Dulsevia

Leaflet accompanying the packaging: patient information

Dulsevia, 30 mg, gastro-resistant hard capsules

Dulsevia, 60 mg, gastro-resistant hard capsules

duloxetine

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Dulsevia and what is it 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 packaging and other information

1. What is Dulsevia and what is it used for

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

• depression,
• generalized anxiety disorder (persistent feeling of anxiety or nervousness),
• diabetic neuropathic pain (usually described as burning, shooting, stabbing, or like an electric shock. There may be loss of sensation, or sensations of touch, heat, or cold, and pressure may cause pain).

In most patients with depression or anxiety, Dulsevia starts working within two weeks of starting treatment, but it may take 2 to 4 weeks before an improvement is noticed. If no improvement is seen after this time, the patient should consult their doctor. Even if the patient's condition improves, the doctor may recommend continuing to take Dulsevia to prevent a relapse of depression or anxiety.
In patients with diabetic neuropathic pain, an improvement in condition may occur after several weeks. The patient should consult their doctor if no improvement is seen after 2 months.

2. Important information before taking Dulsevia

When not to take 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 called a monoamine oxidase inhibitor (MAOI) (see "Dulsevia and other medicines"),
• if the patient is taking fluvoxamine, which is usually used to treat depression, ciprofloxacin, or enoxacin, which are used to treat some infections,
• if the patient is taking other medicines containing duloxetine (see "Dulsevia and other medicines").

The patient should tell their doctor if they have 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 their doctor if any of the following apply:

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

The patient should also contact their doctor:

• if they experience objective and subjective symptoms such as restlessness, hallucinations, loss of coordination, rapid heartbeat, increased blood pressure, increased reflexes, diarrhea, coma, nausea, vomiting, as this may indicate serotonin syndrome.

In severe cases, serotonin syndrome can resemble neuroleptic malignant syndrome (NMS). The symptoms of NMS can include a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, increased muscle enzyme activity (measured by blood tests).
Medicines like Dulsevia (so-called SSRIs or SNRIs) may cause sexual dysfunction (see section 4). In some cases, these symptoms have persisted after stopping treatment.
Dulsevia may cause restlessness or an inability to sit still. If such symptoms occur, the patient should inform their doctor.
Suicidal thoughts and worsening depression or anxiety
Depression and/or anxiety can lead to suicidal thoughts or self-harm. These thoughts may worsen after starting to take antidepressant medicines, as it may take some time, usually two weeks or more, for these medicines to start working.
These thoughts may worsen in:

• patients who have had suicidal thoughts or self-harm in the past,
• young adults. Clinical trial data have shown an increased risk of suicidal behavior in adults under 25 with mental health conditions who were treated with antidepressant medicines.

In case of suicidal thoughts or self-harm, the patient should contact their doctor or go to the hospital immediately.

It may be helpful to inform a relative or close friend about the patient's depression or anxiety and ask them to read this leaflet. The patient can also ask for their opinion on whether their depression or anxiety has worsened or if there are any changes in behavior that cause concern.
Children and adolescents under 18 years of age
Dulsevia should not normally be used in children and adolescents under 18 years of age. In patients under 18 years of age who are taking medicines of this class, there is a greater risk of side effects, such as suicidal attempts, suicidal thoughts, and hostility (mainly aggression, rebellious behavior, and expressions of anger). However, the doctor may recommend Dulsevia for patients under 18 years of age if they decide it is in their best interest. If the doctor recommends Dulsevia for a patient under 18 years of age, the patient or their guardian should contact the doctor again if they have any doubts. The patient or their guardian should inform the doctor if the patient under 18 years of age who is taking Dulsevia experiences any of the above side effects or if they worsen. Additionally, there is a lack of long-term safety data on the use of duloxetine in this age group regarding growth, maturation, and cognitive and behavioral development.

