Pixigan: detailed information

Package leaflet: Information for the patient

Pixigan, 150 mg, modified-release tablets
Bupropioni hydrochloridum
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet so that you can reread it if necessary.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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 the active substance bupropioni hydrochloridum.
Pixigan is a prescription medicine used to treat depression. It acts on chemical substances in the brain called 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 suffers from epilepsy or has experienced seizures,
if the patient has or has previously 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 drinking alcohol or intends to do so,
if the patient has severe liver disease,
if the patient has recently stopped taking sedative medicines or intends to do so during treatment with Pixigan,
if the patient is taking or has taken within the last two weeks antidepressant medicines called monoamine oxidase inhibitors (MAOIs). If any of the above situations apply to the patient, contact the doctor immediately, do not take Pixigan.

Warnings and precautions
Inform your doctor or pharmacist before starting treatment with
Pixigan.
Brugada syndrome
If the patient has Brugada syndrome (a rare, genetically determined condition affecting heart rhythm)
or if there is a family history of cardiac arrest or sudden death.
Severe skin reactions
Severe 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 severe
skin reactions listed in section 4, treatment with Pixigan must be stopped immediately and the patient should
contact a doctor without delay.
Children and adolescents
Pixigan is not indicated 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 behaviours.
Adults
Inform your doctor before starting treatment with Pixigan:

if the patient regularly drinks large amounts of alcohol,
if the patient has diabetes and is using insulin or oral antidiabetic medicines,
if the patient has previously had a serious head injury or head trauma.
Bupropion may cause seizures in approximately 1 in 1000 patients. The risk of this adverse effect is higher in patients in the groups listed above. If seizures occur during treatment, discontinue Pixigan. Do not take any more of this medicine and contact your doctor.
if the patient has bipolar affective disorder (extreme mood swings), as Pixigan may trigger an episode of this condition,
if the patient is taking other medicines used to treat depression, 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 the patient has liver or kidney disease, as adverse effects may be more likely.

If any of the above situations apply to the patient, contact the doctor again before starting treatment with Pixigan. The doctor may decide that treatment should be closely monitored or recommend alternative therapy.
Suicidal thoughts and worsening of depressive symptoms
Patients with depression may sometimes experience thoughts of self-harm or suicide. These behaviours may worsen when the patient first starts taking antidepressant medicines, as it takes time for these medicines to take effect, usually about two weeks, but sometimes longer. Such thoughts may be more frequent:

if the patient previously had suicidal thoughts or thoughts of self-harm,
if the patient is a young adult. Clinical trials have shown an increased risk of suicidal behaviour in adults (under 25 years of age) with psychiatric disorders treated with antidepressants. If the patient ever experiences thoughts of self-harm or suicide, contact the 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 him or her if they believe the patient's depression is worsening or if changes in behaviour become concerning.
Pixigan with other medicines
If the patient is currently taking or has taken within the last fourteen days other antidepressant medicines called monoamine oxidase inhibitors (MAOIs), contact the doctor without taking Pixigan (see also “When not to take Pixigan” in section 2).
Tell the doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines the patient plans to take, including herbal remedies or vitamins, even those available without a prescription. The doctor may adjust the dose of Pixigan, recommend changing the dosing regimen, or discontinuation of other medicines.
Some medicines must not be taken together with 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.
Seizures may occur more frequently than usual if the patient is taking:

other antidepressants or medicines used to treat psychiatric disorders,
theophylline, a medicine for asthma or lung disease,
tramadol, a strong painkiller,
sedatives, or if the patient intends to stop taking them during treatment with Pixigan (see also “When not to take Pixigan”),
antimalarial medicines (such as mefloquine or chloroquine),
stimulants or other medicines that control body weight or appetite,
steroids (oral or injectable),
antibiotics called quinolones,
some types of antihistamines that may cause drowsiness,
antidiabetic medicines. If any of the above situations apply to the patient, contact the doctor immediately before starting treatment with 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 psychiatric disorders (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, coma), and other symptoms such as body temperature above 38°C, rapid heartbeat, unstable blood pressure, increased reflexes, muscle stiffness, lack of coordination and/or gastrointestinal disturbances (e.g. nausea, vomiting, diarrhoea),
medicines used to treat Parkinson's disease (levodopa, amantadine, orphenadrine),
medicines that affect the metabolism of bupropion (carbamazepine, phenytoin, valproic acid),
medicines used to treat malignant tumours (such as cyclophosphamide, ifosfamide),
ticlopidine or clopidogrel, mainly used to prevent stroke,
beta-blockers (such as metoprolol),
medicines used to treat irregular heart rhythm (propafenone and flecainide),
nicotine patches, as an aid to stop smoking. If any of the above situations apply to the patient, contact the doctor immediately before starting treatment with Pixigan.

The effectiveness of Pixigan may be reduced if the patient is taking ritonavir or efavirenz, medicines used to treat HIV infections. If this applies to the patient, inform the doctor. The doctor will assess the effectiveness of Pixigan in the patient. It may be necessary to increase the dose or change the treatment for depression. Do not increase the dose of Pixigan without the doctor's advice, 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, inform the doctor. It may be necessary to change the treatment for depression.
digoxin due to heart conditions. If this applies to the patient, inform the doctor. The doctor may consider adjusting the digoxin dose. Pixigan and alcohol Alcohol may affect the action of Pixigan, and taking them together may, although rarely, cause nervousness or changes in mental state. Some patients become more sensitive to alcohol while taking Pixigan. The doctor may advise abstaining from alcohol (beer, wine, spirits) or significantly reducing alcohol consumption during treatment with Pixigan. If the patient currently drinks large amounts of alcohol, do not stop drinking suddenly, as this may trigger a seizure. Discuss alcohol consumption with the doctor before starting treatment with Pixigan.

Effect on urine tests
Pixigan may affect laboratory test results for the presence of other drugs. If the patient undergoes such a test, he or she should inform the doctor or nurse that Pixigan is being taken.
Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, do not take Pixigan unless advised by a doctor. Consult a doctor or pharmacist before using this 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 due to the use of this medicine.
The components of Pixigan may pass into human milk. Consult a doctor or pharmacist before using Pixigan.
Driving and operating machinery
If Pixigan causes dizziness or a feeling of emptiness in the head, do not drive or operate any tools or machinery.

3. How to take Pixigan

This medicine should always be taken as directed by the physician. The following are usual dosages, but
the prescribing doctor will determine the dose individually for each patient.
If in doubt, consult the doctor or pharmacist.
Improvement in the patient's well-being may occur only after some time. The full effect of the medicine
may become apparent only after several weeks or months. Even when the patient starts to feel
better, the treating physician may recommend continuing treatment with Pixigan to prevent
relapse of depression.

What doses should be taken
The usual recommended dose for adults is one 150 mg tablet once daily.
The treating physician may recommend increasing the dose to 300 mg once daily if there is no
improvement after several weeks of treatment.
The dose should be taken in the morning. Pixigan should not be taken more than once daily.
The tablet has a coating that slowly releases the active substance into the gastrointestinal tract. The
patient may notice in the stool something that looks like a tablet. This is the empty coating shell, which
has been excreted from the body.
Tablets should be swallowed whole. They should not be chewed, crushed, or split – doing so may
lead to overdose due to too rapid release of the active substance 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 the entire treatment
period. The treating physician may recommend this dosage 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 weeks or even months before any improvement is observed.
The patient should regularly consult with the treating physician about symptoms of depression so that
a decision can be made regarding the duration of treatment. If the patient feels better, the treating
physician may recommend continuing treatment with Pixigan to prevent recurrence of depression.

Taking more Pixigan than recommended
Taking too many tablets may cause a seizure. Do not delay. Seek immediate medical attention by
contacting a doctor or the nearest hospital emergency department.

Missing a dose of Pixigan
If a dose is missed, wait and take the next dose at the usual time. Do not take a double dose to make
up for the missed dose.

Stopping treatment with Pixigan
Do not discontinue treatment with Pixigan or reduce the dose without first consulting the treating
physician.

If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
Serious adverse reactions
Seizures
Seizures may occur in approximately 1 in 1,000 patients taking Pixigan. The likelihood is higher in patients taking higher than recommended doses, taking certain other medicines, or belonging to a group at increased risk of seizures. If in doubt, consult your treating physician.
If a seizure occurs, contact your treating physician immediately.
Do not take any more tablets.
Allergic reactions
Some patients may experience allergic reactions to Pixigan. These include:

skin redness or rash (similar to hives) and itchy skin lumps (urticaria),
unusual wheezing or breathing difficulties,
swelling of the eyelids, lips, or tongue,
muscle or joint pain,
collapse or brief loss of consciousness.

If any symptoms of an allergic reaction occur, contact a doctor immediately.
Do not take any more of the medicine.
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 epidermis, 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 determined from available data):
extensive areas of blistering and widespread peeling of the skin, occurring in the severe form of the skin reaction described above (toxic epidermal necrolysis),
widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome). DRESS symptoms are usually delayed in onset (occurring 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 determined from available data)
Lupus is an immune system disorder affecting the skin and other organs.
If lupus flares, skin rash, or skin changes occur (especially in areas of skin exposed to sunlight) during treatment with Pixigan, contact your doctor immediately, as discontinuation of treatment may be necessary.
Other adverse reactions
Very common (may affect more than 1 in 10 patients):

difficulty sleeping; ensure that Pixigan is taken in the morning,
headache,
dry mouth,
nausea, vomiting.

Common (may affect up to 1 in 10 patients):

fever, dizziness, itching, sweating, and skin rash (sometimes due to allergic reaction),
chills, tremors, weakness, fatigue, chest pain,
feeling of anxiety or agitation,
abdominal pain or other gastrointestinal complaints (constipation), altered taste perception, loss of appetite (anorexia),
increased blood pressure, sometimes significantly, facial flushing,
ringing in the ears, vision disturbances.

Uncommon (may affect up to 1 in 100 patients):

feeling of depression (see also section 2: "Thoughts of suicide and worsening of depressive symptoms"),
feeling of disorientation,
difficulty concentrating,
increased heart rate,
weight loss.

Rare (may affect up to 1 in 1,000 patients):

seizures.

Very rare (may affect up to 1 in 10,000 patients):

palpitations, fainting,
muscle twitching, muscle stiffness, uncontrolled movements, problems with walking or coordination,
feeling of uneasiness, irritability, hostility, aggression, unusual dreams, tingling or numbness, memory loss,
yellowing of the skin or whites of the eyes (jaundice), which may be caused by increased liver enzyme activity, 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 (red, thickened skin patches),
unusual hair loss or thinning (alopecia),
feeling 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 determined 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 contact with reality and impaired thinking or judgment (psychosis); other symptoms may include hallucinations and (or) delusions.
sudden and intense feeling 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).
low sodium levels in the blood (hyponatremia).
changes in mental state (e.g. agitation, hallucinations, coma), 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) when 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 of Adverse Drug Reactions at the 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 can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store the medicine Pixigan

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton following EXP. The expiry date refers to the last day of the specified 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 modified-release tablet contains 150 mg of bupropion hydrochloride.
Other components are:
Tablet core:
Povidone K90
Cysteine hydrochloride monohydrate
Glyceryl dibehenate
Anhydrous colloidal silicon dioxide
Magnesium stearate
Coating:
Methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%
Ethylcellulose
Hydrated colloidal silicon dioxide
Povidone K90
Polyethylene glycol 1450
Triethyl citrate
Printing ink:
Shellac
Iron oxide black (E 172)
Propylene glycol

What Pixigan looks like and contents of the pack
Pixigan is a modified-release tablet.
Cream-white to light yellow, round tablets with a black imprint "GS3" on one side and smooth on the other side, approximately 7 mm in diameter and 5 mm in thickness.
Packed in blisters made of OPA/Aluminium/PVC/Aluminium foil, contained in a cardboard box.
Pack sizes: 30 and 90 modified-release tablets.
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/Importer:
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona,
Spain

For further information, 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

This medicinal product is authorised in the European Economic Area countries under the following names:
Denmark: Bupropion hydrochloride Zentiva
Poland: Pixigan
Portugal: Bupropiom Zentiva
Sweden: Bupropion Zentiva
Germany: Bupropion Zentiva 150 mg Tabletten mit veränderter Wirkstofffreisetzung
Norway: Bupropion hydrochloride Zentiva
Italy: Bupropione Zentiva Italia

(logo of the Marketing Authorisation Holder)