Dulsevia

Patient Information Leaflet

Warning! Keep this leaflet! The information on the immediate packaging is in a foreign language.
Dulsevia (Duloxetine Krka 60 mg), 60 mg, enteric hard capsules
Duloxetine
Dulsevia and Duloxetine Krka 60 mg are different trade names for the same medicine.
Please read this leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm others, even if their symptoms are similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Dulsevia is and what it is used for

Dulsevia contains the active substance duloxetine. Dulsevia increases the levels of serotonin and noradrenaline in the nervous system.
Dulsevia is indicated in adults for the treatment of:

• depression,
• generalized anxiety disorder (chronic feelings of anxiety or nervousness),
• diabetic neuropathic pain (typically described as burning, stabbing, shooting, or electric shock-like pain. In certain areas of the body, there may be loss of sensation, or sensations of touch, heat, or cold may occur, and pressure may cause pain).

In most people with depression or anxiety, Dulsevia starts to work within two weeks of starting treatment, but it may take 2 to 4 weeks before improvement is noticeable. If there is no improvement after this time, consult your doctor. Even if the patient's condition improves, the doctor may recommend continuing treatment with Dulsevia to prevent recurrence of depression or anxiety.
In people with diabetic neuropathic pain, improvement may occur after several weeks. Consult your doctor if there is no improvement after 2 months.

2. Important information before using Dulsevia

When not to use Dulsevia:

• if the patient is allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6),
• if the patient has liver disease,
• if the patient has severe kidney disease,
• if the patient is taking or has taken within the last 14 days another medicine which is a monoamine oxidase inhibitor (MAOI) (see "Dulsevia with other medicines"),
• if the patient is taking fluvoxamine, which is usually used to treat depression, ciprofloxacin or enoxacin, medicines used to treat certain infections,
• if the patient is taking other medicines containing duloxetine (see "Dulsevia with other medicines").

Tell the doctor if the patient has high blood pressure or heart disease. The doctor will decide whether the patient should take Dulsevia.

Warnings and precautions

The following are some reasons why Dulsevia may not be suitable for the patient. Before taking Dulsevia, the patient should inform the doctor if any of the following apply:

• taking other antidepressants, triptans, antipsychotic medicines, or buprenorphine. Taking these medicines together with Dulsevia may lead to serotonin syndrome, a potentially life-threatening condition (see "Dulsevia with other medicines" and "Possible side effects"),
• taking herbal medicines containing St John's wort (Hypericum perforatum),
• kidney disease,
• history of seizures,
• current or past episodes of mania,
• bipolar affective disorders,
• eye disorders, such as a specific type of glaucoma (increased pressure in the eye),
• history of bleeding disorders (tendency to bruise easily), especially if the patient is pregnant (see "Pregnancy and breastfeeding"),
• risk of low sodium levels (for example, when taking diuretics, particularly in elderly patients),
• taking other medicines that may cause liver damage,
• taking other medicines containing duloxetine (see "Dulsevia with other medicines").

Medicines such as Dulsevia (so-called SSRIs or SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms may persist after stopping treatment.

Dulsevia may cause feelings of restlessness or an inability to sit still or remain motionless. If such symptoms occur, inform the doctor.

Suicidal thoughts and worsening depression or anxiety

Depression and (or) anxiety may lead to thoughts of self-harm or suicide. These may worsen at the beginning of treatment with antidepressants, because it takes some time, usually two weeks or longer, before these medicines start to work. Such thoughts may increase:

• in patients who previously experienced suicidal thoughts or thoughts of self-harm,
• in young adults. Clinical trial data have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders who were treated with antidepressants.

If thoughts of self-harm or suicide occur, contact a doctor immediately or go directly to hospital.

It may be helpful to inform a relative or close friend about the depressive or anxious condition and ask them to read this leaflet for the patient. You may also ask them whether the depression or anxiety has worsened or whether changes in behaviour are concerning.

Children and adolescents under 18 years of age

Dulsevia is generally not recommended for use in children and adolescents under 18 years of age. In patients under 18 years of age taking medicines of this class, there is an increased risk of adverse reactions such as suicide attempts, suicidal thoughts, and hostility (mainly aggression, defiant behaviour, and anger). However, a doctor may decide to prescribe Dulsevia for patients under 18 years of age if they consider it beneficial. If in doubt, when a doctor prescribes Dulsevia for a patient under 18 years of age, contact the doctor again. Inform the doctor if any of the above-mentioned adverse reactions occur or worsen in a patient under 18 years of age taking Dulsevia. In addition, there is a lack of long-term safety data on the use of duloxetine in this age group regarding growth, puberty, cognitive development, and behavioural development.

Dulsevia with other medicines

Tell the doctor or pharmacist about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take, including those available without a prescription.

Duloxetine, the main ingredient of Dulsevia, is also present in other medicines used to treat other conditions:

• pain in diabetic neuropathy, depression, anxiety, and urinary incontinence.

Avoid taking more than one of these medicines simultaneously. The patient should consult the doctor if taking other medicines containing duloxetine.

The doctor will decide whether it is safe to take Dulsevia together with other medicines. Do not start or stop taking other medicines, including those available without a prescription and herbal preparations, without consulting a doctor.

Inform the doctor if taking any of the following medicines:

Monoamine oxidase inhibitors (MAOIs): Do not take Dulsevia together with another antidepressant called a monoamine oxidase inhibitor (MAOI) or within a short time interval (within 14 days) after stopping an MAOI. Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking MAOIs together with many prescription medicines, including Dulsevia, may cause severe or even life-threatening side effects. At least 14 days must pass after stopping an MAOI before starting Dulsevia. At least 5 days must pass after stopping Dulsevia before starting an MAOI.

Medicines causing drowsiness: These include prescription medicines such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.

Medicines increasing serotonin levels: Triptans, buprenorphine (a medicine used to treat pain or opioid dependence), tramadol, tryptophan, selective serotonin reuptake inhibitors (e.g. paroxetine and fluoxetine), selective norepinephrine reuptake inhibitors (e.g. venlafaxine), tricyclic antidepressants (e.g. clomipramine, amitriptyline), pethidine, St John's wort (Hypericum perforatum), and MAOIs (e.g. moclobemide and linezolid). These medicines increase the risk of adverse effects such as serotonin syndrome (see "Warnings and precautions" and "Possible side effects").

If any symptoms occur while taking these medicines together with Dulsevia, contact the doctor.

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

Dulsevia with food, drink and alcohol

Dulsevia can be taken during or between meals. Exercise caution when consuming alcohol while taking Dulsevia.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a baby, she should consult a doctor before using this medicine.

• The patient should inform the doctor if she becomes pregnant while taking Dulsevia or plans to become pregnant. The patient may take Dulsevia only after discussing with the doctor the expected benefits of treatment and the possible risks to the unborn child.
• The patient should inform the midwife and (or) doctor about taking Dulsevia. Using similar medicines (selective serotonin reuptake inhibitors) during pregnancy may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn, causing the baby to breathe faster and appear blue. These symptoms usually occur within the first 24 hours after birth. If the patient notices these symptoms in her baby, she should contact the midwife and (or) doctor immediately.
• If the patient takes Dulsevia towards the end of pregnancy, certain symptoms may occur in her newborn. These usually appear at birth or within a few days after birth. Symptoms may include muscle weakness, tremor, shakiness, feeding difficulties, breathing problems, and seizures. If the patient notices any of these symptoms or is concerned about her baby's health, she should contact a doctor or midwife for help.
• If the patient takes Dulsevia towards the end of pregnancy, there is an increased risk of excessive vaginal bleeding shortly after delivery, especially if she has a history of bleeding disorders. Inform the doctor or midwife about taking duloxetine so they can recommend appropriate management.
• Available data on the use of Dulsevia during the first three months of pregnancy generally do not show an increased risk of congenital malformations in the child. If the patient takes Dulsevia during the second half of pregnancy, there may be an increased risk of premature delivery, mainly between weeks 35 and 36 of pregnancy (6 additional premature births per 100 women taking Dulsevia during the second half of pregnancy).
• The patient should inform the doctor if she is breastfeeding. Dulsevia is not recommended during breastfeeding. Breastfeeding women should consult a doctor or pharmacist for advice.

Driving and operating machinery

Dulsevia may cause drowsiness or dizziness. The patient should not drive or operate machinery until they know how they react to Dulsevia.

Dulsevia contains sucrose

If the doctor has previously diagnosed the patient with an intolerance to certain sugars, consult the doctor before starting this medicine.

3. How to take Dulsevia

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Dulsevia is available in the following strengths: 30 mg, 60 mg.
Dulsevia is taken orally. The capsule should be swallowed whole with water.
Treatment of depression and diabetic neuropathic pain
The usual dose of Dulsevia is 60 mg taken once daily. However, the doctor will recommend
a dose appropriate for the individual patient.
Treatment of generalized anxiety disorder
The usual initial dose of Dulsevia is 30 mg once daily. In most patients, the dose is subsequently
increased to 60 mg once daily. However, the doctor will recommend the appropriate dose
for the individual patient. The dose may be increased up to 120 mg depending on the patient's
response to treatment.
Taking Dulsevia at the same time each day will help remember to take it.
The doctor will inform the patient how long Dulsevia should be taken. Do not stop
taking Dulsevia or change the dose without consulting the doctor. Proper treatment of the condition
is essential for the patient to feel better. Without treatment, the patient's condition may persist,
worsen, and become difficult to treat.
Taking more Dulsevia than prescribed
If an overdose of Dulsevia is taken, contact a doctor or pharmacist immediately.
Symptoms of overdose include: drowsiness, coma, serotonin syndrome
(a rare reaction which may cause feelings of excessive well-being, drowsiness,
lack of coordination, restlessness, a sensation of drunkenness, fever, sweating,
or muscle stiffness), seizures, vomiting, and rapid heartbeat.
Missing a dose of Dulsevia
If a dose is missed, take it as soon as possible. However, if it is almost time for the next dose,
skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up
for a missed dose. Do not take more than the prescribed daily dose of Dulsevia.
Stopping Dulsevia
Even if feeling better, DO NOT stop taking Dulsevia without consulting the doctor.
If the doctor decides that the patient no longer needs to take Dulsevia, the dose will be reduced
gradually over at least 2 weeks.
In some patients who abruptly stop taking duloxetine, the following symptoms may occur:

• dizziness, tingling sensations like pins and needles or electric shocks (especially in the head), sleep disturbances (vivid dreams, nightmares, difficulty falling asleep), fatigue, drowsiness, restlessness or agitation, anxiety, nausea or vomiting, tremor, headache, muscle pain, irritability, diarrhea, and excessive sweating or dizziness due to vestibular disturbances.

These symptoms are usually not serious and resolve within a few days. However, if they are bothersome,
contact a doctor.
If there are any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Very common adverse effects (may occur in more than 1 in 10 patients):

• headache, drowsiness
• nausea, dry mouth.

Common adverse effects (may occur in up to 1 in 10 patients):

• loss of appetite
• sleep disturbances, restlessness, decreased libido, anxiety, difficulty or inability to achieve orgasm, unusual dreams
• dizziness, feeling of sluggishness, muscle tremor, numbness, including numbness, prickling or tingling sensation of the skin
• blurred vision
• tinnitus (ringing in the ears in the absence of an external sound source)
• palpitations
• increased blood pressure, sudden flushing of the face
• increased yawning
• constipation, diarrhoea, abdominal pain, vomiting, heartburn or indigestion, flatulence
• increased sweating, rash (itchy)
• muscle pain, muscle cramps
• painful urination, frequent urination
• problems achieving erection, changes in ejaculation
• falls (especially in elderly patients), fatigue
• weight loss.

In children and adolescents under 18 years of age with depression treated with duloxetine,
weight loss has been observed after starting the medicine. After 6 months of treatment, body weight
increased and equalized with that observed in other children and adolescents of the same age and
sex.
Uncommon adverse effects (may occur in up to 1 in 100 patients):

• sore throat causing hoarseness
• suicidal thoughts, difficulty falling asleep, teeth grinding, disorientation, lack of motivation
• sudden, involuntary movements or muscle twitching, feeling of restlessness or inability to sit or stand still quietly, irritability, difficulty concentrating, taste disturbances, difficulty controlling movements, e.g. lack of coordination or unintended muscle movements, restless legs syndrome, worsened quality of sleep
• pupil dilation (dark central point of the eye), vision problems
• dizziness, dizziness due to vestibular disorders, ear pain
• rapid and (or) irregular heartbeat
• fainting, dizziness, feeling of emptiness in the head or fainting upon standing, feeling of coldness in the fingers of the hands and (or) feet
• tightness in the throat, nosebleeds
• vomiting blood or black, tarry stools, inflammation of the stomach and intestines, regurgitation of stomach contents, difficulty swallowing
• liver inflammation, which may cause abdominal pain and yellowing of the skin or whites of the eyes
• night sweats, urticaria, cold sweats, photosensitivity, increased tendency to bruising
• muscle stiffness and tremor
• difficulty or inability to urinate, difficulty initiating urination, need to urinate at night, need to urinate more than usual, decreased amount of urine output
• abnormal vaginal bleeding, menstrual disorders, including heavy, painful, irregular or prolonged periods, rarely scanty periods or absence of periods, testicular or scrotal pain
• chest pain, feeling of coldness, thirst, chills, feeling of heat, gait disturbances
• weight gain
• the medicine Dulsevia may cause adverse effects of which one may not be aware, such as increased activity of liver enzymes or blood potassium levels, increased creatine phosphokinase activity, blood glucose or cholesterol levels.

Rare adverse effects (may occur in up to 1 in 1000 patients):

• severe allergic reaction causing breathing difficulties, dizziness with swollen tongue or lips, allergic reactions
• decreased thyroid function, which may cause fatigue or weight gain
• dehydration, low blood sodium levels (especially in elderly patients; symptoms may include: dizziness, weakness, confusion, drowsiness, excessive fatigue, nausea, or vomiting; more severe symptoms include fainting, seizures and falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• suicidal behaviour, manic state (excessive activity, racing thoughts and reduced need for sleep), hallucinations, aggression and outbursts of anger
• "serotonin syndrome" (a rare reaction whose symptoms may include involuntary, rhythmic muscle contractions, including those of the eye muscles, restlessness, hallucinations, coma, excessive sweating, tremor, hyperreflexia, increased muscle tone, body temperature above 38°C, nausea, vomiting, diarrhoea), seizures
• increased intraocular pressure (glaucoma)
• cough, wheezing and shortness of breath, possibly accompanied by fever
• inflammation of the oral cavity, bright red blood in stools, bad breath, inflammation of the large intestine (leading to diarrhoea)
• liver failure, yellowing of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious condition with skin, oral cavity, eye and genital ulceration), severe allergic reaction causing facial or throat swelling (angioedema)
• jaw muscle spasm
• abnormal odour of urine
• menopausal symptoms, abnormal milk production in men or women in the mammary glands
• excessive vaginal bleeding shortly after childbirth (postpartum haemorrhage).

Very rare adverse effects (may occur in up to 1 in 10,000 patients):

• vasculitis of the skin.

Reporting of adverse effects
If any adverse symptoms occur, including any adverse effects not listed
in this leaflet, you should inform your doctor or pharmacist. Adverse effects can be reported
directly to the Department of Monitoring Adverse Effects of Medicinal Products
of 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.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Dulsevia

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This helps protect the environment.

6. Contents of the pack and other information

What Dulsevia contains

• The active substance is duloxetine. Each enteric hard capsule contains 60 mg of duloxetine (as duloxetine hydrochloride).
• Other ingredients are: sucrose, pellets (sucrose, corn starch), hypromellose 6 cP, sucrose, hypromellose phthalate, talc and triethyl citrate. Capsule shell: gelatin, titanium dioxide (E 171), indigo carmine (E 132), yellow iron oxide (E 172), printing ink [shellac, black iron oxide (E 172)]. See section 2, "Dulsevia contains sucrose".

What Dulsevia looks like and contents of the pack
White to almost white pellets in a hard gelatin capsule size 1 (average length: 19.4 mm). The body of the capsule is yellowish-green and the cap is dark blue. On the body of the capsule there is a black marking "60".
Pack sizes: 28 or 56 enteric hard capsules in blisters, packed in a cardboard box.
For more detailed information, please contact the responsible entity or parallel importer.

Marketing Authorisation Holder in Ireland, country of export:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland

Relabeled in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland

Irish Marketing Authorisation Number (country of export): PA1347/051/004
Parallel Import Licence Number: 93/23