RETURN 20 mg Film-Coated Tablets

Зміст інструкції

1. RETURN 40 mg/ml oral drops, solution
   1. What is RETURN and what is it for
   2. Cosa deve sapere prima di prendere RETURN
   3. How to take RETURN
   4. Possible side effects
   5. How to store RETURN
   6. Contents of the pack and other information
2. RETURN 20 mg film-coated tablets
   1. What is RETURN and what is it for
   2. What you need to know before taking RETURN
3. RETURN contains sodium. This medicine contains less than 1 mmol (23 mg) of sodium per
   1. How to take RETURN
   2. Possible side effects
   3. How to store RETURN
   4. Contents of the pack and other information

RETURN 40 mg/ml oral drops, solution

Citalopram
“Equivalent medicine”

Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could 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 you take 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 is RETURN and what is it for

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

2. Cosa deve sapere prima di prendere RETURN

Non prenda RETURN

• Se è allergico al citalopram o ad uno qualsiasi degli altri componenti di questo medicinale (elencati al paragrafo 6).
• Se ha meno di 18 anni di età.
• Se è in trattamento con inibitori delle monoamino ossidasi (MAO-inibitori), medicinali utilizzati per trattare la depressione. La somministrazione contemporanea di inibitori della ricaptazione della serotonina (SSRI) e MAO-inibitori (medicinali usati contro la depressione) può causare gravi effetti indesiderati, a volte letali. Alcuni casi si presentano con le caratteristiche simili alla sindrome serotoninergica (dovuta a un eccesso di serotonina nel sangue).
• Se è in trattamento con inibitori delle monoamino ossidasi (I-MAO), inclusa la selegilina, in dosi giornaliere superiori a 10 mg/giorno.
• Prima di 14 giorni dopo la sospensione di un I-MAO irreversibile o per il tempo specificato

del RIMA.

• Se interrompe il trattamento con citalopram e deve iniziare una nuova terapia con I-MAO. Gli I-MAO non devono essere somministrati prima di 7 giorni dopo la sospensione del citalopram (vedere paragrafi “Avvertenze e precauzioni” e “Altri medicinali e RETURN”).
• Se è in trattamento con linezolid, un inibitore delle monoamino ossidasi reversibile, a meno che non ci siano macchinari per l’attenta osservazione e monitoraggio della pressione sanguigna (vedere paragrafo “Altri medicinali e RETURN”).
• Se è in trattamento con pimozide (un medicinale antipsicotico usato nel trattamento dei disturbi psichiatrici) (vedere paragrafo “Altri medicinali e RETURN”).
• Se è affetto da prolungamento dell’intervallo QT o sindrome congenita del QT lungo.
• Se è in trattamento concomitante con medicinali noti per causare un prolungamento dell’intervallo QT (vedere paragrafo “Altri medicinali e RETURN”).

Avvertenze e precauzioni
Si rivolga al medico o al farmacista prima di prendere RETURN.

Trattamento di pazienti anziani e di pazienti con ridotta funzionalità renale ed epatica, vedere
“Dose, modo e tempo di somministrazione”.
Uso in bambini ed adolescenti al di sotto dei 18 anni di età
Gli antidepressivi non devono essere utilizzati per il trattamento di bambini e adolescenti al di sotto
dei 18 anni di età. Comportamenti suicidari (tentativi di suicidio e ideazione suicidaria) e ostilità
(essenzialmente aggressività, comportamento di opposizione e collera) sono stati osservati con
maggior frequenza negli studi clinici effettuati su bambini e adolescenti trattati con antidepressivi
rispetto a quelli trattati con placebo. Qualora, in base ad esigenze mediche, dovesse essere presa la
decisione di effettuare il trattamento, il paziente deve essere sorvegliato attentamente per quanto
concerne la comparsa di sintomi suicidari.
Per di più, non sono disponibili i dati sulla sicurezza a lungo termine per i bambini e gli adolescenti
per quanto concerne la crescita, la maturazione e lo sviluppo cognitivo e comportamentale.

Prolungamento dell’intervallo QT
Citalopram è risultato causare un prolungamento dose dipendente dell’intervallo QT. Durante
l’esperienza post-marketing sono stati segnalati casi di prolungamento dell’intervallo QT e di aritmie
ventricolari, inclusa Torsione di Punta, prevalentemente in pazienti di sesso femminile, con
ipopotassemia o con un preesistente prolungamento dell’intervallo QT o altre patologie cardiache.
Si consiglia cautela con i pazienti affetti da significativa bradicardia, in pazienti con recente infarto
acuto del miocardio o con insufficienza cardiaca non compensata.
Squilibri elettrolitici come ipopotassiemia e ipomagnesemia aumentano il rischio di aritmie maligne
e devono essere corretti prima di iniziare il trattamento con Citalopram.
Se si trattano pazienti con patologia cardiaca stabile, si deve considerare l’opportunità di effettuare
un controllo ECG prima di iniziare il trattamento.
Se durante il trattamento con Citalopram si dovessero presentare segni di aritmia cardiaca, il
trattamento deve essere sospeso e deve essere effettuato un ECG.
Può essere consigliabile il monitoraggio dell’ECG in condizioni di metabolismo alterato con livelli
di picco aumentati, es. disfunzione epatica.

Iponatremia
L’iponatremia, fenomeno che comporta la riduzione della concentrazione plasmatica di sodio,
sporadicamente viene segnalata come rara reazione avversa, probabilmente dovuta ad inappropriata
secrezione dell’ormone antidiuretico (SIADH). Tale fenomeno è generalmente reversibile dopo
l’interruzione della terapia.
I pazienti anziani di sesso femminile sembrano essere a rischio particolarmente elevato.

Mania
In pazienti con malattia maniaco – depressiva si può verificare un cambio verso la fase maniacale.
Citalopram deve essere interrotto se il paziente entra in una fase maniacale.

Attacchi epilettici
Gli attacchi epilettici sono un potenziale rischio con l’uso di farmaci antidepressivi. Citalopram deve
essere interrotto in tutti i pazienti in cui si manifestano attacchi epilettici. Citalopram deve essere
evitato in pazienti con epilessia instabile ed i pazienti con epilessia controllata devono essere
attentamente monitorati. Citalopram deve essere interrotto se si verifica un aumento nella frequenza
di crisi epilettiche.

Diabete
In pazienti diabetici il trattamento con SSRI può alterare il controllo glicemico. Può essere necessario
aggiustare il dosaggio dell’insulina o degli ipoglicemizzanti orali.

Sindrome serotoninergica
In rari casi è stata riportata una sindrome serotoninergica in pazienti trattati con SSRI.
Un’associazione di sintomi quali agitazione, tremore, mioclono ed ipertermia può indicare lo sviluppo
di questa condizione. Il trattamento con Citalopram deve essere immediatamente interrotto ed iniziata
una terapia sintomatica.

Medicinali serotoninergici
Citalopram non deve essere usato in associazione con medicinali con effetto serotoninergico come
sumatriptan o altri triptani, tramadolo, ossitriptano e triptofano, (vedere “Interazioni”.)

