OXITRIL 30 mg GASTRO-RESISTANT TABLETS

2. What you need to know before you take Oxitril

Do not take Oxitril if:

• you are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6)
• you have liver failure
• you have severe kidney disease
• you are taking or have taken within the last 14 days another medicinal product called a monoamine oxidase inhibitor (MAOI) (see "Other medicines and Oxitril")
• you are taking fluvoxamine, which is usually used to treat depression, ciprofloxacin, or enoxacin, which are used to treat some infections
• you are taking other medicines that contain duloxetine (see "Other medicines and Oxitril")

Consult your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you should take Oxitril.

Warnings and precautions

Oxitril may not be suitable for you due to the following reasons. Consult your doctor or pharmacist before starting to take Oxitril if:

• you are using other medicines to treat depression (see "Other medicines and Oxitril")
• you are taking St. John's Wort, a herbal remedy (Hypericum perforatum)
• you are taking buprenorphine or the combination buprenorphine/naloxone. The use of these medicines with Oxitril may cause serotonin syndrome, a potentially life-threatening disease (see "Other medicines and Oxitril")
• you have any kidney disease
• you have had seizures (epileptic fits)
• you have had mania
• you suffer from bipolar disorder
• you have eye problems, such as certain types of glaucoma (increased eye pressure)
• you have had bleeding problems (tendency to develop bruises), especially if you are pregnant (see "Pregnancy and breast-feeding")
• you are at risk of having low sodium levels (e.g., if you are taking diuretics, especially if you are an elderly person)
• you are being treated with other medicines that may cause liver damage
• you are taking other medicines that contain duloxetine (see "Other medicines and Oxitril")

Oxitril may cause a feeling of restlessness or an inability to sit or stand still. If this happens, you should tell your doctor.

Some medicines of the same class as Oxitril (called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming yourself or suicide. These thoughts may be increased at the start of treatment with antidepressants, as all these medicines take time to work, usually about 2 weeks, but sometimes longer.

It is more likely that you will have these thoughts if:

• you have previously had thoughts of self-harm or suicide
• you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults under 25 years with psychiatric conditions who were treated with an antidepressant

Contact your doctor or go to the hospital immediately if you have any thoughts of self-harm or suicide.

It may be helpful to tell a relative or close friend that you are depressed or have an anxiety disorder 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.

You should also contact your doctor:

If you experience signs and symptoms of restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting, as you may be suffering from serotonin syndrome.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). The signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Children and adolescents

Oxitril should not normally be used in children and adolescents under 18 years. Also, you should know that patients under 18 years who take this type of medicine have an increased risk of side effects such as suicidal thoughts, suicidal attempts, and hostility (mainly aggression, oppositional behavior, and anger). Despite this, your doctor may prescribe Oxitril to patients under 18 years if they decide that it can be beneficial for the patient. If your doctor has prescribed Oxitril to a patient under 18 years and you want to discuss it, please go back to your doctor. You must tell your doctor if any of the above symptoms appear or worsen in patients under 18 years who are taking Oxitril. Additionally, in this age group, the long-term safety effects of Oxitril related to growth, maturation, and cognitive and behavioral development have not yet been demonstrated.

Other medicines and Oxitril

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

The main component of Oxitril, duloxetine, is used in other medicines for other treatments:

• diabetic neuropathic pain, depression, anxiety, and urinary incontinence.

It should be avoided to use more than one of these medicines at the same time. Check with your doctor if you are already using other medicines that contain duloxetine.

Your doctor will decide if you can take Oxitril with other medicines. Do not start or stop taking any medicine, including those obtained without a prescription, and herbal remedies, without first talking to your doctor.

You should also tell your doctor if you are taking any of the following medicines:

Monoamine oxidase inhibitors (MAOIs):You should not take Oxitril if you are taking, or have taken in the last 14 days, another antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking an MAOI with many prescription medicines, including Oxitril, can cause serious side effects, even life-threatening. You should wait at least 14 days after stopping an MAOI before taking Oxitril. Similarly, you should wait at least 5 days after stopping Oxitril before starting an MAOI.

Medicines that cause drowsiness:These include medicines prescribed by your doctor, such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.

Medicines that increase serotonin levels:Triptans, tramadol, tryptophan, selective serotonin reuptake inhibitors (SSRIs, such as paroxetine and fluoxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs, such as venlafaxine), tricyclic antidepressants (such as clomipramine, amitriptyline), pethidine, St. John's Wort, and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of side effects; if you notice any unusual symptoms when using any of these medicines with Oxitril, you should tell your doctor.

Buprenorphine/opioids:Oxitril should be administered with caution when given concomitantly with buprenorphine or the combination buprenorphine/naloxone, as it increases the risk of serotonin syndrome, a partially life-threatening disease (see section 4.4).

Oral anticoagulants or antiplatelet agents:Medicines that thin the blood or prevent blood clots. These medicines may increase the risk of bleeding.

