Important Safety Information

What are the serious warnings and precautions about CONTRAVE^®?

Bupropion, one of the ingredients in CONTRAVE^®, is also used to treat depression. When you first start taking CONTRAVE^® or when your dose is adjusted, you may feel new or worsened feelings of depression, agitation, hostility, anxiety, or impulsivity.

It is important that you and your healthcare professional talk regularly during your treatment about how you are feeling.

You may find it helpful to tell relatives or close friends that you are taking this medicine to help you manage your weight. You might ask them to tell you if they are worried about changes in your behaviour.

If you experience changes in your behaviour, tell your healthcare professional right away.

Bupropion, one of the ingredients in CONTRAVE^®, can increase the risk of suicidal thoughts or actions.

If you have thoughts of harming or killing yourself at any time, tell your healthcare professional or go to a hospital right away. You will be closely monitored by a healthcare professional in this situation.

When should I not use CONTRAVE^®?

Do not use CONTRAVE^® if you are:

• Allergic to naltrexone, bupropion, or any of the other ingredients in CONTRAVE^®.
• Taking thioridazine, an antipsychotic medicine that is typically used to treat schizophrenia and psychosis. An ingredient in CONTRAVE^® may cause the level of thioridazine in your blood to increase.
• Dependent on opioid pain medicines or use medicines to help stop taking opioids (e.g., methadone or buprenorphine), or are in opioid withdrawal.
• Taking medicines called monoamine oxidase inhibitors (MAOIs).
  • Ask your doctor if you are not sure if you take an MAOI.
  • Do not start CONTRAVE^® until you have stopped taking your MAOI for at least 14 days.
• Using other medicines that contain bupropion hydrochloride, such as WELLBUTRIN^® SR, WELLBUTRIN^® XL and ZYBAN^®.
• Pregnant or planning to become pregnant. Tell your doctor right away if you become pregnant while taking CONTRAVE^®.

Do not use CONTRAVE^® if you have:

• High blood pressure that cannot be controlled by medicine.
• Severe liver problems.
• End-stage kidney failure (i.e., kidney failure where the kidneys do not work enough to support the needs of the body).
• Seizures or had seizures in the past.
• An eating disorder (presently or in the past), such as:
  • Anorexia (eating very little).
  • Bulimia (eating too much and throwing up so you don’t gain weight).

Do not use CONTRAVE^® if you drink a lot of alcohol and may abruptly stop drinking, or use medicines called sedatives (medicines that make you sleepy), benzodiazepines, or anti-seizure medicines and you may stop using them all of a sudden.

Driving and using machines: CONTRAVE^® may impair your ability to do tasks requiring judgment, thinking or motor skills. You should not drive or use machines until you know how CONTRAVE^® affects you.

How can I help avoid side effects and ensure that I use CONTRAVE^® properly?

CONTRAVE^® can have potential side effects. Talk about any health conditions or problems you may have to your doctor before you take CONTRAVE^®, including if you have:

• A higher risk of seizures, including if you:
  • Had a serious head injury.
  • Have ever had any fits or seizures in the past, especially if you have ever had a seizure while taking CONTRAVE^®, WELLBUTRIN^® SR, WELLBUTRIN^® XL, or ZYBAN^®.
  • Have or have had a tumour or infection in your brain or spinal cord.
  • Had a stroke (bleeding or blood clot in the brain).
  • Have blood vessel problems.
  • Have low sodium or low sugar levels in your blood.
  • Have low oxygen levels in your body.
  • Have liver problems.
  • Are addicted to cocaine or other drugs that stimulate your central nervous system.
  • Excessively take sedatives or have withdrawal symptoms from discontinuing sedatives.
  • Excessively drink alcohol.
  • Have diabetes and take insulin or other medicines to control your blood sugar (e.g., sulfonylureas and meglitinides).
  • Are taking medications that lower the seizure threshold (e.g., medicines used to treat depression and other mental health problems, theophylline, and systemic steroids).
• Depression or other mental health problems.
• Bipolar disorder or are at higher risk for bipolar disorder (e.g., family history of bipolar disorder, suicidal thoughts or actions, or depression).
• Suicidal thoughts or actions or have attempted suicide in the past.
• Liver problems or had them in the past.
• High blood pressure that is controlled by medicine or have a higher risk of developing high blood pressure.
• A heart attack or had one in the past.
• Kidney problems.
• Significant weight loss.
• Systemic lupus erythematosus (SLE), an autoimmune disease where your body’s immune system attacks your own tissues and organs.
• Anatomically narrow angles. (The space or angle between the cornea and iris is abnormally small.)
• Have or have had a speech disorder where you stammer or stutter (dysphemia). Taking CONTRAVE^® may cause your speech disorder to come back or worsen.

