibiotics medicines (used to treat bacterial infections) such as: erythromycin, clarithromycin, telithromycin, moxifloxacin, levofloxacin, ciprofloxacin)
  • tacrolimus - used to prevent transplanted organ rejection
  • antimalarials medicines (used to treat malaria) such as: quinine, chloroquine
  • antifungal medicines (used to treat fungal infection) such as: ketoconazole,fluconazole, voriconazole
  • domperidone - used to treat gastrointestinal disorders
  • medicines used to treat asthma such as salbutamol
  • medicines used to relieve nausea and vomiting such as: dolasetron, ondansetron
  • medicines in a class called tyrosine kinase inhibitors (used to treat cancer), vandetanib, sunitinib, nilotinib, lapatinib
  • medicines in a class called histone deacetylase inhibitors (used to treat a type of skin cancer) such as vorinostat

• any medicines that cause imbalance in essential minerals (electrolytes) in your body:

  • diuretics (water pills)
  • medicines used to relieve and prevent constipation (laxatives and enemas)
  • amphotericin B
  • high dose corticosteroids
• previous use of anthracyclines medicines (used to treat cancer)

• in a healthcare setting under the care of a healthcare professional who has experience in treating people who have leukemia.
• as an infusion (drip) into your vein over 1 to 2 hours. However, the injection time may be longer if you have side effects during the infusion.

• Arsenic Trioxide for Injection is usually given once a day for a specific period of time.
• Your healthcare professional will work out the right dose of Arsenic Trioxide for Injection for you.
• Use Arsenic Trioxide for Injection as ordered by your healthcare professional. Follow all instructions closely.

• convulsions (seizures)
• muscle weakness
• trouble thinking as clearly or quickly as you normally do (confusion)

• eye irritation, blurred vision
• nausea, diarrhea, vomiting, stomach pain, constipation, indigestion (feeling full or bloated), bleeding in the mouth
• feeling weak or tired
• pain, redness or swelling where the shot was given
• decreased appetite
• pain (joint pain, muscle pain, bone pain, back pain, neck pain, pain in arm or leg)
• headache
• dizziness
• pins and needles feeling, reduced sense of touch, trembling
• trouble sleeping, feeling anxious
• skin irritation, itchiness, bruises, dry skin, redness
• sweating a lot
• flushing, pale skin

Heart problems, including:

• Prolonged QT interval

  (changes in the electrical system of your heart): dizziness, palpitations, fainting or near fainting, seizures

• Torsade de pointes (life-threatening irregular heartbeat)

Blood pressure problems

• Hypertension (high blood pressure): headaches, nosebleeds shortness of breath, fatigue, dizziness or fainting, chest pain or pressure, swelling in your ankles and legs, bluish colour to your lips and skin, racing pulse or heart palpitations
• hypotension (low blood pressure) lightheadedness or dizziness, feeling sick, blurred vision, generally feeling weak, fainting

Haemorrhage (bleeding):

signs include throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop.

You can report any suspected side effects associated with the use of health products to Health Canada by:

• Visiting the Web page on Adverse Reaction Reporting (https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect- canada/adverse-reaction-reporting.html) for information on how to report online, by mail or by fax; or
• Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice.