What is CONTRAVE used for? CONTRAVE should be taken with a reduced-calorie diet and increased physical activity. It is for weight management in:

• obese
• overweight patients who have at least one weight-related condition, such as:
  • high blood pressure that is controlled by medicine
  • Type 2 diabetes
  • a high amount of lipids (cholesterol or other types of fat) in the Blood

It is not known if it is safe to take CONTRAVE with other weight loss products. Other products include prescription drugs, over the counter drugs, and natural health products. It is not known if CONTRAVE changes your risk of heart problems or stroke or of death due to heart problems or stroke. CONTRAVE is not for use in patients 18 years of age and younger. How does CONTRAVE work? CONTRAVE contains two medicines, naltrexone hydrochloride and bupropion hydrochloride. These medicines work on two separate areas of the brain that are involved in controlling eating (hunger and cravings). What are the ingredients in CONTRAVE? Medicinal ingredients: naltrexone hydrochloride and bupropion hydrochloride Non-medicinal ingredients: colloidal silicon dioxide, crospovidone, edetate disodium, FD&C Blue No. 2 indigo carmine aluminum lake, hydroxypropyl cellulose, hypromellose, lactose anhydrous, lactose monohydrate, L-cysteine hydrochloride, macrogol/peg, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol-part hydrolyzed, talc, and titanium dioxide. CONTRAVE comes in the following dosage form: Extended release tablets. Each tablet contains 8 mg naltrexone hydrochloride and 90 mg bupropion hydrochloride. The tablets are blue, round, and have “NB-890” on one side. Do not use CONTRAVE if you:

• are allergic (hypersensitive) to naltrexone, bupropion or any of the other ingredients in CONTRAVE
• have uncontrolled high blood pressure
• have severe liver problems
• have end-stage kidney failure
• have or had seizures
• are taking thioridazine, an antipsychotic An ingredient in CONTRAVE may cause the level of thioridazine in your blood to increase
• use other medicines that contain bupropion such as WELLBUTRIN^® SR, WELLBUTRIN^® XL and ZYBAN^®
• have or had an eating disorder such as:
  • anorexia (eating very little)
  • bulimia (eating too much and throwing up so you don’t gain weight)
• are dependent on opioid pain medicines or use medicines to help stop taking opioids such as methadone or buprenorphine, or are in opioid withdrawal.
• drink a lot of alcohol and abruptly stop drinking, or use medicines called sedatives (these make you sleepy), benzodiazepines, or anti-seizure medicines and you stop using them all of a sudden
• are taking medicines called monoamine oxidase inhibitors (MAOIs).
  • Ask your healthcare provider or pharmacist professional 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
• are pregnant or planning to become Tell your healthcare professional right away if you become pregnant while taking CONTRAVE.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take CONTRAVE. Talk about any health conditions or problems you may have, including if you:

• have or had depression or other mental illnesses (such as bipolar disorder)
• have attempted suicide in the past
• have or had liver problems
• have high blood pressure
• have or had a heart attack
• have kidney problems
• are over the age of 65
• are lactose intolerant because CONTRAVE contains Lactose is an ingredient in milk.
• are breastfeeding or plan to CONTRAVE can pass into your breast milk and may harm your baby. You and your healthcare professional should decide if you should take CONTRAVE or breastfeed. You should not do both.

Other warnings you should know about: New or Worsened Emotional or Behavioral Problems, Including Self-Harm

• One of the ingredients in CONTRAVE is Bupropion has caused some people to experience unusual feelings of agitation, mania (feeling very high, talking fast, taking more risks, and needing less sleep), hostility or anxiety, or have impulsive or disturbing thoughts such as thoughts of self-harm, or harm to others.
• Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or This is very important when you start taking CONTRAVE and when your dose changes.
• Keep all follow-up visits with your healthcare professional as scheduled. Call your healthcare professional between visits as needed, especially if you have concerns about
• Your healthcare professional will monitor you for any signs of suicidal thoughts or
• If you are depressed and taking CONTRAVE, you may experience a worsening of your symptoms, including having suicidal thoughts or behaviors.
• If you, your family, or friends notice mental health changes that are unusual for you while on CONTRAVE, stop taking the drug and talk to your If the symptoms are severe, seek immediate emergency help.

Risk of seizures

• Bupropion, one of the ingredients in CONTRAVE, can cause seizures. The risk of having a seizure while taking CONTRAVE is related to the It is important that you take CONTRAVE exactly as your healthcare professional tells you to.
• If you have a seizure while taking CONTRAVE, stop taking CONTRAVE and call your healthcare provider right away.
• The risk of having a seizure while taking CONTRAVE is higher if you have certain medical conditions. Tell your healthcare professional if you have or had any of the following, as they might increase your risk of seizures:
  • Seizures
  • Head injury
  • Eating disorder
  • Severe stroke
  • Heart problems
  • Tumor or infection in your brain or spine
  • Low blood sugar (hypoglycemia)
  • Low levels of salt (sodium) in your blood (hyponatremia)
  • Liver problems
  • Abuse of alcohol, sedatives (drugs that make you sleepy), street drugs or are in withdrawal from sedatives
  • Have diabetes and are taking insulin or other medicines to control your blood sugar
• The risk of having a seizure while taking CONTRAVE is higher if you take other medicines that increase the risk of seizures, which include:
  • Other drugs that contain bupropion
  • Antipsychotics
  • Other antidepressants (tricyclic antidepressants)
  • Theophylline (used to treat asthma)
  • Steroids (used to treat inflammation)