Talk to your doctor if you are:

• Over 65 years of age.
• Lactose intolerant or have one of the following rare hereditary diseases galactose intolerance, lapp lactase deficiency, glucose-galactose malabsorption because lactose is a non-medical ingredient in CONTRAVE^®.
• Breastfeeding or planning to breastfeed. CONTRAVE^® can pass into your breast milk and may harm your baby. You and your doctor should decide if you should take CONTRAVE^® or breastfeed. You should not do both.
• Dependent on alcohol or being treated for alcohol dependence.

What other warnings should I know about?

CONTRAVE^® can cause the following serious side effects:

• Angle-closure glaucoma (eye pain caused by increased pressure in the eyes): One of the ingredients in CONTRAVE^®, bupropion, can cause an acute attack of glaucoma. Having your eyes checked before you take CONTRAVE^® could help identify if you are at risk of having angle-closure glaucoma. Get immediate medical help if you experience eye pain, changes in vision and/or swelling or redness in or around the eye.
• Blood pressure and heart rate increases: You may be more at risk if you already have high blood pressure.
• Brugada syndrome (serious heart problem): Bupropion, one of the ingredients in CONTRAVE^®, may reveal a hidden heart problem you did not know you had, a problem called Brugada syndrome. Brugada syndrome can be serious and cause sudden death. Get immediate medical help if you experience fainting, dizziness, heart palpitations or abnormal heartbeat while taking CONTRAVE^®.
  • have Brugada syndrome.
  • have unexplained fainting, or a family history of Brugada syndrome or unexplained sudden death before 45 years of age. This could mean you may have Brugada syndrome. Before you start taking CONTRAVE^®, tell your healthcare professional if you:
• Hallucinations, delusions, or paranoia (seeing, sensing or believing things that are not there).
• Hypoglycemia (low blood sugar): You may be more at risk of developing hypoglycemia if you have type 2 diabetes and you lose weight while taking CONTRAVE^®. This applies only if you take medicines to treat type 2 diabetes, such as insulin or sulphonylureas. You may need a change in your medicine used to treat your diabetes.
• Liver problems: This includes hepatitis (inflammation of the liver) and liver dysfunction.
• Seizures (fits): The risk of having a seizure while taking CONTRAVE^® is related to the dose. It is important that you take CONTRAVE^® exactly as your doctor tells you. If you have a seizure while taking CONTRAVE^®, stop taking CONTRAVE^® and get immediate medical help. Your risk of seizures increases especially if:
  • Your dose of CONTRAVE^® increases.
  • You do not take CONTRAVE^® as directed.
  • You take CONTRAVE^® with high-fat meals.
  • You take certain medicines at the same time.
  • You are already at a higher than usual risk of seizures.
• Serotonin toxicity (also known as serotonin syndrome): CONTRAVE^® can cause serotonin toxicity, a rare but potentially life-threatening condition. It can cause serious changes in how your brain, muscles and digestive system work. Serotonin toxicity is more likely to develop when you start taking CONTRAVE^® or when your dose is increased. It may also occur if you take CONTRAVE^® with certain antidepressants or migraine medications. Serotonin toxicity symptoms include fever; sweating; shivering; diarrhea; nausea; vomiting; muscle shakes, jerks, twitches or stiffness; overactive reflexes; loss of coordination; flushing; fast heartbeat; changes in blood pressure; confusion; agitation; restlessness; hallucinations; mood changes; unconsciousness; anxiety; and coma.
• Severe allergic reaction: CONTRAVE^® may cause an allergic reaction. Symptoms may include skin rash, hives, swelling of the face or throat, muscle pain, joint pain, difficulty breathing, severe skin reactions, chest pain or fever. If you have an allergic reaction your symptoms may not go away even after you stop taking CONTRAVE^®.
• Severe skin reactions: Taking CONTRAVE^® may cause serious skin reactions. This included Stevens-Johnson Syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), and erythema multiforme. Stop taking CONTRAVE^® and get immediate medical help if you experience: severe skin rash, peeling of the skin, blisters around the mouth, eyes or genitals. Itching, chest pain, swelling, shortness of breath, body aches, and/or fever.
• SLE and cutaneous lupus erythematosus (CLE): CONTRAVE^® has been associated with new or worsening symptoms in patients susceptible to SLE and CLE. These are autoimmune diseases where your body’s immune system attacks your own tissues and organs. Talk to your doctor right away if you have blotchy rashes mainly on the face, fatigue, joint pain, swelling in the joints, muscle pain, rash, swelling, fever, nausea, or loss of appetite.
• Alcohol: CONTRAVE^® lowers your alcohol tolerance. This means you may feel the effects of alcohol when taking less alcohol than usual. Drinking alcohol while taking CONTRAVE^® may increase your risk of having seizures and allergic reactions. It is best not to drink alcohol at all while taking CONTRAVE^® to avoid side effects.