Taking Oxitril with food, drinks, and alcohol

Oxitril can be taken with or without food. You should be cautious if you drink alcohol while being treated with Oxitril.

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.

• Tell your doctor if you become pregnant or are planning to become pregnant while being treated with Oxitril. You should only use Oxitril after discussing the potential benefits and risks to the fetus with your doctor.
• Make sure your midwife and/or doctor know you are taking Oxitril. Other similar medicines (SSRIs), taken during pregnancy, may increase the risk of a serious condition in babies called persistent pulmonary hypertension of the newborn (PPHN), which makes the baby breathe faster and turn blue. These symptoms usually start during the first 24 hours after the baby is born. If this happens to your baby, you should contact your midwife and/or doctor immediately.
• If you take Oxitril near the end of your pregnancy, your baby may have some symptoms when it is born. These usually start at birth or within the first few days of your baby's life. These symptoms include weak muscles, trembling, overactive reflexes, or poor feeding, breathing difficulties, seizures, and vomiting. If your baby has any of these symptoms when it is born, or if you are worried about your baby's health, contact your doctor or midwife, who will be able to advise you.
• If you take Oxitril near the end of your pregnancy, there is a greater risk of excessive vaginal bleeding shortly after delivery, especially if you have had bleeding problems. Your doctor or midwife should know that you are taking duloxetine so they can advise you.
• Data on the use of Oxitril during the first three months of pregnancy do not show an increased overall risk of birth defects in the baby. If you take Oxitril during the second half of pregnancy, there may be a greater risk that the baby will be born early (6 additional premature babies per 100 women taking Oxitril in the second half of pregnancy), especially between weeks 35 and 36 of pregnancy.
• Tell your doctor if you are breast-feeding. It is not recommended to use Oxitril during breast-feeding. Ask your doctor or pharmacist for advice.

Driving and using machines

During treatment with Oxitril, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how the treatment with Oxitril affects you.

Oxitril contains sucrose and inverted sugar

Oxitril contains compressible sugar which includes sucrose and inverted sugar (glucose and fructose). If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Oxitril

Follow exactly the instructions of your doctor or pharmacist. If you are not sure, ask your doctor or pharmacist again.

Oxitril should be taken by mouth. You should swallow the tablet whole with water.

For depression and diabetic neuropathic pain:

The recommended dose of Oxitril is 60 mg once a day, but your doctor will prescribe the dose that is best for you.

For generalized anxiety disorder:

The usual starting dose of Oxitril is 30 mg once a day, after which most patients will receive 60 mg once a day, but your doctor will prescribe the dose that is best for you. The dose may be adjusted up to 120 mg per day depending on your response to Oxitril.

To help you remember to take Oxitril, it may be helpful to take it at the same time every day.

Discuss with your doctor how long you should take Oxitril. Do not stop taking Oxitril or change your dose without talking to your doctor. It is important to treat your condition properly to help you improve. If you do not treat it, your condition may not disappear and may become more severe and more difficult to treat.

If you take more Oxitril than you should

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

Among the symptoms produced by an overdose are drowsiness, coma, serotonin syndrome (a rare reaction that can cause a feeling of intense happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heartbeat.

If you forget to take Oxitril

If you forget to take a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take a single dose as you normally would. Do not take a double dose to make up for missed doses. Do not take more Oxitril than prescribed for you in a day.

If you stop taking Oxitril

Do not stop taking your tablets without your doctor's advice, even if you feel better. If your doctor thinks you do not need to continue taking Oxitril, they will tell you to reduce your dose over at least 2 weeks before stopping treatment.

Some patients who have stopped taking duloxetine have experienced symptoms such as:

• dizziness, tingling sensations like pins and needles or electric shock-like sensations (especially in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling restless or agitated, feeling anxious, nausea or vomiting, tremor, headache, muscle pain, feeling irritable, diarrhea, and excessive sweating or dizziness.

These symptoms are usually not serious and disappear within a few days, but if you have symptoms that are bothersome, ask your doctor for advice.

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. These effects are usually mild to moderate and disappear, often, in a few weeks.

Very Common Adverse Effects (may affect more than 1 in 10 patients)

• headache, drowsiness
• discomfort (nausea), dry mouth

Common Adverse Effects (may affect up to 1 in 10 patients)

• loss of appetite
• difficulty sleeping, feeling of agitation, decreased sexual desire, anxiety, difficulty or inability to have an orgasm, unusual dreams
• dizziness, feeling of slowness, tremor, numbness, including numbness, itching, or tingling of the skin
• blurred vision
• tinnitus (perception of sounds in the ear when there is no external sound)
• feeling palpitations in the chest
• increased blood pressure, flushing
• increased yawning
• constipation, diarrhea, stomach pain, vomiting, heartburn or indigestion, gas
• increased sweating, rash (itching)
• muscle pain, muscle spasms
• difficulty or pain when urinating, frequent urination
• difficulty getting an erection, changes in ejaculation
• falls (mostly in elderly people), fatigue
• weight loss

Children and adolescents under 18 years of age with depression treated with this medicine suffered a decrease in weight when they started taking this medicine. After 6 months of treatment, the weight increased to similar levels as other children and adolescents of the same age and sex.

Uncommon Adverse Effects (may affect up to 1 in 100 patients)

• inflammation of the throat that causes hoarseness
• suicidal thoughts, difficulty sleeping, teeth grinding, feeling of disorientation, lack of motivation
• muscle spasms and involuntary movements, feeling of restlessness or inability to remain seated or still, nervousness, difficulty concentrating, changes in taste, difficulty controlling movements, e.g., lack of coordination or involuntary muscle movements, restless legs syndrome, poor quality sleep
• dilation of the pupils (the black dot in the center of the eye), vision problems
• feeling of dizziness or vertigo, ear pain
• rapid and/or irregular heartbeats
• fainting, dizziness, feeling of dizziness or fainting when standing up, coldness in the fingers of the hands and/or feet
• throat spasms, nosebleeds
• vomiting blood, or black stools, gastroenteritis, belching, difficulty swallowing
• inflammation of the liver that can cause abdominal pain and yellowing of the skin or the white part of the eyes
• night sweats, rashes, cold sweats, sensitivity to sunlight, increased tendency to bruise
• muscle stiffness, muscle spasms
• difficulty or inability to urinate, difficulty starting urination, need to urinate at night, need to urinate more than usual, decreased urine flow
• abnormal vaginal bleeding, abnormal menstrual periods, including heavy, painful, irregular, or prolonged menstrual periods, exceptionally light or absent menstrual periods, pain in the testicles or scrotum
• chest pain, feeling of cold, thirst, chills, feeling of heat, alteration in gait
• weight gain
• Oxitril may cause effects that you may not be aware of, such as increased liver enzymes or potassium levels in the blood, creatine phosphokinase, sugar, or cholesterol

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

• severe allergic reactions that cause difficulty breathing or dizziness with swelling of the tongue or lips, allergic reactions
• decreased activity of the thyroid gland, which can cause fatigue or weight gain
• dehydration, low sodium levels in the blood (mostly in elderly people; symptoms may include feeling of dizziness, weakness, confusion, sleepiness, or excessive tiredness, nausea, or vomiting, the most serious symptoms are fainting, seizures, or falls), syndrome of inadequate secretion of antidiuretic hormone (SIADH)
• suicidal behavior, mania (hyperactivity, accelerated thinking, and decreased need for sleep), hallucinations, aggression, and anger
• "Serotonin syndrome" (a rare reaction that can cause feelings of intense happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating, or muscle stiffness), seizures
• increased pressure in the eye (glaucoma)
• cough, wheezing, and shortness of breath, which may be accompanied by fever
• inflammation of the mouth, bright red blood in the stool, bad breath, inflammation of the large intestine (leading to diarrhea)
• liver failure, yellowing of the skin or the white part of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious disease with blistering of the skin, mouth, eyes, and genitals), severe allergic reactions that cause swelling of the face or throat (angioedema)
• jaw muscle contractions
• unusual urine odor
• menopausal symptoms, abnormal milk production in men or women
• excessive vaginal bleeding shortly after birth (postpartum hemorrhage)

Very Rare Adverse Effects (may affect up to 1 in 10,000 patients)

• inflammation of the blood vessels in the skin (cutaneous vasculitis)

Frequency Not Known (cannot be estimated from the available data)

• signs and symptoms of a condition called "stress cardiomyopathy", which may include chest pain, difficulty breathing, dizziness, fainting, and irregular heartbeats

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 prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines, website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Oxitril

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

Do not use this medicine after the expiration date that appears on the packaging, after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. 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

Oxitril Composition

-The active ingredient is duloxetine. Each gastro-resistant tablet contains 34.36 mg of duloxetine (as hydrochloride), equivalent to 30 mg of duloxetine.

-The other components (excipients) are:Core of the tablet: 30% dispersion of acrylic acid:ethyl acrylate copolymer (1:1), triethyl citrate, micronized talc, titanium dioxide, and simethicone emulsion.

Appearance of the Product and Package Contents

Oxitril is a white, round, biconvex, and gastro-resistant tablet marked on one side with "( ".

Oxitril is available in packages of 7 and 28 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Adamed Laboratorios, S.L.U.

c/ de las Rosas de Aravaca, 31 – 2ª planta

28023 Aravaca (Madrid)

Manufacturer

Adamed Pharma S.A.

ul. Marszalka Józefa Pilsudskiego, 5

95-200 Pabianice, Poland

Date of the Last Revision of this Prospectus: June 2024.

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