Package Insert: Information for the User

Citalopram Combix 20 mg Film-Coated Tablets

Contents of the package and additional information

Citalopram Combixis a selective serotonin reuptake inhibitor (SSRI) and belongs to a group of medicines known as antidepressants. These medicines help correct certain chemical imbalances in the brain that cause symptoms of your illness.

CitalopramCombixis indicated for the treatment of:

• Depression and prevention of relapses and recurrences.
• Anxiety disorder with or without agoraphobia.
• Obsessive-compulsive disorder (OCD).

Your doctor may, however, prescribe Citalopram Combixfor any other purpose. Ask your doctor if you have any doubts as to why they have prescribed Citalopram Combix.

Do not take CitalopramCombix:

• If you are allergic to citalopram or any of the other components of this medication (listed in section 6).
• If you are taking other medications that belong to a group called monoamine oxidase inhibitors (MAOIs). MAOIs include medications such as phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine, selegiline (used in the treatment of Parkinson's disease), moclobemide (used for the treatment of depression), and linezolid (an antibiotic).
• If you have a congenital heart rhythm disorder or have ever experienced an episode of this type (this is observed with an electrocardiogram, a test that evaluates how the heart functions).

-If you are taking medications for a condition that affects your heart rhythm.

-If you are taking medications that can affect your heart rhythm.

Consult also the section "Other medications and Citalopram Combix” that is located below.

Even if you have finished treatment with MAOIs, you will need to wait 2 weeks before starting your treatment with citalopram.

You must wait a day after taking moclobemide.

After finishing citalopram, you must wait a week before taking any MAOI.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Citalopram Combix.

Please inform your doctor if you have any other condition or disease, as your doctor may need to take it into consideration. In particular, inform your doctor:

• If you have manic episodes or anxiety disorders.
• If you have liver or kidney disease. Your doctor may need to adjust the dose.
• If you have diabetes. The treatment with citalopram may affect blood sugar control. You may need to adjust the dose of insulin and/or oral hypoglycemic medications.
• If you have epilepsy. The treatment with citalopram should be discontinued if seizures occur or if there is an increase in seizure frequency (see also section 4 “Possible side effects”).
• If you have any type of bleeding disorder, or if you are pregnant (see“Pregnancy, breastfeeding, and fertility”).
• If you have a low sodium level in your blood.
• If you are receiving electroconvulsive therapy.
• If you have or have had any heart problems or have recently had a heart attack.

-If when at rest your heart beats slowly (this is known as bradycardia) and/or you think your body may be losing salt, for example, because you have had diarrhea and vomitingintensively for several days or because you have used diuretics (medications to urinate).

-If you have noticed that your heartbeats are rapid or irregular or have fainted or felt dizzy when getting up from a sitting or lying position. This could indicate that you have a heart rhythm disorder.

-If you have a problem with pupil dilation (mydriasis)

Consult your doctor, even if any of the circumstances mentioned above have occurred at any time.

Some patients with manic-depressive illness may enter a manic phase. This is characterized by unusual and rapid changes in ideas, excessive joy, and excessive physical activity. If you experience this, contact your doctor.

Symptoms such as restlessness or difficulty sitting or staying upright (akathisia) may also occur during the first weeks of treatment. Inform your doctor immediately if you experience these symptoms.

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

Special information related to your disease

Like other medications used to treat depression or related conditions, improvement is not immediate. After starting treatment with citalopram, it may take several weeks to experience any improvement.

In the treatment of anxiety disorder, it usually takes 2-4 weeks to observe any improvement.

At the beginning of treatment, some patients may experience an increase in anxiety, which will disappear with continued treatment. Therefore, it is very important that you follow your doctor's instructions exactly and do not interrupt treatment or change the dose without consulting your doctor.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may occasionally have thoughts of harming yourself or taking your life. These may increase when taking antidepressants for the first time, as all these medications require time to start working, usually around 2 weeks, although in some cases it may take longer.

Youare more likely to have these types of thoughts:

• If you have previously had thoughts of harming yourself or taking your life.
• If you are ayoung adult. Information from clinical trials has shown an increased risk of suicidal behavior in young adults (under 25 years) with psychiatric conditions who were treated with an antidepressant.

If you ever have thoughts of harming yourself or taking your life, contact your doctor or go directly to a hospital.

It may be helpful for you to tell a family member or close friendthat you are depressed or have an anxiety disorder and ask them to read this leaflet. You can ask them if they think your depression or anxiety disorder has worsened, or if they are concerned about changes in your attitude.

Children and adolescents

Citalopram should not normally be used to treat children and adolescents under 18 years old.

At the same time, you should know that in patients under 18 years old, there is a higher risk of adverse effects such as suicidal attempts, suicidal thoughts, and hostility (mainly aggression, confrontational behavior, and irritability) when taking this type of medication. However, the doctor who prescribes it may prescribe citalopram to patients under 18 years old when they decide it is best for the patient. If the doctor who prescribes it has prescribed citalopram to a patient under 18 years old and wants to discuss this decision, please return to your doctor. You should inform your doctor if any of the symptoms mentioned above progress or if you experience complications when patients under 18 years old are taking citalopram. At the same time, the long-term effects on safety related to growth, maturity, and cognitive and behavioral development of citalopram in this age group have not yet been demonstrated.

Other medications and Citalopram Combix

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

Some medications may affect the action of others and may cause adverse reactions at times.

Inform your doctor if you are using any of the following medications:

• Non-selective monoamine oxidase inhibitors (MAOIs) containing phenelzine, iproniazid, isocarboxazid, nialamide, and tranylcypromine as active substances. If you have taken any of these medications, you should wait 14 days before starting to take citalopram. After finishing treatment with citalopram, you should wait 7 days before taking any of these medications.

• Selective reversible MAO-A inhibitors containing moclobemide (used for the treatment of depression)
• The antibiotic linezolid
• Lithium (used for the prophylaxis and treatment of manic-depressive disorder) and tryptophan.
• Imipramine and desipramine (both used to treat depression).
• Irreversible MAO-B inhibitors, containing selegiline (used for the treatment of Parkinson's disease); these increase the risk of adverse effects. The dose of selegiline should not exceed 10 mg per day.
• Metoprolol (used for high blood pressure and/or heart disease); the blood levels of metoprolol increase, but no signs of increased effect or adverse effects of metoprolol have been observed.
• Sumatriptan and similar medications (used to treat migraines) and tramadol (used for severe pain) increase the risk of adverse effects, if you experience any unusual symptoms when using this combination, you should see your doctor.
• Cimetidine, lansoprazole, and omeprazole (used to treat stomach ulcers), fluconazole (used to treat fungal infections), fluvoxamine (antidepressant), and ticlopidine (used to reduce the risk of stroke). They may increase the levels of citalopram in the blood.
• Medications that affect platelet function, such as some antipsychotics, aspirin (used for pain), non-steroidal anti-inflammatory drugs (used for arthritis); they slightly increase the risk of bleeding disorders.
• St. John's Wort (Hypericum perforatum) (a herbal remedy used for depression); the concomitant administration with citalopram may increase the risk of adverse effects.
• Mefloquine (used to treat malaria), bupropion (used to treat depression), and tramadol (used for severe pain) due to a possible risk of lowering the seizure threshold.
• Neuroleptics (medications for schizophrenia, psychosis), due to a possible risk of lowering the seizure threshold, and antidepressants.
• Class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobials (sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, medications for malaria, particularly halofantrine), certain antihistamines (astemizol, mizolastine).
• Medications that decrease potassium or magnesium levels in the blood, as this increases the risk of cardiac arrhythmias, which are life-threatening.

Do not take citalopram if you are taking medications because you already have a condition that affects your heart rhythm or if you are taking medications that could affect your heart rhythm.

If you are unsure about this, consult your doctor.

Use of CitalopramCombixwithfoods, beverages, and alcohol

Citalopram can be taken with or without food (see section 3. “How to take Citalopram Combix”).

Citalopram has been observed not to increase the effects of alcohol. However, it is recommended to avoid consuming alcohol during treatment with citalopram.

Pregnancy, breastfeeding, and fertility

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

Pregnant women should not normally take citalopram, and mothers should not breastfeed their babies while taking this medication, unless you and your doctor have analyzed the risks and benefits involved.

If you take citalopram during the last 3 months of your pregnancy and until the date of birth, be aware that the following effects may be observed in the newborn baby: difficulty breathing, blue skin, seizures, changes in body temperature, difficulty feeding, vomiting, low blood sugar, muscle stiffness or weakness, intense reflexes, tremors, restlessness, irritability, drowsiness, and difficulty falling asleep. If your newborn baby has any of these symptoms, please contact your doctor immediately.

If you take Citalopram Combix in the final stage of pregnancy, there may be a higher 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 Citalopram Combix to be able to advise you.

Citalopram passes into breast milk in small amounts. There is a risk of effects on the baby. If you are taking citalopram, inform your doctor before starting breastfeeding.

Make sure your midwife and/or doctor are informed that you are being treated with citalopram.

During pregnancy, particularly in the last 3 months, medications like citalopram may increase the risk of a serious condition in newborns, called persistent pulmonary hypertension of the newborn (PPHN), in which the baby breathes rapidly and turns blue. These symptoms usually start within the first 24 hours after birth. If they appear in your baby, you should contact your midwife and/or doctor immediately.

Citalopram has been shown to reduce sperm quality in animal models. Theoretically, this effect could affect fertility, but until now, it has not been observed in human fertility.

Driving and operating machinery:

During treatment with citalopram, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how citalopram affects you

This medication contains lactose.If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

This medication contains less than 23 mg of sodium (1 mmol) per tablet; this is, essentially “sodium-free”.

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

Adults

Depression

The usual dose is 20 mg per day. If necessary, your doctor may increase this dose up to a maximum of 40 mg per day.

Anxiety disorder

The initial dose is 10 mg per day for the first week before increasing it to 20-30 mg per day. If necessary, your doctor may increase this dose up to a maximum of 40 mg per day.

Obsessive-compulsive disorder

The initial dose is 20 mg per day. If necessary, your doctor may increase this dose up to a maximum of 40 mg per day.

Older adults (65 years and older)

In older adults, treatment should be initiated with half the recommended dose, for example 10-20 mg per day.

Generally, older adults should not take more than 20 mg per day.

Patients with special risks

Patients with liver disease should not take more than 20 mg per day.

Use in children and adolescents

Citalopram should not be administered to children or adolescents. For additional information, please see section 2 “What you need to know before starting to take Citalopram Combix”.

How and when to take Citalopram Combix

Citalopram is taken once a day as a single daily dose.

The tablets can be taken at any time of the day, regardless of meals.

The tablets should be swallowed with a glass of water.Do not chew them (they have a bitter taste).

The tablet can be divided into equal doses.

Treatment duration

Like other depression, anxiety disorder, and obsessive-compulsive disorder medications, it may take several weeks to find some improvement. Continue taking citalopram even if you do not feel any improvement in your condition.

Do not change the medication dose without talking to your doctor first.

The treatment duration is individual, usually at least 6 months. Continue taking the tablets for the recommended time by your doctor. Do not stop taking them unless your doctor tells you to. The underlying disease may persist for a long time, and if you stop treatment too soon, your symptoms may reappear.

Patients with recurrent depression benefit from continued treatment, sometimes for several years, to prevent the occurrence of new depressive episodes.

If you take more Citalopram Combix than you should:

If you think you or someone else has taken more citalopram than they should, contact your doctor or pharmacist immediately, go to the nearest hospital emergency department, or call theToxicology Information Service, phone: 91 562 0420, indicating the medication and the amount taken.

Do this even if you do not observe any discomfort or signs of intoxication.

Bring the medication packaging with you if you visit the doctor or hospital.

Some symptoms of an overdose may include irregular heartbeats with a risk to life, changes in heart rhythm, drowsiness, coma, vomiting, tremors, decreased blood pressure, nausea (feeling dizzy), serotonin syndrome (see section 4. “Possible side effects”), agitation, dizziness, dilated pupils, sweating, blue skin, hyperventilation (increased respiratory rate).

If you forget to take Citalopram Combix:

If you forget to take a dose, take the next dose at the usual time. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Citalopram Combix:

Do not stop taking citalopram until your doctor tells you to. When you have completed your treatment period, it is usually recommended that the citalopram dose be gradually reduced over several weeks.

Abrupt withdrawal of the medication may cause some mild or transient disturbances, such as dizziness, tingling sensation, sleep disturbances (intense dreams, nightmares, inability to sleep), anxiety, headache, dizziness (nausea), vomiting, sweating, restlessness or agitation, tremors, feeling of confusion or disorientation, feelings of emotion or irritability, diarrhea (loose stools), visual disturbances, rapid pulse or palpitations.

When you have finished your treatment period, it is usually recommended that the citalopram dose be gradually reduced over a couple of weeks instead of stopping it abruptly.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Side effects usually disappear after a few weeks of treatment. Please note that many of the side effects can also be symptoms of your illness and will therefore improve when you start to feel better.

Some patients have reported the following serious side effects.

If you have any of the following symptoms, stop taking citalopram and see your doctor immediately.

• High fever, agitation, confusion, tremors, and sudden muscle contractions; these can be signs of a rare condition called serotonin syndrome, which has been reported with the combined use of antidepressants.
• If you notice swelling of the skin, tongue, lips, or face, or have difficulty breathing or swallowing (allergic reaction).
• Unusual bleeding, including gastrointestinal bleeding.

