EXITAL 50 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the Patient

Exital 50 mg prolonged-release tablets EFG

Desvenlafaxine

Read this package leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet:

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

1. What is Exital and what is it used for

Exital is an antidepressant that belongs to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). This group of medicines is used to treat depression. People with depression may have lower levels of serotonin and noradrenaline (also known as norepinephrine) in the brain. It is not fully understood how antidepressants work, but they may help to increase the levels of serotonin and noradrenaline in the brain.

Desvenlafaxine is a treatment for adults.

2. What you need to know before you take Exital

Do not take Exital:

• if you are allergic to desvenlafaxine, venlafaxine or any of the other ingredients of this medicine (listed in section 6).
• if you are also taking, or have taken within the last 14 days, any medicines known as monoamine oxidase inhibitors (MAOIs) used to treat depression, infections or Parkinson's disease. Taking an MAOI (e.g. linezolid or methylene blue) with other medicines like Desvenlafaxine may cause serious or potentially life-threatening side effects. Also, you must wait at least 7 days after you stop taking Desvenlafaxine before taking any MAOI (see also sections "Serotonin syndrome" and "Other medicines").

Warnings and precautions

Tell your doctor if you have had any of the following conditions before taking Desvenlafaxine or if they appear during treatment with this medicine:

• if you or someone in your family has a history of mania (a state of excitement, feeling of euphoria or hyperirritability) or bipolar disorder (extreme mood swings, e.g. from depression to euphoria).
• if you have a history of aggressive behavior.
• if you have eye problems, such as certain types of glaucoma (increased pressure in the eye).
• if you have a history of high blood pressure or hypertension.
• if you have a history of heart problems or heart attack.
• if you have a history of seizures (fits).
• if you have a history of bleeding disorders (tendency to develop bruises), or if you are pregnant (see section Pregnancy, breastfeeding and fertility), or if you are using non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and other medicines that may increase the risk of bleeding when used at the same time as desvenlafaxine.
• if you have a history of kidney problems.
• if you have a history of low sodium levels in the blood (hyponatremia).
• if you have a history of high cholesterol, or if your cholesterol levels increase.
• if you experience the following side effects: agitation (excitability and restlessness), altered consciousness, confusion, coma, palpitations, increased blood pressure, elevated body temperature, excessive sweating, lack of coordination, muscle spasms or stiffness, tremors, nausea, vomiting and diarrhea. Contact your doctor immediately, as you may be suffering from serotonin syndrome (a disorder that can be serious and, in rare cases, potentially life-threatening).
• if you stop treatment abruptly, withdrawal symptoms may occur (e.g. mood changes, irritability, agitation, dizziness, anxiety, confusion, headache, sleep disturbances, tinnitus (ringing in the ears) and seizures). Therefore, it is important to reduce the dose of Desvenlafaxine gradually and under medical supervision, whenever you and your doctor decide to stop treatment.

Some medicines of the same group as Desvenlafaxine (called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Suicidal thoughts and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming or killing yourself. These thoughts may increase when you first start taking antidepressants, as these medicines take time to work, usually around 2 weeks, but sometimes longer.

You may be more likely to think this way:

• If you have previously had thoughts of suicide or self-harm.
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric disorders who were treated with antidepressants.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital directly.

You may find it helpful to tell a relative or close friendthat you are depressed or have an anxiety disorder, and ask them to read this package leaflet. You might 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.

Dry mouth

Dry mouth has been reported in 18% of patients treated with desvenlafaxine. This may increase the risk of tooth decay. Therefore, you should be careful with your oral hygiene.

Elderly patients

In some elderly patients, it cannot be ruled out that they may be more sensitive to desvenlafaxine.

Children and adolescents

Desvenlafaxine should not normally be used in children and adolescents. Additionally, you should know that in patients under 18 years, there is a greater risk of side effects such as suicidal attempts, hostility (mainly aggression, confrontational behavior and irritability) when taking this type of medicine. Nevertheless, the doctor who prescribes the medicine may prescribe it to patients under 18 years when they decide it is the most suitable for the patient. If the doctor who prescribes the medicine has prescribed it to a patient under 18 years and you want to discuss this decision, please go back to your doctor. You should inform your doctor if any of the above symptoms develop or worsen when these patients under 18 years are taking Desvenlafaxine.

Furthermore, the long-term effects on safety, including effects on growth, maturity, and cognitive and behavioral development, have not yet been demonstrated for this medicine.

Other medicines and Exital

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

It is especially important that you tell your doctor if you are taking any of the following medicines:

• monoamine oxidase inhibitors (MAOIs), e.g. medicines containing linezolid (an antibiotic used to treat infections) and methylene blue (see section "Do not take Exital").
• other medicines that contain venlafaxine or desvenlafaxine (also used to treat depression).
• triptans (used for migraine).
• medicines for treating depression, e.g. tricyclic antidepressants, amphetamines, lithium, selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs).
• medicines that contain sibutramine (used for weight loss).
• medicines for pain, e.g. those containing tramadol, fentanyl and its analogs, tapentadol, meperidine, methadone (also used for treatment of narcotic withdrawal syndrome and opioid dependence) and pentazocine.
• medicines that contain dextromethorphan (used for cough).
• products that contain St. John's Wort (also known as "Hypericum perforatum", a natural or herbal remedy used to treat mild depression).
• products that contain tryptophan (used for problems such as sleep and depression).
• medicines that contain ketoconazole (an antifungal).
• Additionally, if you are being treated by other healthcare professionals, inform them that you are taking Desvenlafaxine.

Serotonin syndrome or reactions similar to Neuroleptic Malignant Syndrome (NMS)

Rarely, a disorder called serotonin syndrome or reactions similar to NMS may occur, which can cause significant changes in brain, muscle, and digestive system function due to high levels of serotonin in the body. This potentially life-threatening condition may occur when taking medicines like Desvenlafaxine, particularly when taken with other medicines mentioned above.

See section "Warnings and precautions" or possible side effects related to serotonin syndrome or reactions similar to NMS.

Switching antidepressants

When switching treatment from another antidepressant to desvenlafaxine, withdrawal symptoms from the initial antidepressant have occurred. Your doctor may gradually reduce the dose of your initial antidepressant to help minimize these symptoms.

Interactions with laboratory tests

False positives for certain substances such as phencyclidine (PCP) and amphetamines may occur in urine analysis of patients who are taking or have taken desvenlafaxine, even several days after stopping treatment.

Using Exital with food, drinks and alcohol

Exital tablets can be taken with or without food. You should avoid drinking alcohol while taking this medicine.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

If you take desvenlafaxine in the final stages of pregnancy, there may be an increased risk

of heavy vaginal bleeding shortly after delivery, especially if you have a history of

bleeding disorders. Your doctor or midwife should know that you are taking this medicine so they can advise you. When similar medicines (SSRIs) are taken during pregnancy, there may be an increased risk of a serious effect on the baby called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and turn blue. These symptoms usually start during the first 24 hours after the baby is born. If your baby has these symptoms, you should contact your doctor and/or midwife immediately.

If you take Desvenlafaxine during pregnancy, inform your doctor and/or midwife, as your baby may experience withdrawal symptoms when born. These symptoms may appear shortly after birth and may require hospitalization. The symptoms include difficulty feeding or breathing problems. If your baby has these or other symptoms when born and you are concerned, contact your doctor and/or midwife.

Desvenlafaxine passes into breast milk. There is a risk of an effect on the baby. Therefore, do not use Desvenlafaxine during breastfeeding unless your doctor specifically advises you to do so.

Driving and using machines

This medicine may cause dizziness, drowsiness and blurred vision. Do not drive or use tools or machines until you know how this medicine affects you.

3. How to take Exital

Follow exactly the instructions for taking this medicine given by your doctor. If you are unsure, consult your doctor again.

The recommended dose is 50 mg once a day. Your doctor may increase your dose to 100 mg once a day or even up to a maximum of 200 mg once a day if necessary.

If you have kidney problems or a history of kidney problems, consult your doctor, as you may need to take a different dose of Desvenlafaxine.

This medicine should be taken orally, approximately at the same time each day. The tablets should be swallowed whole with liquid, without dividing, crushing, chewing or dissolving them.

Do not worry if you see the structure of a tablet in your stool after taking Exital.

As the tablet travels through your gastrointestinal tract, the active substance desvenlafaxine is slowly released. The tablet structure does not dissolve and is eliminated in the stool. Therefore, even though you may see the tablet structure in your stool, you will have absorbed your dose of desvenlafaxine.

If you take more Exital than you should

Contact your doctor or pharmacist immediately if you take more Desvenlafaxine than your doctor has prescribed.

In case of overdose or accidental ingestion, consult the Toxicology Information Service, Tel. 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Exital

If you miss a dose, take it as soon as you remember. However, if it is already time for your next dose, skip the missed dose and take only one dose, as usual. Do not take a double dose to make up for the missed dose.

If you stop taking Exital

Do not stop taking Desvenlafaxine, or change the dose, without talking to your doctor first, even if you feel better. Your doctor will probably want to gradually reduce the dose of Desvenlafaxine to avoid side effects. It is known that patients experience side effects when they stop taking this medicine, especially if they have taken a high dose and for a long period. Some of these side effects are: dizziness, nausea, headache, fatigue, irritability, diarrhea, anxiety, nightmares and excessive sweating. Therefore, the dose should be reduced slowly whenever possible, and under medical supervision, in case you and your doctor decide to stop treatment with Desvenlafaxine.

