Dulsevia

Package leaflet: Information for the patient

Dulsevia, 90 mg, hard enteric capsules
Duloxetine
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Dulsevia is and what it is used for
2. What you need to know 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 feeling of anxiety or nervousness).

In most people with depression or anxiety, Dulsevia begins to work within two weeks of starting treatment, although improvement in well-being may take 2 to 4 weeks. If you do not feel better after this time, consult your doctor. Even if your condition improves, your doctor may recommend continuing Dulsevia to prevent recurrence of depression or anxiety.

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

Below are several reasons why Dulsevia may not be suitable for the patient. Before taking Dulsevia, inform the doctor if:

• the patient is 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"),
• the patient is taking herbal medicines containing St John's wort ( Hypericum perforatum ),
• the patient has kidney disease,
• the patient has had seizures in the past,
• the patient has had episodes of mania in the past,
• the patient has bipolar affective disorder,
• the patient has eye diseases, such as a specific type of glaucoma (increased pressure in the eye),
• the patient has had bleeding disorders (tendency to bruise easily), especially if the patient is pregnant (see "Pregnancy and breastfeeding"),
• the patient has been identified as being at risk of developing low sodium levels (for example, when taking diuretics, especially in elderly people),
• the patient is currently taking other medicines that may cause liver damage,
• the patient is taking other medicines containing duloxetine (see "Dulsevia with other medicines").

Also contact the doctor if the patient experiences any of the following symptoms:
anxiety, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, rapid changes in blood pressure, increased reflexes, diarrhoea, drowsiness, nausea, vomiting, as these may indicate serotonin syndrome.

In its most severe form, serotonin syndrome may resemble neuroleptic malignant syndrome (NMS). Symptoms of neuroleptic malignant syndrome may include: a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, and increased levels of muscle enzymes (detected by blood tests).

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 after starting antidepressant treatment, as it usually takes some time, typically two weeks or longer, before these medicines begin 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 friend about the patient's depression or anxiety and ask them to read this leaflet. The patient may ask them to inform him or her if they notice that depression or anxiety worsens or if there are worrying changes in behaviour.

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, the doctor may prescribe Dulsevia for patients under 18 years of age if they decide it is beneficial. If in doubt when the 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. Furthermore, there is a lack of long-term safety data on the use of duloxetine in this age group regarding growth, maturation, and cognitive and behavioural development.

Dulsevia with other medicines

Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including those obtained without a prescription.

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

• diabetic neuropathic pain, 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 Dulsevia can be taken together with other medicines. Do not start or stop taking any other medicines, including those available without a prescription and herbal preparations, without first consulting a doctor.

Inform the doctor if the patient is taking any of the following medicines:

Monoamine oxidase inhibitors (MAOIs): Do not take Dulsevia together with another antidepressant medicine called a monoamine oxidase inhibitor (MAOI) or within a short interval (within 14 days) after stopping an MAOI. 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 become pregnant, 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 the expected benefits of treatment and possible risks to the unborn child with the doctor.
• The patient should inform the midwife and (or) doctor about taking Dulsevia. Taking 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 faster breathing and cyanosis in the baby. 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, her baby may experience certain symptoms. These usually occur at birth or within a few days after birth. Symptoms may include muscle weakness, tremor, jitteriness, 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 the 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 the patient 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 baby. If the patient takes Dulsevia during the second half of pregnancy, there may be an increased risk of premature birth, mainly between weeks 35 and 36 (6 additional premature infants per 100 women taking Dulsevia in 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 the 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 treatment with this medicine.

3. How to take Dulsevia

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
Dulsevia is taken orally. The capsule should be swallowed whole with water.

Treatment of depression
The usual dose of Dulsevia is 60 mg taken once daily. However, your doctor will determine the dose appropriate for you.

Treatment of generalized anxiety disorder
The usual starting dose of Dulsevia is 30 mg once daily. In most patients, the dose is then increased to 60 mg once daily. However, your doctor will determine the appropriate dose for you. The dose may be increased up to 120 mg depending on your response to treatment.

Taking Dulsevia at the same time each day will help you remember to take it.
Your doctor will inform you how long you should continue taking Dulsevia. Do not stop taking Dulsevia or change the dose without consulting your doctor. Proper treatment of the condition is important so that you can feel better. Without treatment, your condition may persist, worsen, and become more difficult to treat.

Taking more Dulsevia than prescribed
If you take more Dulsevia than prescribed, contact your doctor or pharmacist immediately. Symptoms of overdose may include: drowsiness, coma, serotonin syndrome (a rare reaction which may cause feelings of excessive well-being, drowsiness, lack of coordination, restlessness, sensation of drunkenness, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heartbeat.

If you miss a dose of Dulsevia
If you miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your next dose at the regular 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 you feel better, DO NOT stop taking Dulsevia without consulting your doctor. If your doctor decides that you no longer need to take Dulsevia, they will recommend gradually reducing the dose over at least two 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 mild and resolve within a few days. However, if they are bothersome, contact your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

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

• headache, drowsiness
• nausea, dry mouth

Common adverse reactions (may affect 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, tingling or prickling sensation of the skin
• blurred vision
• tinnitus (perception of sound in the ears in the absence of external sound source)
• palpitations
• increased blood pressure, sudden flushing of the face
• excessive 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 treatment. After 6 months of treatment, body weight increased and normalized compared to that observed in other children and adolescents of the same age and sex.

Uncommon adverse reactions (may affect up to 1 in 100 patients):

• throat inflammation causing hoarseness
• suicidal thoughts, difficulty falling asleep, teeth grinding, disorientation, lack of motivation
• sudden involuntary movements or muscle twitching, restlessness or inability to sit still or stay in one place, irritability, difficulty concentrating, taste disturbances, difficulty controlling movements, e.g. lack of coordination or unintended muscle movements, restless legs syndrome, worsened quality of sleep
• dilated pupils (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, cold sensation in fingers of 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
• hepatitis, which may cause abdominal pain and yellowing of the skin or whites of the eyes
• night sweats, hives, cold sweats, photosensitivity, increased tendency to bruising
• muscle stiffness and twitching
• difficulty or inability to urinate, difficulty initiating urination, need to urinate at night, need to urinate more frequently than usual, decreased volume of urine output
• abnormal vaginal bleeding, menstrual disorders, including heavy, painful, irregular or prolonged menstruation, rarely scanty menstruation or absence of menstruation, testicular or scrotal pain
• chest pain, cold sensation, thirst, chills, hot flushes, gait disturbances
• weight gain
• the Dulsevia medicine may cause adverse reactions that are not noticeable, such as increased liver enzyme activity or blood potassium levels, increased creatine phosphokinase activity, blood glucose or cholesterol levels

Rare adverse reactions (may affect up to 1 in 1000 patients):

• severe allergic reaction causing difficulty breathing, 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 anger outbursts
• "serotonin syndrome" (a rare reaction which may include involuntary, rhythmic muscle contractions, including muscles controlling eye movements, restlessness, hallucinations, coma, excessive sweating, tremor, hyperreflexia, increased muscle tone, body temperature above 38°C, nausea, vomiting, diarrhoea), seizures
• increased eye pressure (glaucoma)
• cough, wheezing and shortness of breath, possibly accompanied by fever
• inflammation of the mouth, bright red blood in stool, bad breath, inflammation of the large intestine (leading to diarrhoea)
• liver failure, yellow discoloration of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious illness with ulceration of the skin, mouth, eyes and genital organs), severe allergic reaction causing swelling of the face or throat (angioedema)
• jaw muscle spasm
• abnormal urine odor
• menopausal symptoms, abnormal milk production in men or women in the mammary glands
• excessive vaginal bleeding shortly after childbirth (postpartum haemorrhage)

Very rare adverse reactions (may affect up to 1 in 10,000 patients):

• vasculitis of the skin

Frequency not known (cannot be estimated from available data):

• objective and subjective symptoms of a condition called stress cardiomyopathy, which may include: chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Dulsevia

Keep this medicine out of the 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 30°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 will help protect the environment.

6. Contents of the pack and other information

What Dulsevia contains

• The active substance is duloxetine. Each enteric hard capsule contains 90 mg of duloxetine (as duloxetine hydrochloride).
• Other components are: capsule contents: sucrose, pellets (sucrose, corn starch), hypromellose 6 cP, sucrose, sodium hydroxymethylpropyl cellulose acetate succinate, talc, triethyl citrate and titanium dioxide (E 171); capsule shell: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172); printing ink: shellac (E 904), propylene glycol (E 1520), black iron oxide (E 172), potassium hydroxide (E 525). See section 2 "Dulsevia contains sucrose".

What Dulsevia looks like and contents of the pack
White to slightly coloured pellets in a size 0 hard gelatin capsule (capsule length: approximately 22 mm). The body of the capsule is light orange and the cap is white. A black "90" is printed on the body of the capsule.
Pack sizes: 7, 10, 14, 28, 30, 56, 60, 90 and 100 enteric hard capsules in blister packs contained in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
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

For further information about this medicine, please contact the Marketing Authorisation Holder's representative:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw
tel. 22 57 37 500