Package Insert: Information for the Patient

Exital 50 mg Extended-Release Tablets EFG

Desvenlafaxine

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

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

Desvenlafaxine is a treatment for adults.

Do not take Exital:

• if you are allergic to desvenlafaxine, venlafaxine, or any of the other ingredients in this medication (listed in section 6).
• if you are also taking or have taken within the last 14 days, any medication known as a monoamine oxidase inhibitor (MAOI) used to treat depression, infections, or Parkinson's disease. Taking an MAOI (for example, linezolid or methylene blue) with other medications such as Desvenlafaxine, may produce severe or potentially life-threatening side effects. Additionally, you should wait at least 7 days after stopping Desvenlafaxine before taking any MAOI (see also the sections “Serotonin Syndrome” and “Other Medications”).

Warnings and Precautions

Consult your doctor if you have experienced any of the following conditions before taking Desvenlafaxine or if they occur during treatment with this medication:

• if you or a family member has a history of mania (a state of overexcitement, feeling of euphoria, or irritability) or bipolar disorder (extreme mood swings, for example, from depression to euphoria).
• if you have a history of aggressive behavior.
• if you have eye problems, such as certain types of glaucoma (increased eye pressure).
• if you have a history of high blood pressure or hypertension.
• if you have a history of heart problems or myocardial infarction.
• if you have a history of seizures (convulsions).
• if you have a history of bleeding disorders (tendency to develop petechiae), or if you are pregnant (see the section Pregnancy, Breastfeeding, and Fertility), or if you are using nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and other medications that may increase the risk of bleeding when used with 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 rigidity, tremors, nausea, vomiting, and diarrhea. Contact your doctor immediately, as you may be experiencing serotonin syndrome (a disorder that can be severe and, in rare cases, potentially life-threatening).
• if stopping treatment abruptly may cause withdrawal symptoms (for example, mood changes, irritability, agitation, dizziness, anxiety, confusion, headache, sleep disturbances, tinnitus (ringing in the ears), and seizures). Therefore, it is essential to reduce the dose of Desvenlafaxine gradually and under medical supervision whenever you and your doctor decide to discontinue treatment.

Some medications in the group to which Desvenlafaxine belongs (called SSRIs/SNRIs) may cause sexual dysfunction (see section 4). In some cases, these symptoms persist after discontinuing treatment.

Thoughts of suicide and worsening of depression or anxiety

If you are depressed and/or have anxiety disorders, you may have had thoughts of harming yourself or committing suicide. These thoughts may increase when starting antidepressants, as these medications take time to work, usually two weeks, but sometimes longer.

You may be more likely to have these thoughts:

• if you have had previous thoughts of suicide or self-harm.
• if you are a young adult. Clinical trial information has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric disorders treated with antidepressants.

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

You may find it helpful to tell a close family member or friend who is depressed or has an anxiety disorder, and ask them to read this leaflet. You could also ask them to tell you if they think your depression or anxiety is getting worse, or if they are concerned 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 take good care of your oral hygiene.

Older patients

In some older patients, it cannot be ruled out that there may be increased sensitivity to desvenlafaxine.

Children and adolescents

Desvenlafaxine should not be used normally in children and adolescents. Additionally, you should be aware that, in patients under 18 years of age, there is a higher risk of adverse effects such as suicidal behavior, hostility (predominantly aggression, confrontational behavior, and irritability) when taking this class of medication. Despite this, the doctor who prescribes your medication may prescribe this medication to patients under 18 years of age when they decide it is in the best interest of the patient. If the doctor who prescribes your medication has prescribed this medication to a patient under 18 years of age and wants to discuss this decision, please return to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen when these patients under 18 years of age are taking Desvenlafaxine.

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

Other medications and Exital

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

It is especially important to inform your doctor if you are taking any of the following medications:

• monoamine oxidase inhibitors (MAOIs), for example, medications containing linezolid (an antibiotic used to treat infections) and methylene blue (see the section “Do not take Exital”).
• other medications containing venlafaxine or desvenlafaxine (also used to treat depression).
• triptans (used for migraines).
• medications to treat depression, for example, tricyclic antidepressants, amphetamines, lithium, selective serotonin reuptake inhibitors (SSRIs), or serotonin and norepinephrine reuptake inhibitors (SNRIs).
• medications containing sibutramine (used for weight loss).
• pain medications, for example, those containing tramadol, fentanyl, and its analogs, tapentadol, meperidine, methadone (also used to treat opioid withdrawal and dependence), and pentazocine.
• medications containing dextromethorphan (used for coughs).
• products containing St. John's Wort (also known as “Hypericum perforatum”, a natural remedy or herbal remedy used to treat mild depression).
• products containing tryptophan (used for problems such as sleep and depression).
• medications containing 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)

Occasionally, a rare disorder called serotonin syndrome or reactions similar to NMS may occur, causing significant changes in brain, muscle, and digestive system function due to elevated serotonin levels in the body. This potentially life-threatening state may occur when taking medications like Desvenlafaxine, especially when taken with other medications mentioned above.

See the section “Warnings and Precautions” or the possible side effects related to serotonin syndrome or reactions similar to NMS.

Switching antidepressants

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

Interactions with laboratory tests

Falsely positive results for substances such as phenylcylidine (PCP) and amphetamines may occur in urine tests of patients taking or having taken desvenlafaxine, even several days after stopping treatment.

Use of Exital with food, drinks, and alcohol

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

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, or think you may be pregnant, or if you plan to become pregnant, consult your doctor before using this medication.

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

of excessive vaginal bleeding after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should know that you are taking this medication to advise you. When taking similar medications (SSRIs) during pregnancy, there may be an increased risk of a severe condition in the newborn called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and turn blue. These symptoms usually begin within the first 24 hours after birth. If your baby has these symptoms, 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 occur shortly after birth and may require hospitalization. Symptoms may include difficulty breastfeeding or respiratory 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 operating machinery

This medication may cause dizziness, drowsiness, and blurred vision. Do not drive or operate tools or machinery until you know how this medication affects you.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

The recommended dose is 50 mg once a day. Your doctor may increase your dose up 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 since you may need to take a different dose of Desvenlafaxine.

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

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

As the tablet travels along your gastrointestinal tract, the active ingredient desvenlafaxine is released slowly. The tablet structure does not dissolve and is eliminated in the stool. Therefore, despite the fact that it is possible that the tablet structure may appear in your stool, you will have absorbed your dose of desvenlafaxine.

If you take more Exital than you should

Immediately contact your doctor or pharmacist if you take more Desvenlafaxine than your doctor has prescribed.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, Tel. 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Exital

If you have not taken 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 compensate for the missed dose.

If you interrupt treatment with Exital

Do not stop taking Desvenlafaxine, or change the dose, without your doctor's indication, even if you feel better. Your doctor prefers to gradually reduce the dose of Desvenlafaxine to avoid adverse effects. It is known that patients experience adverse effects when they stop taking this medication, especially if they have taken a high dose and for a prolonged period. Some of these adverse effects are: dizziness, nausea, headache, fatigue, irritability, diarrhea, anxiety, nightmares, and excessive sweating. Therefore, the dose should be reduced gradually whenever possible, and under medical supervision, if you and your doctor decide to interrupt treatment with Desvenlafaxine.

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

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

Like all medications, Desvenlafaxine may cause side effects, although not everyone will experience them.

Severe side effects

Notify your doctor immediately or visit the nearest hospital if you notice any of the following symptoms:

• 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 convulsions.
• Psychiatric problems, such as hyperactivity and euphoria.
• Medication allergy, such as skin rash, throat swelling, or breathing difficulties.

Side effect list

The side effects and frequency (probability of occurrence) listed below have been observed in patients. In general, these side 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

Unknown frequency: (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, rare 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:shakiness, numbness and tingling, attention deficit, alteration of taste

Uncommon: loss of consciousness, abnormal movements (dyskinesia)

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

Eye disorders

Common: dilated pupils, blurred vision

Ear disorders

Common: ringing in the ears, sensation of vertigo

Cardiac disorders

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

Vascular disorders

Common: high blood pressure, hot flashes

Uncommon: peripheral coldness, low blood pressure upon 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, light sensitivity

Musculoskeletal disorders

Common: muscle stiffness

Renal and urinary disorders

Uncommon: difficulty urinating, urinary retention, proteinuria

Reproductive system and breast disorders

Common: erectile dysfunction, delayed ejaculation, ejaculatory insufficiency

Uncommon: sexual dysfunction, ejaculation disorder

Unknown frequency: heavy vaginal bleeding shortly after delivery (postpartum hemorrhage), see "Pregnancy, lactation, and fertility" in section 2 for more information

General disorders

Common: fatigue, weakness, chills, feeling of unease

Medical tests and evaluations

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

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es.

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

Keep this medication out of the sight and reach of children.

Do not use this medication 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 medication does not require special storage conditions.

Medications should not be disposed of through drains or trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

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, and 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 contents of the packaging

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

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

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Laboratorios Alter, S.A.

Mateo Inurria 30

28036 Madrid

Spain

Responsible manufacturer

PharOS MT Ltd.

HF62X, Hal Far Industrial Estate

BBG3000 Birzebbugia (Malta)

Last review date of this leaflet: March 2022

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/