If you experience any of these or other symptoms that bother you, consult your doctor (see section "Warnings and precautions").

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, Desvenlafaxine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

If you notice any of the following signs, inform your doctor immediately or go to the nearest hospital:

• Heart problems, such as rapid heart rate, increased blood pressure, or chest pain.
• Eye problems, such as blurred vision.
• Nervous system problems, such as dizziness, numbness, and tingling, movement disorder (e.g., involuntary muscle movements, restlessness), seizures, or attacks.
• Psychiatric problems, such as hyperactivity and euphoria.
• Drug allergy, such as skin rash, throat swelling, or breathing difficulties.

List of Possible Adverse Effects

The adverse effects and frequency (probability of occurrence) mentioned below have been observed in patients. In general, these adverse effects occurred more frequently during the first week of treatment.

Very common: affects more than 1 in 10 patients

Common: affects between 1 and 10 in 100 patients

Uncommon: affects between 1 and 10 in 1,000 patients

Rare: affects between 1 and 10 in 10,000 patients

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

Immune system disorders

Uncommon: allergic reaction

Metabolism and nutrition disorders

Common: loss of appetite

Rare: hyponatremia (decreased sodium concentration in blood)

Psychiatric disorders

Very common: insomnia

Common: withdrawal syndrome, anxiety, nervousness, strange dreams, irritability, decreased libido, absence of orgasm

Uncommon: distortion of self-image and reality, abnormal orgasm

Rare: mania (state of overexcitement, feeling of euphoria or hyperirritability), hypomania (state of excitement and excessive activity), and hallucinations

Nervous system disorders

Very common: dizziness, headache, somnolence

Common: tremors, numbness, and tingling, attention deficit, alteration of taste

Uncommon: loss of consciousness, abnormal movements (dyskinesia)

Rare: serotonin syndrome (characterized by symptoms such as agitation (excitability and restlessness), altered consciousness, confusion, coma, palpitations, increased blood pressure, elevated body temperature, excessive sweating, lack of coordination, muscle spasms or stiffness, tremors, nausea, vomiting, and diarrhea), seizures (attacks), movement disorders (e.g., involuntary muscle movements, restlessness)

Eye disorders

Common: pupil dilation, blurred vision

Ear and labyrinth disorders

Common: tinnitus, sensation of vertigo

Cardiac disorders

Common: rapid heart rate, palpitations (feeling of rapid, irregular, or strong heartbeat)

Vascular disorders

Common: high blood pressure, hot flashes

Uncommon: peripheral coldness, low blood pressure when changing position

Respiratory disorders

Common: yawning

Uncommon: nasal bleeding

Gastrointestinal disorders

Very common: nausea, dry mouth, constipation

Common: vomiting, diarrhea

Rare: acute pancreatitis (inflammation of the pancreas)

Skin and subcutaneous tissue disorders

Very common: excessive sweating

Common: skin rash

Uncommon: total or partial hair loss

Rare: Stevens-Johnson syndrome (erythema multiforme consisting of a hypersensitivity reaction affecting the skin and mucous membranes), swelling under the skin, sensitivity to light

Musculoskeletal disorders

Common: muscle stiffness

Renal and urinary disorders

Uncommon: difficulty urinating, urinary retention, protein in urine

Reproductive system disorders

Common: erectile dysfunction, delayed ejaculation, ejaculatory failure

Uncommon: sexual dysfunction, ejaculation disorder

Frequency not known: heavy vaginal bleeding shortly after childbirth (postpartum hemorrhage), see "Pregnancy, Breastfeeding, and Fertility" in section 2 for more information

General disorders

Common: fatigue, weakness, chills, feeling of restlessness

Investigations and medical tests

Common: alteration of liver tests, weight gain, weight loss, high blood pressure

Uncommon: increased cholesterol levels in blood, increased triglyceride values in blood, increased prolactin hormone values in blood

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Exital

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and blister, after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Exital

• The active ingredient is desvenlafaxine (as desvenlafaxine benzoate).

• Each tablet contains 50 mg of desvenlafaxine (as desvenlafaxine benzoate).

• The other components are: hypromellose, microcrystalline cellulose, talc, stearic acid, magnesium stearate, anhydrous colloidal silica (E551).

The coating film of the 50 mg tablets contains: poly (vinyl alcohol), titanium dioxide (E171), macrogol, talc, and yellow and red iron oxides (E172).

Appearance of the Product and Package Contents

Light pink, biconvex, round tablet. The tablet dimensions are 9.6 ± 0.2 mm.

Exital 50 mg is available in Alu-PVC/PE/PVdC blisters in packs of 28 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Alter, S.A.

Mateo Inurria 30

28036 Madrid

Spain

Manufacturer

PharOS MT Ltd.

HF62X, Hal Far Industrial Estate

BBG3000 Birzebbugia (Malta)

Date of Last Revision of this Prospectus: March 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/