Dulex

Package leaflet: Information for the user

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

Duloxetine (as hydrochloride)
Equivalent medicine
Read this entire leaflet carefully before starting to take 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Dulex is and what it is used for

Dulex contains the active substance duloxetine. Dulex increases the levels of serotonin and noradrenaline in the nervous system.
Dulex 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, or crushing, or like an electric shock. In the affected area, there may be loss of sensation, or sensations where touch, heat, cold, or pressure may cause pain).

Dulex 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 start to feel better. If you do not begin to feel better after this time, speak to your doctor. Your doctor may continue to prescribe Dulex once you feel better in order 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 should know before taking Dulex

DO NOT take Dulex 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 Dulex’);
• 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 Dulex’).

Tell your doctor if you have high blood pressure or heart disease. Your doctor will advise you whether you can take Dulex.

Warnings and precautions

Reasons why Dulex may not be suitable for you include the following. Talk to your doctor before taking Dulex if:

• you are taking other medicines to treat depression or have other conditions treated with antidepressants. Using these medicines together with Dulex may lead to serotonin syndrome, a condition that can be fatal (see ‘Other medicines and Dulex’);
• you are taking St. John’s wort (Hypericum perforatum), a herbal preparation;
• you have kidney disease;
• you have had seizures (epileptic fits);
• you have experienced a manic episode;
• you suffer from bipolar disorder;
• you have eye problems, including certain types of glaucoma (increased pressure inside the eye);
• you have a history of coagulation disorders (tendency to bruise easily), especially if you are pregnant (see “Pregnancy and breastfeeding”);
• you are at risk of low sodium levels (e.g. if you are taking diuretics, particularly if you are elderly);
• you are being treated with another medicine that may cause liver damage;
• you are taking other medicines containing duloxetine (see ‘Other medicines and Dulex’);
• you are taking medicines containing buprenorphine or buprenorphine/naloxone. Dulex may cause a feeling of restlessness or inability to sit still. If this occurs, inform your doctor.

You should 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, hyperactive reflexes, diarrhea, coma, nausea, or vomiting, as these may indicate 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 Dulex (so-called selective serotonin and serotonin-noradrenaline reuptake inhibitors, SSRIs and 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 suffer from 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 such thoughts if you:

• have previously had thoughts of suicide or self-harm;
• are a young adult. Clinical trial data 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 family member or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may also ask them to inform you if they think your depression or anxiety is worsening, or if they are concerned about changes in your behaviour.

Children and adolescents under 18 years of age

Dulex is generally not recommended for use in children and adolescents under 18 years of age.

Furthermore, you should know that patients under 18 years of age taking this type of medicine may have an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (particularly aggressive, oppositional, and angry behaviour). Nevertheless, your doctor may prescribe Dulex to patients under 18 years of age if they consider it the best treatment option. If your doctor has prescribed Dulex 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 above-mentioned symptoms appear or worsen while patients under 18 years of age are taking Dulex. In addition, long-term effects of Dulex on growth, maturation, and cognitive and behavioural development have not yet been established in this age group.

Other medicines and Dulex

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.

The main component of Dulex, duloxetine, is found in other medicines used for different conditions:

• diabetic neuropathic pain, depression, anxiety, and urinary incontinence. Concurrent use of more than one of these medicines must be avoided. Check with your doctor whether you are already taking medicines containing duloxetine. Your doctor must decide whether you can take Dulex 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 Dulex if you are currently 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 Dulex, may cause serious or even life-threatening side effects. You must wait at least 14 days after stopping an MAOI before starting Dulex. Also, you must wait at least 5 days after stopping Dulex before starting an MAOI.

Medicines that cause drowsiness: These include medicines prescribed by your doctor, such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.

Medicines that increase serotonin levels: Triptans, tramadol, tryptophan, Selective Serotonin Reuptake Inhibitors (SSRIs) (such as paroxetine, fluoxetine, fluvoxamine, sertraline, citalopram, and escitalopram), Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) (such as venlafaxine), tricyclic antidepressants (such as clomipramine, amitriptyline, trimipramine, and doxepine), meperidine, St. John’s wort (hypericum), buprenorphine or buprenorphine/naloxone, and MAOIs (such as moclobemide, tranilcypramine, and linezolid). These medicines may interact with Dulex and cause symptoms such as involuntary rhythmic muscle contractions, including those 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.

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

Dulex with food, drink and alcohol

Dulex can be taken regardless of meals. You should be cautious if you drink alcohol while being treated with Dulex.

Pregnancy and breastfeeding

If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

• Inform your doctor if you become pregnant or are planning a pregnancy while taking Dulex. You should use duloxetine only after discussing with your doctor the potential benefits and any possible risks to the unborn child.
• Make sure your midwife and/or doctor knows that you are taking Dulex. 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 causes the baby to breathe rapidly and appear bluish. These symptoms usually occur within the first 24 hours after birth. If this happens to your newborn, contact your midwife or doctor immediately.
• If you take Dulex near the end of pregnancy, the newborn may show some symptoms shortly after birth. These usually appear at birth or within a few days. Symptoms may include floppy 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.
• If you take Dulex near the end of 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 appropriately.
• Available data on the use of Dulex during the first three months of pregnancy do not show an overall increased risk of birth defects in the child. However, if Dulex is taken during the second half of pregnancy, there may be an increased risk of premature birth (6 additional premature births per 100 women taking Dulex in the second half of pregnancy), mostly between weeks 35 and 36 of pregnancy.
• Inform your doctor if you are breastfeeding. The use of Dulex during breastfeeding is not recommended. Consult your doctor or pharmacist for advice.

Driving and using machines

Dulex may cause drowsiness or dizziness. Do not drive or operate tools or machinery until you know how Dulex affects you.

Dulex contains sucrose

Dulex contains sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Dulex contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially ‘sodium-free’.

3. How to take Dulex

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

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

For generalized anxiety disorder:
The usual starting dose of Dulex is 30 mg once daily. Most patients will then be given 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 per day, depending on your response to Dulex.

To help you remember to take Dulex, it may be easier to take it at the same time each day.
Talk to your doctor about how long you should continue taking Dulex. Do not stop taking Dulex or change the
dose without 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 Dulex than you should
Contact your doctor or pharmacist immediately if you have taken more Dulex than prescribed. Symptoms of
overdose may include drowsiness, coma, serotonin syndrome (a rare reaction that may cause feelings of intense
happiness, drowsiness, clumsiness, restlessness, sensation of drunkenness, fever, sweating or muscle rigidity),
seizures, vomiting and rapid heartbeat.

If you forget to take Dulex
If you miss 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 the next dose at the usual time. Do not take a double dose to make up for a forgotten
dose. Do not take more Dulex than the amount prescribed for one day.

If you stop taking Dulex
Even if you feel better, DO NOT stop taking the capsules without consulting your doctor. If your doctor decides
you no longer need Dulex, they will ask you to gradually reduce the dose over a period of at least two weeks
before stopping treatment completely.

Some patients who stop taking Dulex suddenly 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, feeling restless or agitated, 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. 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 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 achieve orgasm, unusual dreams;
• dizziness, feeling sluggish, tremor, numbness, including a sensation of tingling, prickling or skin tingling;
• blurred vision;
• tinnitus (perception of sound in the ear in the absence of an external auditory stimulus);
• awareness of heartbeat (palpitations);
• increased blood pressure, hot flush;
• increased yawning;
• constipation, diarrhoea, stomach ache, retching (vomiting), heartburn, indigestion, gas accumulation in the intestine;
• increased sweating, skin rash (itchy);
• 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 have experienced some weight loss when first starting treatment. After 6 months of treatment, weight increased to be comparable to that of other children and adolescents of the same age and sex.

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

• inflammation of the throat 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 of impending fainting when standing up, cold sensation in fingers and/or toes;
• 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 (jaundice);
• 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, need to urinate during the night, need to urinate more than normal, reduced urine flow;
• abnormal vaginal bleeding, abnormal menstrual cycles, including heavy, painful, irregular or prolonged periods, periods that are unusually light or absent, testicular or scrotal pain;
• chest pain, feeling cold, thirst, trembling, feeling hot, abnormal gait;
• weight gain;
• Dulex may cause effects you may not be aware of, such as increases in liver enzymes, blood potassium levels, creatine phosphokinase, blood sugar or cholesterol levels.

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 levels of sodium 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 loss of consciousness, 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 that may cause feelings of extreme well-being, drowsiness, clumsiness, restlessness, drunken sensation, 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) (causing diarrhoea);
• liver failure, yellowing of the skin or whites of the eyes (jaundice);
• Stevens-Johnson syndrome (a serious condition with blistering of 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 (postpartum 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 effects, 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 Dulex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack.
This medicine requires no special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Dulex 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 (containing maize starch and sucrose), hypromellose 2910 (E464), crospovidone (type B), talc, sucrose, carboxy-methyl-ethyl-cellulose, povidone, titanium dioxide (E171), macrogol (E1521), polysorbate 80 (E433) (see end of section 2 for further information on sucrose).
Capsule shell (for 30 mg strength): gelatin, titanium dioxide (E171), sodium lauryl sulfate, indigo carmine (E132).
Capsule shell (for 60 mg strength): gelatin, titanium dioxide (E171), sodium lauryl sulfate, indigo carmine (E132), synthetic yellow iron oxide (E172).
Edible gold-coloured ink (for 30 mg strength): shellac (E904), propylene glycol, yellow iron oxide (E172).
Edible white-coloured ink (for 60 mg strength): shellac (E904), propylene glycol, potassium hydroxide, titanium dioxide (E171).

Description of the appearance of Dulex and contents of the pack
Dulex is a hard gastro-resistant capsule. Each Dulex capsule contains duloxetine hydrochloride granules coated to protect them from stomach acid.
Dulex is available in 30 mg and 60 mg strengths.
The 30 mg capsules have an opaque blue cap and an opaque white body, size '3' (15.80 ± 0.40 mm), printed with 'H' on the cap and '191' on the body, filled with pellets ranging in colour from white to off-white.
The 60 mg capsules have an opaque blue cap and an opaque green body, size '1' (19.30 ± 0.40 mm), printed with 'H' on the cap and '192' on the body, filled with pellets ranging in colour from white to off-white.
Dulex 30 mg is available in packs of 7 and 28 capsules.
Dulex 60 mg is available in packs of 28 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Ecupharma S.r.l. - Via Mazzini 20 - 20123 Milan (Italy).

Manufacturers:
Pharmadox Healthcare Ltd.,
KW20A Kordin Industrial Park, Paola
PLA 3000
Malta
Hetero Malta Ltd.,
KW20A Corradino Industrial Estate, Paola
PLA 3000
Malta

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
IT: Dulex