Package leaflet: Information for the user

Dutilox, 30 mg, hard enteric-coated capsules
Dutilox, 60 mg, hard enteric-coated capsules
Duloxetine (as hydrochloride)
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any doubts, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

What Dutilox is and what it is used for
Important information before taking Dutilox
How to take Dutilox
Possible side effects
How to store Dutilox
Contents of the pack and other information

1. What Dutilox is and what it is used for

Dutilox contains the active substance duloxetine. Dutilox increases the levels of serotonin and noradrenaline in the nervous system.
Dutilox 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 a specific part of the body, loss of sensation may occur or touch, heat, cold, or pressure may cause pain).

In most people with depression or anxiety, Dutilox begins to work within two weeks of starting treatment, but it may take 2 to 4 weeks before improvement is noticed. If no improvement occurs by then, consult your doctor. Your doctor may recommend continuing treatment with Dutilox to prevent recurrence of depression or anxiety, even if your condition has improved.
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 Dutilox

When not to use Dutilox

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 "Dutilox with other medicines"),
if the patient is taking fluvoxamine, which is mainly used to treat depression, or ciprofloxacin or enoxacin, medicines used to treat certain infections,
if the patient is taking other medicines containing duloxetine (see "Dutilox 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 Dutilox.

Warnings and precautions

Below are some reasons why Dutilox may not be suitable for the patient. Before starting Dutilox, the patient should inform the doctor if any of the following apply:

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

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

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

Suicidal thoughts and worsening depression or anxiety

Depression and (or) anxiety may lead to suicidal thoughts or self-harm. These may worsen after starting antidepressants, as it usually takes some time, typically two weeks or longer, before the 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 depression or anxiety and ask them to read this leaflet. You may also ask them whether they notice any worsening of depression or anxiety, or any changes in behaviour that concern them.

Contact the doctor if the patient experiences objective and subjective symptoms such as agitation, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, rapid changes in blood pressure, increased reflexes, diarrhoea, coma, nausea, vomiting, as these may indicate serotonin syndrome.

In its most severe form, serotonin syndrome may resemble neuroleptic malignant syndrome. Objective and subjective symptoms of neuroleptic malignant syndrome may include: a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased muscle enzyme activity (detected by blood tests).

Children and adolescents under 18 years of age

Dutilox 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 Dutilox for patients under 18 years of age if they decide it is beneficial. If in doubt, and if the doctor prescribes Dutilox 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 Dutilox. Furthermore, there are no long-term safety data on the use of Dutilox in this age group regarding growth, puberty, cognitive development, and behavioural development.

Dutilox with other medicines

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

Duloxetine, the active substance in Dutilox, 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 at the same time. The patient should consult the doctor if already taking other medicines containing duloxetine.

The doctor will decide whether Dutilox can be taken together with other medicines. Do not start or stop taking any other medicines, including those available without a prescription and herbal products, without consulting the doctor.

Inform the doctor if taking any of the following medicines:

Monoamine oxidase inhibitors (MAOIs): Do not take Dutilox together with 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 Dutilox, may cause severe or even life-threatening adverse reactions. At least 14 days must pass after stopping an MAOI before starting Dutilox. MAOIs may only be started 5 days after stopping Dutilox.

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

Medicines increasing serotonin levels: Triptans, tryptophan, selective serotonin reuptake inhibitors (e.g. paroxetine and fluoxetine), selective noradrenaline reuptake inhibitors (e.g. venlafaxine), tricyclic antidepressants (e.g. clomipramine, amitriptyline), St. John's wort, MAOIs (e.g. moclobemide and linezolid), buprenorphine, tramadol, and pethidine. These medicines may interact with Dutilox and the patient may experience involuntary, rhythmic muscle contractions (including muscles controlling eye movement), agitation, hallucinations, coma, excessive sweating, tremor, hyperreflexia, increased muscle tone, and body temperature above 38°C. Contact the doctor if any of these symptoms occur, as they may indicate a potentially life-threatening condition known as serotonin syndrome.

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

Taking Dutilox with food, drink and alcohol

Dutilox can be taken independently of meals.

Exercise caution when consuming alcohol while taking Dutilox.

Pregnancy and breastfeeding

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

The patient should inform the doctor if she becomes pregnant or plans to become pregnant while taking Dutilox. The patient may take Dutilox after discussing with the doctor the expected benefits of treatment and possible risks to the unborn child.

The patient should inform the midwife and (or) doctor about taking Dutilox.