Emorragia
Con gli SSRI sono stati segnalati tempi di coagulazione prolungati e/o anomalie della coagulazione
quali ecchimosi, emorragie ginecologiche, sanguinamento gastrointestinale ed altre forme di
emorragia cutanea o di sanguinamento delle mucose (vedere “Effetti Indesiderati”). E’ consigliata
cautela in pazienti che assumono SSRI particolarmente in caso di uso concomitante di sostanze attive
che possono influenzare la funzionalità piastrinica o altre sostanze che possono aumentare il rischio
di emorragie, così pure in pazienti con anamnesi di disturbi della coagulazione (vedere “Interazioni”),
o se è in corso una gravidanza [vedere paragrafo “Gravidanza” ( )]

Terapia elettroconvulsivante (ECT)
L’esperienza clinica relativa alla somministrazione contemporanea di ECT e Citalopram è limitata,
pertanto si raccomanda cautela.

Inibitori reversibili selettivi MAO-A
La combinazione del Citalopram con MAO-A inibitori è generalmente sconsigliata a causa del rischio
di comparsa della sindrome serotoninergica (vedere “Interazioni”).
Per altre informazioni sul trattamento concomitante con MAO inibitori irreversibili non selettivi,
vedere “Interazioni”.

Erba di S. Giovanni
Gli effetti indesiderati possono essere più comuni durante l’uso concomitante di Citalopram e
preparazioni erboristiche contenenti l’Erba di S. Giovanni (Hypericum perforatum). Pertanto
Citalopram e le preparazioni contenenti l’Erba di S. Giovanni non devono essere assunte
contemporaneamente (vedere “Interazioni”).

Psicosi
Il trattamento di pazienti psicotici con episodi depressivi può far aumentare i sintomi psicotici.
All’inizio del trattamento si possono manifestare insonnia ed agitazione. In tali casi può essere d’aiuto
un aggiustamento del dosaggio.

Glaucoma ad Angolo Chiuso
Gli SSRI compreso il Citalopram possono provocare midriasi. Questo effetto midriatico ha il
potenziale per ridurre l’angolo dell’occhio con conseguente aumento della pressione intraoculare e
glaucoma ad angolo chiuso, specialmente in pazienti predisposti. Citalopram deve quindi essere usato
con cautela nei pazienti con glaucoma ad angolo chiuso o storia di glaucoma.

Ansia paradossa
Alcuni pazienti con disturbi di panico possono manifestare sintomi di ansia intensificata all’inizio del
trattamento con antidepressivi.
Queste reazioni paradosse generalmente si attenuano entro le prime due settimane dall’inizio del
trattamento. Si consiglia una dose di partenza più bassa per ridurre la probabilità di effetti ansiogeni
paradossi (vedere “Dose, modo e tempo di somministrazione”).

Suicidio/pensieri suicidari o peggioramento del quadro clinico
La depressione è associata ad aumentato rischio di pensieri suicidari, autolesionismo e suicidio
(suicidio/eventi correlati). Questo rischio persiste fino a che si verifichi una remissione significativa.
Poiché possono non verificarsi miglioramenti durante le prime o più settimane di trattamento, i
pazienti devono essere attentamente controllati fino a quando non si verifichi tale miglioramento. E’
esperienza clinica in generale che il rischio di suicidio possa aumentare nelle prime fasi precoci di
miglioramento.
Anche altre patologie psichiatriche per le quali RETURN è prescritto possono anche essere associate
ad un aumentato rischio di eventi correlati al suicidio. Inoltre può esservi co-esistenza di tali patologie
con la depressione maggiore. Le stesse precauzioni adottate nella terapia dei pazienti affetti da
depressione maggiore devono pertanto essere adottate nella terapia dei pazienti affetti da altre
patologie psichiatriche.
I pazienti con storia clinica positiva di eventi correlati al suicidio o coloro che manifestano un grado
significativo di ideazione suicidaria prima dell’inizio della terapia sono maggiormente a rischio di
pensieri suicidari o di tentativi di suicidio, e devono essere attentamente controllati durante il
trattamento. Una metanalisi degli studi clinici condotti con farmaci antidepressivi in confronto con
placebo nella terapia di disturbi psichiatrici, ha mostrato un aumento del rischio di comportamento
suicidario nella fascia di età inferiore a 25 anni dei pazienti trattati con antidepressivi rispetto al
placebo.
La terapia farmacologica con antidepressivi, specialmente nelle fasi iniziali del trattamento e a seguito
di variazioni del dosaggio, deve essere sempre associata ad una stretta sorveglianza dei pazienti, in
particolar modo di quelli ad alto rischio. I pazienti (e le persone che si prendono cura di loro) devono
essere avvertiti della necessità di monitorare ogni peggioramento clinico, il comportamento o pensieri
suicidari e modifiche inusuali del comportamento e qualora tali sintomi si presentino rivolgersi
immediatamente al medico curante.

Inibitori reversibili selettivi MAO-A
La combinazione del Citalopram con MAO-A inibitori è generalmente sconsigliata a causa del rischio
di comparsa della sindrome serotoninergica (vedere “Interazioni”).
Per altre informazioni sul trattamento concomitante con MAO inibitori irreversibili non selettivi,
vedere “Interazioni”.

Acatisia/irrequietezza agitazione psicomotoria
L’uso di SSRI/SNR è stato associato allo sviluppo di acatisia, caratterizzata irrequietezza
soggettivamente spiacevole od angosciante e necessità di muoversi spesso accompagnata da
incapacità di sedersi o restare immobile. È più probabile che tali sintomi si presentino entro le prime
settimane di trattamento. Nei pazienti che sviluppano tali sintomi, l’aumento del dosaggio può essere
dannoso.

Disfunzione sessuale
Medicinali quali RETURN (i cosiddetti inibitori selettivi della ricaptazione della serotonina (SSRI)
e della serotonina-noradrenalina (SNRI) possono causare sintomi di disfunzione sessuale (vedere
paragrafo 4). In alcuni casi, si è osservata la persistenza di questi sintomi dopo l’interruzione del
trattamento.
“Per chi svolge attività sportiva: l’uso del farmaco senza necessità terapeutica costituisce doping e
può determinare comunque positività ai test antidoping.”

Bambini e adolescenti
RETURN non deve essere utilizzato per il trattamento di soggetti al di sotto dei 18 anni di età.

Altri medicinali e RETURN
Informi il medico o il farmacista se sta assumendo, ha recentemente assunto o potrebbe assumere
qualsiasi altro medicinale.

Interazioni farmacodinamiche
A livello farmacodinamico, sono stati riportati casi di sindrome da serotonina con Citalopram e
moclobemide e buspirone.

Contraindicated associations
QT interval prolongation
Pharmacokinetic and pharmacodynamic studies on the association between Citalopram and other
medicines that prolong the QT interval have not been conducted. An additive effect of Citalopram
with such medicines cannot be excluded. Consequently, the co-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, some antimicrobial
agents (such as sparfloxacin, moxifloxacin, IV erythromycin, pentamidine, antimalarial treatments,
particularly halofantrine), some antihistamines (astemizole, mizolastine), etc. is contraindicated.
MAO inhibitors
The concomitant use of Citalopram and MAO inhibitors can cause serious adverse effects, including
serotonin syndrome (see “Do not take RETURN” and “Warnings and precautions”). Cases of serious,
and sometimes fatal, reactions have been reported in patients undergoing treatment with SSRIs
associated with a monoamine oxidase inhibitor (MAO), including selegiline, an irreversible MAO,
and linezolid, a reversible (non-selective) MAO and moclobemide (selective for type IA), and in
patients who had recently discontinued treatment with an SSRI and had started therapy with an MAO.
Some cases presented with characteristics similar to those of serotonin syndrome. The symptoms of
serotonin syndrome include: hyperthermia, rigidity, myoclonus, autonomic nervous system instability
with possible and rapid fluctuations in vital signs, confusion, irritability and agitation, tremor.
If this condition progresses without intervention, it can be fatal due to rhabdomyolysis, central
hyperthermia with acute multi-organ failure, delirium and coma (See "Do not take RETURN").
Pimozide
The 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, who had been
treated with Citalopram 40 mg/day for 11 days, caused only an increase in the AUC and Cmax of
pimozide, although not consistently in the study. The concomitant administration of Citalopram and
pimozide caused an average increase in the QTc interval of approximately 10 msec. Because this
interaction had already been observed after administration of a low dose of pimozide, the concomitant
treatment with Citalopram and pimozide is contraindicated.

Associations that require precautions for use.
Selegiline (selective MAO-B inhibitor)
An interaction pharmacokinetic/pharmacodynamic study with concomitant administration of citalopram
(20 mg per day) and selegiline (10 mg per day) (a selective MAO-B inhibitor) demonstrated
interactions that are not clinically relevant. The concomitant use of citalopram and selegiline (at doses
higher than 10 mg per day) is not recommended (see paragraph “Do not take RETURN”).
Serotoninergic medicines

Lithium and Tryptophan
No pharmacodynamic interactions have been found between lithium and Citalopram; however, an
increased serotonergic effect has been reported when SSRI drugs are administered in association with
lithium or tryptophan. Caution is advised when using Citalopram concurrently with these active
ingredients. 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, the concomitant use of Citalopram
and serotonin agonists (or 5-HT), 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 the 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 those patients who are being treated simultaneously with
anticoagulants, drugs that can affect platelet function, such as non-steroidal anti-inflammatory drugs
(or NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine or other drugs (e.g. atypical
antipsychotics, phenothiazines, tricyclic antidepressants) that can increase the risk of bleeding (see
“Warnings and precautions”).
Electroconvulsive Therapy (ECT)
There are no clinical studies establishing the risk or benefit of the combined use of electroconvulsive
therapy (ECT) and Citalopram (see “Warnings and precautions”).
Alcohol
No pharmacodynamic or pharmacokinetic interactions of Citalopram with alcohol have been
demonstrated; the association between Citalopram and alcohol is, however, not recommended.
Medicines that induce QT prolongation or hypokalemia or hypomagnesemia
Caution is required for the concomitant use of other medicines that prolong the QT interval or drugs
that induce hypokalemia/hypomagnesemia, as they, like Citalopram, potentially prolong the QT
interval. Caution is required for the concomitant use of medicines that induce hypokalemia/
hypomagnesemia as these conditions increase the risk of malignant arrhythmias (see paragraph
“Precautions for use”).
Medicines that lower the seizure threshold
SSRIs can lower the seizure threshold. Caution is recommended when used concomitantly with
medicines capable of lowering the seizure threshold, antidepressants (SSRIs, tricyclics), neuroleptics
(thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol.
Desipramine, Imipramine
In the course of a pharmacokinetic study, no effect was demonstrated on either Citalopram or
imipramine levels, even though desipramine levels, the main metabolite of imipramine, were
increased. When desipramine is associated with Citalopram, an increase in the plasma concentration
of the former is observed; therefore, a reduction of its dosage may be necessary.
Neuroleptics
The use of Citalopram has not shown any clinically relevant interaction with neuroleptics; however, as
with other SSRIs, the possibility of a pharmacodynamic interaction cannot be ruled out a priori.

Pharmacokinetic interactions
The biotransformation of Citalopram into demethylcitalopram is mediated by the cytochrome P450
system 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 (antidepressant) and ticlopidine (used to reduce the
risk of stroke). They can 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 change the
pharmacokinetics of Citalopram.
A pharmacokinetic interaction study of lithium and Citalopram reveals no pharmacokinetic interaction.
Cimetidine
Cimetidine (a potent inhibitor of CYP2D6, 3A4 and 1A2) causes a moderate increase in the average
plasma levels of Citalopram at steady state. Caution is recommended when administering Citalopram in
combination with cimetidine. Dose adjustments may be necessary.
The concomitant administration of escitalopram (the active enantiomer of Citalopram) with omeprazole
(a CYP2C19 inhibitor) 30 mg once daily produced a moderate increase (approximately 50%) in
escitalopram plasma concentrations.
Therefore, caution must be exercised when using inhibitors of CYP2C19 (e.g. omeprazole,
esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Based on the control of adverse
effects during the concomitant administration of other therapy, 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 concurrently with medicines that are primarily
metabolized by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and
metoprolol (when used in heart failure), or some medicines that act on the Central Nervous System and
that are primarily metabolized 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 were 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 were observed or only small changes without clinical relevance were observed when Citalopram
was administered with clozapine and theophylline (substrates of CYP1A2), warfarin (substrate of
CYP2C9), imipramine and mefenytoin (substrates of CYP2C19), sparteine, imipramine, amitriptyline,
risperidone (substrates of CYP2D6) and warfarin, carbamazepine (and its metabolite carbamazepine
epoxide), triazolam (substrates of CYP3A4).
No pharmacokinetic interactions were observed between Citalopram and levopromazine, or digoxin,
(indicating that Citalopram neither induces nor inhibits glycoprotein P).

RETURN and alcohol
The association between citalopram and alcohol is not recommended.

Pregnancy and breastfeeding
If you are pregnant, suspect or are planning a pregnancy, or if you are breastfeeding, ask your doctor or
pharmacist for advice before taking this medicine.
Pregnancy(),
Citalopram can be used during pregnancy, if clinically necessary, taking into consideration the aspects
mentioned below.
Newborns should be monitored if the use of Citalopram by the mother has continued in the late stages of
pregnancy, particularly in the third trimester. A sudden interruption should be avoided during pregnancy.
Following the use by the mother of SSRIs/SNRIs during the late stages of pregnancy, the newborn may
manifest the following symptoms: respiratory disorders, cyanosis, apnea, convulsions, unstable
temperature, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia,
tremors, nervousness, irritability, lethargy, crying, difficulty sleeping. These symptoms may be due to
serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately after birth
or in the hours immediately following (less than 24 hours).
Make sure your doctor and/or midwife is aware that you are taking RETURN.
When taken during pregnancy, especially in the last three months, medicines such as RETURN can
increase the risk of developing a serious condition in newborns, called persistent pulmonary
hypertension (PPHN), which manifests with increased respiratory rate and bluish skin color. These
symptoms usually start within 24 hours of birth. If this happens to your baby, you should 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
soon after delivery, especially if you suffer from bleeding disorders (easy bleeding). Inform your doctor or
midwife/doctor that you are taking RETURN so that they can advise you on what to do.
Breastfeeding
Citalopram is excreted in breast milk. It is estimated that infants who are breastfed will receive
approximately 5% relative to the daily dose taken by the mother (in mg/kg). Only minor events have
been observed in infants. However, the existing information is insufficient to assess the risk in
children. Caution is recommended.