Dulsevia and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or might take, including those obtained without a prescription.
Duloxetine, the active ingredient in Dulsevia, is also found in other medicines used to treat other conditions:

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

The patient should avoid taking more than one of these medicines at the same time. The patient should consult their doctor if they are taking other medicines containing duloxetine.
The doctor will decide whether the patient can take Dulsevia with other medicines. The patient should not
start or stop taking other medicines, including those obtained without a prescription and herbal products, without consulting their doctor.
The patient should inform their doctor if they are taking any of the following medicines:
Monoamine oxidase inhibitors (MAOIs):The patient should not take Dulsevia with another antidepressant medicine called an MAOI or within a short period of time (within 14 days) after stopping an MAOI. Examples of MAOIs are moclobemide (an antidepressant) and linezolid (an antibiotic). Taking MAOIs with many prescription medicines, including Dulsevia, can cause serious or even life-threatening side effects. After stopping an MAOI, the patient must wait at least 14 days before starting to take Dulsevia. Before starting to take an MAOI, the patient must wait at least 5 days after stopping Dulsevia.
Sedative medicines:These include prescription medicines such as benzodiazepines, strong painkillers, antipsychotic medicines, phenobarbital, and antihistamines.
Medicines that increase serotonin levels:Triptans, buprenorphine (a medicine used to treat pain or opioid addiction), tramadol, tryptophan, selective serotonin reuptake inhibitors (e.g., paroxetine and fluoxetine), selective noradrenaline reuptake inhibitors (e.g., venlafaxine), tricyclic antidepressants (e.g., clomipramine and amitriptyline), pethidine, St. John's Wort (Hypericum perforatum), and MAOIs (e.g., moclobemide and linezolid). These medicines increase the risk of side effects, such as serotonin syndrome (see "Warnings and precautions" and "Possible side effects").
If the patient experiences any symptoms while taking these medicines with Dulsevia, they should contact their doctor.
Oral anticoagulants or antiplatelet agents:Medicines that thin the blood or prevent blood clotting. These medicines may increase the risk of bleeding.

Dulsevia with food, drink, and alcohol

Dulsevia can be taken with or without food. The patient should be cautious when consuming alcohol while taking Dulsevia.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor before taking this medicine.

• -The patient should inform their doctor if they become pregnant or plan to become pregnant while taking Dulsevia. The patient can only take Dulsevia after discussing the expected benefits and potential risks to the unborn child with their doctor.
• -The patient should inform their midwife and/or doctor that they are taking Dulsevia. The use of similar medicines (selective serotonin reuptake inhibitors) during pregnancy may increase the risk of a serious condition in children called persistent pulmonary hypertension of the newborn, which causes rapid breathing and bluish skin. These symptoms usually occur within the first 24 hours after birth. If the patient notices these symptoms in their child, they should contact their midwife and/or doctor immediately.
• -If the patient takes Dulsevia towards the end of their pregnancy, certain symptoms may occur in their child at birth. These symptoms usually occur at birth or within a few days after birth. They may include floppiness, trembling, jittering, difficulty feeding, breathing problems, and seizures. If the patient notices any of these symptoms or is concerned about their child's health, they should contact their doctor or midwife for help.
• -If the patient takes Dulsevia towards the end of their pregnancy, there is an increased risk of heavy bleeding from the vagina shortly after delivery, especially if the patient has a history of bleeding disorders. The patient should inform their doctor or midwife that they are taking duloxetine so that they can recommend appropriate action.
• -Available data on the use of Dulsevia during the first three months of pregnancy do not indicate an increased risk of birth defects. If the patient takes Dulsevia during the second half of pregnancy, there may be an increased risk of premature birth, mainly between the 35th and 36th week of pregnancy (6 additional premature births per 100 women taking Dulsevia during the second half of pregnancy).
• -The patient should inform their doctor if they are breastfeeding. It is not recommended to take Dulsevia while breastfeeding. Breastfeeding women should consult their doctor or pharmacist for advice.

Driving and using machines

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

Dulsevia contains sucrose

If the patient's doctor has previously told them that they have an intolerance to some sugars, they should contact their doctor before taking this medicine.

3. How to take Dulsevia

The patient should always take this medicine exactly as their doctor or pharmacist has told them. If they are unsure, they should ask their doctor or pharmacist.
Dulsevia is taken by mouth. 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 a day. However, the doctor will prescribe the dose that is right for the patient.
Treatment of generalized anxiety disorder
The usual starting dose of Dulsevia is 30 mg once a day. For most patients, the dose is then increased to 60 mg once a day. However, the doctor will prescribe the dose that is right for the patient. The dose may be increased up to 120 mg depending on the patient's response to treatment.
Taking Dulsevia at the same time every day will help the patient remember to take it.
The doctor will tell the patient how long to take Dulsevia. The patient should not stop taking Dulsevia or change their dose without consulting their doctor. It is important to treat the condition properly so that the patient feels better. If the condition is not treated, the patient's symptoms may persist or worsen and become difficult to treat.

Taking a higher dose of Dulsevia than recommended

If the patient takes more Dulsevia than they should, they should contact their doctor or pharmacist immediately. Symptoms of overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause excessive happiness, drowsiness, coordination problems, restlessness, drunkenness, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heartbeat.

Missing a dose of Dulsevia

If the patient misses a dose, they should take it as soon as possible. However, if it is almost time for their next dose, they should skip the missed dose and take their usual dose. The patient should not take a double dose to make up for a missed dose. The patient should not take more than the recommended daily dose of Dulsevia.

Stopping treatment with Dulsevia

Even if the patient feels better, they should notstop taking Dulsevia without consulting their doctor. If the doctor decides that the patient no longer needs to take Dulsevia, they will recommend gradually reducing the dose over at least 2 weeks.
In some patients who stop taking duloxetine abruptly, the following symptoms may occur:

• dizziness, tingling sensations like pins and needles or electric shock sensations (especially in the head), sleep disturbances (vivid dreams, nightmares, difficulty sleeping), fatigue, drowsiness, restlessness or agitation, anxiety, nausea or vomiting, tremors, headaches, muscle aches, irritability, diarrhea, and excessive sweating or dizziness due to balance problems.

These symptoms are usually not serious and go away within a few days. However, if they are troublesome, the patient should contact their doctor.
If the patient has any further questions about their medicine, they should ask their doctor or pharmacist.

4. Possible side effects

Like all medicines, Dulsevia can cause side effects, although not everybody gets them.
Very common side effects (may affect more than 1 in 10 people):

• headache, drowsiness
• nausea, dry mouth

Common side effects (may affect up to 1 in 10 people):

• loss of appetite
• sleep disturbances, restlessness, decreased libido, anxiety, difficulty or inability to achieve orgasm, unusual dreams
• dizziness, feeling slowed down, tremors, numbness, including numbness, tingling, or prickling sensations of the skin
• blurred vision
• ringing in the ears (hearing a sound in the ears when there is no external source of the sound)
• palpitations
• increased blood pressure, flushing
• increased yawning
• constipation, diarrhea, abdominal pain, vomiting, heartburn or indigestion, gas
• increased sweating, rash (itching)
• muscle aches, muscle cramps
• painful urination, frequent urination
• difficulty or inability to achieve an erection, changes in ejaculation
• falls (especially in the elderly), fatigue
• weight loss

In children and adolescents under 18 years of age with depression, treated with duloxetine, a decrease in weight has been observed after starting treatment. After 6 months of treatment, the weight increased and was comparable to that of other children and adolescents of the same age and sex.
Uncommon side effects (may affect up to 1 in 100 people):

• pharyngitis causing hoarseness
• suicidal thoughts, difficulty sleeping, teeth grinding, disorientation, lack of motivation
• sudden, involuntary movements or muscle twitching, restlessness or an inability to sit still, agitation, difficulty concentrating, changes in taste, difficulty controlling movements, e.g., lack of coordination or involuntary muscle movements, restless legs syndrome, poor sleep quality
• pupil dilation (the dark center of the eye), vision problems
• dizziness, dizziness due to balance problems, ear pain
• rapid or irregular heartbeat
• fainting, dizziness, feeling of emptiness in the head or fainting when standing up, feeling of coldness in the fingers of the hands and/or feet
• throat tightness, nosebleeds
• vomiting blood or black, tarry stools, gastritis, reflux, difficulty swallowing
• liver inflammation, which can cause abdominal pain and yellowing of the skin or whites of the eyes
• night sweats, hives, cold sweats, sensitivity to sunlight, increased tendency to bruise
• muscle stiffness and twitching
• difficulty or inability to urinate, frequent urination, need to urinate at night, need to urinate more often than usual, decreased amount of urine
• abnormal vaginal bleeding, menstrual disorders, including heavy, painful, irregular, or prolonged menstrual periods, or rare light or absent menstrual periods, testicular pain or swelling
• chest pain, feeling of coldness, thirst, chills, feeling of warmth, gait disturbances
• weight gain
• Dulsevia may cause side effects that the patient may not be aware of, such as increased liver enzyme activity or potassium levels in the blood, increased creatine phosphokinase activity, blood glucose or cholesterol levels

Rare side effects (may affect up to 1 in 1,000 people):

• severe allergic reaction causing difficulty breathing, dizziness with swollen tongue or lips, allergic reactions
• decreased thyroid function, which can cause fatigue or weight gain
• dehydration, low sodium levels in the blood (especially in the elderly; symptoms may include dizziness, weakness, confusion, drowsiness, excessive tiredness, nausea or vomiting, more severe symptoms include fainting, seizures, and falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• suicidal behavior, manic excitement (excessive activity, racing thoughts, and decreased need for sleep), hallucinations, aggression, and anger
• serotonin syndrome (a rare reaction, the symptoms of which may include involuntary, rhythmic muscle contractions, including those that control eye movements, agitation, hallucinations, coma, excessive sweating, tremors, increased reflexes, muscle stiffness, body temperature above 38°C, nausea, vomiting, diarrhea), seizures
• increased eye pressure (glaucoma)
• cough, wheezing, and shortness of breath, which may be accompanied by fever
• mouth inflammation, red blood in the stool, unpleasant breath, colitis (leading to diarrhea)
• liver failure, yellowing of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (a severe disease with skin, mouth, eye, and genital ulcers), severe allergic reaction causing facial or throat swelling (angioedema)
• jaw muscle spasm
• abnormal urine odor
• menopausal symptoms, abnormal milk production in men or women in the breasts
• excessive vaginal bleeding shortly after delivery (postpartum hemorrhage)

Very rare side effects (may affect up to 1 in 10,000 people):

• skin blood vessel inflammation

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

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

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Dulsevia

The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after "EXP". The expiry date refers to the last day of that month.
Do not store above 25°C.
Store in the original packaging to protect from moisture.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the packaging and other information

What Dulsevia contains

• The active substance is duloxetine. Each gastro-resistant hard capsule contains 30 mg or 60 mg of duloxetine (as duloxetine hydrochloride).
• The other ingredients are: capsule contents:sucrose, sugar spheres (sucrose, corn starch), hypromellose 6 cP, sucrose, hypromellose phthalate HP-50, talc, and triethyl citrate capsule shell:gelatin, titanium dioxide (E 171), indigo carmine (E 132), iron oxide yellow (E 172) - only in 60 mg capsules, ink [shellac (E 904), iron oxide black (E 172)] See section 2, "Dulsevia contains sucrose".

What Dulsevia looks like and contents of the pack

30 mg: white to off-white pellets in a hard gelatin capsule, size 3 (average length: 15.9 mm). The capsule body is white and the capsule cap is dark blue. The capsule body is marked with a black inscription "30".
60 mg: white to off-white pellets in a hard gelatin capsule, size 1 (average length: 19.4 mm). The capsule body is yellow-green and the capsule cap is dark blue. The capsule body is marked with a black inscription "60".
Packaging: 7, 10, 14, 28, 30, 56, 60, 90, and 100 gastro-resistant hard capsules in blisters in a cardboard box.
Not all pack sizes may be marketed.

Marketing authorization 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 more information about this medicine, the patient should contact the representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5
02-235 Warsaw
phone: 22 57 37 500

Date of last revision of the leaflet: