Contrave 8 mg/90 mg Prolonged-Release Tablets

Contrave contains 2 active ingredients: naltrexone hydrochloride and bupropion hydrochloride and is used in obese or overweight adults to manage weight together with a reduced calorie diet and physical exercise. This medicine works on areas on the brain involved in the control of food intake and energy expenditure. Obesity in adults over 18 years of age is defined as a body mass index of greater than or equal to 30 and overweight in adults over 18 years of age is defined as a body mass index greater than or equal to 27 and less than 30. The body mass index is calculated as the measured body weight (kg) divided by the measured height squared (m2). Contrave may be discontinued by your doctor after 16 weeks if you have not lost at least 5 percent of your initial body weight. Your doctor may also recommend stopping treatment if there are concerns about increased blood pressure, or other concerns with the safety or tolerability of this medicine.

Do not take Contrave:

• if you are hypersensitive (allergic) to naltrexone, to bupropion or to any of the other ingredients Contrave (listed in section 6);
• if you have an abnormally high blood pressure (hypertension) that is not controlled using a medicinal product;
• if you have a condition that causes fits (seizures) or if you have a history of fits;
• if you have a brain tumour;
• if you are usually a heavy drinker and you have just stopped drinking alcohol, or are going to stop while you are taking Contrave;
• if you have recently stopped taking sedatives or medicines to treat anxiety (especially benzodiazepines), or if you are going to stop them while you are taking Contrave;
• if you have a bipolar disorder (extreme mood swings);
• if you are using any other medicines which contain bupropion or naltrexone;
• if you have an eating disorder or had one in the past (for example, bulimia or anorexia nervosa);
• if you are currently dependent on chronic opiates or opiate agonists (for example methadone), or you are going through acute withdrawal (cold turkey);
• if you are taking medicines for depression or Parkinson’s disease called monoamine oxidase inhibitors (MAOIs) or have taken them in the last 14 days;
• if you have severe liver disease;
• if you have end stage kidney disease;
• if you are under 18 years of age.

Warnings and precautions

Talk to your doctor or healthcare provider before taking Contrave:

• if you feel depressed, consider suicide, have a history of attempting suicide, panic attacks or any other mental health problems, you should inform your doctor before taking this medicine
• if you have seizures (fits). Contrave has been shown to cause fits in up to 1 in 1000 patients (see section 4). If you have a fit (seizure), you should stop taking Contrave and consult your doctor immediately
• if you have had a serious head injury or head trauma
• if you regularly drink alcohol (see “Contrave with alcohol”)
• if you regularly use medicines to help you to sleep (sedatives)
• if you are currently dependent on or addicted to cocaine or other stimulating products
• if you have diabetes and use insulin or oral medicines that may lower sugar levels in your blood (hypoglycaemia)
• if you have a heart condition and are currently taking medicines such as digoxin
• if you are taking medicines that may increase the risk of fits (see “Other medicines and Contrave”).

Do not share medicines prescribed for you with any other person. Always take Contrave exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The initial dose is usually one tablet, once a day in the morning. The dose will be gradually changed as follows:

• Week 1: One tablet once a day in the morning
• Week 2: One tablet twice a day, one in the morning and one in the evening
• Week 3: Three tablets every day, two in the morning and one in the evening
• Week 4 and onward: Two tablets twice a day, two in the morning and two in the evening

The maximum recommended daily dose of Contrave is two tablets taken twice a day. Your doctor will tell you how long your treatment with Contrave will last. After 16 weeks and each year after your treatment initiation, your doctor will evaluate whether you should continue to take Contrave. If you have the impression that the effect of Contrave is too strong or too weak, tell your doctor or pharmacist.

If you have problems with your liver or kidney, or if you are older than 65, and depending on the severity of your problems, your doctor may carefully consider whether this medicine is suitable for you or recommend that you take a different dose, and monitor you more closely for potential side effects. Your doctor may test your blood before initiating treatment with Contrave if you have high blood sugar (diabetes) or if you are older than 65, so that your doctor can decide if you should take this medicine or if you need to take a different dose.

This medicine is for oral use. Swallow your tablets whole. Do not cut them, chew them or crush them. The tablets should preferably be taken with food.

If you take more Contrave than you should

In the event of overdosage, consult your doctor or pharmacist immediately. If neither is available, contact the nearest hospital or poison centre. If you take too many tablets, you may be more likely to have a fit or other side effects similar to those described in section 4 below.

If you forget to take Contrave

Do not take a double dose to make up for forgotten individual doses.

If you stop taking Contrave

You may need to take Contrave for at least 16 weeks to have its full effect. Do not stop taking Contrave without talking to your doctor first.

Contrave can have side effects. Not all side effects reported for Contrave are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking Contrave, please consult your healthcare provided for advice. If any of the following happens, stop taking Contrave and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Suicidal thoughts and feeling depressed
• Fits (seizures): Symptoms of a fit include convulsions and usually loss of consciousness. Someone who has had a fit may be confused afterwards and may not remember what has happened. Fits are more likely if you take too much, if you take some other medicines or if you are at a higher than usual risk of fits (see section 2);
• Erythema multiforme and Stevens Johnson Syndrome
• Rhabdomyolysis
• Lupus skin rash or worsening of lupus symptoms
• Serotonin syndrome, that can manifest as mental status changes (e.g. agitation, hallucinations, coma), and other effects, such as body temperature above 38°C, increase in heart rate, unstable blood pressure, and exaggeration of reflexes, muscular rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea), while taking Contrave together with medicines used for treatment of depression (such as paroxetine, citalopram, escitalopram, fluoxetine and venlafaxine (see section 2).

Not known - frequency cannot be estimated from the available data in people taking CONTRAVE)

Tell your doctor if you notice any of the following:

frequent side effects:

• feeling sick (nausea), being sick (vomiting),
• pain in the abdomen,
• constipation,
• headache,
• difficulty in sleeping (make sure you do not take Contrave close to bedtime),
• anxiety, agitation,
• joint and muscle pain,
• low amount of certain white blood cells (lymphocyte count decreased),
• dizziness, feeling of dizziness or “spinning” (vertigo),
• feeling shaky (tremor),
• increased energy, irritability,
• feeling depressed, mood disorders,
• chills, fever,
• decreased appetite, diarrhoea,
• changes in the taste of food (dysgeusia), dry mouth, toothache,
• difficulty concentrating,
• feeling of tiredness (fatigue) and sleepiness, drowsiness or lack of energy (lethargy),
• ringing in the ears (tinnitus),
• fast or irregular heartbeat,
• hot flush,
• watery eyes,
• pain in the upper part of the abdomen,
• delayed ejaculation,
• chest pain, change to electrocardiogram (record of the electrical activity of the heart),
• excessive sweating (hyperhidrosis),
• hives, rash, itching (pruritus),
• hair loss (alopecia).

Less frequent side effects:

• cold sores (oral herpes),
• itching, blisters, cracking, and scaling of the skin between the toes (athlete's foot or tinea pedis),
• swollen glands in the neck, armpit or groin (lymphadenopathy),
• excessive loss of body water (dehydration),
• loss of appetite (anorexia),
• increased appetite, weight gain,
• abnormal dreams, nightmares,
• flushing,
• feeling nervous, feeling spacey, tension, agitation, mood swings, hallucinations, confusion, severe suspiciousness (paranoia), disorientation,
• loss of sexual desire,
• tremor of the head or a limb which increases when trying to perform a particular function (intention tremor),
• balance disorder,
• loss of memory (amnesia), mental impairment,
• almost fainting (presyncope),
• motion sickness,
• ear pain, ear discomfort,
• visual disturbances, blurred vision, eye irritation, pain or swelling, increased sensitivity to light (photophobia),
• nasal discomfort, congestion, runny nose, sneezing, sinus disorder,
• sore throat, increase in mucus that is coughed up, difficulty in breathing, disorder of the voice, cough, yawning,
• fluctuating or increased blood pressure (sometimes severe),
• pain in the lower part of the abdomen,
• burping,
• swelling of the lips,
• passage of fresh blood through the anus usually in or with stool (haematochezia),
• projection of an organ or the tissue encompassing an organ through the wall of the cavity that normally contains it (hernia),
• passing wind (flatulence), haemorrhoids, ulcer, cavities,
• inflammation of the gallbladder (cholecystitis),
• a problem with the spine where supporting disc between two bones (vertebra) bulges out (intervertebral disc protrusion),
• jaw and groin pain,
• a disorder characterised by a sudden compelling urge to urinate (micturition urgency), abnormally frequent urination, painful urination,
• irregular menstrual cycle, vaginal bleeding, dryness of the female vulva and vagina,
• difficulty in getting or keeping an erection,
• feeling abnormal, weakness (asthenia),
• thirst, feeling hot,
• coldness of extremities (hands, feet),
• increased creatinine levels in the blood (indicating loss of kidney function),
• increased liver enzymes and bilirubin levels, liver disorders, hepatitis
• decreased haematocrit (indicating loss of red blood cell volume)
• acne, oily skin,
• unusual bleeding or bruising under the skin,
• changes in blood sugar levels,
• feeling irritable or hostile,
• suicidal thoughts, suicide attempts, feeling of observing yourself from outside your body or sense of unreality of surroundings (depersonalisation),
• muscle stiffness, uncontrolled movements, problems with walking or coordination,
• memory impairment,
• fainting, loss of consciousness,
• tingling or numbness of the hands or feet,
• widening of blood vessels, low blood pressure when you stand up from sitting or lying down (postural hypotension),
• your skin or the whites of your eyes turning yellow (jaundice),
• erythema multiforme (a severe condition of the skin that may affect the mouth and other parts of the body, with red, often itchy spots starting on the limbs), Stevens Johnson Syndrome (a rare skin condition with severe blisters and bleeding in the lips, eyes, mouth, nose and genitals),
• worsening of psoriasis (thickened patches of red skin),
• muscle twitching,
• urinary retention,
• fixed, irrational ideas (delusions), aggression, abnormal muscle breakdown which can lead to kidney problems (rhabdomyolysis).

Frequency cannot be estimated for the following side effects:

• psychosis,
• abdominal discomfort,
• indigestion,
• rash,
• an inflammatory disease caused when the immune system attacks its own tissues (lupus)
• increased blood pressure
• Feeling of acute and disabling anxiety (panic attack)

Reporting of side effects

If you get side effects, talk to your doctor of pharmacist. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/index/8. By reporting side effects, you can provide more information on the safety of Contrave. Alternately you can contact Litha Pharma (Pty) Ltd at +27 11 516 1700. Website: www.acino.co.za.

Store all medicines out of reach of children. Store at or below 30 °C. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).