MYSIMBA 8 MG/90 MG PROLONGED-RELEASE TABLETS

Introduction

Patient Information Leaflet

Mysimba 8 mg/90 mg prolonged-release tablets

naltrexone hydrochloride/bupropion hydrochloride

This medicine is subject to additional monitoring, which will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Mysimba and what is it used for
2. What you need to know before you take Mysimba
3. How to take Mysimba
4. Possible side effects
5. Storing Mysimba
6. Contents of the pack and other information

1. What is Mysimba and what is it used for

Mysimba contains two active substances — naltrexone hydrochloride and bupropion hydrochloride — and is used in adults who are obese or overweight to help control their weight, in combination with a low-calorie diet and exercise. This medicine works in areas of the brain involved in controlling food intake and energy expenditure.

Obesity in adults aged 18 years and over is defined as a body mass index (BMI) of 30 or more. Overweight in adults aged 18 years and over is defined as a BMI of 27 or more and less than 30. BMI is calculated by dividing your weight in kilograms by your height in metres squared.

The use of Mysimba has been approved in patients with an initial BMI of 30 or more. It can also be given to people with a BMI of 27-30 if they have weight-related conditions such as controlled high blood pressure, type 2 diabetes or high levels of fats (lipids) in the blood.

Your doctor may stop treatment with Mysimba after 16 weeks if you do not achieve a weight loss of at least 5% of your initial weight. Your doctor may also recommend stopping treatment if there is an increase in blood pressure or if there are other safety or tolerability concerns with this medicine.

2. What you need to know before you take Mysimba

Do not take Mysimba:

• if you are allergic to naltrexone, bupropion or any of the other ingredients of this medicine (listed in section 6).
• if you have uncontrolled high blood pressure.
• if you have any condition that causes seizures (fits) or if you have had seizures in the past.
• if you have a brain tumour.
• if you have a high intake of alcohol and have just stopped drinking alcohol or plan to stop drinking alcohol while taking Mysimba.
• if you have recently stopped taking sedatives or medicines for anxiety (especially benzodiazepines) or if you plan to stop taking them while taking Mysimba.
• if you have bipolar disorder (extreme mood swings).
• if you are taking other medicines that contain bupropion or naltrexone.
• if you have had an eating disorder (such as bulimia or anorexia nervosa) or if you have had one in the past.
• if you are currently addicted to opioids or are experiencing acute withdrawal (such as with methadone).
• if you are taking medicines for depression or Parkinson's disease called monoamine oxidase inhibitors (MAOIs), such as phenelzine, selegiline or rasagiline. You must stop taking these medicines at least 14 days before starting treatment with Mysimba (see the section "Do not take Mysimba").

if you have severe liver disease.

• if you have end-stage kidney disease.

Warnings and precautions

Tell your doctor or pharmacist before you start taking Mysimba.

This is important because some diseases make you more likely to have side effects (see also section 4).

If you feel depressed, have suicidal thoughts, have a history of attempted suicide or other mental disorder, you must tell your doctor before taking this medicine.

Seizures (fits)

Mysimba has been shown to cause seizures in up to 1 in 1000 patients (see also section 4). You must tell your doctor before taking this medicine:

• if you have had a severe head or brain injury.
• if you regularly drink alcohol (see the section "Taking Mysimba with alcohol").
• if you regularly take sleeping medicines (sedatives).
• if you currently have a withdrawal syndrome or are addicted to cocaine or other stimulants.
• if you have diabetes and use insulin or oral medicines that can lower blood sugar levels (hypoglycaemia).
• if you are taking other medicines that may increase the risk of having seizures (see the section "Taking Mysimba with other medicines").

If you have a seizure, you must stop taking Mysimba and see your doctor immediately.

If you have any symptoms of an allergic reaction, such as swelling of the throat, tongue, lips or face, difficulty swallowing or breathing, feeling dizzy, fever, rash, joint or muscle pain, hives or itching after taking this medicine, stop taking Mysimba immediately and see your doctor (see also section 4).

You must tell your doctor, especially if:

• You have high blood pressure before taking Mysimba, as it may get worse. Before you start taking Mysimba and during treatment, your blood pressure and heart rate will be checked. If your blood pressure or heart rate increases significantly, you may need to stop taking Mysimba.
• You have uncontrolled coronary artery disease (a heart disease caused by insufficient blood flow in the blood vessels of the heart), with symptoms such as angina (characterized by chest pain) or a recent heart attack.
• You have had a condition that affects blood flow to the brain (cerebrovascular disease).
• You have had liver problems before starting treatment with Mysimba.
• You have had kidney problems before starting treatment with Mysimba.
• You have a history of mania (a feeling of euphoria or over-excitement that leads to unusual behaviour).
• You are taking medicines for depression, as taking them with Mysimba may cause a potentially life-threatening condition called serotonin syndrome (see "Taking Mysimba with other medicines" in this section and section 4).

Elderly patients

If you are 65 years or older, you should be cautious when taking Mysimba. Mysimba is not recommended in patients over 75 years.

Children and adolescents

Studies have not been conducted in children and adolescents under 18 years. Therefore, Mysimba should not be used in children and adolescents under 18 years.

Taking Mysimba with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take Mysimba with:

• monoamine oxidase inhibitors (medicines for depression or Parkinson's disease), such as phenelzine, selegiline or rasagiline. You must stop taking these medicines at least 14 days before starting treatment with Mysimba (see the section "Do not take Mysimba").
• opioids or medicines that contain opioids for treating, for example, cough and cold (such as mixtures containing dextromethorphan or codeine), opioid addiction (such as methadone), pain (such as morphine and codeine) or diarrhoea (such as paregoric elixir). You must stop taking any opioid medicine at least 7-10 days before starting treatment with Mysimba. Your doctor may do blood tests to make sure there are no remains of these medicines in your blood before you start treatment. Naltrexone blocks the effects of opioids. If you take high doses of opioids to overcome the effects of naltrexone, you may have a potentially life-threatening opioid overdose. After you stop treatment with Mysimba, you may be more sensitive to low doses of opioids (see the section "Do not take Mysimba").

Tell your doctor if you are taking any of the following medicines, as your doctor will monitor you closely for side effects:

• medicines that may increase the risk of seizures, either alone or in combination with naltrexone/bupropion, such as:
• medicines for treating depression and other mental disorders.
• corticosteroids (except eye drops, creams or lotions and inhalers for treating respiratory disorders such as asthma).
• medicines used to prevent malaria.
• quinolones (antibiotics such as ciprofloxacin for treating infections).
• tramadol (a painkiller that belongs to the opioid class).
• theophylline (used in treating asthma).

• antihistamines (medicines for treating allergic rhinitis, itching and other allergic reactions) that cause drowsiness (such as chlorphenamine); medicines for lowering blood sugar levels (such as insulin, sulfonylureas like glibenclamide and meglitinides like nateglinide or repaglinide
• medicines for helping you sleep (sedatives like diazepam).

• medicines for treating depression(such as amitriptyline, desipramine, imipramine, venlafaxine, paroxetine, fluoxetine, citalopram and escitalopram) or other psychiatric disorders (such as risperidone, haloperidol and thioridazine). Mysimba may interact with some medicines used for treating depression and you may experience serotonin syndrome. The symptoms are changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as body temperature above 38°C, increased heart rate, unstable blood pressure and exaggerated reflexes, muscle stiffness, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 4).

• (such as desipramine, venlafaxine, imipramine, paroxetine and citalopram) or other psychiatric disorders (such as risperidone, haloperidol and thioridazine).
• some medicines used for treating high blood pressure(beta-blockers like metoprolol and clonidine, a centrally acting anti-hypertensive).
• some medicines used for treating irregular heart rhythm(such as propafenone and flecainide).
• some medicines used for treating cancer(such as cyclophosphamide, ifosfamide and tamoxifen).
• some medicines for Parkinson's disease(such as levodopa, amantadine or orphenadrine).
• ticlopidine or clopidogrel, mainly used for treating heart disease or stroke.
• medicines used for treating HIV and AIDS, such as efavirenz and ritonavir.
• medicines used for treating epilepsy, such as valproate, carbamazepine, phenytoin or phenobarbital.

Your doctor will monitor you closely for side effects and may decide to adjust the dose of your other medicines or Mysimba.

Taking Mysimba with alcohol

Drinking too much alcohol during treatment with Mysimba may increase the risk of having a seizure or mental health problems or may decrease your tolerance to alcohol.

Your doctor will ask you not to drink alcohol while taking Mysimba or to drink as little as possible. If you currently drink a lot, do not stop suddenly, as this may cause you to have a seizure.

Pregnancy and breastfeeding

Mysimba must not be used during pregnancy or breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

During treatment with Mysimba, you may feel sleepy or dizzy.

Do not drive or use tools or machines until you know how Mysimba affects you.

Mysimba contains lactose (a type of sugar).

If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Mysimba

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

The recommended starting dose is one tablet (8 mg naltrexone hydrochloride/90 mg bupropion hydrochloride) once a day, taken in the morning. The dose will be gradually adjusted 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 a day, two in the morning and one in the evening.
• Week 4 and after: two tablets, twice a day, two in the morning and two in the evening.

The maximum recommended daily dose of Mysimba is two tablets, taken twice a day.

Your doctor will assess you after 16 weeks and every year to see if you should continue taking Mysimba.

If you have liveror kidneyproblems or are over 65 years, depending on the severity of your condition, your doctor may decide whether this medicine is suitable for you or recommend that you take a different dose, and monitor you closely for side effects. If you have diabetes or are over 65 years, your doctor will do blood tests before starting treatment with Mysimba to decide whether you should take this medicine or a different dose.

This medicine is taken by mouth. Swallow the tablets whole, without dividing, chewing or crushing them. The tablets should be taken preferably with food.

If you take more Mysimba than you should

If you take too many tablets, you are more likely to have a seizure or side effects similar to those listed in section 4. Do not delay, contact your doctor or the emergency department of your nearest hospital immediately.

If you forget to take Mysimba

Miss the dose you forgot and take the next tablet at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Mysimba

You may need to take Mysimba for at least 16 weeks to get the full effect. Do not stop taking Mysimba without talking to your doctor first.

If you have any other questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

If you experience any of the following severe adverse effects, inform your doctor immediately:

• Suicidal Thoughts and Depression

The frequency of adverse effects of suicide attempts, suicidal behavior, suicidal thoughts, and depression is unknown and cannot be calculated based on the available data from people taking Mysimba.

There have been reports of depression, suicidal thoughts, and suicide attempts during treatment with Mysimba. If you have thoughts of harming yourself or others, or if you are depressed and notice that you are getting worse or experiencing new symptoms, contact your doctor or go to a hospital immediately.

• Epileptic Seizures (Convulsions):

Rare: may affect up to 1 in 1,000 people taking Mysimba with a risk of having an epileptic seizure.

The symptoms of the seizure include convulsions and, often, loss of consciousness. After having a seizure, the patient may be confused and not remember what happened. Seizures are more likely if you take too much medication, if you take other medications, or if you have a higher than normal risk of having epileptic seizures (see section 2).

• Stevens-Johnson Syndrome and Erythema Multiforme

Frequency unknown - the frequency cannot be calculated based on the available data from people taking Mysimba. Erythema multiforme is a severe skin disease that can affect the mouth and other parts of the body, with red spots, usually itchy, that start on the legs. Stevens-Johnson syndrome is a rare skin disease that manifests with severe blisters and bleeding of the lips, eyes, mouth, nose, and genitals.

• Rhabdomyolysis

Frequency unknown - the frequency cannot be calculated based on the available data from people taking Mysimba. Rhabdomyolysis is an abnormal muscle breakdown that can cause kidney problems. Its symptoms include intense muscle cramps, muscle pain, or muscle weakness.

• Lupus Eruption or Worsening of Lupus Symptoms

Frequency unknown - the frequency cannot be calculated based on the available data from people taking Mysimba. Lupus is an immune system disorder that affects the skin and other organs. If you experience lupus flare-ups, rash, or skin lesions (especially in sun-exposed areas) while taking Mysimba, contact your doctor immediately, as it may be necessary to interrupt treatment.

• Serotonin Syndrome, which can manifest with changes in mental status (e.g., agitation, hallucinations, coma) and other effects, such as body temperature above 38°C, increased heart rate, unstable blood pressure, and exaggerated reflexes, muscle stiffness, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), when taking Mysimba along with medications used to treat depression (such as paroxetine, citalopram, escitalopram, fluoxetine, and venlafaxine) (see section 2). Frequency unknown (cannot be estimated from the available data from people who took Mysimba)

Other Adverse Effects Are:

Adverse effects very common(may affect more than 1 in 10 people):

• Nausea, vomiting, constipation
• Headache

Adverse effects common(may affect up to 1 in 10 people):

• Anxiety
• Dizziness, feeling of dizziness or spinning sensation (vertigo)
• Tremors - Difficulty falling asleep (make sure not to take Mysimba before bedtime)
• Alterations in food taste (dysgeusia), dry mouth, toothache
• Difficulty concentrating
• Feeling of fatigue (fatigue and drowsiness), drowsiness, or lack of energy (lethargy)
• Ringing in the ears (tinnitus)
• Fast or irregular heartbeat
• Hot flashes
• Increased blood pressure (sometimes severe)
• Pain in the upper abdomen
• Excessive sweating (hyperhidrosis)
• Skin rash, itching (pruritus)
• Hair loss (alopecia)
• Irritability
• Feeling of restlessness

Adverse effects uncommon(may affect up to 1 in 100 people):

• Urticaria
• Hypersensitivity
• Abnormal dreams
• Feeling of nervousness, feeling absent, tension, agitation, mood changes
• Tremor of the head or a limb, which increases when trying to perform a specific activity (intentional tremor)
• Balance disorder
• Memory loss (amnesia) Numbness or tingling of the hands or feet
• Dizziness
• Belching
• Abdominal discomfort
• Indigestion
• Inflammation of the gallbladder (cholecystitis)
• Increased creatinine levels in the blood (indicating a decrease in kidney function)
• Increased liver enzyme and bilirubin levels, liver disorders
• Difficulty getting or maintaining an erection
• Abnormal sensation, weakness (asthenia)
• Thirst, feeling of heat
• Chest pain
• Increased appetite, weight gain

Adverse effects rare(may affect up to 1 in 1,000 people):

• Low count of certain white blood cells (lymphocyte count decrease)
• Decreased hematocrit (indicating a decrease in red blood cell volume)
• Swelling of the eyelids, face, lips, tongue, or throat, which can cause great difficulty breathing (angioedema)
• Excessive loss of body water (dehydration)
• Hallucinations
• Fainting, loss of consciousness, feeling of fainting (presyncope)
• Epileptic seizures
• Anal bleeding, usually with stools (hematochezia)
• Protrusion of an organ or tissue that surrounds an organ towards the wall of the cavity that normally contains it (hernia)
• Toothache
• Tooth decay
• Pain in the lower abdomen
• Liver injury due to drug toxicity
• Jaw pain
• A disorder characterized by a sudden and urgent need to urinate (urinary urgency)
• Irregular menstrual cycles, vaginal bleeding, vaginal and vulvar dryness
• Feeling of cold in the extremities (hands and feet)

Adverse effects of unknown frequency(the frequency cannot be estimated from the available data):

• Inflammation of the lymph nodes in the neck, armpits, or groin (lymphadenopathy)
• Mood disorders
• Irrational ideas (delirium)
• Psychosis
• Loss of sexual desire
• Feeling of hostility
• Severe suspicion (paranoia)
• Aggression
• Attention disorder
• Nightmares
• Confusion, disorientation
• Memory impairment
• Restlessness
• Muscle stiffness, uncontrolled movements, walking or coordination problems
• Blurred vision, eye pain, eye irritation, eye swelling, tearing, increased sensitivity to light (photophobia)
• Ear pain, ear discomfort
• Breathing difficulties
• Nasal discomfort, congestion, runny nose, sneezing, sinus disorder
• Sore throat, voice disorders, cough, yawning
• Hemorrhoids, ulcer
• Diarrhea
• Gas (flatulence)
• Hepatitis
• Acne
• Groin pain
• Muscle pain

• Joint pain

• Abnormal frequent urination, pain while urinating
• Chills
• Increased energy

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Mysimba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the box and blister after "EXP". The expiration date is the last day of the month indicated.

Do not store above 30°C.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Mysimba Composition

• The active ingredients are naltrexone hydrochloride and bupropion hydrochloride. Each tablet contains 8 mg of naltrexone hydrochloride, equivalent to 7.2 mg of naltrexone, and 90 mg of bupropion hydrochloride, equivalent to 78 mg of bupropion.
• The other ingredients (excipients) are:

Core of the tablet: microcrystalline cellulose, hydroxypropylcellulose, anhydrous lactose, lactose monohydrate, (see section 2), cysteine hydrochloride, crospovidone, magnesium stearate, hypromellose, disodium edetate, colloidal silicon dioxide, and aluminum lake indigo carmine (E-132). Coating: polyvinyl alcohol, titanium dioxide (E-171), macrogol 3350, talc, and aluminum lake indigo carmine (E-132).

Appearance of the Product and Package Contents

Mysimba prolonged-release tablets are blue, biconvex, and round, with the inscription "NB-890" on one side. Mysimba is available in packs of 28, 112 tablets. Some pack sizes may only be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Orexigen Therapeutics Ireland Limited

2nd Floor

Palmerston House, Fenian Street

Dublin 2

Ireland

Manufacturer

MIAS Pharma Ltd

Suite 2 Stafford House, Strand Road, Portmarnock, Co. Dublin,

Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: {June/2021}

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website http://www.ema.europa.eu.

Updated detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.