Package leaflet: Information for the patient

Pixigan, 300 mg, modified-release tablets
Bupropioni hydrochloridum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

What Pixigan is and what it is used for
Important information before taking Pixigan
How to take Pixigan
Possible side effects
How to store Pixigan
Contents of the pack and other information

1. What Pixigan is and what it is used for

Pixigan contains an active substance called bupropion and is a prescription medicine used for the treatment of depression. It is believed to act on chemical substances in the brain known as noradrenaline and dopamine.

2. Important information before taking Pixigan

When not to take Pixigan

if the patient is allergic to bupropion or any of the other ingredients of this medicine (listed in section 6),
if the patient is taking any other medicines containing bupropion,
if the patient has epilepsy or has experienced seizures,
if the patient has or has had eating disorders (e.g. bulimia or anorexia nervosa),
if the patient has a brain tumour,
if the patient who abuses alcohol has recently stopped or intends to stop drinking alcohol,
if the patient has severe liver disease,
if the patient has recently stopped taking sedative medicines or intends to discontinue them while taking Pixigan,
if the patient is taking or has taken antidepressant medicines called monoamine oxidase inhibitors (MAOIs) within the past 14 days.

If any of the above situations apply to the patient, they should contact their doctor immediately, without taking Pixigan.
Warnings and precautions
Before starting treatment with Pixigan, discuss this with your doctor or pharmacist.
Brugada syndrome

if the patient has diagnosed Brugada syndrome (a rare, genetically determined condition affecting heart rhythm) or if there is a family history of cardiac arrest or sudden death.

Serious skin reactions
Serious skin reactions have been reported with the use of Pixigan, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If the patient develops symptoms indicating serious skin reactions listed in section 4, treatment with Pixigan must be stopped immediately and medical advice sought without delay.
Children and adolescents
Pixigan is not recommended for use in children under 18 years of age.
In children under 18 years of age treated with antidepressants, there is an increased risk of suicidal thoughts and suicidal behaviour.
Adults
The patient should inform their doctor before starting treatment with Pixigan:

if they regularly consume large amounts of alcohol,
if they have diabetes and are using insulin or antidiabetic medicines,
if they have previously had a serious head injury or head trauma. Bupropion has been shown to cause seizures in approximately 1 in 1000 people. The occurrence of this adverse effect is more likely in patients in the groups listed above. If seizures occur during treatment, Pixigan should be discontinued and the patient should contact their doctor.
if they have bipolar affective disorder (extreme mood swings), as bupropion may trigger an episode of this condition,
if they are taking other antidepressants, as concomitant use of these medicines with Pixigan may lead to serotonin syndrome, a potentially life-threatening condition (see “Pixigan with other medicines” in this section).
if they have liver or kidney disease, as adverse effects may be more likely.

If any of the above situations apply to the patient, they should contact their doctor again before starting treatment with Pixigan. The doctor may decide that treatment should be carried out under close supervision or recommend alternative treatment.
Suicidal thoughts and worsening of depression symptoms
Patients with depression may sometimes experience thoughts of self-harm or suicide. These may worsen when the patient first starts taking antidepressant medicines, as all these medicines usually take about 2 weeks to start working, but sometimes longer. Such thoughts are more likely to occur:

if the patient has previously had suicidal thoughts or self-harm,
if the patient is a young adult. Clinical studies have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders who were treated with antidepressants. If the patient ever experiences thoughts of self-harm or suicide, they should contact their doctor immediately or go to hospital.

It may be helpful to inform a relative or friend that the patient has depression and ask them to read this leaflet. The patient may ask them to inform them if they believe the patient's depression is worsening or if changes in their behaviour become concerning.
Pixigan with other medicines
If the patient is currently taking or has taken within the past 14 days other antidepressant medicines called monoamine oxidase inhibitors (MAOIs), they should contact their doctor without taking Pixigan (see also: “When not to take Pixigan” above).
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take, including herbal remedies or vitamins, even those purchased without a prescription. The doctor may adjust the dose of Pixigan or recommend changing other medicines being taken.
Some medicines should not be taken at the same time as Pixigan. Some of these may increase the risk of seizures or convulsions. Other medicines may increase the risk of other adverse effects. Examples of such medicines are listed below, but this is not a complete list.
The likelihood of seizures may be higher than usual:

