Bioxetin

Leaflet accompanying the packaging: patient information

BIOXETIN, 20 mg, tablets

Fluoxetine

It is essential to carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed for a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Bioxetin and what is it used for
• 2. Important information before taking Bioxetin
• 3. How to take Bioxetin
• 4. Possible side effects
• 5. How to store Bioxetin
• 6. Contents of the packaging and other information

1. What is Bioxetin and what is it used for

Bioxetin is available in the form of tablets and contains fluoxetine as the active substance.
Bioxetin belongs to a group of antidepressant medicines called selective serotonin reuptake inhibitors (SSRIs).
Bioxetin is indicated for the treatment of:
In adults:

• episodes of major depression,
• obsessive-compulsive disorder,
• bulimia (psychological overeating): Bioxetin is used in combination with psychotherapy to reduce the frequency of bulimic episodes, self-induced vomiting, or the use of laxatives.

In children aged 8 and older and adolescents:

• moderate to severe depression, if there is no improvement after 4-6 psychotherapy sessions. Bioxetin may be recommended for children and adolescents with moderate or severe depression only in combination with psychotherapy.

2. Important information before taking Bioxetin

When not to take Bioxetin:

• if the patient is allergic (hypersensitive) to fluoxetine or any of the other ingredients of this medicine (listed in section 6). Allergy may manifest as a rash, itching, swelling of the face or lips, or shortness of breath.
• if the patient is taking non-selective, irreversible monoamine oxidase inhibitors (MAOIs) (e.g., iproniazid), as this may cause severe or even life-threatening side effects.
• if the patient is taking metoprolol (a medicine used to treat heart failure)

Treatment with fluoxetine can be started no earlier than 2 weeks after stopping non-selective, irreversible MAOIs (e.g., iproniazid), due to their prolonged effect – up to two weeks.
Treatment with fluoxetine can be started the next day after stopping reversible MAOIs of type A (e.g., moclobemide, linezolid).
Non-selective, irreversible monoamine oxidase inhibitors (MAOIs) should not be used for at least 5 weeks after stopping Bioxetin. If Bioxetin has been used for a long time and/or in high doses, the doctor may consider a longer interval before starting treatment with MAOIs.
MAOIs include, among others: nialamide, iproniazid, selegiline, moclobemide, phenelzine, tranylcypromine, isocarboxazid, and toloxatone.

Warnings and precautions

Before starting treatment with Bioxetin, the patient should discuss the following with their doctor:

• if a rash or other allergic reactions occur (e.g., itching, swelling of the lips or face, or shortness of breath); the patient should stop taking the medicine and contact their doctor immediately.
• if the patient has epilepsy or has had seizures in the past; if a seizure occurs or the frequency of seizures increases, the patient should contact their doctor immediately, as it may be necessary to stop taking fluoxetine.
• if the patient has had manic episodes in the past; if a manic episode occurs, the patient should contact their doctor immediately, as it may be necessary to stop taking fluoxetine.
• if the patient has diabetes; it may be necessary to adjust the dose of insulin or other antidiabetic medicines.
• if the patient has liver or kidney dysfunction (it may be necessary to adjust the dose of the medicine).
• if the patient has heart disease.
• if the patient is taking diuretics, especially if they are elderly.
• if the patient is undergoing electroconvulsive therapy.
• if the patient has a history of bleeding or bruising or if they are pregnant (see "Pregnancy").
• if the patient is taking other medicines that affect blood clotting (see "Bioxetin and other medicines").
• if the patient has increased intraocular pressure or is at risk of acute angle-closure glaucoma.
• if the patient experiences fever, stiffness, or muscle tremors, changes in mental status, such as disorientation, irritability, and extreme agitation; this may be a serotonin syndrome or a malignant neuroleptic syndrome. Although this syndrome is rare, it can have life-threatening consequences; the patient should contact their doctor immediately, as it may be necessary to stop taking fluoxetine.
• if the patient experiences acute or chronic pain or other conditions treated with opioid medicines (tramadol, buprenorphine). Taking these medicines with Bioxetin may lead to serotonin syndrome (see "Bioxetin and other medicines").
• if the patient experiences suicidal thoughts or self-harm (see section 4, "Possible side effects").
• medicines like fluoxetine (so-called SSRIs - selective serotonin reuptake inhibitors/SNRIs - serotonin and norepinephrine reuptake inhibitors) may cause sexual dysfunction symptoms (see section 4). In some cases, these symptoms may persist after stopping treatment.

