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 any 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 pack 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:

• 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 such as 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 doctor should be consulted. 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 doctor should be consulted if an improvement is not 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, medicines used to treat some infections,
• if the patient is taking other medicines containing duloxetine (see "Dulsevia and other medicines").

The doctor should be told 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 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 doctor should also be contacted:

• if the patient experiences 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). Objective and subjective symptoms of NMS 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 symptoms of 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 doctor should be informed.
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 longer, 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 years of age with mental health conditions who were treated with antidepressant medicines.

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

It may be helpful to inform a relative or close friend about the depressive or anxious state and ask them to read this leaflet. You can also ask for their opinion on whether the depressive or anxious state has worsened, or if changes in behavior are causing 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 the use of Dulsevia in patients under 18 years of age if they decide it is beneficial for them. If there are any doubts when the doctor recommends the use of Dulsevia in a patient under 18 years of age, the doctor should be consulted again. The doctor should be informed if the patient under 18 years of age 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 doctor or pharmacist should be told about all medicines the patient is taking, has 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 doctor should be consulted if the patient is taking other medicines containing duloxetine.
The doctor will decide whether Dulsevia can be taken with other medicines. Do notstart or stop taking other medicines, including those obtained without a prescription and herbal products, without consulting a doctor.
The doctor should be informed if the patient is taking any of the following medicines:
Monoamine oxidase inhibitors (MAOIs):Dulsevia should not be taken with another antidepressant medicine called a monoamine oxidase inhibitor (MAOI) or within a short period of time (within 14 days) after stopping an MAOI. Examples of MAOIs include 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, at least 14 days must pass before starting to take Dulsevia. Before starting to take an MAOI, at least 5 days must pass 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 any symptoms occur while taking these medicines with Dulsevia, the doctor should be consulted.
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. Caution should be exercised 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 child, 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 may take Dulsevia only 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 discoloration in the baby. These symptoms usually occur within the first 24 hours after birth. If the patient notices these symptoms in their baby, 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 baby 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 baby'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 excessive bleeding from the uterus shortly after delivery, especially if they have a history of bleeding disorders. The doctor or midwife should be informed about the use of duloxetine so that they can recommend appropriate action.
• -Available data on the use of Dulsevia during the first three months of pregnancy do not generally 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 in 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 doctor has previously determined that the patient has an intolerance to some sugars, they should consult their doctor before taking this medicine.

3. How to take Dulsevia

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. In case of doubts, the doctor or pharmacist should be consulted.
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 a day. However, the doctor will prescribe the dose suitable for the patient.
Treatment of generalized anxiety disorder
The usual initial dose of Dulsevia is 30 mg once a day. In most patients, the dose is then increased to 60 mg once a day. However, the doctor will prescribe the dose suitable 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 remember to take it.
The doctor will inform the patient how long they should take Dulsevia. Dulsevia should not be stopped or the dose changed without consulting the doctor. Proper treatment of the condition is essential for the patient to feel better. If left untreated, the patient's condition may persist or worsen and become difficult to treat.

What to do if too much Dulsevia is taken

In case of overdose, the doctor or pharmacist should be contacted 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.

What to do if a dose of Dulsevia is missed

If a dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the usual dose taken as scheduled. A double dose should not be taken to make up for a missed dose. The patient should not take more than the prescribed daily dose of Dulsevia.

What to do if treatment with Dulsevia is stopped

Even if the patient feels better, they should not stop 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, symptoms may occur, such as:

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

These symptoms are usually not serious and resolve within a few days. However, if they are troublesome, the doctor should be consulted.
In case of any further doubts about taking this medicine, the doctor or pharmacist should be consulted.

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 sensation 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, sudden flushing of the face
• increased yawning
• constipation, diarrhea, abdominal pain, vomiting, heartburn or indigestion, gas
• increased sweating, rash (itching)
• muscle pain, muscle spasms
• 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, weight loss has been observed after starting treatment. After 6 months of treatment, 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, feeling restless 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 (dark central point of the eye), vision problems
• dizziness, dizziness due to balance problems, ear pain
• rapid and/or irregular heartbeat
• fainting, dizziness, feeling of emptiness in the head or fainting when standing up, feeling cold in the fingers and/or toes
• throat constriction, 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 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 or scrotal pain
• chest pain, feeling cold, thirst, chills, feeling hot, gait disturbances
• weight gain
• Dulsevia may cause side effects that are not apparent, such as increased liver enzyme activity or potassium levels in the blood, increased creatine phosphokinase activity, glucose or cholesterol levels in the blood

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, 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 reduced 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 bleeding from the uterus shortly after delivery (postpartum hemorrhage)

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

• inflammation of the blood vessels in the skin

Frequency not known (cannot be estimated from the 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 side effects

If any side effects occur, including any not listed in this leaflet, the doctor or pharmacist should be informed. 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 gather more information on the safety of this medicine.

5. How to store Dulsevia

The medicine should be stored out of sight and reach of children.
This medicine should not be taken after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the 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 pharmacist should be asked how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack 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).
• Other ingredients are: capsule contents:sucrose, pellets (sucrose, cornstarch), hypromellose 6 cP, sucrose, hypromellose phthalate HP-50, talc, and triethyl citrate capsule shell:gelatin, titanium dioxide (E 171), indigo carmine (E 132), yellow iron oxide (E 172) - only in 60 mg capsules, ink [shellac (E 904), black iron oxide (E 172)] See section 2, "Dulsevia contains sucrose".

What Dulsevia looks like and contents of the pack

30 mg: white to almost 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 "30" inscription.
60 mg: white to almost 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 "60" inscription.
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 on this medicine, the representative of the marketing authorization holder should be contacted:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw
phone: 22 57 37 500

Date of last revision of the leaflet: