Return

Package leaflet: Information for the user

RETURN 40 mg/ml oral drops, solution

Citalopram
“Generic 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 give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What RETURN is and what it is used for

RETURN contains the active substance citalopram and belongs to a group of medicines called selective serotonin reuptake inhibitors (SSRIs), also known as antidepressants.
RETURN is used to treat endogenous depressive disorders and to prevent relapses and recurrences.
RETURN is also used for anxiety disorders with panic attacks, with or without agoraphobia (fear of leaving home).

2. What you need to know before taking RETURN

Do not take RETURN

• If you are allergic to citalopram or to any of the other ingredients of this medicine (listed in section 6).
• If you are under 18 years of age.
• If you are being treated with monoamine oxidase inhibitors (MAO inhibitors), medicines used to treat depression. The simultaneous administration of serotonin reuptake inhibitors (SSRIs) and MAO inhibitors (medicines used for depression) may cause serious adverse effects, sometimes fatal. Some cases present with features similar to serotonin syndrome (caused by excess serotonin in the blood).
• If you are being treated with monoamine oxidase inhibitors (MAOIs), including selegiline, at daily doses exceeding 10 mg/day.
• Within 14 days after stopping an irreversible MAO inhibitor or within the time specified after discontinuation of a reversible MAO inhibitor (RIMA), as indicated in the RIMA’s package leaflet.
• If you stop treatment with citalopram and need to start a new therapy with MAO inhibitors. MAO inhibitors must not be administered until at least 7 days after stopping citalopram (see sections “Warnings and precautions” and “Other medicines and RETURN”).
• If you are being treated with linezolid, a reversible monoamine oxidase inhibitor, unless adequate equipment is available for careful observation and monitoring of blood pressure (see section “Other medicines and RETURN”).
• If you are being treated with pimozide (an antipsychotic medicine used to treat psychiatric disorders) (see section “Other medicines and RETURN”).
• If you have QT interval prolongation or congenital long QT syndrome.
• If you are concurrently taking medicines known to cause QT interval prolongation (see section “Other medicines and RETURN”).

Warnings and precautions
Talk to your doctor or pharmacist before taking RETURN.
Treatment of elderly patients and patients with impaired renal or hepatic function, see
“Dosage, method and duration of administration”.
Use in children and adolescents under 18 years of age
Antidepressants should not be used for the treatment of children and adolescents under 18 years of age. Suicidal behaviour (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behaviour and anger) have been observed more frequently in clinical trials conducted on children and adolescents treated with antidepressants compared to those treated with placebo. If, based on medical necessity, a decision is made to initiate treatment, the patient must be closely monitored for the emergence of suicidal symptoms.
Moreover, long-term safety data regarding growth, maturation, and cognitive and behavioural development in children and adolescents are not available.
QT interval prolongation
Citalopram has been shown to cause a dose-dependent prolongation of the QT interval. During post-marketing experience, cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported, mainly in female patients, patients with hypokalaemia, or those with pre-existing QT interval prolongation or other cardiac conditions.
Caution is advised in patients with significant bradycardia, recent acute myocardial infarction, or uncompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and must be corrected before starting citalopram treatment.
If treating patients with stable cardiac disease, consideration should be given to performing an ECG before starting treatment.
If signs of cardiac arrhythmia occur during citalopram treatment, treatment must be discontinued and an ECG performed.
ECG monitoring may be advisable in conditions of altered metabolism with increased peak levels, e.g. hepatic dysfunction.
Hyponatraemia
Hyponatraemia, a condition characterised by reduced plasma sodium concentration, has been reported occasionally as a rare adverse reaction, probably due to inappropriate secretion of antidiuretic hormone (SIADH). This phenomenon is generally reversible after discontinuation of therapy.
Elderly female patients appear to be at particularly high risk.
Mania
In patients with bipolar disorder, a switch to the manic phase may occur. Citalopram should be discontinued if the patient enters a manic phase.
Seizures
Seizures are a potential risk with the use of antidepressant medicines. Citalopram should be discontinued in any patient who experiences seizures. Citalopram should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored. Citalopram should be discontinued if there is an increase in the frequency of epileptic seizures.
Diabetes
In diabetic patients, treatment with SSRIs may alter glycaemic control. Adjustment of insulin or oral hypoglycaemic agent dosage may be necessary.
Serotonin syndrome
In rare cases, serotonin syndrome has been reported in patients treated with SSRIs.
A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. Treatment with citalopram must be immediately discontinued and symptomatic treatment initiated.
Serotonergic medicines
Citalopram must not be used in combination with medicines having serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan, and tryptophan (see “Interactions”).
Bleeding
Prolonged coagulation times and/or coagulation abnormalities such as bruising, gynaecological bleeding, gastrointestinal bleeding, and other forms of cutaneous or mucosal bleeding have been reported with SSRIs (see “Adverse effects”). Caution is advised in patients taking SSRIs, particularly if used concomitantly with substances that may affect platelet function or other substances that may increase the risk of bleeding, as well as in patients with a history of coagulation disorders (see “Interactions”), or during pregnancy [see section “Pregnancy” ( )].
Electroconvulsive therapy (ECT)
Clinical experience with the simultaneous administration of ECT and citalopram is limited; therefore, caution is recommended.
Reversible selective MAO-A inhibitors
Combination of citalopram with MAO-A inhibitors is generally not recommended due to the risk of serotonin syndrome (see “Interactions”).
For further information on concomitant treatment with non-selective irreversible MAO inhibitors, see “Interactions”.
St. John’s Wort
Adverse effects may be more common during concomitant use of citalopram and herbal preparations containing St. John’s Wort (Hypericum perforatum). Therefore, citalopram and preparations containing St. John’s Wort should not be taken simultaneously (see “Interactions”).
Psychosis
Treatment of psychotic patients with depressive episodes may increase psychotic symptoms. Insomnia and agitation may occur at the beginning of treatment. In such cases, dosage adjustment may be helpful.
Closed-angle glaucoma
SSRIs, including citalopram, may cause mydriasis. This mydriatic effect has the potential to narrow the eye angle, leading to increased intraocular pressure and closed-angle glaucoma, especially in predisposed patients. Citalopram should therefore be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
Paradoxical anxiety
Some patients with panic disorders may experience intensified anxiety symptoms at the beginning of antidepressant treatment.
These paradoxical reactions usually diminish within the first two weeks of treatment. A lower starting dose is recommended to reduce the likelihood of paradoxical anxiogenic effects (see “Dosage, method and duration of administration”).
Suicide/suicidal thoughts or worsening of clinical condition
Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicide/suicide-related events). This risk persists until significant remission occurs.
Since improvement may not occur during the first few weeks or longer of treatment, patients should be closely monitored until such improvement occurs. Clinical experience generally shows that the risk of suicide may increase in the early stages of improvement.
Other psychiatric disorders for which RETURN is prescribed may also be associated with an increased risk of suicide-related events. Additionally, such disorders may coexist with major depression. The same precautions taken in treating patients with major depression should therefore be applied when treating patients with other psychiatric disorders.
Patients with a positive clinical history of suicide-related events or those exhibiting a significant degree of suicidal ideation before starting therapy are at higher risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment. A meta-analysis of clinical trials conducted with antidepressant medicines compared to placebo in the treatment of psychiatric disorders showed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to placebo.
Pharmacological treatment with antidepressants, especially during the initial stages of treatment and following dosage adjustments, should always be accompanied by close monitoring of patients, particularly those at high risk. Patients (and those caring for them) should be warned to monitor for any worsening of their condition, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical advice if such symptoms occur.
Reversible selective MAO-A inhibitors
Combination of citalopram with MAO-A inhibitors is generally not recommended due to the risk of serotonin syndrome (see “Interactions”).
For further information on concomitant treatment with non-selective irreversible MAO inhibitors, see “Interactions”.
Akathisia/restlessness/psychomotor agitation
The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by subjectively unpleasant or distressing restlessness and an urge to move, often accompanied by an inability to sit still or remain motionless. These symptoms are more likely to occur within the first weeks of treatment. In patients who develop such symptoms, increasing the dosage may be harmful.
Sexual dysfunction
Medicines such as RETURN (so-called selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have been observed to persist after discontinuation of treatment.
“For those engaged in sports: using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.”
Children and adolescents
RETURN must not be used for the treatment of individuals under 18 years of age.
Other medicines and RETURN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pharmacodynamic interactions
Cases of serotonin syndrome have been reported with citalopram and moclobemide and buspirone.
Contraindicated combinations
QT interval prolongation
No pharmacokinetic and pharmacodynamic studies have been conducted on the combination of citalopram and other medicines that prolong the QT interval. An additive effect of citalopram with such medicines cannot be excluded. Therefore, concomitant administration of citalopram with medicines that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (such as phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (such as sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarial treatments, particularly halofantrine), certain antihistamines (astemizole, mizolastine), etc., is contraindicated.
MAO inhibitors
Concomitant use of citalopram and MAO inhibitors may cause serious adverse effects, including serotonin syndrome (see “Do not take RETURN” and “Warnings and precautions”).
Serious, and sometimes fatal, reactions have been reported in patients treated with SSRIs in combination with a monoamine oxidase inhibitor (MAOI), including selegiline, an irreversible MAOI, linezolid, a reversible (non-selective) MAOI, and moclobemide (selective for type IA), and in patients who recently discontinued SSRI treatment and started MAOI therapy.
Some cases presented with features similar to serotonin syndrome. Symptoms of serotonin syndrome include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, confusion, irritability, and agitation, tremor. If this condition progresses without intervention, it may be fatal due to rhabdomyolysis, central hyperthermia with acute multi-organ failure, delirium, and coma (see “Do not take RETURN”).
Pimozide
Concomitant use of citalopram and pimozide is contraindicated (see “Do not take RETURN”). The concomitant administration of a single 2 mg dose of pimozide to healthy volunteers treated with citalopram 40 mg/day for 11 days caused only an increase in pimozide AUC and Cmax, although not consistently across the study. Concomitant administration of citalopram and pimozide caused a mean increase in QTc interval of approximately 10 msec. Since this interaction was already observed after administration of a low dose of pimozide, concomitant treatment with citalopram and pimozide is contraindicated.
Combinations requiring precautions in use
Selegiline (selective MAO-B inhibitor)
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of citalopram (20 mg daily) and selegiline (10 mg daily) (a selective MAO-B inhibitor) showed no clinically relevant interactions. Concomitant use of citalopram and selegiline (at doses exceeding 10 mg daily) is not recommended (see section “Do not take RETURN”).
Serotonergic medicines
Lithium and Tryptophan
No pharmacodynamic interactions have been observed between lithium and citalopram; however, an increased serotonergic effect has been reported when SSRIs are administered in combination with lithium or tryptophan. Caution is advised when using citalopram concomitantly with these active substances. Routine monitoring of lithium levels should continue as usual.
Sumatriptan and tramadol
The serotonergic effect of sumatriptan and tramadol may be potentiated by selective serotonin reuptake inhibitors (SSRIs); until further information is available, concomitant use of citalopram and serotonin (or 5-HT) agonists, such as sumatriptan and other triptans, as well as tramadol, is not recommended (see “Warnings and precautions”).
St. John’s Wort
Adverse effects may be more frequent during concomitant administration of citalopram and herbal preparations containing St. John’s Wort (Hypericum perforatum) (see “Warnings and precautions”). Pharmacokinetic interactions have not been investigated.
Bleeding
Particular caution is required for patients being treated concomitantly with anticoagulants, medicines that may affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine, or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) that may increase the risk of bleeding (see “Warnings and precautions”).
Electroconvulsive therapy (ECT)
There are no clinical studies establishing the risk or benefit of combined use of electroconvulsive therapy (ECT) and citalopram (see “Warnings and precautions”).
Alcohol
No pharmacodynamic or pharmacokinetic interactions between citalopram and alcohol have been demonstrated; however, the combination of citalopram with alcohol is not recommended.
Medicines that induce QT interval prolongation or hypokalaemia or hypomagnesaemia
Caution is required for concomitant use of other medicines that prolong the QT interval or drugs that induce hypokalaemia/hypomagnesaemia, as they, like citalopram, may potentially prolong the QT interval. Caution is required for concomitant use of medicines that induce hypokalaemia/hypomagnesaemia, as these conditions increase the risk of malignant arrhythmias (see section “Precaution for use”).
Medicines that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is recommended when concomitantly using medicines capable of lowering the seizure threshold, such as antidepressants (SSRIs, tricyclics), neuroleptics (thioxanthenes and butyrophenones), mefloquine, bupropion, and tramadol.
Desipramine, Imipramine
In a pharmacokinetic study, no effect was demonstrated on citalopram or imipramine levels, although desipramine levels, the main metabolite of imipramine, were increased. When desipramine is combined with citalopram, an increase in plasma concentration of the former substance is observed; therefore, a reduction in its dosage may be necessary.
Neuroleptics
The use of citalopram has not shown any clinically relevant interaction with neuroleptics; however, as with other SSRIs, a pharmacodynamic interaction cannot be excluded a priori.
Pharmacokinetic interactions
The biotransformation of citalopram to demethylcitalopram is mediated by cytochrome P450 isoenzymes, CYP2C19 (approximately 38%), CYP3A4 (approximately 31%), and CYP2D6 (approximately 31%).
Cimetidine, lansoprazole, omeprazole (used to treat gastric ulcers), fluconazole (used to treat fungal infections), fluvoxamine (an antidepressant), and ticlopidine (used to reduce the risk of stroke) may cause an increase in blood levels of citalopram.
Food
No effects of food on the absorption and other pharmacokinetic properties of citalopram have been reported.
Influence of other medicines on the pharmacokinetics of citalopram
Co-administration with ketoconazole (a potent CYP3A4 inhibitor) does not alter the pharmacokinetics of citalopram.
A pharmacokinetic interaction study of lithium and citalopram revealed no pharmacokinetic interaction.
Cimetidine
Cimetidine (a potent inhibitor of CYP2D6, 3A4, and 1A2) causes a moderate increase in mean plasma levels of citalopram at steady state. Caution is recommended when citalopram is administered in combination with cimetidine. Dose adjustments may be necessary.
Concomitant administration of escitalopram (the active enantiomer of citalopram) with omeprazole (a CYP2C19 inhibitor) 30 mg once daily resulted in a moderate increase (approximately 50%) in plasma concentrations of escitalopram.
Therefore, caution should be exercised when using concomitantly CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Based on monitoring of adverse effects during concomitant administration of other therapies, a reduction in the dose of citalopram may be necessary.
Metoprolol
Escitalopram (the active enantiomer of citalopram) is an inhibitor of the CYP2D6 enzyme. Caution is recommended when citalopram is administered concomitantly with medicines primarily metabolised by this enzyme and having a narrow therapeutic index, e.g. flecainide, propafenone, and metoprolol (when used in heart failure), or certain central nervous system-acting medicines primarily metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine, and nortriptyline, or antipsychotics such as risperidone, thioridazine, and haloperidol. Dose adjustments may be necessary. Co-administration with metoprolol results in a doubling of plasma levels of the latter. No clinically significant effects on blood pressure or heart rate have been observed.
Effects of citalopram on other medicines
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a doubling of plasma levels of metoprolol, but no clinically significant effects of metoprolol on blood pressure or heart rate were observed in healthy volunteers.
Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1, and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19, and CYP2D6, compared to other SSRIs known as significant inhibitors.
Levomepromazine, digoxin, carbamazepine.
No changes or only minor changes without clinical relevance were observed when citalopram was administered with clozapine and theophylline (CYP1A2 substrates), warfarin (CYP2C9 substrate), imipramine and mephenytoin (CYP2C19 substrates), sparteine, imipramine, amitriptyline, risperidone (CYP2D6 substrates), and warfarin, carbamazepine (and its metabolite carbamazepine epoxide), triazolam (CYP3A4 substrates).
No pharmacokinetic interactions were observed between citalopram and levomepromazine or digoxin (indicating that citalopram neither induces nor inhibits P-glycoprotein).
RETURN and alcohol
The combination of citalopram and alcohol is not recommended.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy( ),
Citalopram may be used during pregnancy if clinically necessary, taking into account the aspects mentioned below.
Newborns should be monitored if maternal use of citalopram continued into the late stages of pregnancy, particularly in the third trimester. Abrupt discontinuation during pregnancy should be avoided.
Following maternal use of SSRIs/SNRIs during the late stages of pregnancy, newborns may exhibit the following symptoms: respiratory distress, cyanosis, apnoea, seizures, unstable temperature, feeding difficulties, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremors, restlessness, irritability, lethargy, persistent crying, somnolence, and sleep difficulties. These symptoms may be due to serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately after birth or within the following hours (less than 24 hours).
Ensure that your doctor and/or midwife are aware that you are taking RETURN.
When taken during pregnancy, particularly in the last three months, medicines like RETURN may increase the risk of a serious condition in newborns called persistent pulmonary hypertension (PPHN), which presents with increased breathing rate and bluish skin colour. These symptoms usually begin within 24 hours after birth. If this occurs for your baby, you must contact your midwife and/or doctor immediately.
If you take RETURN near the end of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (tendency to bleed easily). Inform your doctor or midwife that you are taking RETURN so they can advise you on what to do.
Breastfeeding
Citalopram is excreted in breast milk. It is estimated that breastfed infants receive approximately 5% of the relative daily dose taken by the mother (in mg/kg). Only mild events have been observed in infants. However, existing information is insufficient to assess the risk in children. Caution is recommended.
Male fertility
Citalopram has been shown in animal studies to reduce sperm quality.
In theory, this could affect fertility, but the impact on human fertility has not yet been observed.
Driving and using machines
Citalopram has minimal or moderate influence on the ability to drive and use machines.
Psychotropic medicines may reduce judgement and reactivity in emergency situations. It may affect your ability to drive vehicles or use machinery.
RETURN contains