Use of Bioxetin in children and adolescents from 8 to 18 years old

In patients under 18 years old taking antidepressant medicines of this class, the risk of suicidal behavior (attempts and suicidal thoughts) and hostility (mainly aggression, rebellious behavior, and anger) is increased.
Bioxetin may be used in children and adolescents from 8 to 18 years old for the treatment of episodes of depression of moderate to severe intensity (in combination with psychotherapy), but it should not be used for other indications.
Available data on the long-term safety of fluoxetine in this age group, including effects on growth, pubertal development, and cognitive, emotional, and behavioral development, are limited. Nevertheless, the doctor may recommend Bioxetin for patients under 18 years old for the treatment of severe or moderate episodes of major depression, in combination with psychotherapy, if they consider it beneficial for their health. If the doctor has prescribed Bioxetin for a patient under 18 years old and the patient has any doubts, they should consult their doctor. If any of the above symptoms occur or worsen in a patient under 18 years old taking Bioxetin, the doctor should be informed.
Bioxetin should not be used to treat children under 8 years old.

Bioxetin and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. This medicine may affect the action of other medicines (interactions).
The following medicines should not be taken during treatment with Bioxetin:

• non-selective, irreversible monoamine oxidase inhibitors (MAOIs) (used to treat depression, e.g., iproniazid). Non-selective MAOIs should not be taken with Bioxetin, as this may cause severe or even life-threatening side effects (serotonin syndrome) (see "When not to take Bioxetin").
• metoprolol used to treat heart failure

The following medicines should not be taken with Bioxetin:

• tamoxifen (a medicine used to treat breast cancer)
• type A monoamine oxidase inhibitors (linezolid, methylthioninium chloride, moclobemide); these medicines can be taken with Bioxetin under close medical supervision.
• mizolastine (an antihistamine)

The patient should exercise caution when taking the following medicines with Bioxetin:

• phenytoin (an antiepileptic medicine); Bioxetin may affect the levels of this medicine in the blood, and closer monitoring may be necessary when starting or stopping treatment with phenytoin and Bioxetin.
• lithium, tryptophan, opioid medicines (buprenorphine, tramadol), selegiline, triptans (migraine medicines) - MAO-B inhibitors, St. John's Wort (Hypericum perforatum); the risk of serotonin syndrome is increased when these medicines are taken with Bioxetin. When fluoxetine and lithium are taken together, closer monitoring of the patient is necessary.
• clozapine (a medicine used to treat certain mental illnesses); there is an increased risk of developing hypertension.
• flecainide, propafenone, nebivolol, or encainide (medicines used to treat heart conditions), atomoxetine (a medicine used to treat attention deficit hyperactivity disorder (ADHD)), carbamazepine (an antiepileptic medicine), tricyclic antidepressants (e.g., imipramine, desipramine, and amitriptyline), risperidone (an antipsychotic medicine), antiarrhythmic medicines of classes IA and III, antipsychotic medicines (e.g., phenothiazine derivatives, pimozide, haloperidol), certain antibacterial medicines (e.g., sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), antimalarial medicines, especially halofantrine, and certain antihistamines (astemizole, mizolastine); Bioxetin may affect the action of these medicines.

The patient should exercise caution when taking the following medicines with Bioxetin:

• warfarin or other anticoagulant medicines (including acetylsalicylic acid and non-steroidal anti-inflammatory medicines); Bioxetin may affect the action of these medicines. If the patient is taking warfarin and it is necessary to start or stop treatment with Bioxetin, the doctor may recommend certain tests.
• cyproheptadine; it may reduce the antidepressant effect of Bioxetin.
• medicines that cause hyponatremia (low sodium levels in the blood), such as diuretics: desmopressin, carbamazepine, and oxcarbazepine.
• medicines that lower the seizure threshold, such as tricyclic antidepressants, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, bupropion, tramadol.

Bioxetin with food, drink, and alcohol

Bioxetin can be taken with or without food.
The patient should not drink alcohol during treatment.

Pregnancy, breastfeeding, and fertility

Before taking any medicine, the patient should consult their doctor or pharmacist.
Pregnancy
If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
In children of mothers who took fluoxetine during the first months of pregnancy, the risk of birth defects, particularly heart defects, is increased. In the general population, about 1 in 100 children is born with a heart defect.
This risk increases to about 2 in 100 children in mothers who took fluoxetine. The patient should consult their doctor about whether to stop taking fluoxetine during pregnancy. However, in some cases, the doctor may decide that it is better to continue taking fluoxetine.
The patient should inform their doctor and/or midwife about taking Bioxetin. Taking medicines like Bioxetin during pregnancy, especially in the last three months, may increase the risk of a newborn developing persistent pulmonary hypertension (PPHN), a condition characterized by rapid breathing and bluish discoloration, usually occurring within the first day of life. If such symptoms occur in the newborn, the patient should contact their doctor and/or midwife immediately.
The patient should exercise caution when taking Bioxetin during pregnancy, especially in the last trimester or shortly before delivery, as it has been reported that newborns may experience symptoms such as irritability, tremors, weakness, constant crying, feeding or sleeping problems.
Taking Bioxetin at the end of pregnancy may increase the risk of severe postpartum hemorrhage, especially if the patient has a history of bleeding disorders. If the patient is taking Bioxetin, they should inform their doctor or midwife so that they can provide appropriate advice.
Breastfeeding
Fluoxetine passes into breast milk and may cause side effects in the child.
Breastfeeding is possible during treatment only if absolutely necessary. In breastfeeding women, a lower dose of fluoxetine may be recommended.
Fertility
In animal studies, fluoxetine has been shown to decrease sperm quality. Although this may affect fertility, no effect on fertility has been observed in humans so far.

Driving and using machines

Although Bioxetin has no or negligible influence on the ability to drive and use machines, the patient should avoid driving and using machines.
Although fluoxetine has not been shown to affect psychomotor function in healthy volunteers, many central nervous system-acting medicines can impair psychomotor function.

Bioxetin contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially "sodium-free".

3. How to take Bioxetin

Bioxetin should always be taken as directed by the doctor or pharmacist. In case of doubts, the patient should consult their doctor or pharmacist.
Recommended dose:
Episodes of major depression:
The recommended dose is 20 mg per day. If necessary, the doctor may change the dose after re-evaluating it, within 3 to 4 weeks after starting treatment, and later if necessary. If necessary, the dose can be gradually increased to a maximum of 60 mg per day. The dose should be increased with caution to ensure the patient is taking the smallest effective dose. The first effects of treatment may not be noticeable until after some time. In the case of depression, improvement usually occurs after several weeks of treatment. Patients with depression should take the medicine for at least 6 months to ensure complete recovery from the illness.
Obsessive-compulsive disorder:
The recommended dose is 20 mg per day. If necessary, the doctor may change the dose after 2 weeks of treatment. If necessary, the dose can be gradually increased to a maximum of 60 mg per day. If there is no improvement within 10 weeks, the doctor should re-evaluate the treatment with Bioxetin.
Bulimia (psychological overeating):
The recommended dose is 60 mg per day.
Depression in children and adolescents from 8 to 18 years old
Treatment should be initiated and supervised by a specialist. The initial dose is 10 mg per day. For a dose of 10 mg, a suitable product containing 10 mg of fluoxetine should be used. The doctor may increase the dose to 20 mg per day after one or two weeks.
The dose should be increased with caution to ensure the patient is taking the smallest effective dose. Children with a lower body weight may require a lower dose. The doctor should consider the need for treatment for a period longer than 6 months. If there is no improvement, the doctor should re-evaluate the treatment.
Elderly patients:
In elderly patients, the dose can be increased with caution. The daily dose should not exceed 40 mg. The maximum dose is 60 mg per day.
Liver dysfunction:
In case of liver dysfunction or when taking other medicines that may affect the action of fluoxetine, the doctor may recommend a lower dose or taking Bioxetin every other day.

Method of administration

The tablets should be swallowed with water.
If the patient feels that the effect of Bioxetin is too strong or too weak, they should consult their doctor.

Overdose of Bioxetin

In case of overdose, the following symptoms may occur: nausea, vomiting, seizures, cardiovascular disorders, from arrhythmias without symptoms to cardiac arrest, respiratory disorders, from stimulation to coma. It is recommended to monitor cardiac function and vital signs and to use general symptomatic and supportive treatment. There is no specific antidote. If the patient has taken more than the recommended dose, they should contact their doctor or pharmacist immediately.

Missed dose of Bioxetin

• If a dose is missed, the patient should take the next dose at the usual time the next day. A double dose should not be taken to make up for a missed dose.
• Taking the medicine at the same time every day helps to remember to take it.