if the patient is taking other antidepressants or other medicines used to treat mental illnesses,
if the patient is taking theophylline, a medicine for asthma or lung disease,
if the patient is taking tramadol, a strong painkiller,
if the patient has recently taken or is currently taking sedatives or intends to discontinue them while taking Pixigan (see also “When not to take Pixigan” above),
if the patient is taking antimalarial medicines (such as mefloquine or chloroquine),
if the patient is taking stimulants or other medicines that control body weight or appetite,
if the patient is taking steroids (orally or by injection),
if the patient is taking antibiotics called quinolones,
if the patient is taking certain types of antihistamines that may cause drowsiness,
if the patient is taking antidiabetic medicines.

If any of the above situations apply to the patient, they should contact their doctor immediately before starting Pixigan. The doctor will assess the risks and benefits of using Pixigan.
The likelihood of other adverse effects may increase if:

the patient is taking other antidepressants (such as amitriptyline, fluoxetine, paroxetine, citalopram, escitalopram, venlafaxine, dosulepin, desipramine or imipramine) or medicines for other mental illnesses (such as clozapine, risperidone, thioridazine or olanzapine). Pixigan may interact with medicines used to treat depression, and the patient may experience changes in mental state (e.g. agitation, hallucinations, stupor) and other symptoms such as body temperature above 38°C, rapid heartbeat, unstable blood pressure, increased reflexes, muscle rigidity, lack of coordination, and/or gastrointestinal disturbances (e.g. nausea, vomiting, diarrhoea).
the patient is taking medicines used to treat Parkinson's disease (levodopa, amantadine, orphenadrine),
the patient is taking medicines that affect the metabolism of bupropion (carbamazepine, phenytoin, valproic acid),
the patient is taking certain medicines used to treat cancer (such as cyclophosphamide, ifosfamide),
the patient is taking ticlopidine or clopidogrel, mainly used to prevent stroke,
the patient is taking beta-blockers (such as metoprolol),
the patient is taking certain medicines for irregular heartbeat (propafenone and flecainide),
the patient is using nicotine patches to help stop smoking.

If any of the above situations apply to the patient, they should contact their doctor immediately before starting Pixigan.
Pixigan may be less effective if:

the patient is taking ritonavir or efavirenz, medicines used to treat HIV infections.

If any of the above situations apply to the patient, they should inform their doctor. The doctor will assess the effectiveness of Pixigan in the patient. It may be necessary to increase the dose or change the method of treating depression. Do not increase the dose of Pixigan without consulting the doctor, as this may increase the risk of adverse effects, including seizures.
Pixigan may reduce the effectiveness of certain medicines if:

the patient is taking tamoxifen, used to treat breast cancer. If this applies to the patient, they should inform their doctor. It may be necessary to change the method of treating depression.
the patient is taking digoxin for a heart condition. If this applies to the patient, they should inform their doctor. The doctor may consider adjusting the digoxin dose.

