DULOXETINE KRKA 60 mg GASTRO-RESISTANT HARD CAPSULES

2. What you need to know before you take Duloxetine Krka

Do not take Duloxetine Krka

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

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

Warnings and precautions

Duloxetine may not be suitable for you due to the following reasons. Consult your doctor before taking this medicine if:

• you are using other medicines for depression, triptans, antipsychotics, buprenorphine. The use of these medicines with Duloxetine Krka may cause serotonin syndrome, a potentially life-threatening disease (see "Other medicines and Duloxetine Krka" and "Possible side effects")
• you are taking St. John's Wort, a herbal remedy (Hypericum perforatum)
• you have kidney disease
• you have had seizures (epileptic fits)
• you have had mania
• you have bipolar disorder
• you have eye problems, such as certain types of glaucoma (increased eye pressure)
• you have had bleeding problems (a 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 Duloxetine Krka")

You should also tell your doctor:

If you experience signs and symptoms of agitation, hallucinations, loss of coordination, rapid heart rate, 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 can include a combination of fever, rapid heart rate, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

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

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

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 or killing yourself. These thoughts may be increased when you first start taking antidepressants, as all these medicines take time to work, usually about two weeks, but sometimes longer.

You are more likely to 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 aged less than 25 years with psychiatric conditions who were treated with an antidepressant

Tell 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 might 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.

Children and adolescents under 18 years

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

Other medicines and Duloxetine Krka

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

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

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

You should avoid using 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 duloxetine with other medicines. Do not start or stop taking any medicine, including those obtained without a prescription, and herbal remedies, without talking to your doctor first.

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

Monoamine oxidase inhibitors (MAOIs): you should not take duloxetine if you are taking, or have taken within 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 duloxetine, can cause serious side effects, even life-threatening ones. You should wait at least 14 days after stopping an MAOI before taking duloxetine. Similarly, you should wait at least 5 days after stopping duloxetine before taking 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, buprenorphine (a medicine to treat pain or addiction to opioids), 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 such as serotonin syndrome (see "Warnings and precautions" and "Possible side effects"). If you notice any unusual symptoms when using any of these medicines with duloxetine, you should tell your doctor.

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

Taking Duloxetine Krka with food, drinks, and alcohol

Duloxetine can be taken with or without food. You should be careful if you drink alcohol while being treated with duloxetine.

Pregnancy, breast-feeding, and fertility

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 duloxetine. You should only use duloxetine after discussing the potential benefits and risks with your doctor.

• Make sure your midwife and/or doctor know you are taking duloxetine. 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 duloxetine 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, poor feeding, breathing difficulties, and seizures. 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 Duloxetine Krka 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 Duloxetine Krka during the first three months of pregnancy do not show an increased overall risk of birth defects in the baby. If you take Duloxetine Krka during the second half of your pregnancy, there may be a greater risk that your baby will be born early (6 additional premature babies per 100 women taking Duloxetine Krka in the second half of pregnancy), especially between weeks 35 and 36 of pregnancy.

• Tell your doctor if you are breast-feeding. Duloxetine is not recommended during breast-feeding. Ask your doctor or pharmacist for advice.

Driving and using machines

While being treated with duloxetine, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how the treatment with duloxetine affects you.

Duloxetine Krka contains sucrose

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

3. How to take Duloxetine Krka

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Duloxetine should be taken by mouth. You should swallow the capsule whole with water.

For depression and diabetic neuropathic pain:

The recommended dose of duloxetine 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 duloxetine 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 duloxetine.

To help you remember to take duloxetine, it may be helpful to take it at the same times each day.

Discuss with your doctor how long you should take duloxetine. Do not stop taking duloxetine, 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 your condition, it may not get better and may become more serious and more difficult to treat.

If you take more Duloxetine Krka than you should

If you have taken more duloxetine than you should, talk to a doctor or go to a hospital immediately. Take the medicine pack with you. Symptoms of overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause intense happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heart rate.

If you forget to take Duloxetine Krka

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 usual. Do not take a double dose to make up for a forgotten dose. Do not take more duloxetine than you should in a day.

If you stop taking Duloxetine Krka

Do not stop taking your capsules without talking to your doctor first, even if you feel better. If your doctor thinks you do not need to take duloxetine anymore, they will tell you how to reduce your dose over at least 2 weeks before stopping treatment.

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

• dizziness, sensations like pins and needles, or electric shock-like sensations (especially in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, drowsiness, restlessness or agitation, anxiety, nausea or vomiting, tremor, headache, muscle pain, irritability, diarrhea, and excessive sweating or dizziness

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

If you have any other questions about 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, within 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, tremors, 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 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, 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
• liver inflammation 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 menstruation, exceptionally light or absent menstruation, pain in the testicles or scrotum
• chest pain, feeling of cold, thirst, chills, feeling of heat, alteration in gait
• weight gain
• duloxetine 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, convulsions, 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 whose symptoms may include involuntary rhythmic muscle contractions, including the muscles that control eye movement, agitation, hallucinations, coma, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, body temperature above 38°C, nausea, vomiting, diarrhea, convulsions;
• increased pressure in the eye (glaucoma);
• cough, wheezing, and difficulty breathing, which may be accompanied by high 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);
• contractions of the jaw muscle;
• unusual odor of urine;
• 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 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 national reporting system: 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 Duloxetine Krka

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.

Do not store at a temperature above 25°C.

Keep in the original packaging to protect it from moisture.

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

6. Package Contents and Additional Information

Composition of Duloxetine Krka

• The active ingredient is duloxetine. Each hard gastro-resistant capsule contains 60 mg of duloxetine (as hydrochloride).
• The other ingredients are:

Capsule content:sugar spheres (cornstarch and sucrose), hypromellose 6Cp, sucrose, hypromellose phthalate, talc (E553b), and triethyl citrate (E1505)

Capsule shell:gelatin (E441), titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172), ink (shellac (E904), black iron oxide (E172)).

See section 2 "Duloxetine Krka contains sucrose".

Product Appearance and Package Contents

White to almost white granulate in a hard gelatin capsule of size 1. The body of the capsule is yellow-green and the cap is dark blue. The body of the capsule is printed with 60 in black.

Duloxetine Krka is available in packages of 7 and 28 hard gastro-resistant capsules in blisters.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

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

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, Pta. Baja, Oficina 1, 28108 Alcobendas, Madrid, Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the Last Revision of this Prospectus: September 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/