Stopping treatment with Bioxetin

The patient should not stop taking Bioxetin without consulting their doctor.

It is essential to continue taking the medicine without interruption.

• The patient should not stop treatment without consulting their doctor, even if they feel better.
• The patient should ensure that they never run out of medicine to continue treatment.

After stopping Bioxetin, the following symptoms may occur:
dizziness; tingling sensation; sleep disturbances (vivid dreams, nightmares, insomnia); restlessness or agitation; fatigue or weakness; anxiety; nausea or vomiting; tremors; headaches.
In most patients, any symptoms that occur after stopping Bioxetin are mild and disappear on their own within a few weeks. If any symptoms occur after stopping treatment, the patient should contact their doctor.
When stopping Bioxetin, the doctor will recommend gradually reducing the dose over a period of 1 to 2 weeks to minimize the risk of withdrawal symptoms.
The patient should consult their doctor or pharmacist if they need more information about Bioxetin.

4. Possible side effects

Like all medicines, Bioxetin can cause side effects, although not everybody gets them.

• In case of a rash or allergic reaction, such as itching, swelling of the lips or tongue, or wheezing, the patient should stop taking the medicine and contact their doctor immediately.
• If the patient experiences restlessness and a feeling of being unable to sit still, these may be symptoms of akathisia; increasing the dose of Bioxetin may worsen the condition. In this case, the patient should contact their doctor.
• If the patient experiences skin redness, followed by blisters and peeling skin, they should inform their doctor immediately. This condition is very rare.
• If the patient experiences skin changes with a concentric pattern, resembling a target (which may be symptoms of erythema multiforme).

In some patients, the following have been reported:

• several symptoms at the same time (so-called serotonin syndrome), including unexplained fever with rapid breathing or heart rate, excessive sweating, stiffness or tremors, disorientation, extreme agitation or drowsiness (rarely);
• weakness, drowsiness, or disorientation - mainly in elderly patients and patients (elderly) taking diuretics;
• prolonged and painful erections;
• irritability and extreme agitation.

In case of any of the above symptoms, the patient should inform their doctor immediately. Suicidal thoughts, worsening depression, or anxiety disorders:

Patients with depression or anxiety disorders may sometimes have thoughts of self-harm or suicide. Such symptoms or behavior may worsen at the beginning of treatment with antidepressant medicines, as these medicines usually start working after 2 weeks, sometimes later.
The risk of suicidal thoughts is higher if:

• the patient has had suicidal thoughts or self-harm in the past;
• the patient is a young adult; clinical trial data suggest an increased risk of suicidal behavior in patients under 25 years old with mental disorders who are being treated with antidepressant medicines.

If the patient experiences suicidal thoughts or self-harm, they should immediatelycontact their doctor or go to the hospital.
It may be helpful for the patient to inform their relatives or friends about their depression or anxiety disorder and ask them to read this leaflet. The patient can ask their relatives or friends to monitor them and inform them if they notice any worsening of depression or anxiety or any worrying changes in behavior.
Side effects are listed below by frequency of occurrence:

Very common (may affect more than 1 in 10 patients)

• insomnia (including early morning awakening, difficulty falling asleep, difficulty maintaining sleep),
• headache,
• diarrhea, nausea,
• fatigue (including weakness).

Common (may affect up to 1 in 10 patients)

• decreased appetite (including anorexia),
• anxiety, nervousness, restlessness, tension, decreased libido (including loss of libido), sleep disturbances, unusual dreams (including nightmares),
• concentration disorders, dizziness, taste disorders, lethargy, drowsiness (including excessive drowsiness, sedation), tremors,
• blurred vision,
• palpitations, prolonged QT interval on the ECG,
• sudden flushing (including hot flashes),
• yawning,
• vomiting, dyspepsia,
• rash (including erythema, flushing), urticaria, itching, excessive sweating,
• joint pain,
• frequent urination (including urinary frequency),
• bleeding from the genital tract (including irregular menstrual bleeding, heavy or prolonged menstrual bleeding, more frequent menstrual bleeding, postmenopausal bleeding, uterine bleeding), erectile dysfunction, ejaculation disorders (including absent ejaculation, ejaculatory failure, premature ejaculation, delayed ejaculation, retrograde ejaculation),
• feeling of trembling, chills,
• weight loss.