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 (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 Dutilox towards the end of pregnancy, certain symptoms may occur in her newborn after birth. These usually appear 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 the baby's health, she should contact the doctor or midwife, who will provide appropriate advice.

If the patient takes Dutilox towards the end of pregnancy, there is an increased risk of excessive vaginal bleeding shortly after delivery, especially if there is 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 Dutilox during the first trimester of pregnancy generally do not show an increased risk of congenital malformations in the child. If the patient takes Dutilox 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 Dutilox during the second half of pregnancy).

The patient should inform the doctor if she is breastfeeding. Dutilox is not recommended during breastfeeding. Breastfeeding women should consult a doctor or pharmacist for advice.

Driving and using machines

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

Dutilox contains sucrose

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

Dutilox contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e. the medicine is considered "sodium-free".

3. How to take Dutilox

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
please consult your doctor or pharmacist.
Dutilox capsules are taken orally. The capsule should be swallowed whole with water.
Treatment of depression and diabetic neuropathic pain
The usual dose of Dutilox 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 Dutilox 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 each patient.
The dose may be increased up to 120 mg depending on the patient's response to treatment.
Taking Dutilox at the same time each day may help you remember to take it.
Your doctor will inform you how long you should take Dutilox. Do not stop taking Dutilox 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 Dutilox than prescribed
If you take more Dutilox than prescribed, contact your doctor or pharmacist immediately.
Symptoms of overdose include: drowsiness, coma, serotonin syndrome (a rare reaction which may
cause excessive feelings of well-being, drowsiness, lack of coordination, restlessness, alcohol-like
intoxication, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heartbeat.
If you miss a dose of Dutilox
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 daily dose of Dutilox prescribed by your
doctor.
Stopping Dutilox
DO NOT stop taking Dutilox capsules without consulting your doctor, even if you feel better. If
your doctor decides you should stop taking Dutilox, they will advise reducing the dose gradually
over at least 2 weeks.
Some patients who stopped taking Dutilox suddenly have experienced symptoms such as:

dizziness, tingling sensations, or electric shock-like feelings (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, diarrhoea, excessive sweating, or dizziness caused by vestibular disturbances.
These symptoms are usually not serious 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
These effects are usually mild or moderate and typically resolve within a few weeks.

Very common adverse effects (may affect more than 1 in 10 people)

headache, drowsiness,
nausea, dry mouth.

Common adverse 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 of sluggishness, muscle tremors, numbness, including numbness, prickling or tingling sensations in 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,
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 this medicine,
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 effects (may affect up to 1 in 100 people)

throat inflammation causing hoarseness,
suicidal thoughts, difficulty falling asleep, teeth grinding or clenching, disorientation, lack of motivation,
sudden involuntary movements or muscle twitching, feeling uneasy 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 sleep quality,
pupil dilation (dark central point of the eye), vision problems,
dizziness, vertigo 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,
sore 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 tremors,
difficulty or inability to urinate, difficulty initiating urination, need to urinate at night, need to urinate more frequently than usual, weak urine stream,
abnormal vaginal bleeding, menstrual disorders, including heavy, painful, irregular or prolonged menstruation, abnormally light menstruation or absence of menstruation, testicular or scrotal pain,
chest pain, cold sensation, thirst, chills, hot flushes, gait disturbances,
weight gain,
Dutilox may cause adverse effects that are not noticeable, such as increased liver enzyme activity or blood potassium levels, increased creatine phosphokinase activity, or increased blood glucose or cholesterol levels.

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

severe allergic reaction causing breathing difficulties, dizziness with swelling of the tongue or lips, allergic reactions,
reduced 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 or nausea, or vomiting; more severe symptoms include fainting, seizures, and falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH),
suicidal behaviour, mania (excessive activity, racing thoughts and reduced need for sleep), hallucinations, aggression and anger outbursts,
"serotonin syndrome" (a rare reaction which may cause feelings of excessive well-being, drowsiness, impaired motor coordination, restlessness, especially motor restlessness, alcohol-like intoxication, fever, sweating or muscle stiffness), seizures,
increased intraocular pressure (glaucoma),
cough, wheezing and shortness of breath, possibly accompanied by fever,
inflammation of the oral cavity, 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 condition with ulceration of the skin, mouth, eyes and genital organs), severe allergic reaction causing facial or throat swelling (angioedema),
jaw muscle spasm,
abnormal urine odour,
menopausal symptoms, abnormal milk production in men or women,
excessive vaginal bleeding shortly after childbirth (postpartum haemorrhage).

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

cutaneous vasculitis (inflammation of blood vessels in the skin).

Frequency not known (cannot be estimated from available data)

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects 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
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Dutilox

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack/bottle and outer carton after EXP. The expiry date refers to the last day of the stated month.

30 mg:
OPA/Aluminium/PVC/Aluminium blisters:
No special requirements regarding storage temperature.
Store in the original packaging to protect from light and moisture.

PVC/PVDC/Aluminium blisters:
Store below 30°C.
Store in the original packaging to protect from light and moisture.

Bottle:
No special requirements regarding storage temperature.
Store in the original packaging to protect from light and moisture.

60 mg:
OPA/Aluminium/PVC/Aluminium blisters:
No special requirements regarding storage temperature.
Store in the original packaging to protect from moisture.

PVC/PVDC/Aluminium blisters:
Store below 30°C.
Store in the original packaging to protect from moisture.

Bottle:
No special requirements regarding storage temperature.
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. Such measures will help protect the environment.

6. Contents of the pack and other information

What Dutilox contains

The active substance is duloxetine. 30 mg: each enteric hard capsule contains 30 mg of duloxetine (as hydrochloride). 60 mg: each enteric hard capsule contains 60 mg of duloxetine (as hydrochloride).
Other ingredients are:
Capsule contents: hypromellose, talc, titanium dioxide (E 171), methacrylic acid and ethyl acrylate copolymer (1:1), 30% dispersion, triethyl citrate, granulated sucrose and sucrose.

Capsule shell: gelatin, titanium dioxide (E 171), indigo carmine (E 132), purified water,
printing ink (black iron oxide (E 172), potassium hydroxide and shellac), yellow iron oxide (E 172) (only in 60 mg capsules).

What Dutilox looks like and contents of the pack

Dutilox is an enteric hard capsule. Each Dutilox capsule contains duloxetine hydrochloride granules coated with a protective layer resistant to gastric juice.

30 mg capsules with imprint (cap E/body 127) are opaque blue and opaque white in colour.
60 mg capsules with imprint (cap E/body 129) are opaque blue and opaque green in colour.

Dutilox is available in:
30 mg:
OPA/Aluminium/PVC/Aluminium blisters containing:
7, 10, 14, 20, 28, 30, 50, 56, 60, 84, 98 (2x49) and 504 (8x63) (hospital pack) enteric hard capsules.
PVC/PVDC/Aluminium blisters containing:
7, 10, 14, 20, 28, 30, 50, 56, 60, 84, 98 and 504 (4x126) (hospital pack) enteric hard capsules.
HDPE bottle with PP cap and tamper-evident closure, containing a desiccant sachet:
500 enteric hard capsules (hospital pack).

60 mg:
OPA/Aluminium/PVC/Aluminium blisters containing:
7, 10, 14, 20, 28, 30, 50, 56, 60 (2x30), 84 (2x42), 98 (2x49) and 504 (8x63) (hospital pack) enteric hard capsules.
PVC/PVDC/Aluminium blisters containing:
7, 10, 14, 20, 28, 30, 50, 56, 60, 84, 98 and 504 (4x126) (hospital pack) enteric hard capsules.
HDPE bottle with PP cap and tamper-evident closure, containing a desiccant sachet:
500 enteric hard capsules (hospital pack).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Farmak International Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
Poland

Manufacturer
TOWA Pharmaceutical Europe S.L.
C/ de Sant Martí, 75-97,
Martorelles, 08107 Barcelona
Spain
TERAPIA SA
Str. Fabricii, nr.124,
Cluj-Napoca, Judet Cluj,
400632, Romania

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: Dutilox 30 mg magensaftresistente Hartkapseln
Dutilox 60 mg magensaftresistente Hartkapseln
Austria: Dutilox 30 mg magensaftresistente Hartkapseln
Dutilox 60 mg magensaftresistente Hartkapseln
Netherlands: Dutilox 30 mg maagsapresistente capsules, harde
Dutilox 60 mg maagsapresistente capsules, harde
Poland: Dutilox
Romania: Duloxetină Terapia 30 mg capsule gastrorezistente
Duloxetină Terapia 60 mg capsule gastrorezistente
Belgium: {FR}: Dutilox 30 mg, gélules gastro-résistantes
{NL}: Dutilox 30 mg maagsapresistente capsules, hard
{DE}: Dutilox 30 mg magensaftresistente Hartkapseln
Belgium: {FR}: Dutilox 60 mg, gélules gastro-résistantes
{NL}: Dutilox 60 mg maagsapresistente capsules, hard
{DE}: Dutilox 60 mg magensaftresistente Hartkapseln