• Ethanol. This medicine contains 56.8 mg of alcohol (ethanol) per dose, equivalent to 71 mg/ml. The volume amount of this medicine is equivalent to less than 2 ml of beer or 1 ml of wine.
• methylhydroxybenzoate and propylhydroxybenzoate. May cause allergic reactions (including delayed reactions).

3. How to take RETURN

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Endogenous depressive syndromes
Adults
The recommended dose of RETURN oral drops 40 mg/ml solution is a single daily oral
dose of 16 mg (8 drops).
Depending on your individual response, the dose may be increased by your doctor up to a maximum
of 32 mg (16 drops) per day.
The antidepressant effect usually appears within 2–4 weeks after starting treatment; it is
advisable that you remain under medical supervision until remission of the depressive state is achieved.
Since antidepressant treatment is symptomatic, it should be continued for an appropriate
period of time, generally 4–6 months in manic-depressive illness.
If you suffer from recurrent unipolar depression, long-term maintenance therapy may be necessary to prevent new depressive episodes.
Anxiety disorders with panic attacks, with or without agoraphobia
During the first week of treatment, the recommended dose is 8 mg (4 drops). Subsequently, the dose
should be increased to 16 mg (8 drops) per day. Depending on your individual response, the dose may
be increased by your doctor up to a maximum of 32 mg (16 drops) per day.
In disorders with panic attacks, treatment is long-term. Maintenance of clinical response
has been demonstrated during prolonged treatment (up to 1 year).
If insomnia or severe restlessness occurs, additional treatment with sedatives is recommended during the acute phase.
Withdrawal symptoms observed following discontinuation of treatment
Abrupt discontinuation of treatment should be avoided. When stopping treatment with
RETURN, the dose should be gradually reduced over a period of at least 1–2 weeks to reduce
the risk of withdrawal reactions (see “Warnings and precautions” and “Possible unwanted
effects”).
If intolerable symptoms occur following dose reduction or upon discontinuation of
treatment, consideration should be given to reinstating the previously prescribed dose.
Subsequently, your doctor may continue reducing the dose, but more gradually.
Elderly patients (> 65 years of age)
The dose should be reduced to half the recommended dose, for example 8 mg (4 drops) up to 16 mg
(8 drops) per day. The maximum recommended dose for elderly patients is 16 mg (8 drops) per day.
Use in children and adolescents under 18 years of age
RETURN must not be taken by children and adolescents under 18 years of age (see
“Do not take RETURN”).
Patients with particular risk factors
Reduced liver function
If you suffer from mild or moderate hepatic impairment, the recommended initial dose for the first two
weeks of treatment is 8 mg (4 drops) per day. Depending on the patient's individual response, the dose may be increased by the doctor up to a maximum of 16 mg (8 drops) per day.
Caution and closer monitoring during dose titration are advised if you have severely impaired liver function.
Renal impairment
You should adhere to the lowest recommended dosage.
Poor metabolizers of CYP2C19
If you are a poor metabolizer regarding CYP2C19, an initial dose of 8 mg (4
drops) per day is recommended during the first two weeks of treatment. Depending on your individual response, the dose may be increased by your doctor up to a maximum of 16 mg (8 drops) per
day.
When deciding to discontinue treatment, doses should be gradually reduced to minimize the severity of withdrawal symptoms.
Administration instructions
The drops may be mixed with water, orange juice, or apple juice.
1 drop = 2 mg of Citalopram.
Citalopram oral drops solution has higher bioavailability compared to tablets,
approximately 25% higher. Therefore, the dose equivalences between tablets and drops are as follows:

Use in children and adolescents under 18 years of age
RETURN must not be taken by individuals under 18 years of age.

If you take more RETURN than you should
In case of accidental ingestion/overdose of RETURN, contact your doctor immediately or go to the nearest hospital.

Toxicity
Fatal cases due to overdose of Citalopram alone have been reported; however, most fatal cases are associated with overdose when the medicinal product is taken together with other medicines.
In case of overdose, ECG monitoring is recommended if you have congestive heart failure/bradyarrhythmias, if you are taking concomitant medications that prolong the QT interval, or if you have metabolic disturbances, such as hepatic impairment.

Symptoms
The following adverse effects have been reported in cases of overdose: seizures, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, electrical conduction block in the heart, QRS prolongation (electrocardiogram changes), hypertension, mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, and atrioventricular arrhythmia. Rhabdomyolysis is rare. Possible symptoms with a dose up to 600 mg include fatigue, weakness, sedation, tremor, nausea, and tachycardia.
Seizures may occur within a few hours after ingestion of doses exceeding 600 mg. ECG changes may also occur, and rhabdomyolysis, although rarely.
Fatal outcome following overdose is rare. One adult patient survived after ingesting 5,200 mg of Citalopram.

Treatment
There are no known specific antidotes for Citalopram. Treatment should be symptomatic and supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate), and gastric lavage should be considered. If consciousness is impaired, the patient should be intubated. ECG and vital signs should be closely monitored.
Administer oxygen in case of hypoxia and diazepam in case of seizures. Medical supervision for approximately 24 hours is recommended, as well as ECG monitoring if the ingested dose exceeds 600 mg. Widening of the QRS complex (electrocardiogram changes) may be corrected by infusion of hypertonic NaCl. ECG monitoring is recommended in case of overdose in patients with congestive heart failure/bradyarrhythmias, in patients taking concomitant medications that prolong the QT interval, or in patients with metabolic disturbances, such as hepatic impairment.
ECG monitoring is recommended in case of overdose if you have congestive heart failure/bradyarrhythmias, if you are taking concomitant medications that prolong the QT interval, or if you have metabolic disturbances, such as hepatic impairment.

If you forget to take RETURN
Do not take a double dose to make up for the missed dose.

If you stop taking RETURN
An abrupt discontinuation of treatment should be avoided.

Withdrawal symptoms observed following discontinuation of SSRI treatment
Withdrawal symptoms commonly occur upon stopping treatment, especially if discontinuation is abrupt (see "Possible side effects"). In a clinical study on recurrence prevention, adverse events occurred in 40% of patients after discontinuation of treatment, compared to 20% of patients who continued Citalopram treatment. The risk of withdrawal symptoms may depend on several factors, including duration and dosage of therapy, and the rate of dose reduction.

The most commonly reported adverse effects are: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances. Generally, these symptoms are mild to moderate in severity; however, in some patients they may be severe. They usually appear within the first few days after stopping treatment; however, very rare cases of withdrawal symptoms have been reported in patients who inadvertently missed a single dose. These symptoms usually resolve spontaneously within two weeks without the need for medication, although in some patients they may persist (2–3 months or longer). Therefore, if treatment needs to be discontinued, it is recommended to gradually reduce the dose of Citalopram over a period of several weeks or months, according to individual patient needs (see "How to take RETURN").

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects observed with citalopram are generally mild in intensity and transient. They usually occur during the first or second week of treatment and then gradually diminish.
The following side effects have been shown to have a dose-response relationship: increased sweating, dry mouth, insomnia, drowsiness, diarrhoea, nausea, and fatigue.

Very common (may affect more than 1 in 10 people)

• Drowsiness
• Insomnia
• Headache
• Dry mouth (dryness of the mouth)
• Nausea
• Increased sweating

Common (may affect up to 1 in 10 people)

• Decreased appetite, weight loss
• Restlessness
• Decreased sexual desire (reduced libido)
• Anxiety, nervousness
• Confusional state
• Abnormal orgasm (in women)
• Sleep disturbances (dream disturbances)
• Tremor, paraesthesia
• Dizziness
• Attention disturbances
• Ringing, buzzing, or other sounds in the ear (tinnitus)
• Yawning
• Diarrhoea
• Vomiting
• Constipation
• Itching
• Muscle and joint pain (myalgia, arthralgia)
• Impotence, ejaculation disorders, delayed or absent ejaculation
• Fatigue

Uncommon (may affect up to 1 in 100 people)

• Increased appetite, weight gain
• Aggression
• Feeling detached from one's body (depersonalisation)
• Seeing or hearing things that are not real (hallucinations), fixation (mania)
• Drop in blood pressure (syncope)
• Dilatation of the pupil (mydriasis)
• Slowing of the heart rate (bradycardia)
• Increase in heart rate (tachycardia)
• Appearance of red, raised spots on the skin (urticaria)
• Hair loss (alopecia)
• Skin redness (rash), appearance of small pinpoint skin haemorrhages (purpura)
• Increased sensitivity to light (photosensitivity reaction)
• Urinary retention
• Excessive menstrual blood loss (menorrhagia in women)
• Oedema

Rare (may affect from 1 to less than 10 in 10,000 people)

• Low sodium levels in the blood (hyponatraemia)
• Seizures (epilepsy, grand mal)
• Alternating rapid and slow movements (dyskinesia)
• Taste disturbances
• Bleeding
• Hepatitis
• Fever (pyrexia)

Not known (frequency cannot be estimated from the available data)

• Reduced potassium concentration in the blood (hypokalaemia)
• Panic attacks
• Muscle contractions of the mouth with teeth grinding (bruxism)
• Restlessness
• Suicidal ideation, suicidal behaviour
• Seizures
• Increased serotonin levels in the blood (serotonin syndrome)
• Movement disturbances and lack of coordination (extrapyramidal disorders)
• Inability to remain still (akathisia), movement disorders
• Visual disturbances
• QT interval prolongation
• Severe disturbances in heart rhythm and rate (ventricular arrhythmias, including torsade de pointes)
• Drop in blood pressure when standing (orthostatic hypotension)
• Nosebleeds (epistaxis)
• Gastrointestinal haemorrhage (including rectal bleeding)
• Abnormal liver function tests
• Appearance of subcutaneous haematomas (bruising)
• Sudden swelling of the skin and mucous membranes, membranes lining certain internal organs (angioedema)
• Abnormal, heavy and prolonged vaginal bleeding occurring between two consecutive menstrual periods (metrorrhagia in women)
• Persistent and abnormal erection (priapism)
• Increased blood levels of the hormone prolactin (hyperprolactinaemia)
• Milky discharge from the nipples in men (galactorrhoea)
• Reduced platelet count (thrombocytopenia)
• Hypersensitivity
• Severe allergic reaction affecting multiple organs (anaphylactic reaction)
• Water retention in the body and reduced urine production (inappropriate secretion of ADH hormone)
• Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage), see section 2, Pregnancy ( ), for further information

Bone fractures:
An increased risk of fractures has been observed in patients taking this type of medicine.

QT interval prolongation:
During post-marketing experience, cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported, primarily in female patients, in patients with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac conditions.

Withdrawal symptoms observed following discontinuation of treatment:
Stopping treatment with citalopram (especially if abrupt) usually leads to withdrawal symptoms.
The most commonly reported adverse effects have been dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances.
These events are generally mild to moderate and self-limiting; however, in some patients they may be severe and/or prolonged. It is therefore recommended that, if treatment with citalopram is no longer required, discontinuation should be gradual, achieved by a stepwise reduction of the dose (see section 3 “How to take RETURN” and “Warnings and precautions”).

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
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 RETURN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the product in its original unopened packaging, correctly stored.
Do not store above 25°C.
Keep in the original packaging to protect the medicine from light.
The shelf life after first opening the bottle is 4 months.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What RETURN contains

• The active substance is citalopram. 1 ml (= 20 drops) of solution contains 44.48 mg of citalopram hydrochloride, equivalent to 40 mg of citalopram.
• The other components are: Methylparahydroxybenzoate, propylparahydroxybenzoate, ethanol, methylcellulose, purified water.

Description of the appearance of RETURN and package contents
40 mg/ml oral drops, solution - 15 ml bottle
Marketing Authorization Holder
EURO PHARMA S.r.l. Via Garzigliana, 8. 10127 Turin.
Manufacturer
Special Product's Line S.p.a. Via Fratta Rotonda 1– 03012 Anagni (FR)

Package leaflet: information for the user

RETURN 20 mg film-coated tablets

Citalopram
“Generic medicinal product”
Please read 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 give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

6. What RETURN is and what it is used for

RETURN contains the active substance citalopram and belongs to a group of medicines called
selective serotonin reuptake inhibitors (SSRIs), also known as antidepressants.
RETURN is used to treat endogenous depressive disorders and to prevent relapses and recurrences.
RETURN is also used for anxiety disorders with panic attacks, with or without agoraphobia (fear of leaving home).

7. What you need to know before taking RETURN

Do not take RETURN

• If you are allergic to citalopram or any of the other ingredients of this medicine (listed in section 6).
• If you are under 18 years of age.
• If you are being treated with monoamine oxidase inhibitors (MAO inhibitors), medicines used to treat depression. The simultaneous administration of serotonin reuptake inhibitors (SSRIs) and MAO inhibitors (medicines used for depression) may cause serious adverse effects, sometimes fatal. Some cases present features similar to serotonin syndrome (caused by excess serotonin in the blood).
• If you are being treated with monoamine oxidase inhibitors (MAOIs), including selegiline, at daily doses exceeding 10 mg/day.
• Within 14 days after stopping an irreversible MAOI, or within the time specified after discontinuation of a reversible MAOI (RIMA), as indicated in the RIMA’s package leaflet.
• If you stop treatment with citalopram and need to start a new therapy with MAOIs. MAOIs must not be administered until at least 7 days after stopping citalopram (see sections “Warnings and precautions” and “Other medicines and RETURN”).
• If you are being treated with linezolid, a reversible monoamine oxidase inhibitor, unless appropriate equipment is available for careful observation and monitoring of blood pressure (see section “Other medicines and RETURN”).
• If you are being treated with pimozide (an antipsychotic medicine used in the treatment of psychiatric disorders) (see section “Other medicines and RETURN”).
• If you have QT interval prolongation or congenital long QT syndrome.
• If you are concurrently treated with medicines known to cause QT interval prolongation (see section “Other medicines and RETURN”).

Warnings and precautions
Talk to your doctor or pharmacist before taking RETURN.
Treatment of elderly patients and patients with reduced renal or hepatic function, see
“Dosage, method and duration of administration”.
Use in children and adolescents under 18 years of age
Antidepressants must not be used to treat children and adolescents under 18 years of age. Suicidal behaviour (suicide attempts and suicidal ideation) and hostility (mainly aggression, oppositional behaviour and anger) have been observed more frequently in clinical trials conducted on children and adolescents treated with antidepressants compared to those treated with placebo. If, based on medical need, treatment is decided, the patient must be closely monitored for the emergence of suicidal symptoms.
Moreover, long-term safety data on growth, maturation, and cognitive and behavioural development in children and adolescents are not available.
QT interval prolongation
Citalopram has been shown to cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported during post-marketing experience, mainly in female patients, patients with hypokalaemia, or those with pre-existing QT interval prolongation or other cardiac conditions.
Caution is advised in patients with significant bradycardia, recent acute myocardial infarction, or uncompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and must be corrected before starting treatment with Citalopram.
If treating patients with stable cardiac disease, consideration should be given to performing an ECG before starting treatment.
If signs of cardiac arrhythmia occur during treatment with Citalopram, treatment must be discontinued and an ECG performed.
ECG monitoring may be advisable under conditions of altered metabolism with increased peak levels, e.g. hepatic dysfunction.
Hyponatraemia
Hyponatraemia, a condition involving reduced plasma sodium concentration, has been occasionally reported as a rare adverse reaction, probably due to inappropriate antidiuretic hormone secretion (SIADH). This condition is generally reversible after discontinuation of therapy.
Elderly female patients appear to be at particularly high risk.
Mania
In patients with bipolar disorder, a switch to the manic phase may occur. Citalopram must be discontinued if the patient enters a manic phase.
Seizures
Seizures are a potential risk with the use of antidepressant medicines. Citalopram must be discontinued in any patient who develops seizures. Citalopram should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored. Citalopram must be discontinued if there is an increase in seizure frequency.
Diabetes
In diabetic patients, treatment with SSRIs may alter glycaemic control. Adjustment of insulin or oral hypoglycaemic agent dosage may be necessary.
Serotonin syndrome
In rare cases, serotonin syndrome has been reported in patients treated with SSRIs.
A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. Treatment with Citalopram must be immediately discontinued and symptomatic therapy initiated.
Serotonergic medicines
Citalopram must not be used in combination with medicines having serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan and tryptophan (see “Interactions”).
Bleeding
Prolonged coagulation times and/or coagulation abnormalities such as bruising, gynaecological bleeding, gastrointestinal bleeding, and other forms of skin bleeding or mucosal bleeding have been reported with SSRIs (see “Adverse effects”). Caution is advised in patients taking SSRIs, particularly if used concomitantly with active substances that may affect platelet function or other substances that may increase the risk of bleeding, as well as in patients with a history of coagulation disorders (see “Interactions”), or during pregnancy [see section “Pregnancy” ( )].
Electroconvulsive therapy (ECT)
Clinical experience with the concomitant administration of ECT and Citalopram is limited; therefore, caution is recommended.
Reversible selective MAO-A inhibitors
The combination of Citalopram with MAO-A inhibitors is generally not recommended due to the risk of serotonin syndrome (see “Interactions”).
For further information on concomitant treatment with non-selective irreversible MAO inhibitors, see “Interactions”.
St. John’s Wort
Adverse effects may be more common during concomitant use of Citalopram and herbal preparations containing St. John’s Wort (Hypericum perforatum). Therefore, Citalopram and preparations containing St. John’s Wort must not be taken simultaneously (see “Interactions”).
Psychosis
Treatment of psychotic patients with depressive episodes may increase psychotic symptoms. Insomnia and agitation may occur at the beginning of treatment. In such cases, dosage adjustment may be helpful.
Closed-angle glaucoma
SSRIs, including Citalopram, may cause mydriasis. This mydriatic effect has the potential to reduce the eye angle, leading to increased intraocular pressure and closed-angle glaucoma, especially in predisposed patients. Citalopram should therefore be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
Paradoxical anxiety
Some patients with panic disorders may experience intensified anxiety symptoms at the beginning of treatment with antidepressants.
These paradoxical reactions generally diminish within the first two weeks of treatment. A lower starting dose is recommended to reduce the likelihood of paradoxical anxiogenic effects (see “Dosage, method and duration of administration”).
Suicide/suicidal thoughts or worsening of clinical condition
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide/suicide-related events). This risk persists until significant remission occurs.
Since improvement may not occur during the first few weeks or more of treatment, patients must be closely monitored until such improvement occurs. Clinical experience shows that the risk of suicide may increase during the early phases of improvement.
Other psychiatric disorders for which RETURN is prescribed may also be associated with an increased risk of suicide-related events. Additionally, such disorders may coexist with major depression. Therefore, the same precautions taken in treating patients with major depression should be applied when treating patients with other psychiatric disorders.
Patients with a positive clinical history of suicide-related events or those showing a significant degree of suicidal ideation before starting therapy are at higher risk of suicidal thoughts or suicide attempts and must be closely monitored during treatment. A meta-analysis of clinical trials conducted with antidepressant medicines compared to placebo in the treatment of psychiatric disorders showed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to placebo.
Pharmacological treatment with antidepressants, especially in the initial phases of treatment and following dosage adjustments, must always be accompanied by close monitoring of patients, particularly those at high risk. Patients (and those caring for them) must be warned to monitor any clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour, and to contact their doctor immediately if such symptoms occur.
Reversible selective MAO-A inhibitors
The combination of Citalopram with MAO-A inhibitors is generally not recommended due to the risk of serotonin syndrome (see “Interactions”).
For further information on concomitant treatment with non-selective irreversible MAO inhibitors, see “Interactions”.
Akathisia/restlessness/psychomotor agitation
The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by subjectively unpleasant or distressing restlessness and a need to move, often accompanied by an inability to sit still or remain motionless. These symptoms are more likely to occur within the first weeks of treatment. In patients who develop such symptoms, increasing the dose may be harmful.
Sexual dysfunction
Medicines such as RETURN (the so-called selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have been observed to persist after discontinuation of treatment.
“For athletes: using the medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.”
Children and adolescents
RETURN must not be used for the treatment of individuals under 18 years of age.
Other medicines and RETURN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pharmacodynamic interactions
Cases of serotonin syndrome have been reported with Citalopram and moclobemide and buspirone at the pharmacodynamic level.
Contraindicated combinations
QT interval prolongation
No pharmacokinetic and pharmacodynamic studies have been conducted on the combination of Citalopram and other medicines that prolong the QT interval. An additive effect of Citalopram with such medicines cannot be excluded. Therefore, co-administration of Citalopram with medicines that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarial treatments, particularly halofantrine), certain antihistamines (astemizole, mizolastine), etc., is contraindicated.
MAO inhibitors
Concomitant use of Citalopram and MAO inhibitors may cause serious adverse effects, including serotonin syndrome (see “Do not take RETURN” and “Warnings and precautions”).
Serious, and sometimes fatal, reactions have been reported in patients treated with SSRIs in combination with a monoamine oxidase inhibitor (MAO), including selegiline, an irreversible MAOI, and linezolid, a reversible (non-selective) MAOI, and moclobemide (selective for type IA), and in patients who recently discontinued an SSRI and started treatment with an MAOI.
Some cases presented features similar to serotonin syndrome. Symptoms of serotonin syndrome include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, confusion, irritability and agitation, tremor. If this condition progresses without intervention, it may result in fatality due to rhabdomyolysis, central hyperthermia with acute multi-organ failure, delirium and coma (see “Do not take RETURN”).
Pimozide
Concomitant use of Citalopram and pimozide is contraindicated (see “Do not take RETURN”). The concomitant administration of a single 2 mg dose of pimozide to healthy volunteers treated with Citalopram 40 mg/day for 11 days caused only an increase in pimozide AUC and Cmax, although inconsistently across the study. Concomitant administration of Citalopram and pimozide caused a mean increase in QTc interval of approximately 10 msec. Since this interaction was already observed after administration of a low dose of pimozide, concomitant treatment with Citalopram and pimozide is contraindicated.
Combinations requiring precautions in use
Selegiline (selective MAO-B inhibitor)
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of citalopram (20 mg daily) and selegiline (10 mg daily) (a selective MAO-B inhibitor) showed no clinically relevant interactions. Concomitant use of citalopram and selegiline (at doses exceeding 10 mg daily) is not recommended (see section “Do not take RETURN”).
Lithium and Tryptophan
No pharmacodynamic interactions have been observed between lithium and Citalopram; however, an increased serotonergic effect has been reported when SSRIs are administered in combination with lithium or tryptophan. Caution is advised when using Citalopram concomitantly with these active substances. Routine monitoring of lithium levels should continue as usual.
Sumatriptan and tramadol
The serotonergic effect of sumatriptan and tramadol may be potentiated by selective serotonin reuptake inhibitors (SSRIs); until further information is available, concomitant use of Citalopram and serotonin (or 5-HT) agonists, such as sumatriptan and other triptans, as well as tramadol, is not recommended (see “Warnings and precautions”).
St. John’s Wort
Adverse effects may be more frequent during concomitant administration of Citalopram and herbal preparations containing hypericum (Hypericum perforatum) (see “Warnings and precautions”). Pharmacokinetic interactions have not been investigated.
Bleeding
Particular caution is required for patients being treated concomitantly with anticoagulants, medicines that may affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine, or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) that may increase the risk of bleeding (see “Warnings and precautions”).
Electroconvulsive therapy (ECT)
There are no clinical studies establishing the risk or benefit of combined use of electroconvulsive therapy (ECT) and Citalopram (see “Warnings and precautions”).
Alcohol
No pharmacodynamic or pharmacokinetic interactions between Citalopram and alcohol have been demonstrated; however, the combination of Citalopram and alcohol is not recommended.
Medicines that induce QT interval prolongation or hypokalaemia/hypomagnesaemia
Caution is required for concomitant use of other medicines that prolong the QT interval or induce hypokalaemia/hypomagnesaemia, as they, like Citalopram, may potentially prolong the QT interval. Caution is required for concomitant use of medicines that induce hypokalaemia/hypomagnesaemia, as these conditions increase the risk of malignant arrhythmias (see section “Precaution for use”).
Medicines that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is recommended when using concomitantly medicines capable of lowering the seizure threshold, antidepressants (SSRIs, tricyclics), neuroleptics (thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol.
Desipramine, Imipramine
In a pharmacokinetic study, no effect was demonstrated on Citalopram or imipramine levels, although desipramine levels, the main metabolite of imipramine, were increased. When desipramine is combined with Citalopram, an increase in the plasma concentration of the former substance is observed; therefore, a reduction in its dosage may be necessary.
Neuroleptics
The use of Citalopram has not shown any clinically relevant interaction with neuroleptics; however, as with other SSRIs, a pharmacodynamic interaction cannot be excluded a priori.
Pharmacokinetic interactions
The biotransformation of Citalopram into demethylcitalopram is mediated by cytochrome P450 isoenzymes, CYP2C19 (approximately 38%), CYP3A4 (approximately 31%) and CYP2D6 (approximately 31%).
Cimetidine, lansoprazole and omeprazole (used for the treatment of gastric ulcers), fluconazole (used for the treatment of fungal infections), fluvoxamine (an antidepressant) and ticlopidine (used to reduce the risk of stroke) may cause an increase in blood levels of Citalopram.
Food
No effects of food on the absorption and other pharmacokinetic properties of Citalopram have been reported.
Influence of other medicines on the pharmacokinetics of Citalopram
Co-administration with ketoconazole (a potent CYP3A4 inhibitor) does not alter the pharmacokinetics of Citalopram.
A pharmacokinetic interaction study of lithium and Citalopram revealed no pharmacokinetic interaction.
Cimetidine
Cimetidine (a potent CYP2D6, 3A4 and 1A2 inhibitor) causes a moderate increase in mean plasma levels of Citalopram at steady state. Caution is recommended when administering Citalopram in combination with cimetidine. Dose adjustments may be necessary.
Concomitant administration of escitalopram (the active enantiomer of Citalopram) with omeprazole (a CYP2C19 inhibitor) 30 mg once daily resulted in a moderate increase (approximately 50%) in plasma concentrations of escitalopram.
Therefore, caution must be exercised when using concomitantly CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Based on monitoring of adverse effects during concomitant administration of other therapies, a reduction in the dose of Citalopram may be necessary.
Metoprolol
Escitalopram (the active enantiomer of Citalopram) is an inhibitor of the CYP2D6 enzyme. Caution is recommended when Citalopram is administered concomitantly with medicines primarily metabolised by this enzyme and having a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in heart failure), or certain central nervous system-acting medicines primarily metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline, or antipsychotics such as risperidone, thioridazine and haloperidol. Dose adjustments may be necessary. Co-administration with metoprolol results in a doubling of metoprolol plasma levels. No clinically significant effects on blood pressure or heart rate have been observed.
Effects of Citalopram on other medicines
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of Citalopram and metoprolol (a CYP2D6 substrate) showed a doubling of metoprolol plasma levels, but no clinically significant effects of metoprolol on blood pressure or heart rate were observed in healthy volunteers.
Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6, compared to other SSRIs known as significant inhibitors.
Levomepromazine, digoxin, carbamazepine.
No changes or only minor changes without clinical relevance were observed when Citalopram was administered with clozapine and theophylline (CYP1A2 substrates), warfarin (CYP2C9 substrate), imipramine and mephenytoin (CYP2C19 substrates), sparteine, imipramine, amitriptyline, risperidone (CYP2D6 substrates) and warfarin, carbamazepine (and its metabolite carbamazepine epoxide), triazolam (CYP3A4 substrates).
No pharmacokinetic interactions were observed between Citalopram and levomepromazine or digoxin (indicating that Citalopram neither induces nor inhibits P-glycoprotein).
RETURN and alcohol
The combination of citalopram and alcohol is not recommended.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy( ),
Citalopram may be used during pregnancy if clinically necessary, taking into account the aspects mentioned below.
Newborns must be monitored if maternal use of Citalopram continued into the late stages of pregnancy, particularly in the third trimester. Abrupt discontinuation during pregnancy must be avoided.
Following maternal use of SSRIs/SNRIs during the late stages of pregnancy, newborns may exhibit the following symptoms: respiratory distress, cyanosis, apnoea, seizures, unstable temperature, feeding difficulties, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremors, nervousness, irritability, lethargy, persistent crying, somnolence and sleep difficulties. These symptoms may be due to serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately after birth or within the first few hours (less than 24 hours).
Ensure that your doctor and/or midwife are aware that you are taking RETURN.
When taken during pregnancy, particularly in the last three months, medicines like RETURN may increase the risk of a serious condition in newborns called persistent pulmonary hypertension (PPHN), which manifests as increased breathing rate and bluish skin colour. These symptoms usually begin within 24 hours after birth. If this occurs for your baby, you must contact the midwife and/or doctor immediately.
If you take Return near the end of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (tendency to bleed easily). Inform your doctor or midwife that you are taking Return so they can advise you on what to do.
Breastfeeding
Citalopram is excreted in breast milk. It is estimated that breastfed infants receive approximately 5% of the maternal daily dose (in mg/kg). Only mild events have been observed in infants. However, existing information is insufficient to assess the risk in children. Caution is recommended.
Male fertility
Citalopram, in animal studies, has been shown to reduce sperm quality.
In theory, this could affect fertility, but the impact on human fertility has not yet been observed.
Driving and operating machinery
Citalopram has minimal or moderate influence on the ability to drive and use machinery.
Psychotropic medicines may reduce judgment and reactivity in emergency situations. It may affect your ability to drive vehicles or operate machinery.
RETURN contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
RETURN contains sodium. This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

