Siloxezol

Package leaflet: Information for the user

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

duloxetine (as hydrochloride)
Generic medicine
Please read all of this leaflet carefully before you take this medicine because 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 give it to other people, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effects, including 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 taking 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 Siloxezol is and what it is used for

Siloxezol contains the active substance duloxetine. Siloxezol increases the levels of serotonin and
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, sharp, stabbing, shooting, pressing, or like an electric shock. In the affected area, there may be loss of sensation, or sensations in which touch, heat, cold, or pressure can cause pain).

Siloxezol starts 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 start to feel better.
Contact your doctor if you do not start to feel better after this time. Your doctor may
continue your treatment with Siloxezol once you feel better to prevent depression or anxiety
from returning.
In people with diabetic neuropathic pain, it may take several weeks before you start to feel better.
Inform 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 to any of the other ingredients of this medicine (listed in section 6)
• have liver disease
• have 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, or ciprofloxacin or enoxacin, which are used to treat certain infections
• are taking other medicines containing duloxetine (see "Other medicines and Siloxezol")

Tell your doctor if you have high blood pressure or heart disease. Your doctor will advise you whether you can take Siloxezol.
Warnings and precautions
Reasons why Siloxezol may not be suitable for you include the following. Consult 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 lead to serotonin syndrome, a condition that can be fatal (see "Other medicines and Siloxezol")
• are taking St. John’s Wort (Hypericum perforatum), a herbal preparation
• have kidney disease
• have had seizures (epileptic fits)
• have experienced a manic episode
• suffer from bipolar disorder
• have eye problems, such as certain types of glaucoma (increased pressure inside the eye)
• have a history of coagulation disorders (tendency to bruise easily), especially if you are pregnant (see "Pregnancy and breastfeeding")
• are at risk of low sodium levels (for example, if you are taking diuretics, particularly if you are elderly)
• are being treated with another medicine that may cause liver damage
• are taking other medicines containing duloxetine (see "Other medicines and Siloxezol")

Siloxezol may cause a feeling of restlessness or inability to sit still. If this happens, inform your doctor.
Also contact your doctor if you experience signs and symptoms such as restlessness, hallucinations, loss of coordination, rapid heartbeat, elevated 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 may resemble neuroleptic malignant syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (detected by a blood test).
Medicines such as Siloxezol (so-called selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms may persist after discontinuation of treatment.
Suicidal thoughts and worsening of depression and anxiety disorders
If you are depressed and/or have anxiety disorders, you may occasionally have thoughts of harming yourself or of suicide. These thoughts may increase when you first start treatment with antidepressants, as these medicines require some time to become effective, usually about 2 weeks but sometimes longer.
You may be more likely to have these thoughts if you:

• have previously had thoughts of suicide or self-harm
• are a young adult. Clinical studies have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders treated with an antidepressant.

If at any time you have thoughts of harming yourself or of suicide, contact your doctor or go to hospital immediately.
You may find it helpful to inform a close family member or friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to tell you if they notice your depression or anxiety worsening, or if they are concerned about changes in your behaviour.
Children and adolescents under 18 years of age
Siloxezol is normally not recommended for use in children and adolescents under 18 years of age. In addition, you should know that patients under 18 years of age taking this type of medicine have an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (particularly aggressive behaviour, oppositional behaviour, and anger). Nevertheless, your doctor may prescribe Siloxezol to patients under 18 years of age if they consider it the best option for them. If your doctor has prescribed Siloxezol to a patient under 18 years of age and you have questions, consult your doctor again. You must inform your doctor if any of the symptoms listed above appear or worsen while patients under 18 years of age are taking Siloxezol. Furthermore, in this age group, the long-term effects of Siloxezol on growth, maturation, and cognitive and behavioural development have not yet been established.
Other medicines and Siloxezol
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
The main component of Siloxezol, duloxetine, is also found in other medicines for different conditions:

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

Concomitant use of more than one of these medicines should be avoided. Check with your doctor if you are already taking medicines containing duloxetine.
Your doctor must decide whether you can take Siloxezol with other medicines. Do not start or stop taking any medicine, including over-the-counter medicines and herbal preparations, without first consulting your doctor.
Also inform 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 medicine 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, may cause serious or even life-threatening side effects. You must wait at least 14 days after stopping an MAOI before starting Siloxezol. Also, you must wait at least 5 days after stopping Siloxezol before starting an MAOI.
Medicines that cause drowsiness: These include prescription medicines such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.
Medicines containing buprenorphine: These medicines may interact with Siloxezol and may cause symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movements, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, and fever above 38°C. Contact your doctor if you experience 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), meperidine, St. John’s Wort, and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of adverse effects; if you experience any unusual symptoms while taking any of these medicines together with Siloxezol, consult your doctor.
Oral anticoagulants and antiplatelet agents: Medicines that thin the blood or prevent blood clots. These medicines may increase the risk of bleeding.
Siloxezol with food, drink and alcohol
Siloxezol can be taken regardless of meals. Be cautious if you drink alcohol while being treated with Siloxezol.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

• Inform your doctor if you are pregnant or planning to become pregnant while taking Siloxezol. You should use Siloxezol only after discussing with your doctor the potential benefits and any potential risks for the unborn child.
• Make sure your midwife and/or doctor knows that you are taking Siloxezol. Medicines like this (SSRIs) taken during pregnancy may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes the baby to breathe rapidly and appear blue. These symptoms usually occur during the first 24 hours after birth. If this happens to your baby, contact your midwife or doctor immediately.
• If you take Siloxezol near the end of your pregnancy, the newborn may show some symptoms shortly after birth. These usually appear at birth or within a few days. Symptoms may include weak muscles, tremors, irritability, feeding difficulties, breathing problems, and seizures. If your newborn shows any of these symptoms after birth, or if you are concerned about your baby’s health, contact your doctor or midwife for advice.
• If you take Siloxezol near the end of your pregnancy, there is an increased risk of excessive vaginal bleeding immediately after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should be informed that you are taking duloxetine so they can advise you accordingly.

Available data on the use of duloxetine during the first three months of pregnancy do not show an increased overall risk of birth defects in the child. If Siloxezol is taken during the second half of pregnancy, there may be an increased risk that the baby will be born prematurely (6 additional premature births per 100 women taking Siloxezol in the second half of pregnancy), mostly between weeks 35 and 36 of pregnancy.

• Inform your doctor if you are breastfeeding. The use of Siloxezol during breastfeeding is not recommended. Seek advice from your doctor or pharmacist.

Driving and using machines
Siloxezol may cause drowsiness or dizziness. Do not drive or operate tools or machinery until you know how Siloxezol affects you.
Siloxezol contains sucrose. If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Siloxezol

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Siloxezol is taken orally. Swallow the capsule whole, without chewing, with a
glass of water.

For depression and diabetic neuropathic pain:
The recommended dose of Siloxezol is 60 mg once daily, but your doctor will prescribe the dose they consider appropriate for you.

For generalized anxiety disorder:
The recommended starting dose of Siloxezol is 30 mg once daily. Most patients will then receive 60 mg once daily, but your doctor will prescribe the dose they consider appropriate for you. The dose may be adjusted up to 120 mg daily, depending on your response to Siloxezol.

To help you remember to take Siloxezol, it may be easier to take it at the same time each day.
Talk to your doctor about how long you should continue taking Siloxezol. Do not stop taking Siloxezol or change the dose without first discussing it with your doctor. Appropriate treatment of the condition is important to help you feel better. If left untreated, the condition may not improve and could become worse and more difficult to treat.

If you take more Siloxezol than you should
Contact your doctor or pharmacist immediately if you have taken more Siloxezol than prescribed. Symptoms of overdose may include drowsiness, coma, serotonin syndrome (a rare reaction that may cause feelings of extreme happiness, drowsiness, clumsiness, restlessness, sensation of drunkenness, 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 it is almost time for your next dose, skip the missed dose and take only your next dose as usual. Do not take a double dose to make up for the forgotten dose. Do not take more Siloxezol than prescribed 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 decides you no longer need Siloxezol, they will ask you to gradually reduce the dose over a period of at least 2 weeks before stopping treatment completely.

Some patients who stop taking Siloxezol abruptly have experienced symptoms such as:

• dizziness, tingling sensations like pins and needles or electric shock sensations (particularly in the head), sleep disturbances (intense dreams, nightmares, inability to sleep), fatigue, drowsiness, feelings of restlessness or agitation, anxiety, nausea or malaise (vomiting), tremor, headache, muscle pain, irritability, diarrhoea, excessive sweating, or vertigo.

Usually, these symptoms are not severe and disappear within a few days. However, if you experience bothersome symptoms, 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. These side effects are usually mild to moderate and often disappear after a few weeks.

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

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

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

• loss of appetite
• difficulty falling asleep, feeling restless, reduced sex drive, anxiety, difficulty or inability to reach orgasm, unusual dreams
• dizziness, feeling sluggish, tremor, numbness, including a sensation of tingling, prickling or skin tingling
• blurred vision
• tinnitus (perception of ringing in the ears in the absence of external sound stimuli)
• feeling your heart beating in your chest
• increased blood pressure, flushing
• increased yawning
• constipation, diarrhoea, stomach ache, retching (vomiting), heartburn or indigestion, gas accumulation in the intestine
• increased sweating, skin rash (causing itching)
• muscle pain, muscle spasm
• painful urination, frequent urination
• difficulty achieving 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 experienced some weight loss when first starting treatment. After 6 months of treatment, their weight increased to match that of other children and adolescents of the same age and sex.

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

• throat inflammation causing hoarseness
• suicidal thoughts, difficulty falling asleep, teeth grinding or clenching, feeling disoriented, lack of motivation
• sudden and involuntary muscle spasms or contractions, feeling restless or unable to sit still or remain motionless, feeling nervous, difficulty concentrating, changes in taste sensation, difficulty controlling movements such as lack of coordination or involuntary muscle movements, restless legs syndrome, poor quality of sleep
• pupil dilation (the dark centre of the eye), visual disturbances
• feeling dizzy or lightheaded (vertigo), ear pain
• rapid or irregular heartbeat
• fainting, dizziness, feeling of emptiness in the head or impending faint when standing, cold sensation in fingers of hands and/or feet
• sensation of throat tightness, nosebleeds
• vomiting blood or passing black, tar-like stools, gastroenteritis, belching, difficulty swallowing
• liver inflammation which may 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, muscle contraction
• difficulty or inability to urinate, difficulty starting urination, need to urinate at night, need to urinate more than normal, reduced urinary 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, cold sensation, thirst, trembling, hot sensation, abnormal gait
• weight gain
• Siloxezol may cause effects you may not be aware of, such as increased liver enzymes, or blood levels of potassium, creatine phosphokinase, blood sugar, or cholesterol

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

• severe allergic reaction causing breathing difficulties or dizziness with swelling of the tongue and lips, allergic reactions
• reduced activity of the thyroid gland which may cause tiredness or weight gain
• dehydration, low sodium levels in the blood (especially in elderly people; symptoms may include dizziness, weakness, confusion, drowsiness or extreme tiredness, nausea or feeling like vomiting; more severe symptoms include fainting, seizures or falls), syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• suicidal behaviour, mania (hyperactivity, racing thoughts and reduced need for sleep), hallucinations, aggressive behaviour and anger
• “serotonin syndrome” (a rare reaction which may cause feelings of extreme well-being, drowsiness, clumsiness, restlessness, drunken feeling, 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 stools, bad breath, inflammation of the large intestine (colon) (leading to diarrhoea)
• liver failure, yellowing of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (a serious illness causing 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 odour of urine
• menopausal symptoms, abnormal production of breast milk in men and women
• excessive vaginal bleeding immediately after childbirth (post-partum haemorrhage)

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 experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 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 via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Siloxezol contains

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

Description of the appearance of Siloxezol and package contents
Siloxezol is a hard gastro-resistant capsule. Each Siloxezol capsule contains granules of
duloxetine hydrochloride coated to protect them from stomach acidity.
Siloxezol is available in two strengths: 30 mg and 60 mg.
The 30 mg capsules have an opaque grey body printed with “DLX 30” and an opaque blue cap printed with “DLX 30”, 18.0 mm in length.
The 60 mg capsules have an opaque grey body printed with “DLX 60” and an opaque white cap printed with “DLX 60”, 20.4 mm in length.
Siloxezol is available in OPA/Al/PVC/Al blisters and in plastic containers (HDPE) with 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 Rome
Italy
Manufacturer
Balkanpharma-Dupnitsa AD,
3 Samokovsko Shosse Str.,
Dupnitsa 2600,
Bulgaria

This medicinal product is authorised in the European Economic Area countries under the following names:
Italy: Siloxezol