SILOXEZOL 30 mg Enteric-Coated Hard Capsule

Зміст інструкції

1. Siloxezol 30 mg hard gastro-resistant capsules, 60 mg hard gastro-resistant capsules
   1. What is Siloxezol and what is it used for
   2. What you need to know before taking Siloxezol
   3. How to take Siloxezol
   4. Possible side effects
   5. How to store Siloxezol
   6. Package contents and other information

Siloxezol 30 mg hard gastro-resistant capsules, 60 mg hard gastro-resistant capsules

duloxetine (as hydrochloride)
Generic medicine

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Siloxezol is and what it is used for
• 2. What you need to know before you take Siloxezol
• 3. How to take Siloxezol
• 4. Possible side effects
• 5. How to store Siloxezol
• 6. Contents of the pack and other information

1. What is Siloxezol and what is it used for

Siloxezol contains the active ingredient duloxetine. Siloxezol increases the levels of serotonin and of
noradrenaline in the nervous system.
Siloxezol is used in adults to treat:

• depression
• generalized anxiety disorder (chronic feeling of anxiety or nervousness)
• diabetic neuropathic pain (often described as burning, cutting, stabbing, shooting, or oppressive, or as an electric shock. In the affected area, there may be loss of sensation, or sensations in which contact, heat, cold or pressure can cause pain).

Siloxezol begins to be effective in most people with depression or anxiety within
two weeks of starting treatment, but it may take 2-4 weeks before you feel
better. Contact your doctor if you do not begin to feel better after this time. Your doctor may
continue to give you Siloxezol when you feel better to prevent depression or anxiety from
returning.
In people with diabetic neuropathic pain, it may take several weeks before you
feel better. Tell your doctor if you do not feel better after 2 months.

2. What you need to know before taking Siloxezol

Do not take Siloxezol if you:

• are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6)
• have a liver disease
• have a severe kidney disease
• are taking, or have taken within the last 14 days, another medicine known as a Monoamine Oxidase Inhibitor (MAOI) (see “Other medicines and Siloxezol”)
• are taking fluvoxamine which is commonly used to treat depression, ciprofloxacin or enoxacin which are used to treat some infections
• are taking other medicines that contain duloxetine (see “Other medicines and Siloxezol”)

Tell your doctor if you have high blood pressure or a heart condition. Your doctor will tell you if you can
take Siloxezol.

Warnings and precautions
The reasons why Siloxezol might not be suitable for you are as follows. Talk to your doctor or
pharmacist before taking Siloxezol if you:

• are taking other medicines to treat depression (see “Other medicines and Siloxezol”)
• are taking medicines containing buprenorphine. Using these medicines together with Siloxezol may result in serotonin syndrome, a condition that can be life-threatening (see “Other medicines and Siloxezol”)
• are taking St. John's Wort ( Hypericum perforatum), a herbal medicinal product
• have a kidney disease
• have had seizures (convulsions)
• have had a manic episode
• suffer from bipolar disorder
• have problems with your eyes, such as certain types of glaucoma (increased pressure inside the eye)
• have a history of bleeding disorders (tendency to bruise easily), especially if you are pregnant (see “Pregnancy and breastfeeding”)
• are at risk of having low sodium levels (for example if you are taking diuretics, especially if you are an elderly person)
• are being treated with another medicine that can cause liver damage
• are taking other medicines that contain duloxetine (see “Other medicines and Siloxezol”).

Siloxezol may cause a feeling of restlessness or inability to sit still. If this
happens to you, you should tell your doctor.
Also tell your doctor if you experience signs and symptoms of restlessness, hallucinations, loss of
coordination, rapid heartbeat, increased body temperature, rapid changes in
blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting, you may be suffering from serotonin
syndrome.
In its most severe form, serotonin syndrome can resemble neuroleptic malignant syndrome
(NMS). The signs and symptoms of NMS may include a combination of fever, rapid heartbeat,
sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).
Medicines such as Siloxezol (so-called selective serotonin reuptake inhibitors (SSRIs) and
serotonin-noradrenaline reuptake inhibitors (SNRIs)) can cause symptoms of sexual dysfunction (see
section 4). In some cases, persistence of these symptoms has been observed after discontinuation of
treatment.

Thoughts of suicide and worsening of depression and anxiety
If you are depressed and/or anxious sometimes you may have thoughts of harming yourself or of
killing yourself. These thoughts may increase when you first start taking
antidepressants, as these medicines take time to work, usually about 2 weeks but sometimes longer.
You may be more likely to have these thoughts if you:

• have had thoughts of killing yourself or harming yourself in the past
• are young adult. Data from clinical studies have shown an increased risk of suicidal behavior in adults under 25 years of age with psychiatric disorders who were treated with an antidepressant.

If at any time you have thoughts of harming yourself or killing yourself, contact your doctor or go
to hospital immediately.
You may find it helpful to tell a relative or close friend that you are depressed or anxious, and ask them to read this leaflet. You can ask them to tell you if they think your
depression or anxiety is getting worse, or if they are worried about changes in your
behavior.

Children and adolescents under 18 years of age
Siloxezol is normally not used in children and adolescents under 18 years of
age. Also, you should know that patients under 18 years of age, when taking this type of
medicines, have an increased risk of side effects such as suicide attempts, suicidal thoughts and hostile
behavior (especially aggressive behavior, oppositional behavior and anger). However, your doctor may prescribe Siloxezol to patients under 18 years of age if
they believe that this is the best solution for them. If your doctor has prescribed Siloxezol to a patient
under 18 years of age and you would like clarification, return to your doctor. You should inform your doctor if any
of the above symptoms appear or worsen when patients under 18 years of age are
taking Siloxezol. Furthermore, long-term safety effects regarding growth, maturity and cognitive and
behavioral development have not yet been demonstrated in this age group.

Other medicines and Siloxezol
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines, including those available without a prescription.
The main component of Siloxezol, duloxetine, is found in other medicines for other conditions:

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

The simultaneous use of more than one of these medicines should be avoided. Check with your doctor if
you are already taking medicines that contain duloxetine.
Your doctor needs to decide if you can take Siloxezol with other medicines. Do not start or stop
taking any medicine, including those bought without a prescription and
herbal medicinal products, before consulting your doctor.
Also tell your doctor if you are taking any of the following medicines:

Monoamine Oxidase Inhibitors (MAOIs): you must not take Siloxezol if you are taking, or have
recently taken (within the last 14 days) another antidepressant called a monoamine
oxidase inhibitor (MAOI). Examples of MAOI medicines include moclobemide (an
antidepressant) and linezolid (an antibiotic). Taking an MAOI together with many prescription
medicines, including Siloxezol, can cause serious or even life-threatening side effects. You must wait at least 14 days after you have stopped taking an
MAOI before you can take Siloxezol. Also, you must wait at least 5 days after you have
stopped taking Siloxezol before taking an MAOI.

Medicines that cause drowsiness: these include medicines prescribed by your doctor, such as
benzodiazepines, strong painkillers, antipsychotics, phenobarbital and antihistamines.
Medicines containing buprenorphine: these medicines may interact with Siloxezol and may
manifest symptoms such as involuntary and rhythmic muscle contractions, including the muscles
that control eye movement, agitation, hallucinations, coma, excessive sweating, tremor,
increased muscle contraction, fever above 38°C. Contact your doctor in
the presence of such symptoms.

Medicines that increase serotonin levels: triptans, tramadol, tryptophan, Selective
Serotonin Reuptake Inhibitors (SSRIs) (such as paroxetine and fluoxetine), Serotonin-Noradrenaline
Reuptake Inhibitors (SNRIs) (such as venlafaxine), tricyclic antidepressants
(such as clomipramine, amitriptyline), pethidine, St. John's Wort and MAOIs (such as moclobemide and
linezolid). These medicines increase the risk of side effects; if you experience any unusual symptoms while taking one of these medicines together with Siloxezol, you should consult
your doctor.

Oral anticoagulants and antiplatelet agents: medicines that thin the blood or prevent
blood clots from forming. These medicines may increase the risk of bleeding.

Siloxezol with food, drink and alcohol
Siloxezol can be taken independently of meals. You should be careful if you drink alcohol while
being treated with Siloxezol.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor or
pharmacist for advice before taking this medicine.

• Tell your doctor if you are pregnant, or planning to become pregnant, while taking Siloxezol. You should only use Siloxezol after discussing the potential benefits and any potential risks to the unborn child with your doctor.
• Make sure your midwife and/or doctor knows that you are being treated with Siloxezol. When taken during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition in newborns, called persistent pulmonary hypertension of the newborn (PPHN), which involves the newborn having a fast breathing rate and a bluish skin color. These symptoms usually appear during the first 24 hours after birth. If this happens to the newborn, contact your midwife or doctor immediately.
• If you take Siloxezol near the end of your pregnancy, the newborn may experience some symptoms shortly after birth. Generally these appear at birth or within a few days of birth. These symptoms may include floppy muscles, tremor, nervousness, difficulty breastfeeding, a breathing disorder and seizures. If the newborn experiences any of these symptoms after birth, or you are worried about the health of the baby, contact your doctor or midwife who will be able to advise you.
• If you take Siloxezol near the end of your pregnancy there is an increased risk of excessive vaginal bleeding shortly after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should be informed that you are taking duloxetine so that they can advise you.

Available data on the use of duloxetine during the first 3 months of pregnancy do not show an
increased risk of overall birth defects in the baby. If Siloxezol
is taken during the second half of pregnancy there may be an increased risk that
the newborn may be born prematurely (6 more newborns born prematurely per 100 women who
take Siloxezol in the second part of pregnancy), mostly between weeks 35 and 36
of pregnancy.

• Tell your doctor if you are breastfeeding. The use of Siloxezol during breastfeeding is not recommended. Ask your doctor or pharmacist for advice.

Driving and using machines
Siloxezol may cause you to feel drowsy or dizzy. Do not drive or use tools or
machinery until you know how Siloxezol affects you.

Siloxezol contains sucrose.If you have been diagnosed with an intolerance to certain sugars, contact
your doctor before taking this medicine.

3. How to take Siloxezol

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
Siloxezol is taken orally. Swallow the capsule without chewing, with the help of a
glass of water.

For depression and diabetic neuropathic pain:
The recommended dose of Siloxezol is 60 mg once a day, but your doctor will prescribe the dose
that he/she considers right for you.

For generalized anxiety disorder:
The recommended starting dose of Siloxezol is 30 mg once a day, after which most
patients will receive 60 mg once a day, but your doctor will prescribe the dose that he/she considers
right for you. The dose may be adjusted up to 120 mg per day, based on your response to
Siloxezol.
To help you remember to take Siloxezol, it may be easier for you to take it every day at the same
time.
Talk to your doctor to find out how long you should continue taking Siloxezol. Do not stop
taking Siloxezol, or change the dose, without talking to your doctor. Appropriate treatment of the
disorder is important to help you feel better. If left untreated, the disorder may not
improve and may become more serious and difficult to treat.

If you take more Siloxezol than you should
Contact your doctor or pharmacist immediately if you have taken a quantity of Siloxezol
greater than what your doctor has prescribed. Symptoms of overdose include
drowsiness, coma, serotonin syndrome (a rare reaction that can cause feelings of
great happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating
or muscle stiffness), seizures, vomiting and increased heart rate.

If you forget to take Siloxezol
If you forget a dose, take it as soon as you remember. However, if this is the time to take
the next dose, skip the forgotten dose and take only a single dose as usual. Do not
take a double dose to make up for a missed dose. Do not take more than the amount of
Siloxezol that has been prescribed for you for one day.

If you stop taking Siloxezol
Even if you feel better, DO NOT stop taking the capsules without consulting your
doctor. If your doctor believes you no longer need Siloxezol, he/she will ask you to reduce
the dose gradually over a period of at least 2 weeks before stopping treatment completely.
Some patients who suddenly stop taking Siloxezol have experienced symptoms
such as:

• dizziness, sensations of tingling like pinpricks and needles or electric shock-like sensations (especially in the head), sleep disturbances (intense dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling restless or agitated, feeling anxious, nausea or unwell (vomiting), tremor, headache, muscle pain, feeling irritable, diarrhea, excessive sweating or dizziness.

Usually these symptoms are not serious and disappear within a few days, but if you experience symptoms that
are bothersome, you should consult your doctor.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Normally these effects are mild to moderate and often disappear after a few
weeks.

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

• headache, feeling sleepy
• feeling unwell (nausea), dry mouth

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

• loss of appetite
• difficulty sleeping, feeling restless, decreased sexual drive, anxiety, difficulty or inability to reach orgasm, unusual dreams
• dizziness, feeling sluggish, tremor, numbness, including a sensation of tingling or pins and needles in the skin
• blurred vision
• tinnitus (perception of a sound in the ear in the absence of an external sound stimulus)
• feeling your heart beating in your chest
• increased blood pressure, flushing
• increased yawning
• constipation, diarrhea, stomach pain, retching (vomiting), heartburn or indigestion, build-up of gas in the intestines
• increased sweating, rash (which is itchy)
• muscle pain, muscle spasm
• painful urination, frequent urination
• difficulty getting an erection, changes in ejaculation
• falls (especially in elderly people), fatigue
• weight loss

Children and adolescents under 18 years of age with depression treated with this medicine
have experienced some weight loss when they first started taking this
medicine. After 6 months of treatment the weight increased to be equal to that of other
children and adolescents of the same age and sex.

Uncommon side effects (may affect up to 1 in 100 people)

• inflammation of the throat causing a hoarse voice
• suicidal thoughts, difficulty falling asleep, teeth grinding or clenching, feeling disoriented, lack of motivation
• sudden and involuntary spasms or contractions of the muscles, feeling restless or inability to sit still or remain quiet, feeling nervous, difficulty concentrating, changes in taste, difficulty controlling movements such as lack of coordination or involuntary muscle movements, restless legs syndrome, poor sleep quality
• pupil dilation (the dark center of the eye), visual disturbances
• feeling dizzy or “lightheaded” (vertigo), ear pain
• increased or irregular heartbeat
• fainting, dizziness, feeling lightheaded or about to faint when standing up, feeling cold in the hands and/or feet
• feeling of constriction in the throat, nosebleeds
• blood in vomit or black, tarry stools, gastroenteritis, belching, 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 develop bruises
• muscle stiffness, muscle contraction
• difficulty or inability to urinate, difficulty starting urination, needing to urinate during the night, needing to urinate more than usual, reduced urine flow
• abnormal vaginal bleeding, abnormal menstrual cycles, including heavy, painful, irregular or prolonged periods, unusually light or absent periods, testicular or scrotal pain
• chest pain, feeling cold, thirst, trembling, feeling hot, abnormal gait
• weight gain
• Siloxezol may cause effects of which you may not be aware, such as increases in liver enzymes, or levels in the blood of potassium, creatine phosphokinase, sugars or cholesterol

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

• severe allergic reaction causing difficulty breathing or dizziness with swelling of the tongue and lips, allergic reactions
• decreased activity of the thyroid gland which can cause fatigue or weight gain
• dehydration, low levels of sodium in the blood (especially in elderly people; symptoms may include feeling dizzy, weak, confused, sleepy or very tired, or feeling sick or being sick, more serious symptoms are fainting, seizures or falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• suicidal behavior, mania (hyperactivity, racing thoughts and decreased need for sleep), hallucinations, aggressive behavior and anger
• “serotonin syndrome” (a rare reaction that can cause feelings of great happiness, sleepiness, clumsiness, restlessness, feeling drunk, fever, sweating or muscle stiffness), seizures
• increased pressure inside the eye (glaucoma)
• cough, wheezing and shortness of breath possibly accompanied by fever
• inflammation of the mouth, presence of bright red blood in the stools, bad breath, inflammation of the large intestine (colon) (leading to diarrhea)
• liver failure, yellowing of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious illness with the appearance of blisters on the skin, mouth, eyes and genitals), severe allergic reaction causing swelling of the face or throat (angioedema)
• contraction of the muscles of the mouth
• altered smell of urine
• symptoms of menopause, abnormal production of breast milk in men and women
• excessive vaginal bleeding immediately after childbirth (postpartum hemorrhage)

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

• Inflammation of blood vessels in the skin (cutaneous vasculitis)

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

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

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Siloxezol

Keep this medicine out of the sight and reach of children.
Do not store at a temperature above 25°C.
Do not use this medicine after the expiry date which is stated on the carton and label after
“Exp.”. The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Siloxezol contains

• The active ingredient is duloxetine. Each capsule contains 30 or 60 mg of duloxetine (as hydrochloride).
• The other ingredients are: Capsule content: sugar granules (sucrose, corn starch), hypromellose phthalate (HP-55), hypromellose (E15 LV), triethyl citrate, hydroxypropyl cellulose, talc 30 mg capsule shell: hypromellose (E464), titanium dioxide (E171), Brilliant Blue FCF (E133), black iron oxide (E172), printing ink 60 mg capsule shell:hypromellose (E464), titanium dioxide (E171), black iron oxide (E172), printing ink The printing ink contains:shellac, propylene glycol, black iron oxide (E172), potassium hydroxide.

Description of Siloxezol and package contents
Siloxezol is a hard, gastro-resistant capsule. Each Siloxezol capsule contains granules of
duloxetine hydrochloride with a coating to protect them from stomach acidity.
Siloxezol is available in 2 strengths: 30 mg and 60 mg.
The 30 mg capsules have an opaque grey body, imprinted with “DLX 30” and an opaque blue head, imprinted with “DLX 30”, length 18.0 mm.
The 60 mg capsules have an opaque grey body, imprinted with “DLX 60” and an opaque white head, imprinted with “DLX 60”, length 20.4 mm.
Siloxezol is available in OPA/Al/PVC/Al blisters and plastic containers (HDPE) with a screw cap
and desiccant.

Blisters: 7 or 28 capsules.
Containers: 28 capsules
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder
S.F. Group S.r.l
Via Tiburtina 1143, 00156 Roma
Italy

Manufacturer
Balkanpharma-Dupnitsa AD,
3 Samokovsko Shosse Str.,
Dupnitsa 2600,
Bulgaria

This medicinal product is authorised in the Member States of the European Economic Area under the
following designations:
Italy: Siloxezol