Male fertility
Citalopram, in studies on animals, has shown to reduce the quality of sperm.
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 operate machinery.
Psychotropic drugs can reduce the ability to judge and react in emergency situations.
It may affect the ability to drive vehicles or operate machinery.

RETURN contains

• Ethanol. This medicine contains 56.8 mg of alcohol (ethanol) in each dose, which is equivalent to 71 mg/ml. The volume of this medicine is equivalent to less than 2 ml of beer or 1 ml of wine.
• methylparahydroxybenzoate and propylparahydroxybenzoate.They may cause allergic reactions (including delayed reactions).

3. How to take RETURN

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.

Endogenous depressive syndromes
Adults
The recommended dose of RETURN oral drops 40mg/ml solution is a single daily oral dose of
16 mg (8 drops).
Based on your individual response, the doctor may increase the dose up to a maximum
of 32 mg (16 drops) per day.
The antidepressant effect usually manifests within 2-4 weeks of starting therapy; it
is advisable that you be followed by your doctor until remission of the depressive state.
Since treatment with an antidepressant is symptomatic, it must be continued for an appropriate
period of time, generally 4-6 months in manic-depressive illnesses.
If you suffer from recurrent unipolar depression, it may be necessary to continue maintenance therapy for a
long time in order to prevent new depressive episodes.

Anxiety disorders with panic attacks, with or without agoraphobia
For the first week of treatment, the recommended dose is 8 mg (4 drops), subsequently the dose
is increased to 16 mg (8 drops) per day. Based on your individual response, the doctor may
increase the dose 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 (1 year).
In case of insomnia or severe restlessness, additional treatment with sedatives is recommended
in the acute phase.

Discontinuation symptoms observed following discontinuation of treatment
An abrupt discontinuation of treatment should be avoided. When stopping treatment with
RETURN, the dose must be reduced gradually over a period of at least 1-2 weeks to reduce
the risk of withdrawal reactions (see “Warnings and precautions” and “Possible side
effects”).
If symptoms that are not tolerable should occur, following dose reduction or at the time of discontinuation of
treatment, restoring the previously prescribed dose may be considered.
Subsequently, the doctor may continue to reduce the dose, but more gradually.

Elderly (> 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 the elderly is 16 mg (8 drops) per day.

Use in children and adolescents under the age of 18 years
RETURN should not be taken by children and adolescents under the age of 18 years, (see
“Do not take RETURN”).

Patients with particular risk factors
Reduced liver function
If you suffer from mild or moderate hepatic insufficiency, the recommended initial dose for the first two
weeks of treatment is 8 mg (4 drops) per day. Based 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 greater attention to dosage titration are advised if you suffer from severely reduced liver function.
Renal insufficiency
You should adhere to the minimum recommended dosage.
Slow CYP2C19 metabolizers
If you are a slow metabolizer with respect to CYP2C19, a starting dose of 8 mg (4
drops) per day is recommended during the first two weeks of treatment. Based on your response
the dose may be increased by the doctor up to a maximum of 16 mg (8 drops) per
day.
When deciding to discontinue treatment, the doses must be reduced gradually to
minimize the extent of withdrawal symptoms.

Route of administration
The drops can be mixed with water, orange juice or apple juice.
1 drop = 2 mg of Citalopram.
Citalopram oral drops, solution has a higher bioavailability compared to tablets
approximately 25%. Consequently, the correspondences between the doses of tablets and those
of drops are as follows:

Use in children and adolescents under the age of 18 years
RETURN should not be taken by subjects under the age of 18 years.

If you take more RETURN than you should
In case of accidental ingestion/intake of an excessive dose of RETURN, immediately warn
your doctor or go to the nearest hospital.
Toxicity
Fatal cases of Citalopram overdose alone have been reported; however, most
fatal cases are due to overdose when the medicine is taken together with other medicines.
In case of overdose, ECG monitoring is recommended if you suffer from congestive heart failure
/ bradyarrhythmias, if you are using concomitant medications that prolong the QT interval, or if
you suffer from alterations in metabolism, for example hepatic insufficiency.

Symptoms
The following adverse effects have been reported in cases of overdose: seizures, tachycardia,
drowsiness, prolongation of the QT interval, coma, vomiting, tremor, hypotension, cardiac arrest,
nausea, serotonin syndrome, agitation, bradycardia, dizziness, conduction block
in the heart, prolonged QRS (changes in the electrocardiogram), hypertension, mydriasis,
torsades de pointes, stupor, sweating, cyanosis, hyperventilation and atrioventricular arrhythmia. The

rhabdomyolysis is rare. Possible symptoms with a dose of up to 600 mg are: fatigue, weakness,
sedation, tremor, nausea and tachycardia.
With doses higher than 600 mg, seizures may occur within a few hours of taking it.
Alterations in the ECG and, rarely, rhabdomyolysis may also occur.
Fatal overdose is rare. An adult patient survived after ingesting 5,200
mg of Citalopram.

Treatment
No specific antidotes to Citalopram are known. Treatment should be symptomatic and
supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate) and gastric lavage should be considered.
In the presence of impaired consciousness, the patient should
be intubated. ECG and vital signs should be monitored.
Administer oxygen in case of hypoxia and diazepam in case of seizures. Medical supervision is recommended for about 24 hours, as well as ECG monitoring if the ingested dose is greater
than 600 mg. A widening of the QRS complex (changes in the electrocardiogram) can be
normalized by an infusion of hypertonic NaCl. In case of overdose, ECG monitoring is recommended in patients affected by congestive heart failure / bradyarrhythmias, in patients
using concomitant medications that prolong the QT interval or in patients with alterations
of metabolism. for example hepatic insufficiency
In case of overdose, ECG monitoring is recommended if you suffer from congestive heart failure
/ bradyarrhythmias, if you are using concomitant medications that prolong the QT interval, or if
you suffer from alterations in metabolism, for example hepatic insufficiency.

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

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

Discontinuation symptoms observed following discontinuation of treatment with SSRIs
The onset of discontinuation symptoms is common when stopping treatment, particularly
if the discontinuation is sudden (see “Possible side effects”). In a clinical study on
relapse prevention, adverse events occurred in 40% of patients after
discontinuation of treatment, compared to 20% of patients who continued treatment with
Citalopram. The risk of withdrawal symptoms may depend on several factors, including the 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, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability,
irritability and visual disturbances. Generally, these symptoms are mild to moderate, however in some
patients they can be severe. They usually appear within the first days of
discontinuation of treatment; very rare cases of withdrawal symptoms in
patients who had inadvertently forgotten to take a dose have also been reported. Generally these symptoms resolve spontaneously without the need for medication, within 2 weeks, although in
some patients they may be prolonged (2-3 months or more). If treatment is to be discontinued,
it is therefore advisable to reduce the dose of Citalopram gradually over a period of several weeks
or months, according to the patient's needs (see “How to take RETURN”).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The side effects observed with citalopram are, in general, mild and transient in nature.
They occur mainly during the first or second week of therapy, then tend to subside.
A dose-response relationship has been found for the following side effects: increased
sweating, dry mouth, insomnia, drowsiness, diarrhea, 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 sexual desire (decreased libido)
• Anxiety, nervousness
• Confusional state
• Abnormal orgasm (in women)
• Sleep disorders (dream activity disturbances)
• Tremor, paresthesia
• Dizziness
• Attention disorders
• Sound formation in the ear, ringing, whistling, etc. (tinnitus)
• Yawning
• Diarrhea
• Vomiting
• Constipation
• Itching
• Muscle and joint pain (myalgia, arthralgia)
• Impotence, failed ejaculation disorders, absent ejaculation
• Fatigue

Uncommon (affects up to 1 in 100 people)

• Increased appetite, weight gain
• Aggression
• Feeling of detachment from one's body (depersonalization)
• Seeing or hearing phenomena that do not exist in reality (hallucination), fixation (mania)
• Lowering of blood pressure (syncope)
• Pupil dilation (mydriasis)
• Decreased heart rate (bradycardia)
• Increased heart rate (tachycardia)
• Appearance of red and raised patches on the skin (urticaria)
• Hair loss (alopecia)
• Skin redness (skin rash), appearance of small pinpoint skin hemorrhages (purpura)
• Increased sensitivity to light (photosensitivity reaction)
• Urinary retention
• Excessive menstrual bleeding (menorrhagia in women)
• Edema.

Rare (affects 1 to less than 10 people in 10,000)

• Lowering of sodium in the blood (hyponatremia)
• Convulsions (epilepsy, grand mal)
• Alternating fast and slow movements (dyskinesia)
• Taste alterations
• Bleeding
• Hepatitis
• Fever (pyrexia)

Not known (frequency cannot be estimated from available data)

• Reduction of potassium concentration in the blood (hypokalaemia)
• Panic attacks
• Contractions of the mouth muscles with teeth grinding (bruxism)
• Restlessness
• Suicidal ideation, suicidal behavior
• Convulsions
• Increased serotonin in the blood (serotonin syndrome)
• Alteration and incoordination of movements (extrapyramidal disorders)
• Inability to stand still (akathisia), movement disorders
• Visual disturbances
• Prolongation of the QT interval
• Severe disturbances of the rhythm and rate of heartbeat (ventricular arrhythmias, including Torsades de Pointes)
• Lowering of blood pressure when standing up (orthostatic hypotension)
• Nosebleeds (epistaxis)
• Gastrointestinal bleeding (including rectal bleeding)
• Abnormal liver function tests
• Appearance of subcutaneous bruises (ecchymosis)
• Sudden swelling of the skin and mucous membranes, internal organ linings (angioedema)
• Atypical, abundant and prolonged vaginal bleeding that occurs during the interval between two consecutive menstrual periods (metrorrhagia in women) Persistent and abnormal erection (priapism)
• Increased blood levels of the hormone prolactin (hyperprolactinemia)
• Secretion of a milky substance from the nipples in men (galactorrhea)
• Reduced platelets (thrombocytopenia)
• Hypersensitivity
• Severe allergic reaction affecting multiple organs (anaphylactic reaction)
• Water retention in the body and poor urine production (inappropriate secretion of the ADH hormone) Abundant vaginal bleeding shortly after childbirth (postpartum hemorrhage), see paragraph 2, Pregnancy (), for more information Bone fractures:

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

QT Prolongation:
Cases of QT interval prolongation and ventricular arrhythmias, including Torsades de Pointes, have been reported during post-marketing experience, predominantly in female patients,
with hypokalaemia or with pre-existing QT interval prolongation or other cardiac
diseases.

Discontinuation symptoms observed after stopping treatment:
Discontinuation of treatment with citalopram (especially if abrupt) generally leads to discontinuation
symptoms.
The most commonly reported adverse effects have been 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.
Generally these events are mild to moderate and self-limiting, however, in some patients
they can be severe and/or prolonged. It is therefore recommended that, if treatment with citalopram is no longer required,
a gradual discontinuation be implemented, conducted through a
gradual decrease in the dose (see paragraph 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, please tell your
doctor or pharmacist. You can also report side effects directly through
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverseReporting side effects you
can contribute to providing more information on the safety of this medicine.

5. How to store RETURN

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Do not store at a temperature above 25°C.
Store 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 in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What RETURN contains

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

Description of the appearance of RETURN and contents of the pack
40mg/ml oral drops, solution - Bottle of 15 ml

Marketing Authorisation 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)

RETURN 20 mg film-coated tablets

Citalopram
“Generic medicine”

Read this leaflet carefully before you start taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even 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 you take 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 is RETURN and what is it for

RETURN contains the active ingredient citalopram and belongs to the group of medicines called
selective serotonin reuptake inhibitors (SSRIs), also known as antidepressants.
RETURN is used for the treatment of endogenous depressive syndromes and the prevention of
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 selective serotonin reuptake inhibitors (SSRIs) and MAO inhibitors (medicines used against depression) can cause serious side effects, sometimes fatal. Some cases present with characteristics similar to serotonin syndrome (due to an excess of serotonin in the blood).
• If you are being treated with monoamine oxidase inhibitors (I-MAO), including selegiline, in daily doses greater than 10 mg/day.
• Before 14 days after stopping an irreversible I-MAO or for the time specified

of the RIMA.

• If you stop treatment with citalopram and need to start a new therapy with I-MAO. MAO inhibitors should not be administered before 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 there are facilities for careful observation and monitoring of blood pressure (see section “Other medicines and RETURN”).
• If you are being treated with pimozide (a medicine antipsychotic used in the treatment of psychiatric disorders) (see section “Other medicines and RETURN”).
• If you suffer from prolongation of the QT interval or congenital long QT syndrome.
• If you are being treated concomitantly with medicines known to cause a prolongation of the QT interval (see section “Other medicines and RETURN”).

Warnings and precautions
Consult your doctor or pharmacist before taking RETURN.

Treatment of elderly patients and patients with impaired renal and hepatic function, see
“Dosage, method of administration and duration of treatment”.
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 behaviors (suicide attempts and suicidal ideation) and hostility
(essentially aggression, oppositional behavior and anger) have been observed more frequently in clinical studies conducted on children and adolescents treated with antidepressants
compared to those treated with placebo. If, based on medical needs, a decision is made to
carry out the treatment, the patient must be carefully monitored for the appearance of suicidal symptoms.
Furthermore, there is no data on long-term safety for children and adolescents
regarding growth, maturation and cognitive and behavioral development.

Prolongation of the QT interval
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, predominantly in female patients, with
hypokalemia or with pre-existing prolongation of the QT interval or other heart conditions
Caution is advised in patients with significant bradycardia, in patients with recent acute myocardial infarction or with uncompensated heart failure.
Electrolyte imbalances such as hypokalemia and hypomagnesemia increase the risk of malignant arrhythmias
and must be corrected before starting treatment with Citalopram.
If patients with stable heart disease are treated, it is advisable to consider performing
an ECG before starting treatment.
If signs of cardiac arrhythmia occur during treatment with Citalopram, the
treatment should be discontinued and an ECG should be performed.
ECG monitoring may be advisable in conditions of altered metabolism with increased peak levels, e.g. hepatic dysfunction.

Hyponatremia
Hyponatremia, a phenomenon involving a reduction in plasma sodium concentration,
is sporadically reported as a rare adverse reaction, probably due to inappropriate
secretion of the 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 manic-depressive illness, a shift towards 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 drugs. Citalopram should be
discontinued in all patients in whom seizures occur. Citalopram should be
avoided in patients with unstable epilepsy and patients with controlled epilepsy should be
carefully monitored. Citalopram should be discontinued if an increase in the frequency
of seizures occurs.

Diabetes
In diabetic patients, treatment with SSRIs may alter glycemic control. It may be necessary
to adjust the dosage of insulin or oral hypoglycemic agents.

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 should be immediately discontinued and symptomatic therapy started.

Serotonergic medicines
Citalopram should not be used in association with medicines with serotonergic effects such as
sumatriptan or other triptans, tramadol, oxitriptan and tryptophan (see “Interactions”).

Bleeding
Prolonged coagulation times and/or coagulation abnormalities have been reported with SSRIs
such as bruising, gynecological bleeding, gastrointestinal bleeding and other forms of
cutaneous or mucosal bleeding (see “Adverse Effects”). Caution is advised in patients taking SSRIs, particularly in case of concomitant use of active substances that can 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 if pregnancy is in progress [see paragraph “Pregnancy” ( )]

Electroconvulsive therapy (ECT)
Clinical experience regarding the simultaneous administration of ECT and Citalopram is limited,
therefore caution is recommended.

Selective reversible 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 more information on concomitant treatment with irreversible non-selective MAO inhibitors,
see “Interactions”.

St. John's Wort
Adverse effects may be more common during the 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, an adjustment of the dosage may be helpful.

Angle-closure glaucoma
SSRIs including Citalopram can cause mydriasis. This mydriatic effect has the
potential to reduce the angle of the eye with a consequent increase in intraocular pressure and
angle-closure glaucoma, especially in predisposed patients. Citalopram should therefore be used
with caution in patients with angle-closure glaucoma or a history of glaucoma.

Paradoxical anxiety
Some patients with panic disorder may experience intensified anxiety symptoms at the beginning of
treatment with antidepressants.
These paradoxical reactions generally subside within the first two weeks of treatment. A lower starting dose is recommended to reduce the likelihood of paradoxical anxiogenic effects (see “Dosage, method of administration and duration of treatment”).

Suicide/suicidal thoughts or worsening of clinical picture
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide
(suicide/related events). This risk persists until significant remission occurs. Because improvements may not occur during the first or more weeks of treatment, patients should be carefully monitored until such improvement occurs. It is
clinical experience in general that the risk of suicide may increase in the early stages of
improvement.
Other psychiatric conditions for which RETURN is prescribed may also be associated
with an increased risk of suicide-related events. Furthermore, there may be co-existence of these conditions
with major depression. The same precautions taken in the therapy of patients affected by
major depression should therefore be taken in the therapy of patients affected by other
psychiatric conditions.
Patients with a positive clinical history of suicide-related events or those who exhibit a significant degree
of suicidal ideation before the start of therapy are at greater risk of
suicidal thoughts or suicide attempts, and must be carefully monitored during the
treatment. A meta-analysis of clinical studies conducted with antidepressant drugs compared with
placebo in the therapy of psychiatric disorders, has shown an increased risk of suicidal behavior in the under 25 age group of patients treated with antidepressants compared to
placebo.
Pharmacological therapy with antidepressants, especially in the early stages of treatment and following
dosage changes, must always be associated with close monitoring of patients, in
particular those at high risk. Patients (and those who care for them) must
be warned of the need to monitor any clinical worsening, behavior or suicidal thoughts and unusual changes in behavior and if such symptoms occur, to consult
their doctor immediately.

Selective reversible 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 more information on concomitant treatment with irreversible non-selective MAO inhibitors,
see “Interactions”.

Akathisia/restlessness psychomotor agitation
The use of SSRIs/SNRIs has been associated with the development of akathisia, characterized by subjectively unpleasant or distressing restlessness and a need to move often accompanied by
inability to sit still or remain immobile. These symptoms are more likely to occur within the first
weeks of treatment. In patients who develop these symptoms, increasing the dosage may be
harmful.

Sexual dysfunction
Medicines such as RETURN (so-called selective serotonin reuptake inhibitors (SSRIs) and
serotonin-noradrenaline (SNRIs) can cause symptoms of sexual dysfunction (see
paragraph 4). In some cases, persistence of these symptoms has been observed after discontinuation of
treatment.
“For those who engage in sports: the use of the drug without therapeutic necessity constitutes doping and
may still result in positive doping tests.”

Children and adolescents
RETURN should not be used for the treatment of subjects under 18 years of age.

Other medicines and RETURN
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Pharmacodynamic interactions
Serotonin syndrome has been reported in cases with Citalopram and
moclobemide and buspirone at the pharmacodynamic level.

Contraindicated associations
QT interval prolongation
Studies of pharmacokinetics and pharmacodynamics on the association between Citalopram
have not been conducted with other medicines that prolong the QT interval. An additive effect of
Citalopram with such medicines cannot be excluded. Consequently, the co-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, some
antimicrobial agents (such as sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial
treatments, in particular halofantrine), some antihistamines (astemizole, mizolastine), etc. is contraindicated.
MAO inhibitors
The simultaneous use of Citalopram and MAO inhibitors can cause serious adverse effects, including
serotonin syndrome (see “Do not take RETURN” and “Warnings and precautions”).
Cases of serious, and sometimes fatal, reactions have been reported in patients undergoing treatment with
SSRIs associated with a monoamine oxidase inhibitor (MAO), including selegiline, an irreversible MAO,
and linezolid, a reversible (non-selective) MAO and moclobemide (selective for type IA), and in patients
who had recently discontinued treatment with an SSRI and had started therapy with an MAO.
Some cases presented with characteristics similar to those of serotonin syndrome. The symptoms of
serotonin syndrome include: hyperthermia, rigidity, myoclonus, instability of the autonomic nervous system
with possible and rapid fluctuations in vital signs, confusion, irritability and agitation, tremor. If this
condition progresses without intervention, it can be fatal following rhabdomyolysis, central hyperthermia
with acute multi-organ failure, delirium and coma (See “Do not take RETURN”).
Pimozide
The concomitant use of Citalopram and pimozide is contraindicated (see “Do not take RETURN”). The
concomitant administration of a single dose of 2 mg of pimozide to healthy volunteers, who had been
treated with Citalopram 40 mg/day for 11 days, caused only an increase in the AUC and Cmax of pimozide
although not consistently in the study. The concomitant administration of Citalopram and pimozide caused
an average increase in the QTc interval of approximately 10 msec). Since this interaction had already been
observed after administration of a low dose of pimozide, the concomitant treatment with Citalopram and
pimozide is contraindicated.

Associations that require precautions for use.
Selegiline (selective MAO-B inhibitor)
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of citalopram (20 mg
per day) and selegiline (10 mg per day) (a selective MAO-B inhibitor) demonstrated interactions that were not
clinically relevant. The concomitant use of citalopram and selegiline (at doses greater than 10 mg per day)
is not recommended (see paragraph “Do not take RETURN”).

Lithium and Tryptophan
No pharmacodynamic interactions have been found between lithium and Citalopram; however, an increased
serotonergic effect has been reported when SSRI drugs are administered in association with lithium or
tryptophan. Caution is advised when using Citalopram concurrently with these active ingredients. 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, the 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 the 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 those patients who are being treated simultaneously with anticoagulants,
drugs that can affect platelet function, such as non-steroidal anti-inflammatory drugs (or NSAIDs), acetylsalicylic
acid, dipyridamole, and ticlopidine or other drugs (for example 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 the combined use of electroconvulsive therapy
(ECT) and Citalopram (see “Warnings and precautions”).
Alcohol
No pharmacodynamic or pharmacokinetic interactions of Citalopram with alcohol have been demonstrated;
however, the association between Citalopram and alcohol is discouraged.

Pharmacokinetic interactions
The biotransformation of Citalopram into demethylcitalopram is mediated by the cytochrome P450 system
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 (antidepressant) and ticlopidine (used to reduce the risk of
stroke). They can 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.

Effects of other medicines on the pharmacokinetics of Citalopram
Co-administration with ketoconazole (a potent CYP3A4 inhibitor) does not change the pharmacokinetics of
Citalopram.
A pharmacokinetic interaction study of lithium and Citalopram reveals no pharmacokinetic interaction.
Cimetidine
Cimetidine (a potent CYP2D6, 3A4 and 1A2 inhibitor) causes a moderate increase in the average plasma levels
of Citalopram at steady state. Caution is recommended when administering Citalopram in combination with
cimetidine. Dose adjustments may be necessary.
The concomitant administration of escitalopram (the active enantiomer of Citalopram) with omeprazole (a
CYP2C19 inhibitor) 30 mg once daily produced a moderate increase (approximately 50%) in escitalopram
plasma concentrations.
Therefore, caution must be exercised when using CYP2C19 inhibitors (e.g. omeprazole, esomeprazole,
fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Based on control of adverse effects during
concomitant administration of other therapy, 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 concurrently with medicines that are primarily metabolized
by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when
used in heart failure), or some medicines that act on the Central Nervous System and that are primarily
metabolized 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 were observed.

Effects of Citalopram on other medicines
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of Citalopram and
metoprolol (a CYP2D6 substrate) has shown 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 were observed or only small changes without clinical relevance were observed when Citalopram was
administered with clozapine and theophylline (substrates of CYP1A2), warfarin (substrate of CYP2C9),
imipramine and mefenytoin (substrates of CYP2C19), sparteine, imipramine, amitriptyline, risperidone
(substrates of CYP2D6) and warfarin, carbamazepine (and its metabolite carbamazepine epoxide), triazolam
(substrates of CYP3A4).

RETURN and alcohol
The association between citalopram and alcohol is discouraged.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor or
pharmacist for advice 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 the use of Citalopram by the mother has continued in the late stages of
pregnancy, particularly in the third trimester. A sudden interruption should be avoided during pregnancy.
Following the use by the mother of SSRIs/SNRIs during the late stages of pregnancy, the newborn may
manifest the following symptoms: respiratory distress, cyanosis, apnea, convulsions, unstable temperature,
difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, nervousness,
irritability, lethargy, crying, sleep disturbances. These symptoms may be due to serotonergic effects or
withdrawal symptoms. In most cases, the complications begin immediately after birth or in the hours
immediately following (less than 24 hours).
Make sure your doctor and/or midwife is aware of the fact that you are taking RETURN.
When taken during pregnancy, especially in the last three months, medicines such as RETURN may increase
the risk of developing a serious condition in newborns, called persistent pulmonary hypertension (PPHN),
which manifests with increased respiratory rate and bluish skin discoloration. These symptoms usually begin
within 24 hours of birth. If this happens to your baby, you should 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 suffer from bleeding disorders (easy bleeding). Inform your treating doctor or
midwife/obstetrician that you are taking Return, so that they can advise you on what to do.
Breastfeeding
Citalopram is excreted in breast milk. It is estimated that infants who are breastfed will receive approximately
5% relative to the daily dose taken by the mother (in mg/kg). Only minor events have been observed in infants.
However, the existing information is insufficient to assess the risk in children. Caution is recommended.

Male fertility
Citalopram, in animal studies, has shown to reduce the quality of sperm.
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 operate machinery.
Psychotropic drugs can reduce the ability to judge and react in emergency situations.
It may affect the ability to drive vehicles or operate machinery.

RETURN contains lactose.If your doctor has diagnosed you with intolerance to some sugars, contact
him/her before taking this medicine

RETURN contains sodium. This medicine contains less than 1 mmol (23 mg) of sodium per

tablet, meaning it is essentially ‘sodium-free’.

8. How to take RETURN

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.

Endogenous depressive syndromes
Adults
RETURN should be administered as a single oral daily dose of 20 mg.
Based on the individual patient's response, the dose may be increased up to a maximum
of 40 mg per day.
The antidepressant effect usually manifests within 2-4 weeks of starting therapy; it is
advisable that the patient be followed up by the doctor until remission of the depressive state.
Since treatment with an antidepressant is symptomatic, it should be continued for an appropriate
period of time, typically 4-6 months in manic-depressive illnesses.
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
For the first week of treatment, the recommended dose is 10 mg, subsequently the dose is
increased to 20 mg per day. Based on the individual patient's response, the dose may be
increased by the doctor 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 case of insomnia or severe restlessness, additional treatment with sedatives is recommended
in the acute phase.

Discontinuation symptoms observed following treatment interruption
An abrupt interruption 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, the doses should be reduced gradually to
minimize the severity of withdrawal symptoms.
If symptoms should occur, following dose reduction or upon discontinuation of the
treatment, restoring the previously prescribed dose may be considered.
Subsequently, the doctor may continue to reduce the dose, but more gradually.

Elderly (> 65 years of age)
For elderly patients, the dose should be reduced to half the recommended dose, for example 10-20
mg per day. The maximum recommended dose for the elderly is 20 mg per day.

Use in children and adolescents under the age of 18 years
RETURN should not be taken by children and adolescents under the age of 18 years (see “Do not
take RETURN”).

Patients with particular risk factors
Reduced liver function
For patients with mild or moderate hepatic insufficiency, 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 doctor up to a maximum of 20 mg per day. Caution and greater attention to dose
titration are advised in patients with severely reduced liver function.
Renal insufficiency
In these patients, it is advisable to adhere to the minimum recommended dosage.
Poor CYP2C19 metabolizers
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 response of the patient, 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/intake of an excessive dose of RETURN, immediately
inform your doctor or go to the nearest hospital.
Toxicity
Fatal cases of Citalopram overdose alone have been reported; however, most fatal cases are due to
overdose when the medicine is taken together with other medicines.
In case of overdose, ECG monitoring is recommended if you suffer from congestive heart failure
/ bradyarrhythmias, if you are using concomitant medicines that prolong the QT interval, or if
you suffer from alterations in metabolism, for example, hepatic insufficiency.

Symptoms
In cases of overdose, the following undesirable effects have been reported: convulsions, tachycardia,
drowsiness, prolongation of the QT interval, coma, vomiting, tremor, hypotension, cardiac arrest,
nausea, serotonin syndrome, agitation, bradycardia, dizziness, conduction block in the
heart, prolongation of the QRS complex (changes in the electrocardiogram), hypertension, mydriasis,
torsades de pointes, stupor, sweating, cyanosis, hyperventilation, and atrioventricular arrhythmia.
Rhabdomyolysis is rare. Possible symptoms with a dose of up to 600 mg are: fatigue, weakness,
sedation, tremor, nausea and tachycardia.
With doses greater than 600 mg, seizures may occur within a few hours of taking the medicine.
Changes in the ECG and, rarely, rhabdomyolysis may also occur.
Fatal overdose is rare. An adult patient survived after ingesting 5,200
mg of Citalopram.

Treatment
No specific antidotes to Citalopram are known. Treatment should be symptomatic and
supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate), and gastric lavage should be considered.
In the presence of impaired consciousness, the patient should
be intubated. ECG and vital signs should be monitored.
Administer oxygen in case of hypoxia and diazepam in case of seizures. Medical monitoring is recommended for about 24 hours, as well as ECG monitoring if the ingested dose is greater
than 600 mg. A widening of the QRS complex (changes in the electrocardiogram) can be
normalized by an infusion of hypertonic NaCl. In case of overdose, ECG monitoring is recommended in patients with congestive heart failure / bradyarrhythmias, in patients
using concomitant medicines that prolong the QT interval, or in patients with alterations
of metabolism, for example, hepatic insufficiency.

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

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

Discontinuation symptoms observed following treatment interruption with SSRIs
The onset of discontinuation symptoms is common when stopping treatment, particularly
if the discontinuation is sudden (see “Possible undesirable effects”). In a clinical study on
relapse prevention, adverse events occurred in 40% of patients after
treatment discontinuation, compared to 20% of patients who continued treatment with
Citalopram. The risk of withdrawal symptoms may depend on several factors, including the duration and
dosage of therapy, and the rate of dose reduction.
The most commonly reported undesirable effects are: dizziness, sensory disturbances (including
paresthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or
vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability,
irritability, and visual disturbances. Generally, these symptoms are mild to moderate, however, in some
patients they may be severe. They usually appear within the first few days of
treatment discontinuation; however, very rare cases of withdrawal symptoms have been reported in
patients who inadvertently forgot to take a dose. Generally, these symptoms resolve spontaneously without the need for medication, within 2 weeks, although in
some patients they may be prolonged (2-3 months or more). If treatment needs to be discontinued,
it is therefore advisable to gradually reduce the dose of Citalopram over a period of several weeks
or months, according to the 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, in general, mild and transient in nature. They usually occur during the first or second week of therapy, then
subside subsequently.
For the following side effects, a dose-response relationship has been found: increased
sweating, dry mouth, insomnia, drowsiness, diarrhea, 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 (sexual desire)
• Anxiety, nervousness
• Confusion
• Abnormal orgasm (in women)
• Sleep disturbances (disturbances of dream activity)
• Tremor, paresthesia
• Dizziness
• Attention disorders
• Sound formation in the ear, ringing, whistling, etc. (tinnitus)
• Yawning
• Diarrhea
• Vomiting
• Constipation
• Itching
• Muscle and joint pain (myalgia, arthralgia)
• Impotence, failed ejaculation and absent ejaculation
• Fatigue

Uncommon (affects up to 1 in 100 people)

• Increased appetite, weight gain
• Aggression
• Feeling of detachment from one's body (depersonalization)
• Seeing or hearing phenomena that do not exist in reality (hallucination), fixation (mania)
• Lowering of blood pressure (syncope)
• Pupil dilation (mydriasis)
• Slowing of the heart rate (bradycardia)
• Increased heart rate (tachycardia)
• Appearance of red and raised patches on the skin (urticaria)
• Hair loss (alopecia)
• Skin redness (rash), appearance of small pinpoint hemorrhages on the skin (purpura)
• Increased sensitivity to light (photosensitivity reaction)
• Urinary retention
• Excessive menstrual bleeding (menorrhagia in women)
• Edema.

Rare (affects 1 to less than 10 people in 10,000)

• Lowering of sodium in the blood (hyponatremia)
• Convulsions (epilepsy, grand mal)
• Alternating fast and slow movements (dyskinesia)
• Taste alterations
• Bleeding
• Hepatitis
• Fever (pyrexia)

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

• Reduction of potassium concentration in the blood (hypokalemia)
• Panic attacks
• Contractions of the mouth muscles with teeth grinding (bruxism)
• Restlessness
• Suicidal ideation, suicidal behavior
• Convulsions
• Increased serotonin in the blood (serotonin syndrome)
• Alteration and incoordination of movements (extrapyramidal disorders)
• Inability to stay still (akathisia), movement disorders
• Visual disturbances
• Prolongation of the QT interval
• Severe alterations of the rhythm and frequency of the heartbeat (ventricular arrhythmias, including Torsades de Pointes)
• Lowering of blood pressure when standing up (orthostatic hypotension)
• Nosebleeds (epistaxis)
• Gastrointestinal bleeding (including rectal bleeding)
• Abnormal liver function tests
• Appearance of subcutaneous bruises (ecchymosis)
• Sudden swelling of the skin and mucous membranes, lining membranes of some internal organs (angioedema)
• Atypical, abundant and prolonged vaginal bleeding that occurs during the interval between two consecutive menstrual periods (metrorrhagia in women) Persistent and abnormal erection (priapism)
• Increased levels of the hormone prolactin in the blood (hyperprolactinemia)
• Secretion of a milky substance from the nipples in men (galactorrhea)
• Reduced platelets (thrombocytopenia)
• Hypersensitivity
• Severe allergic reaction affecting multiple organs (anaphylactic reaction)
• Water retention in the body and poor urine production (inappropriate secretion of the hormone ADH)
• Abundant vaginal bleeding shortly after childbirth (postpartum hemorrhage), 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 prolongation:
During post-marketing experience, cases of QT interval prolongation and
ventricular arrhythmias, including Torsades de Pointes, have been reported, predominantly in
female patients, with hypokalemia or with a pre-existing prolongation of the QT interval or
other heart conditions.

Discontinuation symptoms observed after stopping treatment:
Discontinuation of treatment with citalopram (especially if abrupt) generally leads to
discontinuation symptoms.
The most commonly reported adverse effects have been 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.
Generally these events are mild to moderate and self-limiting, however, in some patients
they can be severe and/or prolonged. It is therefore recommended that, if treatment with
citalopram is no longer required, a gradual discontinuation be implemented, conducted through
a gradual decrease in the dose (see section 3 “How to take RETURN” and “Warnings and
precautions”).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly to
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 sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What RETURN contains

• The active ingredient is citalopram. Each film-coated tablet contains 24.98 mg of citalopram hydrobromide equivalent to 20 mg of citalopram.
• The other ingredients are: Corn starch, Lactose monohydrate, 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, blister pack of 28 divisible tablets

Marketing Authorisation 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)