Dulsevia

Package leaflet: Information for the patient

Dulsevia, 30 mg, hard enteric-coated capsules
Dulsevia, 60 mg, hard enteric-coated capsules
Duloxetine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet so that you can read it again if needed.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual only. Do not pass it on to others. This medicine may harm someone else, 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. 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 feelings of anxiety or nervousness),
• diabetic neuropathic pain (usually described as burning, shooting, stabbing, aching, or electric-shock-like pain. In certain areas of the body, there may be loss of sensation or abnormal sensations to touch, heat, or cold, and pressure may cause pain).

In most people with depression or anxiety, Dulsevia begins to work within two weeks of starting treatment; however, it may take 2 to 4 weeks before improvement is noticed. If no improvement occurs after this time, consult your doctor. Even if your condition improves, your 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 no improvement occurs 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 and other medicines"),
• if the patient is taking fluvoxamine, which is usually used to treat depression, or ciprofloxacin or enoxacin, medicines used to treat certain infections,
• if the patient is taking other medicines containing duloxetine (see "Dulsevia and other medicines").

Tell your 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, 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 and 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 disorder,
• eye diseases such as a specific type of glaucoma (increased pressure in the eye),
• history of bleeding disorders (tendency to bruise easily), particularly if the patient is pregnant (see "Pregnancy and breastfeeding"),
• risk of developing low sodium levels (for example, when taking diuretics, especially in elderly people),
• taking other medicines that may cause liver damage,
• taking other medicines containing duloxetine (see "Dulsevia and other medicines").

You should also contact your doctor:

If the patient experiences any objective or subjective symptoms such as agitation, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, fluctuating 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 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 antidepressants, because it usually takes a few weeks, typically two weeks or longer, before these medicines begin to work. These thoughts may worsen:

• 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. You may also ask them whether they have noticed any worsening of depression or anxiety or any changes in behaviour that cause concern.

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 (predominantly aggression, defiant behaviour, and anger). However, the doctor may decide to prescribe Dulsevia for patients under 18 years of age if they consider it beneficial. If in doubt, when Dulsevia is prescribed for a patient under 18 years of age, contact the doctor again. Inform the doctor if any of the adverse reactions listed above occur or worsen in a patient under 18 years of age taking Dulsevia. In addition, there are no long-term safety data on the use of duloxetine in this age group regarding growth, puberty, and cognitive and behavioural development.

Dulsevia and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including those obtained without a prescription, as well as any the patient plans to take.

Duloxetine, the main ingredient in 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 it is safe to take Dulsevia together with other medicines. Do not start or stop taking any other medicines, including those available without a prescription and herbal supplements, without first consulting your doctor.

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

Monoamine oxidase inhibitors (MAOIs): Do not take Dulsevia at the same time as another antidepressant called a monoamine oxidase inhibitor (MAOI) or within a short 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 (used to treat pain or opioid dependence), tramadol, tryptophan, selective serotonin reuptake inhibitors (e.g. paroxetine and fluoxetine), selective noradrenaline 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 her 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 (PPHN), 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 at birth. These usually appear at birth or within a few days after birth. Symptoms may include muscle weakness, tremors, shakiness, feeding difficulties, breathing problems, and seizures. If the patient notices any of these symptoms or is concerned about the 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 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 birth, mainly between weeks 35 and 36 (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 their 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 use Dulsevia

This medicine should always be taken as directed by the physician or pharmacist. If in doubt,
consult a physician or pharmacist.
Dulsevia is taken orally. The capsule should be swallowed whole with water.
Treatment of depression and pain in diabetic neuropathy
The usual dose of Dulsevia is 60 mg once daily. However, the physician will determine the 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 physician will determine 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 physician will inform the patient how long Dulsevia should be taken. Do not discontinue
treatment with Dulsevia or change the dose without consulting the physician. Proper treatment
of the condition is essential for the patient to feel better. Without treatment, the patient's
condition may persist, worsen, and become more difficult to treat.
Taking more Dulsevia than prescribed
If more Dulsevia than prescribed has been taken, contact a physician or pharmacist immediately.
Symptoms of overdose include: drowsiness, coma, serotonin syndrome (a rare reaction which may
cause excessive feelings of well-being, drowsiness, impaired motor coordination, restlessness,
alcohol-like intoxication, 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 regular time. Do not take a double dose to make
up for a missed dose.
Do not take more Dulsevia in a day than prescribed by the physician.
Stopping Dulsevia treatment
Even if feeling better, DO NOT stop taking Dulsevia without consulting the physician. If the
physician decides that the patient no longer needs to take Dulsevia, the dose will be gradually
reduced over at least 2 weeks.
In some patients who abruptly discontinue duloxetine, symptoms may occur such as:

• dizziness, tingling sensations like being pricked by pins or needles or electric shock sensations (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 the physician.
If there are any further doubts about the use of this medicine, consult a physician 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 occur in more than 1 in 10 patients):

• headache, drowsiness
• nausea, dry mouth

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

• loss of appetite
• sleep disturbances, restlessness, reduced 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 (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, a decrease in body weight has been observed after starting treatment. After 6 months of treatment, body weight increased and became comparable to that observed in other children and adolescents of the same age and sex.
Uncommon adverse reactions (may occur in 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 or stand still quietly, agitation, difficulty concentrating, taste disturbances, difficulty controlling movements, e.g. lack of coordination or unintended muscle movements, restless legs syndrome, worsened sleep quality
• 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 and (or) toes
• 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, urticaria, 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 than usual, reduced amount of urine excreted
• 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, 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, increased blood glucose or cholesterol levels

Rare adverse reactions (may occur in 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 with symptoms such as involuntary, rhythmic muscle contractions, including muscles controlling eye movement, restlessness, hallucinations, coma, excessive sweating, tremor, hyperreflexia, increased muscle rigidity, 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 mouth, bright red blood in stool, 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 illness with skin, mouth, eye and genital ulceration), severe allergic reaction causing facial or throat swelling (angioedema)
• jaw muscle spasm
• abnormal urine odour
• 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 occur in up to 1 in 10,000 patients):

• inflammation of blood vessels in 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 effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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 sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following the abbreviation
"EXP". The expiry date refers to the last day of the specified 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 delayed-release, hard capsule contains 30 mg or 60 mg of duloxetine (as duloxetine hydrochloride).
• The other ingredients are:
  Capsule contents: saccharose, pellets (saccharose, corn starch), hypromellose 6 cP, saccharose, ascorbic acid, hypromellose acetate succinate, talc, triethyl citrate and titanium dioxide (E 171)
  Capsule shell: gelatin, titanium dioxide (E 171), indigo carmine (E 132), iron oxide yellow (E 172) – only in 60 mg capsules, printing ink [shellac (E 904), propylene glycol (E 1520), iron oxide black (E 172), potassium hydroxide (E 525)]. See section 2 "Dulsevia contains saccharose".

What Dulsevia looks like and contents of the pack
30 mg: white to slightly coloured pellets in a size 3 hard gelatin capsule (capsule length: approximately 16 mm). The capsule body is white and the cap is dark blue. A black "30" is printed on the body of the capsule.
60 mg: white to slightly coloured pellets in a size 1 hard gelatin capsule (capsule length: approximately 19 mm). The capsule body is yellowish-green and the cap is dark blue. A black "60" is printed on the body of the capsule.
Pack sizes: 7, 10, 14, 28, 30, 56, 60, 90 and 100 delayed-release hard capsules in blister packs contained in a cardboard carton.
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 more detailed information about this medicinal product, please contact the representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw, Poland
Tel: 22 57 37 500