Uncommon (may affect up to 1 in 100 patients)

• depersonalization (feeling of losing one's identity), elevated mood, euphoria, thought process disorders, orgasm disorders (including absent orgasm), bruxism (grinding teeth), suicidal thoughts and behaviors (including suicide attempts, suicidal thoughts, intentional self-injury, suicidal ideation). These symptoms may be related to the underlying disease,
• excessive psychomotor activity, dyskinesia (uncoordinated and involuntary movements of the face and tongue), ataxia (disorder of movement coordination), balance disorders, seizures, memory disorders,
• pupil dilation,
• tinnitus,
• hypotension,
• dyspnea, epistaxis,
• dysphagia (difficulty swallowing), gastrointestinal bleeding (including most commonly gingival bleeding, hematemesis, melena, rectal bleeding, hematochezia, tarry stools),
• alopecia, increased bruising, cold sweats,
• muscle tremors,
• dysuria (painful urination),
• sexual function disorders,
• malaise, changed mental status, feeling of cold, feeling of heat,
• increased liver enzyme activity.

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

• blood disorders - decreased platelet count, decreased neutrophil count, decreased white blood cell count,
• anaphylactic reactions (immediate allergic reactions, occurring after re-exposure to the allergen), serum sickness,
• inappropriate antidiuretic hormone secretion,
• hyponatremia (low sodium levels in the blood),
• hypomania, mania, hallucinations, agitation, panic attacks, confusion, stuttering, aggression,
• seizures, akathisia (symptoms including psychomotor agitation, restlessness, anxiety, irritability), involuntary and uncontrolled movements of the face and tongue, serotonin syndrome,
• ventricular arrhythmias, including torsades de pointes,
• vasculitis, vasodilation,
• pharyngitis, pulmonary disorders (various inflammatory and/or fibrotic processes in the lungs, including pulmonary fibrosis, interstitial lung disease),
• esophageal pain,
• hepatitis,
• angioedema (swelling of the skin or mucous membranes or severe allergic reaction causing swelling of the face or throat, which may make breathing difficult), purpura, photosensitivity, erythema multiforme (skin hypersensitivity syndrome of varying severity), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome)
• muscle pain,
• urinary retention, urinary disorders,
• galactorrhea, hyperprolactinemia (elevated prolactin levels in the blood), priapism (prolonged, painful erection),
• bleeding from mucous membranes.

Unknown frequency (cannot be estimated from the available data)

• severe postpartum hemorrhage, occurring shortly after delivery (postpartum hemorrhage), see additional information in the "Pregnancy" subsection of section 2.

In patients over 50 years old taking SSRIs and tricyclic antidepressants, there is an increased risk of fractures.

Additional side effects in children and adolescents

In children and adolescents taking antidepressant medicines of this class, suicidal behavior (attempts and suicidal thoughts), hostility (mainly anger, irritability, aggression, restlessness, hyperactivity), manic episodes (including mania and hypomania), and nosebleeds have been reported.
In children and adolescents taking fluoxetine, isolated cases of growth delay and side effects indicating potential delay in pubertal development or sexual function disorders have been reported.
In clinical trials with children, treatment with fluoxetine was associated with decreased alkaline phosphatase activity.
Reporting side effects
If any side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps to gather more information on the safety of the medicine.

5. How to store Bioxetin

The medicine should be stored out of sight and reach of children.
The medicine should not be taken after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month.
No special storage precautions are required. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Bioxetin contains

• The active substance of the medicine is fluoxetine. Each tablet contains 20 mg of fluoxetine (as fluoxetine hydrochloride).
• The other ingredients are: microcrystalline cellulose, sodium carboxymethylcellulose, magnesium stearate.

What Bioxetin looks like and contents of the pack

Round, flat tablets with beveled edges, 5.8-6.2 mm in diameter.
White or almost white, without spots, stains, or cracks.
One pack contains 30 or 100 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder:
neuraxpharm Arzneimittel GmbH
Elisabeth-Selbert Str. 23
40764 Langenfeld
Germany
Manufacturer:
Opella Healthcare Poland Sp. z o.o.
Branch in Rzeszów
ul. Lubelska 52
35-233 Rzeszów
To obtain more detailed information about this medicine, the patient should contact the local representative of the marketing authorization holder:
Neuraxpharm Polska Sp. z o.o.
ul. Poleczki 35
02-822 Warsaw
info-poland@neuraxpharm.com

Date of last revision of the leaflet: