PAXTIBI 25 mg FILM-COATED TABLETS

2. What you need to know before you take Paxtibi

Do not take Paxtibi

• if you are allergic to nortriptyline or any of the other ingredients of this medicine (listed in section 6),
• if you have recently had a heart attack (myocardial infarction) or have heart rhythm disturbances detected on an electrocardiogram (ECG) or any other heart problems,
• if you have bipolar disorder,
• if you are taking medicines called monoamine oxidase inhibitors (MAOIs - other medicines used for depression) or selegiline (used to treat Parkinson's disease) or have taken them in the last 14 days: if you have taken any of these medicines, you must wait 14 days before starting to take this medicine,

(MAOIs - other medicines used for depression or selegiline (used to treat Parkinson's disease)):

• if you have taken moclobemide (for depression treatment), you must wait one day before starting to take this medicine.

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine.

Suicidal thoughts and worsening of depression

If you are depressed and/or have anxiety disorders, you may sometimes have thoughts of harming or killing yourself. These kinds of thoughts can increase when you first start taking antidepressants, as all these medicines take time to work, usually about two weeks, but sometimes longer.

You may be more likely to have these kinds of thoughts:

• If you have had thoughts of killing or harming yourself in the past.
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately.

It may be helpful to tell a relative or close friendthat you are depressed and ask them to read this leaflet. You can ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behavior.

Tell your doctor if you have or have had any medical problems, especially:

• if you have epilepsy, a history of seizures or epileptic fits,
• if you are agitated, overactive or have schizophrenia,
• if you have difficulty urinating,
• if you have an enlarged prostate,
• if you have severe liver disease,
• if you have severe heart disease,
• if you have thyroid disease,
• if you have narrow-angle glaucoma (loss of vision due to abnormally high pressure in the eye),
• if you are being treated for diabetes, as your diabetic medication may need to be adjusted when you start treatment with Paxtibi,
• if you have any other mental disorder (psychiatric disorder) other than depression,
• if you are going to have an operation. Inform your doctor that you are taking this medicine,
• if you have low blood pressure,
• if you have a sore throat, fever, and flu-like symptoms in the first 10 weeks,
• if you have pyloric stenosis (narrowing of the stomach outlet) and paralytic ileus (blockage of the intestine),
• if you have a high fever (hyperpyrexia),

• if you have a heart condition called Brugada syndrome,
• if you are taking opioids (e.g., buprenorphine). The use of these medicines with Paxtibi may cause serotonin syndrome, a potentially life-threatening condition (see "Other medicines and Paxtibi").

Some patients with manic-depressive illness may enter a manic phase. This is characterized by unusual and rapidly changing thoughts, excessive joy, and excessive physical activity. In these cases, it is essential to consult your doctor.

Prolonged QT interval

A heart problem called "prolonged QT interval" (which appears on an electrocardiogram [ECG]) and heart rhythm disorders (fast or irregular heartbeat) have been reported with nortriptyline. Tell your doctor if:

• you have a slow heart rate,
• you have or have had a problem where your heart cannot pump blood to your body as it should (a situation called heart failure),
• you are taking any other medication that may cause heart problems, or
• you have a problem that causes low potassium or magnesium or high potassium levels in your blood.

If you are scheduled for surgery, your treatment with nortriptyline may need to be stopped before you are given anesthetics. In the case of emergency surgery, the anesthesiologist should be informed about your treatment with nortriptyline, as it may increase the risk of arrhythmias and hypotension.

• If you have an overactive thyroid gland or are taking thyroid medication.

If you are taking antidepressants like selective serotonin reuptake inhibitors (SSRIs), your doctor may consider changing your dose of the medicine (see also section 2 "Taking Paxtibi with other medicines" and section 3).

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age for these treatments, as safety and efficacy have not been established in this age group.

Elderly

The dosage should be reduced in the elderly. Elderly people are more likely to suffer from certain side effects, such as dizziness when standing up due to low blood pressure (see also section 4 "Possible side effects").

Other medicines and Paxtibi

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines may affect the way other medicines work, and this can sometimes cause serious side effects.

You should be particularly careful if you are taking any of the following medicines: monoamine oxidase inhibitors (MAOIs) such as moclobemide (for depression treatment) or selegiline (used to treat Parkinson's disease). These medicines must not be taken at the same time as nortriptyline (see section 2 "Do not take Paxtibi"):

• certain antihypertensive drugs such as clonidine and methyldopa. Medicines like Paxtibi may counteract the antihypertensive action,
• thioridazine (used to treat schizophrenia),
• tramadol (for pain relief),
• opioids, e.g., buprenorphine, may interact with Paxtibi and you may experience symptoms such as involuntary muscle contractions, including muscles that control eye movements, agitation, hallucinations, coma, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor if you experience these symptoms,
• substances with a stimulating effect on a certain part of the nervous system (sympathomimetics), such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine, and phenylpropanolamine (which may be present in cough and cold medicines and in some anesthetics),
• anticholinergic drugs such as certain medicines for Parkinson's disease and gastrointestinal disorders (e.g., atropine),
• medicines for high blood pressure such as, for example, calcium channel blockers (e.g., diltiazem, verapamil),
• medicines for fungal infections (e.g., fluconazole, terbinafine, ketoconazole, and itraconazole),
• sedatives (e.g., barbiturates),
• antidepressants (e.g., SSRIs [fluoxetine, paroxetine, fluvoxamine], duloxetine, and bupropion),
• medicines for certain heart conditions (e.g., beta-blockers and antiarrhythmics),
• cimetidine (used to treat stomach ulcers),
• methylphenidate (used to treat ADHD),
• rifampicin (for infection treatment),
• phenytoin and carbamazepine (used to treat epilepsy),
• thyroid medicines,
• valproic acid (a medicine used to treat epilepsy and bipolar disorder),
• anticoagulant medicines derived from coumarin or indandione,
• St. John's Wort (Hypericum perforatum), a herbal medicine used for depression.

You should also tell your doctor if you are taking or have recently taken medicines that may affect your heart rhythm, such as medicines for irregular heartbeats (e.g., quinidine and sotalol):

• astemizole and terfenadine (used to treat allergies and seasonal rhinitis),
• medicines used to treat certain mental illnesses (e.g., pimozide and sertindole),
• cisapride (used to treat certain types of indigestion),
• halofantrine (used to treat malaria),
• methadone (used to treat pain and for detoxification),
• diuretics ("water tablets" such as, e.g., furosemide).

Taking Paxtibi with alcohol

It is not recommended to drink alcohol during treatment with this medicine, as it may increase its sedative effect.

Pregnancy and breast-feeding

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

Nortriptyline is not recommended during pregnancy unless your doctor considers it clearly necessary and only after careful consideration of the benefit and risk. If you have taken this medicine during the last part of your pregnancy, the newborn may have withdrawal symptoms such as irritability, increased muscle tone, tremor, irregular breathing, poor sucking, loud crying, urinary retention, and constipation.

Your doctor will advise you whether to start/continue/stop breast-feeding or interrupt the use of this medicine, taking into account the benefit of breast-feeding for the child and the benefit of treatment for you.

Driving and using machines

This medicine may cause drowsiness and dizziness, especially at the start of treatment. Do not drive or use tools or machinery until you know how the treatment with nortriptyline affects you.

Paxtibi contains lactose and orange yellow S

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

This medicine contains orange yellow S (E110, azoic dye). This medicine may cause allergic reactions.

3. How to take Paxtibi

Follow exactly the instructions of administration of this medicine given by your doctor. If you are in doubt, consult your doctor or pharmacist again.

