Ezequa

Package leaflet: Information for the patient

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

duloxetine hydrochloride
Equivalent medicine
Please read all of this leaflet carefully before taking 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 pass it on 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, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Ezequa is and what it is used for

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

• depression
• generalized anxiety disorder (chronic feelings of anxiety or nervousness)
• diabetic neuropathic pain (often described as burning, sharp, stabbing, shooting, crushing, or like an electric shock. In the affected area, there may be loss of sensation, or sensations where touch, heat, cold, or pressure can cause pain)

Ezequa 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. Contact your doctor if you do not begin to feel better by then. Your doctor may continue your Ezequa treatment after 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 Ezequa

Do not take Ezequa if:

• you are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6)
• you have liver disease
• you have severe kidney disease
• you are taking or have taken within the last 14 days another medicine known as a Monoamine Oxidase Inhibitor (MAOI) (see ‘Other medicines and Ezequa’)
• you are taking fluvoxamine, which is commonly used to treat depression, or ciprofloxacin or enoxacin, which are used to treat certain infections
• you are taking other medicines containing duloxetine (see ‘Other medicines and Ezequa’)
  Tell your doctor if you have high blood pressure or heart disease. Your doctor will advise whether you should take Ezequa.

Warnings and precautions
Reasons why Ezequa may not be suitable for you include the following. Talk to your doctor or pharmacist
before taking Ezequa if:

• you are taking other medicines to treat depression or other conditions treated with antidepressants. Using these medicines together with Ezequa may lead to serotonin syndrome, a condition that can be fatal (see ‘Other medicines and Ezequa’)
• 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, such as 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 Ezequa’)

Ezequa may cause a feeling of restlessness or inability to sit still. If this happens to you, 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, diarrhoea, 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 Ezequa (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 committing 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
• you 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 committing suicide, contact your doctor or go
immediately to hospital.
You may find it helpful to inform a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to inform you if they believe your depression or anxiety is worsening, or if they are concerned about changes in your behaviour.

Children and adolescents under 18 years of age
Ezequa is normally not to be used 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 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 Ezequa to patients under 18 years of age if he/she considers it the best treatment option. If your doctor has prescribed Ezequa to a patient under 18 years of age and you require clarification, 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 Ezequa. In addition, long-term effects of Ezequa on growth, maturation, and cognitive and behavioural development have not yet been established in this age group.

Other medicines and Ezequa
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 active ingredient in Ezequa, duloxetine, is also found in other medicines used for other 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 Ezequa 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): do not take Ezequa 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 Ezequa, may cause serious or even life-threatening side effects. You must wait at least 14 days after stopping an MAOI before starting Ezequa. Also, you must wait at least 5 days after stopping Ezequa 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, meperidine (pethidine), St. John’s wort (hypericum). These medicines increase the risk of adverse effects; if you experience any unusual symptoms while taking one of these medicines together with Ezequa, consult your doctor.

Antidepressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, doxepin or trimipramine, buprenorphine used for treatment of acute or chronic pain, and opioid antagonists used to block opioid effects (e.g. naloxone).
These medicines may interact with Ezequa 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.

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

Ezequa with food, drinks and alcohol
Ezequa can be taken regardless of meals. You should be cautious about drinking alcohol while being treated with Ezequa.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Inform your doctor if you become pregnant or are planning a pregnancy while taking Ezequa. You should use Ezequa only after discussing with your doctor the potential benefits and any potential risks to the unborn child.
Ensure that your midwife and/or doctor know that you are taking Ezequa. 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 Ezequa near the end of your pregnancy, the newborn may experience certain symptoms shortly after birth. These usually appear at birth or within a few days after birth. These 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 who will be able to advise you.

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

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

Driving and using machines
Ezequa may cause drowsiness or dizziness. Do not drive or operate tools or machinery until you know how Ezequa affects you.

Ezequa contains sucrose
Ezequa contains sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking this medicine.
Ezequa contains less than 23 mg of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to take Ezequa

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Ezequa is taken orally. Swallow the capsule whole with a glass of water.

For depression and diabetic neuropathic pain
The recommended dose of Ezequa 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 Ezequa is 30 mg once daily. Most patients are then increased to
60 mg once daily, but your doctor will determine the dose they consider appropriate for you.
The dose may be adjusted up to 120 mg per day, depending on your response to Ezequa.

To help you remember to take Ezequa, it may be easier to take it at the same time every day.
Talk to your doctor about how long you should continue taking Ezequa. Do not stop taking
Ezequa or change the dose without first discussing it with your doctor. Appropriate treatment
of the disorder 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 Ezequa than you should
Contact your doctor or pharmacist immediately if you have taken more Ezequa than prescribed.
Symptoms of overdose may include drowsiness, coma, serotonin syndrome (a rare reaction that
may cause feelings of extreme well-being, drowsiness, clumsiness, restlessness, sensations of
intoxication, fever, sweating, or muscle rigidity), seizures, vomiting, and rapid heartbeat.

If you forget to take Ezequa
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 only your next dose at the usual time. Do not take a double
dose to make up for the missed one. Do not take more Ezequa than the amount prescribed for
you in one day.

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

Some patients who stop taking Ezequa 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, diarrhea, excessive sweating, or vertigo.
Usually, these symptoms are not severe and disappear within a few days. However, 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 everyone experiences them. Normally, these side 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, drowsiness
• 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 sexual desire, anxiety, difficulty or inability to achieve orgasm, unusual dreams
• dizziness, feeling sluggish, tremor, numbness, including a sensation of tingling, prickling or pins and needles in the skin
• blurred vision
• tinnitus (perception of sound in the ear in the absence of an external auditory stimulus)
• awareness of your 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 (pruritic)
• 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, their 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, cold sensation in fingers and/or toes
• sensation of throat tightness, nosebleeds
• vomiting blood or passing black, tarry 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 develop bruises
• muscle stiffness, muscle contraction
• difficulty or inability to urinate, difficulty initiating urination, need to urinate during the 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, feeling cold, thirst, trembling, feeling hot, abnormal gait
• weight gain

Ezequa may cause effects that you may not be aware of, such as increases in liver enzymes, blood potassium levels, creatine phosphokinase, blood sugar levels, 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 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, 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, 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 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 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 www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Ezequa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp".
The expiry date refers to the last day of that month.
For PVC-PVDC-Aluminium blister packs: store in the original packaging to protect from moisture. Keep the blister in the original carton to protect the medicine from light. Do not store above 30 °C.
For Aluminium-Aluminium blister packs: this medicine does not require any special storage temperature. Store in the original blister to protect the medicine from light and moisture.
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. Package contents and other information

What Ezequa contains

• The active substance is duloxetine. Each capsule contains 30 or 60 mg of duloxetine (as hydrochloride).
• The other components are: Capsule contents: hypromellose, methacrylic acid-ethyl acrylate copolymer dispersion 30% (sodium lauryl sulfate and polysorbate 80), sucrose, sugar spheres, talc, titanium dioxide (E171), triethyl citrate (see end of section 2 for further information on sucrose). Capsule shell: gelatin, titanium dioxide (E171), indigo carmine (E132), iron oxide yellow (E172) (only for the 60 mg strength), and black ink.

Description of the appearance of Ezequa and the contents of the pack
Ezequa is a hard gastro-resistant capsule. Each Ezequa capsule contains granules of duloxetine hydrochloride coated to protect them from the acidity of the stomach.
Ezequa is available in two strengths: 30 mg and 60 mg.
The 30 mg capsules have an opaque white body printed with “127” and an opaque blue cap printed with “E”.
The 60 mg capsules have an opaque green body printed with “129” and an opaque blue cap printed with “E”.
Ezequa 30 mg is available in packs of 7 and 28 capsules.
Ezequa 60 mg is available in packs of 28 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Mylan S.p.A.
Via Vittor Pisani 20,
20124 Milan - Italy
Manufacturer
Towa Pharmaceutical Europe S.L.
C/ San Martí, 75-97, Martorelles
08107 Barcelona, Spain