Pixigan and alcohol
Alcohol may affect the action of bupropion, and when used together may rarely cause nervousness or changes in mental state. Some patients may become more sensitive to alcohol while taking Pixigan. The doctor may advise abstaining from alcohol (beer, wine, spirits) or significantly reducing alcohol consumption while taking Pixigan. If the patient currently drinks large amounts of alcohol, they should not stop suddenly, as this may trigger a seizure. The patient should discuss alcohol consumption with their doctor before starting Pixigan.
Effect on urine tests
Bupropion may affect laboratory test results for the presence of other drugs. If the patient is undergoing such a test, they should inform the doctor or nurse that they are taking Pixigan.
Pregnancy, breastfeeding and fertility
Do not take Pixigan during pregnancy, if pregnancy is suspected, or if planning to become pregnant, unless advised otherwise by a doctor. Consult a doctor or pharmacist before taking any medicine during pregnancy.
Some, but not all, studies suggest an increased risk of congenital malformations, particularly heart defects, in children whose mothers took Pixigan. It is not known whether this was caused by taking this medicine.
The ingredients of Pixigan may pass into human milk. Consult a doctor or pharmacist before taking Pixigan.
Driving and operating machinery
If Pixigan causes dizziness or drowsiness, the patient should not drive or operate machinery.
Pixigan contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is considered "sodium-free".
3. How to take Pixigan
This medicine should always be taken exactly as prescribed by the doctor or pharmacist.
The doctor will determine the dose individually for the patient. If in doubt, consult the doctor or pharmacist.
Improvement in the patient's well-being may take some time. The full effect of the medicine may only become apparent after several weeks or months. Even when the patient starts to feel better, the doctor may recommend continuing treatment with Pixigan to prevent recurrence of depression.
What dose should be taken
The usual recommended dose for adults is one 150 mg tablet once daily.
The doctor may increase the dose to 300 mg once daily if there is no improvement after several weeks of treatment.
The dose of Pixigan should be taken in the morning. Do not take Pixigan more than once daily.
The tablet has a coating that slowly releases the medicine into the gastrointestinal tract. The patient may notice something in the stool that looks like a tablet. This is the empty shell that has been excreted from the body.
Swallow Pixigan tablets whole. Do not chew, crush, or divide them – doing so may result in overdose due to too rapid release of the medicine into the body. This may increase the risk of adverse effects, including seizures.
For some patients, a dose of 150 mg once daily may be sufficient throughout treatment. The doctor may recommend this dose if the patient has liver or kidney disease.
How long to continue treatment
Only the doctor together with the patient can decide how long treatment with Pixigan should continue. It may take several weeks or months before improvement is observed. The patient should regularly discuss their symptoms with the doctor to determine how long treatment should continue. If the patient feels better, the doctor may recommend continuing treatment with Pixigan to prevent recurrence of depression.
Taking more Pixigan than prescribed
Taking too many tablets may increase the risk of seizures. Do not delay. Contact a doctor or the nearest hospital emergency department immediately.
Missing a dose of Pixigan
If a dose is missed, wait and take the next tablet at the usual time. Do not take a double dose to make up for a missed dose.
Stopping treatment with Pixigan
Do not stop treatment with Pixigan or reduce the dose without first consulting the doctor.
If there are any further questions about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Serious adverse reactions

Seizures
Seizures or convulsions may occur in approximately 1 in 1,000 patients taking bupropion. The likelihood of such an event is higher in patients taking higher than recommended doses, taking certain other medicines, or who are in a group at increased risk of seizures. If a seizure occurs, contact your doctor immediately. Do not continue taking the tablets.

Allergic reactions
Some patients may experience allergic reactions to bupropion. These include:

Skin redness or rash (similar to hives) and itchy lumps (urticaria) on the skin.
Unusual wheezing or difficulty breathing
Swelling of the eyelids, lips or tongue
Muscle or joint pain
Fainting or brief loss of consciousness.

If any symptoms of an allergic reaction occur, contact your doctor immediately. Do not take any more tablets. Allergic reactions may last a long time. If your doctor has prescribed medication to relieve allergic symptoms, complete the full course of treatment.

Severe skin reactions

If any of the following symptoms occur, stop taking bupropion and seek immediate medical help:

Very rare (may occur in no more than 1 in 10,000 patients): red, non-elevated, target-like or circular spots on the trunk, often with central blisters, peeling of the skin, ulcers in the mouth, throat, nose, genital organs and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
Frequency not known (frequency cannot be estimated from available data):
Large areas of blisters and extensive peeling of the skin, occurring in the severe form of the skin reaction described above (toxic epidermal necrolysis),
Widespread rash, high fever and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome). DRESS syndrome symptoms are usually delayed in time (occur 2–6 weeks after starting treatment),
Red, peeling, widespread rash with subcutaneous nodules and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).

Lupus-like skin rash or worsening of lupus symptoms (frequency not known – frequency cannot be estimated from available data).
Lupus is an immunological disorder affecting the skin and other organs.

If lupus symptoms worsen, or if skin rash or skin changes occur (especially on areas of skin exposed to sunlight) while taking Pixigan, contact your doctor immediately, as treatment may need to be discontinued.

Other adverse reactions

Very common (may occur in more than 1 in 10 patients):

Difficulty sleeping. Pixigan should be taken in the morning.
Headache.
Dry mouth.
Nausea, vomiting.