Adults

The daily dose in adults is 25 mg, 3 or 4 times a day, starting therapy with a low level and adjusting the dose. It can be given once a day, usually at night, or 3 or 4 times a day.

It may take between 2 and 4 weeks to achieve a response. Doses above 150 mg daily are not recommended.

Elderly

The dosage for elderly patients is 25 to 50 mg per day in divided doses.

Treatment should be started with a low dose (10-20 mg daily) and increased as needed up to a maximum dose of 50 mg.

If it is considered necessary to increase the dose in an elderly patient, the ECG should be checked and nortriptyline plasma levels should be monitored.

Pediatric population

Do not give this medicine to children and adolescents under 18 years of age for these treatments, as safety and efficacy have not been established in this age group.

Hepatic and renal impairment

The dose should be reduced in cases of hepatic or renal impairment, as nortriptyline is extensively metabolized in the liver and mainly eliminated via the kidneys.

How to take Paxtibi

The tablets should be taken with water.

Duration of treatment

Do not change the dose of the medicine or stop treatment with it without consulting your doctor first. Keep taking this medicine for as long as your doctor recommends.

The underlying illness may persist for a long time. If you stop treatment too early, the symptoms may come back.

It is recommended to continue treatment for at least 6 months after you feel better.

If you take more Paxtibi than you should

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you have taken one more Paxtibi tablet than you should by mistake, side effects like drowsiness, dry mouth, dizziness, or nausea may appear or worsen.

Symptoms of overdose may include:

• drowsiness or excitement
• agitation and hallucinations
• loss of consciousness
• difficulty breathing, blue discoloration of the skin
• pupil dilation
• seizures/convulsions
• heart disorders, including cardiac arrhythmias (observed on an ECG, an investigation to evaluate heart function)
• hypotension, weak pulse, paleness
• metabolic disorders
• dry mouth and tongue
• pulmonary edema
• fever
• coma
• urinary retention in the bladder due to alterations in bladder emptying (urinary retention)
• reduced intestinal movements (which can cause obstruction [constipation])
• confusion

Treatment for overdose should be done with general measures, gastric lavage, and assisted respiration.

If you forget to take Paxtibi

Take the next dose at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Paxtibi

Your doctor will decide when and how to stop treatment to avoid any unpleasant symptoms that may occur if treatment is stopped abruptly (e.g., headache, feeling unwell, insomnia, and irritability).

Therefore, treatment with nortriptyline should not be stopped suddenly. The dose should be gradually reduced over a week or more.

If you have any further 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.

If you notice any of the following symptoms, you should see your doctor immediately:

A heart problem "prolonged QT interval" (which can be seen on your electrocardiogram). Frequent adverse effect, may affect up to 1 in 10 people

Rare adverse effects (may affect up to 1 in 1,000 people).

• Yellowing of the skin and the white part of the eyes (jaundice). Your liver may be affected.
• Bruises, bleeding, paleness, or throat pain and persistent fever.

• These symptoms may be the first signs of a possible blood or bone marrow disorder. Blood effects can be a decrease in the number of red blood cells (which carry oxygen throughout the body), white blood cells (which help fight infections), and platelets (which help with blood clotting).
• Suicidal thoughts or behaviors.
• Involuntary and rhythmic muscle contractions, including muscles that control eye movements, agitation, hallucinations, coma, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, body temperature above 38 °C (signs of serotonin syndrome, a potentially life-threatening condition).
• Severe constipation, stomach swelling, fever, and vomiting. These symptoms may be due to paralysis of parts of the intestine.

Very rare adverse effects (may affect up to 1 in 10,000 people).

• Intermittent blurred vision, rainbow vision, and eye pain.

You should have an eye examination immediately before being able to continue treatment with this medicine. These symptoms may be a sign of acute glaucoma (very rare adverse effect, may affect up to 1 in 10,000 people).

The following adverse effects have been reported at the following frequencies:

Very frequent: may affect more than 1 in 10 people

• drowsiness/somnolence
• tremor, dizziness, headache
• irregular, strong, or rapid heartbeat (palpitations)
• dry mouth
• constipation
• nausea
• excessive sweating
• weight gain
• aggression
• nasal congestion
• eye accommodation disorders, disorder of adaptation to see from afar (accommodation disorder that makes objects appear blurry)

Frequent: may affect up to 1 in 10 people

• confusion
• sexual disorders (decreased sexual appetite, erection problems)
• attention disorders
• changes in taste
• numbness or tingling in the arms or legs
• coordination disorders
• dilated pupils (mydriasis)
• cardiac abnormalities observed as changes in the electrocardiogram (ECG)
• dizziness when standing up due to low blood pressure (orthostatic hypotension)
• fatigue
• low sodium levels in the blood
• urinary disorders
• feeling of thirst

Infrequent: may affect up to 1 in 100 people

• excitement, anxiety, difficulty sleeping, nightmares
• seizures
• ringing in the ears (tinnitus)
• increased blood pressure
• diarrhea, vomiting
• skin rash, hives (urticaria), swelling of the face and tongue
• difficulty urinating

• increased milk production during lactation or milk secretion without lactation

• increased pressure in the eyeball
• collapse situations
• worsening of heart failure
• worsening of liver function (e.g., cholestatic liver disease)

Rare: may affect up to 1 in 1,000 people

• decreased appetite
• delirium (especially in elderly patients), hallucinations
• abnormal heart rhythm or cardiac pattern
• swelling of the salivary glands
• hair loss
• increased sensitivity to sunlight
• increased breast size in men
• fever
• weight loss
• abnormal liver function test results
• decrease in blood cells, such as white blood cells, eosinophils, and platelets

Very rare: may affect up to 1 in 10,000 people

• heart muscle diseases
• acute increase in eye pressure
• particular forms of abnormal heart rhythm (also called torsades de pointes)
• allergic inflammation of the pulmonary alveolus and lung tissue

Frequency not known (cannot be estimated from available data)

• loss of appetite
• increase or decrease in blood sugar levels
• feeling of restlessness and need to be in constant motion
• agitation
• suicidal thoughts or behaviors
• movement disorders (involuntary or decreased movements)
• hypersensitivity inflammation of the heart muscle
• elevated body temperature
• hepatitis
• orgasm disorder in women, increased libido
• Brugada syndrome (unmasking) (symptoms may include rapid heartbeats, dizziness, fainting, seizures). Report immediately to your doctor if you experience these symptoms
• low sodium levels in the blood

An increased risk of bone fractures has been observed in patients treated with this type of medication.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Paxtibi

Keepthis medicineout of sight and reach of children.

This medicine does not require special storage conditions.

Do not use this medicine after the expiration date that appears on the packaging after CAD.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Paxtibi Composition

• The active ingredient is nortriptyline hydrochloride.

Each tablet contains 25 mg of nortriptyline hydrochloride.

• The other excipients are: lactose monohydrate, calcium phosphate dibasic, cornstarch, magnesium stearate, orange yellow S (E110), hydroxypropyl methylcellulose, ethylcellulose, and glycerin.

Product Appearance and Package Contents

Paxtibi 25 mg coated tablets are round, orange, convex, film-coated tablets.

The tablets are presented in aluminum/PVC blister packs of 25 coated tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Teva B.V.

Swensweg 5, 2031 GA Haarlem

Netherlands

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

Biowise Pharmaceuticals

C/Teixidors nº 22, Polígono industrial Can Robiols

07141 Marratxi, Balearic Islands

Spain

Manufacturer:

Lilly, S.A.

Avda. de la Industria, 30

Alcobendas, Madrid 28108

Spain

or

TOLL MANUFACTURING SERVICES, S.L.

Aragoneses, 2

Alcobendas, Madrid, 28108

Spain

Date of the last revision of this prospectus:August 2024

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/)