What should I know about pregnancy during CONTRAVE^® treatment?

Do not take CONTRAVE^® if you are pregnant. Tell your healthcare professional right away if you become pregnant while taking CONTRAVE^®. They will discuss the risks of birth defects and complications after birth if you take CONTRAVE^® during pregnancy.

Talk to your healthcare professional if you are breastfeeding or thinking of breastfeeding. CONTRAVE^® passes into breastmilk. You should not breastfeed while you are taking CONTRAVE^®.

What should I know about opioid overdose during CONTRAVE^® treatment?

The ingredient naltrexone in CONTRAVE^® can increase your chance of having an opioid overdose. Examples of opioids or medicines that contain opioids include heroin, prescription pain medicines, and methadone.

It is important that you tell your family and the people closest to you of this increased sensitivity to opioids and the risk of overdose.

What should I know about opioid withdrawal during CONTRAVE^® treatment?

You should not use any type of opioid for at least 7 to 10 days before starting CONTRAVE^®. This includes street drugs; prescription pain medicines (including tramadol); cough, cold, or diarrhea medicines that contain opioids; or opioid-dependence treatments (e.g., buprenorphine or methadone). Using opioids in the 7 to 10 days before you start taking CONTRAVE^® may cause you to suddenly have symptoms of opioid withdrawal when you take it. Sudden opioid withdrawal can be severe, and you may need to go to the hospital. Tell your doctor if you are taking CONTRAVE^® before a medical procedure or surgery.

Will I need to do testing and check-ups?

Your doctor may perform certain tests (e.g., blood tests) to monitor:

• Your blood pressure and heart rate before and regularly during your treatment with CONTRAVE^®, especially if you have type 2 diabetes.
• Your blood sugar and red blood cell levels before and during your treatment with CONTRAVE^®, especially if you have type 2 diabetes.
• Any emotional and behavioural changes for the first few months after you start your treatment, and when your dose changes. This can include the emergence of anxiety, agitation, irritability, behavioural changes, or suicidal thoughts and behaviour.
• Your kidney and liver function.

If you take a urine drug screening test, CONTRAVE^® may give a positive test result for amphetamines. Tell the laboratory technician that you are taking CONTRAVE^®. A more specific drug screening test can be made available for you.

Are there any drug interactions with CONTRAVE^®?

Serious drug interactions with CONTRAVE^® include:

• Medicines that contain bupropion hydrochloride (e.g., WELLBUTRIN^® XL, WELLBUTRIN^® SR, and ZYBAN^®).
• MAOIs taken within the last 14 days, which are used to treat depression (e.g., phenelzine, selegiline, or rasagiline).
• Medicines that contain thioridazine, typically used to treat schizophrenia and psychosis.

Do not take CONTRAVE^® if you are taking any of these medicines. Ask your doctor if you are unsure.

Tell your doctor about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

What are possible side effects from using CONTRAVE^®?

These are not all the possible side effects you may feel when taking CONTRAVE^®. If you experience any side effects not listed here, contact your doctor.

The common side effects of CONTRAVE^® include:

• Abdominal pain
• Abnormal dreams
• Blurred vision
• Constipation
• Diarrhea
• Dizziness
• Dry mouth
• Excessive sweating (more than usual)
• Feeling off balance or like everything is spinning (vertigo)
• Flu
• Foul, salty, rancid or metallic taste in the mouth
• Hair loss
• Headache or migraine
• Indigestion
• Upset stomach
• Itching
• Nausea
• Rash
• Ringing in the ear
• Shaking (tremor)
• Sleepiness, feeling tired, lack of energy
• Trouble paying attention
• Trouble sleeping
• Vomiting

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, talk to your doctor.

Serious side effects and what to do about them

Talk to your healthcare professional if you have any of the following side effects:

• New or worsened anxiety.
• New or worsened depression.
• Angle-closure glaucoma.
• Unusual changes in behaviour or mood (agitation, sadness, feeling over-excited).
• Blood pressure and heart rate increases.
• Liver problems.
• Hypoglycemia (low blood sugar).
• SLE and CLE.

Stop taking CONTRAVE^® and get immediate medical help if you have any of the following side effects:

• Seizures.
• New or worsened emotional or behavioural problems.
• Suicidal thoughts and actions.
• Severe allergic reaction.
• Serotonin toxicity.
• Manic episodes.
• Panic attacks.
• Hallucinations, delusions, or paranoia.
• Opioid withdrawal symptoms if you had taken opioid medicines less than 7–10 days before taking CONTRAVE^®.
• Opioid overdose if you take opioid medicines while taking CONTRAVE^®.