Rare but serious side effects (can affect up to 1 in 1,000 people):

If you have any of the following symptoms, stop taking citalopram and see your doctor immediately.

• Hypontremia: low sodium levels in the blood that can cause fatigue, confusion, and muscle cramps.
• Fast and irregular heartbeats or a feeling of dizziness, which could be symptoms of a serious heart condition called torsade de pointes.

The following side effects are generally mild and usually disappear after a few days of treatment. Please be aware that several of the side effects mentioned below can be symptoms of your illness and will therefore improve when you start to feel better.

If the side effects are bothersome or last longer than a few days, consult your doctor.

Dry mouth increases the risk of tooth decay. Therefore, you should brush your teeth more frequently than usual.

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

-Drowsiness

-Difficulty sleeping,

-Increased sweating,

-Dry mouth,

-Nausea (feeling que you are going to be sick)

-Headaches

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

-Loss of appetite

-Agitation

-Decreased libido

-Anxiety

-Nervousness

-Confusion

-Abnormal dreams

-Tremors

-Numbness or tingling in hands or feet

-Dizziness

-Disturbances in attention

-Tinnitus (ringing in the ears)

-Yawning

-Diarrhea

-Vomiting

-Constipation

-Rash

-Muscle and joint pain

-Men may experience problems with ejaculation and erection

-Women may experience difficulty reaching orgasm

-Fatigue

-Fever

-Itching

-Weight loss

Rare side effects (can affect up to 1 in 100 people):

-Cutaneous hemorrhagic disorders (easy bruising)

-Increased appetite

-Aggression

-Depersonalization

-Hallucinations

-Mania

-Fainting

-Dilated pupils

-Rapid heartbeats

-Slow heartbeats

-Urticaria

-Hair loss

-Skin rash

-Photophobia (sensitivity to light)

-Difficulty urinating

-Excessive menstrual bleeding

-Swelling of arms and legs

-Weight gain

Rare (can affect up to 1 in 1,000 people):

-Seizures

-Involuntary movements

-Taste disturbances

-Bleeding

-Hepatitis

-Fever

Unknown frequency (cannot be estimated from available data):

-Thoughts of self-harm or suicidal thoughts, see also the section “Warnings and precautions”

-Reduced platelet count in the blood, which increases the risk of bleeding or bruising (hematoma)

-Hypersensitivity (rash)

-Severe allergic reaction that causes difficulty breathing or dizziness

-Increased urine production

-Hypokalemia: low potassium levels in the blood that can cause muscle weakness, cramps, or irregular heartbeats

-Panic attacks

-Teeth chattering

-Restlessness

-Abnormal muscle movements or stiffness

-Akathisia (involuntary muscle movements)

-Visual disturbances

-Low blood pressure

-Nosebleeds

-Hemorrhagic disorders including skin and mucous membrane bleeding (ecchymosis)

-Sudden skin or mucous membrane swelling

-Painful erections

-Milk leakage in men and women who are not breastfeeding

-Irregular menstrual periods

-Altered liver function tests

-Orthostatic hypotension (significant drop in blood pressure when standing up).

-There has been an observed increase in the risk of bone fractures in patients treated with this type of medication.

-Abnormal heart rhythm

-Postpartum hemorrhage (excessive vaginal bleeding after childbirth), see “Pregnancy, lactation, and fertility” in section 2 for more information.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the 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.

This medication does not require special conservation conditions.

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

Do not usethis medicationafter the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection pointat 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.

Citalopram CompositionCombix:

The active ingredient is citalopram (hydrobromide). Each tablet contains 20 mg of citalopram.

The other components (excipients) are:

Core: cornstarch without gluten, microcrystalline cellulose, copovidone, croscarmellose sodium, magnesium stearate, glycerol, lactose monohydrate.

Coating: hypromellose E5, macrogol 400, titanium dioxide (E-171).

Product Appearance and Packaging Content:

CitalopramCombixis presented in the form of film-coated tablets with a white color, oval, biconvex with a notch. It is presented in packaging of 14, 28 or 56 tablets,and clinical packaging of 500 tablets.

Only some packaging sizes may be commercially marketed.

Marketing Authorization Holder and Responsible Manufacturer:

Marketing Authorization Holder:

Combix, S.L.U. Laboratories

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible Manufacturer:

VIR, S.A. Chemical and Pharmaceutical Industry

C/ Laguna 66-68-70

28923 Alcorcón (Madrid)

Spain

Last Review Date of this Prospectus:January 2021

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