Risk of opioid overdose Naltrexone, one of the ingredients in CONTRAVE, can increase your chance of having an opioid overdose if you take opioid medicines while taking CONTRAVE. Examples of opioids or opioid-containing medicines include heroin, prescription pain medicines, and methadone. You can accidentally overdose in 2 ways:

• Naltrexone blocks the effects of opioids. Because of this, do not take large amounts of opioids to try to overcome the opioid-blocking effects of It can lead to serious injury, coma, or death.
• After you take naltrexone, its blocking effect slowly decreases and goes away over
  • If you have used opioid street drugs or opioid-containing medicines in the past, using opioids in amounts that you used before treatment with CONTRAVE can lead to overdose and death.
  • You may also be more sensitive to the effects of lower amounts of opioids:
    • after you have gone through detoxification
    • when your next dose of CONTRAVE is due
    • if you miss a dose of CONTRAVE
    • after you stop CONTRAVE treatment

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. Sudden opioid withdrawal

• People who take CONTRAVE must 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, such as 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 healthcare professional you are taking CONTRAVE before a medical procedure or surgery.

Increase in Blood Pressure and Heart Rate

• CONTRAVE may cause an increase in blood pressure and heart rate. Your healthcare professional will monitor you before you start taking CONTRAVE and during
• You may be more at risk if you already have high blood
• If you have a significant increase in your blood pressure or heart rate while taking CONTRAVE, your treatment will be stopped.

Patients with Type 2 Diabetes Mellitus who are Taking Antidiabetic Medicines

• You may be more at risk of developing low blood sugar (hypoglycemia) if you have Type 2 diabetes and you lose weight while taking This applies only if you take medicines to treat Type 2 diabetes such as insulin or sulphonylureas. Your healthcare professional will monitor your blood sugar levels before and during treatment with CONTRAVE.
• You may need a change in your antidiabetic

Angle-Closure Glaucoma CONTRAVE may cause an acute attack of glaucoma. Get immediate medical attention if you have:

• eye pain
• changes in vision
• swelling or redness in or around the

Liver Damage CONTRAVE may cause damage to your liver. See your healthcare professional right away if you have any of the following symptoms:

• abdominal pain
• dark urine
• diarrhea
• fatigue
• fever
• headache
• loss of appetite
• yellowing of the skin and the whites of the eyes
• nausea and vomiting

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.  The following may interact with CONTRAVE:

•  Medicines to treat depression or Parkinson’s disease (monoamine oxidase inhibitors such as phenelzine, selegiline, or rasagiline).
• Alcohol:
  • You should only drink a very small amount of alcohol or none at all while taking
• Opioids and opioid-containing medicines, used to treat:
  • cough and cold (mixtures containing dextromethorphan or codeine)
  • opiate addiction (methadone)
  • pain (morphine, codeine, tramadol)
  • diarrhea (loperamide).
• Medicines used to prevent
• Antibiotics to treat infections (quinolones such as ciprofloxacin).
• Medicines to treat asthma (theophylline).
• Medicines to treat hay fever, itch, swelling and other allergic reactions (antihistamines and steroids).
• Medicines to lower sugar levels in your blood (metformin, insulin, glyburide or glibenclamide, nateglinide or repaglinide).
• Medicines to help you to sleep (sedatives such as diazepam).
• Medicines to treat depression (desipramine, venlafaxine, imipramine, paroxetine, citalopram) or other mental health problems (risperidone, haloperidol, thioridazine).
• Some medicines used to treat high blood pressure (metoprolol, clonidine).
• Some medicines used to treat irregular heart rhythm (propafenone, flecainide).
• Some medicines used to treat cancer (cyclophospamide, ifosphamide, tamoxifen).
• Some medicines for Parkinson’s disease (levodopa, amantadine or orphenadrine).
• Medicines mainly used in the treatment of heart disease or stroke (ticlopidine, digoxin, or clopidogrel).
• Medicines used in the treatment of HIV infection and AIDS (efavirenz, lopinavir and ritonavir).
• Medicines used to treat epilepsy (valproate, carbamazepine, phenytoin or phenobarbital).

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. They can do a more specific drug screening test for you. How to take CONTRAVE:

•  Use CONTRAVE with a reduced calorie-diet and increased physical
• Take CONTRAVE exactly as your healthcare professional tells you
  • Do not change your CONTRAVE dose without talking with your healthcare
  • Do not take more CONTRAVE than your healthcare professional tells you to, or it may increase your risk of seizures.
  • Your healthcare professional will change your dose if
  • Your healthcare professional should tell you to stop taking CONTRAVE if you have not lost a certain amount of weight after 16 weeks of treatment.
• Your healthcare professional will monitor:
  • your blood pressure and heart rate before you take CONTRAVE and during your
  • you for side effects if you have kidney or liver
• Swallow CONTRAVE tablets Do not cut, chew, or crush the tablets. Tell your healthcare professional if you cannot swallow CONTRAVE tablets whole.
• Take each dose of CONTRAVE with Do not take CONTRAVE with high-fat meals. It may increase your risk of seizures.
• Your dose may be decreased if you:
  • have kidney or liver
  • take certain
• Do not drink a lot of alcohol while taking CONTRAVE. Talk with your healthcare professional if you drink a lot of If you suddenly stop drinking alcohol, you may increase your chance of having a seizure.

Usual dose: The table below explains how your dose of CONTRAVE will be slowly increased over the first 4 weeks. At week 4, you will be taking the usual adult dose:

• 2 tablets in the morning and 2 tablets in the
• This is also the maximum daily dose for It is important that you not take more than the maximum daily dose:
  • Do not take more than 2 tablets in the morning and 2 tablets in the evening.
  • Do not take more than 2 tablets at the same time or more than 4 tablets in 1 day.

	Morning Dose	Evening Dose
Week 1	1 tablet	None
Week 2	1 tablet	1 tablet
Week 3	2 tablets	1 tablet
Week 4 and Onward	2 tablets	2 tablets

Overdose:  Risk of opioid overdose: You may be at risk of having an opioid overdose if you take opioid medicines while taking CONTRAVE. You should get emergency medical help right away if you:

• have trouble breathing
• become very drowsy with slowed breathing
• have slow, shallow breathing (little chest movement with breathing)
• feel faint, very dizzy, confused, or have unusual symptoms

Missed Dose:  If you miss a dose of CONTRAVE, wait until your next regular time to take it. Do not take more than 1 dose of CONTRAVE at a time. This will help reduce your risk of having a seizure. What are the 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 healthcare professional. Please also see the warnings section. In clinical trials, patients who were elderly, had Type 2 diabetes or kidney problems had more of certain side effects than other patients. The common side effects of CONTRAVE include: Nausea

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

Serious side effects and what to do about them
Symptom / effect	Talk to your healthcare professional		Stop taking drug and get immediate medical help
	Only if severe	In all cases
VERY COMMON New or worse anxiety
COMMON New or worse depression
UNCOMMON Visual problems (angle-closure glaucoma): – eye pain; – changes in vision; – swelling or redness in or around the eye.
Unusual changes in behavior or mood: agitation, sadness, feeling over-excited.
Increases in blood pressure or heart rate: your blood pressure and heart rate should be monitored during your treatment. Symptoms may include: headaches, nosebleeds, dizziness, a flushed face, fatigue, and fast heart rate.
Liver damage or hepatitis: –   pain in the stomach area lasting more than a few days; –   dark urine; –   yellowing of the whites of your eyes; –   tiredness.
RARE Seizures
New or Worsened Emotional or Behavioral Problems: –   thoughts about suicide or dying; –   attempts to commit suicide; –   new or worse irritability.
Increased risk of low blood sugar (hypoglycemia) in people with Type 2 diabetes mellitus who also take medicines to treat their diabetes: you should check your blood sugar before you start taking CONTRAVE and while you take CONTRAVE. Symptoms may include: sweating, nervousness, shaking, faintness, palpitations, and hunger.
VERY RARE Severe allergic reactions: –   chest pain; –   fever; –   hives; –   itching in your eyes; –   painful sores in your mouth or around; –   rash; –   swelling of your lips or tongue; –   swollen lymph glands; –   trouble breathing.
New or Worsened Emotional or Behavioral Problems: feeling very agitated or restless; acting aggressive; being angry or violent; acting on dangerous impulses.
UNKNOWN Manic episodes: mania (feeling very high, talking fast, taking more risks, and needing less sleep).
Panic attacks: sudden intense fear and discomfort.
Hallucinations: Sensing or seeing things that are not there.
If you had taken opioid medicines less than 7 – 10 days before taking CONTRAVE. Opioid withdrawal: nausea and vomiting, anxiety, insomnia, hot and cold flushes, perspiration, muscle cramps, diarrhea.
If you take opioid medicines while taking CONTRAVE. Opioid overdose: having trouble breathing, becoming very drowsy with slowed breathing, having slow, shallow breathing, feeling faint, very dizzy, confused, or having unusual symptoms.

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 healthcare professional. Tell your healthcare professional about any side effect that does not go away. Storage: Store CONTRAVE at room temperature between 15°C to 25°C. eep out of reach and sight of children. If you want more information about CONTRAVE:

• Talk to your healthcare
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website (https://health-products.canada.ca/dpd-bdpp/index-eng.jsp) or by calling the manufacturer at 1-800-361-4261