Common (may occur in no more than 1 in 10 patients):

Fever, dizziness, itching, sweating, skin rash (sometimes due to allergic reaction).
Chills, tremors, weakness, fatigue, chest pain.
Feelings of anxiety or agitation.
Abdominal pain or other gastrointestinal complaints (constipation), altered taste sensation, loss of appetite (anorexia).
Increased blood pressure (sometimes significantly), facial flushing.
Ringing in the ears, visual disturbances.

Uncommon (may occur in no more than 1 in 100 patients):

Feelings of depression (see also section 2: "Warnings and precautions", under "Suicidal thoughts and worsening of depression symptoms").
Feelings of disorientation.
Difficulty concentrating.
Increased heart rate.
Weight loss.

Rare (may occur in no more than 1 in 1,000 patients):

Seizures.

Very rare (may occur in no more than 1 in 10,000 patients):

Palpitations, fainting.
Tremors, muscle stiffness, uncontrolled movements, problems with walking or coordination.
Feelings of restlessness, irritability, hostility, aggression, strange dreams, tingling or numbness, memory loss.
Yellowing of the skin or whites of the eyes (jaundice), which may be due to increased liver enzyme activity or hepatitis.
Severe allergic reactions; rash accompanied by muscle and joint pain.
Changes in blood sugar levels.
Urinating more or less frequently than usual.
Urinary incontinence (involuntary urination, uncontrolled leakage of urine).
Worsening of psoriasis (thickening of red skin patches).
Unusual hair loss or thinning (alopecia).
Feelings of unreality or detachment (depersonalization), seeing or hearing things that are not there (hallucinations), experiencing or believing in unreal things (delusions), excessive suspiciousness (paranoia).

Frequency not known (frequency cannot be estimated from available data):

Thoughts of self-harm or suicide during treatment with Pixigan or shortly after stopping it (see section 2 "Important information before taking Pixigan"). If the patient has such thoughts, contact a doctor or go to hospital immediately.
Loss of touch with reality and inability to think or judge situations clearly (psychosis); other symptoms may include hallucinations and (or) delusions.
Sudden and intense feelings of fear (panic attack).
Stuttering.
Reduced number of red blood cells (anaemia), reduced number of white blood cells (leukopenia), and reduced number of platelets (thrombocytopenia).
Decreased sodium levels in the blood (hyponatremia).
Changes in mental state (e.g. agitation, hallucinations, stupor), and other symptoms such as body temperature above 38°C, rapid heartbeat, unstable blood pressure, exaggerated reflexes, muscle rigidity, lack of coordination and (or) gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) while taking Pixigan together with medicines used to treat depression (such as paroxetine, citalopram, escitalopram, fluoxetine and venlafaxine).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist.

Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse reactions may also be reported to the responsible entity.

Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store the medicine Pixigan

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after: EXP.
The expiry date refers to the last day of the stated month.
No special storage instructions apply for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What the medicine Pixigan contains

The active substance is bupropion hydrochloride. Each tablet contains 300 mg of bupropion hydrochloride.
Other ingredients are:
Tablet core: povidone, L-cysteine hydrochloride monohydrate, colloidal silicon dioxide, anhydrous, glycerol dibehenate, magnesium stearate
Tablet coating: ethylcellulose, povidone, macrogol, methacrylic acid-ethyl acrylate copolymer (1:1), sodium lauryl sulfate, polysorbate 80, colloidal silicon dioxide, hydrated, triethyl citrate
Printing ink: shellac, iron oxide black (E 172), propylene glycol

What Pixigan looks like and contents of the pack
Pixigan 300 mg prolonged-release tablets are round, cream-white to light yellow tablets, printed with "GS2" on one side and smooth on the other. The tablet diameter is approximately 9 mm.
Blister packs made of OPA/Aluminium/PVC-Aluminium foil containing 7, 30, 60 and 90 prolonged-release tablets, in a cardboard carton. Also available in perforated blister strips of OPA/Aluminium/PVC-Aluminium foil divided into single doses, containing 30×1 prolonged-release tablet, in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Zentiva k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer:
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain

This medicine is authorised in the following names in the Member States of the European Economic Area:
Poland: Pixigan
Portugal: Bupropiom Zentiva
Germany: Bupropion Zentiva 300 mg Tabletten mit veränderter Wirkstofffreisetzung
Norway: Bupropion hydrochloride Zentiva
Sweden: Bupropion Zentiva
Italy: Bupropione Zentiva

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00