8. How to take RETURN

Take this medicine exactly as prescribed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Endogenous depressive syndromes
Adults
RETURN should be administered as a single daily oral dose of 20 mg.
Depending on the individual patient's response, the dose may be increased up to a maximum
of 40 mg per day.
The antidepressant effect usually becomes evident within 2–4 weeks after starting treatment;
the patient should continue to be monitored by the physician until remission of the depressive state is achieved.
Since antidepressant treatment is symptomatic, it should be continued for an appropriate
period of time, generally 4–6 months in manic-depressive illness.
In patients with recurrent unipolar depression, long-term maintenance therapy may be necessary to prevent new depressive episodes.
Anxiety disorders with panic attacks, with or without agoraphobia
During the first week of treatment, the recommended dose is 10 mg, subsequently increased to 20 mg per day. Depending on the individual patient's response, the dose may be increased by the physician up to a maximum of 40 mg per day.
Maximum efficacy is achieved after approximately 3 months of treatment.
In anxiety disorders with panic attacks, treatment is long-term. Maintenance of clinical response has been demonstrated during prolonged treatment (1 year).
In cases of insomnia or marked restlessness, adjunctive treatment with sedatives is recommended during the acute phase.
Withdrawal symptoms observed following discontinuation of treatment
Abrupt discontinuation of treatment should be avoided. When stopping treatment with
RETURN, the dose should be gradually reduced over a period of at least 1–2 weeks to reduce
the risk of withdrawal reactions (see "Warnings and precautions" and "Undesirable effects").
When deciding to discontinue treatment, doses should be reduced gradually to minimize the severity of withdrawal symptoms.
If intolerable symptoms occur following dose reduction or upon discontinuation of treatment, consideration should be given to reinstating the previously prescribed dose.
Subsequently, the physician may continue reducing the dose, but more gradually.
Elderly patients (> 65 years of age)
For elderly patients, the dose should be halved compared to the recommended dose, e.g., 10–20 mg per day. The maximum recommended dose for elderly patients is 20 mg per day.
Use in children and adolescents under 18 years of age
RETURN must not be taken by children and adolescents under 18 years of age (see “Do not take RETURN”).
Patients with specific risk factors
Reduced liver function
For patients with mild or moderate hepatic impairment, the recommended initial dose for the first two weeks of treatment is 10 mg per day. Based on the individual patient's response, the dose may be increased by the physician up to a maximum of 20 mg per day. Caution and closer monitoring are advised in dose titration for patients with severely impaired liver function.
Renal impairment
In these patients, it is advisable to follow the lowest recommended dosage.
Poor metabolizers of CYP2C19
For patients known to be poor metabolizers regarding CYP2C19, an initial dose of 10 mg per day is recommended during the first two weeks of treatment. Based on the individual patient's response, the dose may be increased up to a maximum of 20 mg per day.
If you take more RETURN than you should
In case of accidental ingestion/overdose of RETURN, contact your doctor immediately or go to the nearest hospital.
Toxicity
Fatal cases due to overdose of Citalopram alone have been reported; however, most fatal cases are associated with overdose when the medicine is taken together with other medicinal products.
In case of overdose, ECG monitoring is recommended if you have congestive heart failure/bradyarrhythmias, if you are taking concomitant medicines that prolong the QT interval, or if you have metabolic disturbances such as hepatic impairment.
Symptoms
The following adverse effects have been reported in cases of overdose: seizures, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, electrical conduction block in the heart, QRS prolongation (electrocardiogram abnormalities), hypertension, mydriasis, torsades de pointes, stupor, sweating, cyanosis, hyperventilation, and atrioventricular arrhythmia. Rhabdomyolysis is rare. Possible symptoms with a dose up to 600 mg include fatigue, weakness, sedation, tremor, nausea, and tachycardia.
With doses exceeding 600 mg, seizures may occur within a few hours of ingestion.
ECG abnormalities may also occur, and rhabdomyolysis is rare.
Fatal outcomes following overdose are rare. An adult patient survived after ingesting 5,200 mg of Citalopram.
Treatment
There are no known specific antidotes for Citalopram. Treatment should be symptomatic and supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate), and gastric lavage should be considered. If consciousness is impaired, the patient should be intubated. ECG and vital signs should be closely monitored.
Administer oxygen in case of hypoxia and diazepam in case of seizures. Medical supervision for approximately 24 hours is advisable, as well as ECG monitoring if the ingested dose exceeds 600 mg. Widening of the QRS complex (electrocardiogram abnormalities) may be corrected by infusion of hypertonic NaCl. ECG monitoring is recommended in case of overdose in patients with congestive heart failure/bradyarrhythmias, in patients taking concomitant medicines that prolong the QT interval, or in patients with metabolic disturbances such as hepatic impairment.
If you forget to take RETURN
Do not take a double dose to make up for the forgotten dose.
If you stop taking RETURN
Abrupt discontinuation of treatment should be avoided.
Withdrawal symptoms observed after discontinuation of SSRI treatment
Withdrawal symptoms commonly occur upon stopping treatment, especially if discontinuation is abrupt (see "Possible undesirable effects"). In a clinical study on recurrence prevention, adverse events occurred in 40% of patients after discontinuation of treatment, compared to 20% of patients who continued Citalopram treatment. The risk of withdrawal symptoms may depend on several factors, including duration and dosage of therapy, and the rate of dose reduction.
The most commonly reported adverse effects are: dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. These symptoms are generally mild to moderate, but in some patients they may be severe. They usually appear within the first few days after stopping treatment; however, very rare cases of withdrawal symptoms have been reported in patients who inadvertently missed a single dose. These symptoms usually resolve spontaneously within 2 weeks without requiring medication, although in some patients they may persist (2–3 months or longer). Therefore, if treatment needs to be discontinued, it is recommended to gradually reduce the dose of Citalopram over a period of several weeks or months, according to the individual patient's needs (see "How to take RETURN").

9. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects observed with citalopram are generally mild in intensity and transient. They usually occur during the first or second week of treatment and then tend to diminish over time.
The following side effects have shown a dose-response relationship: increased sweating, dry mouth, insomnia, drowsiness, diarrhoea, nausea, and fatigue.

Very common (affects more than 1 in 10 people)

• Drowsiness
• Insomnia
• Headache
• Dry mouth
• Nausea
• Increased sweating

Common (affects up to 1 in 10 people)

• Decreased appetite, weight loss
• Agitation
• Decreased libido (reduced sexual desire)
• Anxiety, restlessness
• Confusional state
• Abnormal orgasm (in women)
• Sleep disturbances (dream disturbances)
• Tremor, paraesthesia
• Dizziness
• Attention disturbances
• Ringing, buzzing, or other sounds in the ears (tinnitus)
• Yawning
• Diarrhoea
• Vomiting
• Constipation
• Itching
• Muscle and joint pain (myalgia, arthralgia)
• Impotence, ejaculation disorders, absence of ejaculation
• Fatigue

Uncommon (affects up to 1 in 100 people)

• Increased appetite, weight gain
• Aggression
• Feeling detached from oneself (depersonalization)
• Seeing or hearing things that are not real (hallucinations), fixation (mania)
• Low blood pressure (syncope)
• Pupil dilation (mydriasis)
• Slowed heart rate (bradycardia)
• Increased heart rate (tachycardia)
• Appearance of red, raised skin patches (urticaria)
• Hair loss (alopecia)
• Skin redness (rash), appearance of small pinpoint skin haemorrhages (purpura)
• Increased sensitivity to light (photosensitivity reaction)
• Urinary retention
• Excessive menstrual bleeding (menorrhagia in women)
• Oedema

Rare (affects between 1 and fewer than 10 in 10,000 people)

• Low sodium levels in the blood (hyponatraemia)
• Seizures (epilepsy, grand mal)
• Alternating fast and slow movements (dyskinesia)
• Taste disturbances
• Bleeding
• Hepatitis
• Fever (pyrexia)

Not known (frequency cannot be estimated from the available data)

• Reduced potassium concentration in the blood (hypokalaemia)
• Panic attacks
• Jaw muscle contractions with teeth grinding (bruxism)
• Restlessness
• Suicidal ideation, suicidal behaviour
• Seizures
• Increased serotonin levels in the blood (serotonin syndrome)
• Impaired and uncoordinated movement (extrapyramidal disorders)
• Inability to remain still (akathisia), movement disorders
• Visual disturbances
• QT interval prolongation
• Severe disturbances in heart rhythm and rate (ventricular arrhythmias, including torsade de pointes)
• Low blood pressure when standing (orthostatic hypotension)
• Nosebleeds (epistaxis)
• Gastrointestinal bleeding (including rectal bleeding)
• Abnormal liver function tests
• Appearance of subcutaneous bruises (ecchymoses)
• Sudden swelling of the skin and mucous membranes, lining membranes of certain internal organs (angioedema)
• Prolonged and heavy abnormal uterine bleeding occurring between two consecutive menstrual periods (metrorrhagia in women)
• Persistent and abnormal erection (priapism)
• Increased blood levels of the hormone prolactin (hyperprolactinaemia)
• Milky discharge from the nipples in men (galactorrhoea)
• Reduced platelet count (thrombocytopenia)
• Hypersensitivity
• Severe allergic reaction affecting multiple organs (anaphylactic reaction)
• Water retention in the body and reduced urine output (inappropriate secretion of ADH hormone)
• Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); see section 2, Pregnancy, for further information.

Bone fractures:
An increased risk of bone fractures has been observed in patients taking this type of medicine.

QT interval prolongation:
During post-marketing experience, cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported, primarily in female patients, patients with hypokalaemia, or those with pre-existing QT interval prolongation or other cardiac conditions.

Withdrawal symptoms observed following discontinuation of treatment:
Stopping treatment with citalopram (especially if abrupt) generally leads to withdrawal symptoms.
The most commonly reported adverse effects include dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances.
These events are usually mild to moderate and self-limiting; however, in some patients they may be severe and/or prolonged. It is therefore recommended that if treatment with citalopram is no longer required, discontinuation should be gradual, achieved by gradually reducing the dose (see section 3 “How to take RETURN” and “Warnings and precautions”).

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:
reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

10. How to store RETURN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack.
The expiry date refers to the product in its original packaging, stored correctly.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What RETURN contains

• The active substance is citalopram. Each film-coated tablet contains 24.98 mg of citalopram hydrobromide, equivalent to 20 mg of citalopram.
• The other ingredients are: Maize starch, Monohydrate lactose, Microcrystalline cellulose, Copovidone, Glycerol, Sodium croscarmellose, Magnesium stearate, Titanium dioxide, Hypromellose, Macrogol 400.

Description of the appearance of RETURN and contents of the pack
20 mg film-coated tablets, box containing 28 divisible tablets
Marketing Authorization Holder
EURO PHARMA S.r.l., Via Garzigliana, 8, 10127 Torino.
Manufacturer
Special Product's Line S.p.a., Via Fratta Rotonda 1 – 03012 Anagni (FR)