Cilift 20 Mg Tablets

CILIFT 20 mg TABLET is indicated for the treatment of:

• Depression and prevention of relapse.
• Panic disorder with or without agoraphobia.
• Obsessive compulsive disorder (OCD).

Posology

Adults

Treating depression

CILIFT 20 mg TABLET should be administered as a single oral dose of 20 mg (1 tablet) daily. Dependent on individual patient response, this may be increased to a maximum of 40 mg (two tablets) daily. The dose may be taken in the morning or the evening, not necessarily with food. Duration of treatment The antidepressant effect usually sets in after 2 to 4 weeks. Treatment with CILIFT 20 mg TABLET is symptomatic and must therefore be continued for an appropriate length of time, usually up to 6 months after recovery in order to prevent relapse.

Treating panic disorder

A single dose of 10 mg (half a tablet) daily is recommended for the first week before increasing the dose to 20 mg (1 tablet) daily. The dose may be further increased, up to a maximum of 40 mg (2 tablets) daily, dependent on individual patient response.

Treating Obsessive Compulsive disorder (OCD)

An initial dose of 20 mg (one tablet) is recommended. Dependent on individual patient response, the dose can be increased in increments of 20 mg (one tablet) to a maximum of 40 mg (two tablets) daily if necessary, based on clinical judgement. Duration of Treatment The onset of action in treating OCD is 2 to 4 weeks with further improvement over time.

Special populations

Elderly patients (> 65 years) and patients with hepatic impairment For elderly patients the dose should be decreased to half of the recommended dose, e.g. 10 mg to 20 mg daily. Depending on individual patient response. The recommended maximum dose is 20 mg (one tablet) daily. Reduced hepatic function Dosage should be halved. An initial dose of 10 mg daily for the first two weeks of treatment is recommended in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function. Reduced renal function Dosage adjustment is not necessary in cases of mild or moderate renal impairment. CILIFT 20 mg TABLET is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min) (see section 4.3 and section 5.2). Poor metabolisers of CYP2C19 An initial dose of 10 mg daily during the first two weeks of treatment is recommended for patients who are known to be poor metabolisers with respect to CYP2C19. The dose may be increased to a maximum of 20 mg daily depending on individual patient response. Withdrawal symptoms seen on discontinuation of CILIFT 20 mg TABLET Abrupt discontinuation of CILIFT 20 mg TABLET should be avoided. When stopping treatment with CILIFT 20 mg TABLET the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the doctor may continue decreasing the dose, but at a more gradual rate (see section 4.8 and section 4.4). Paediatric population Children and adolescents (< 18 years of age) CILIFT 20 mg TABLET should not be used in the treatment of children and adolescents under the age of 18 years (see section 4.3 and section 4.4).

Method of administration

For oral administration. CILIFT 20 mg TABLET is administered as a single daily dose. CILIFT 20 mg TABLET can be taken at any time of the day without regard to food intake.

CILIFT 20 mg TABLET is contraindicated in:

• Patients with hypersensitivity to citalopram or to any excipients in CILIFT 20 mg TABLET (see section 6.1).
• Severely impaired renal function (creatinine clearance of less than 30 ml/min) (see section 5.2).
• Children and adolescents under the age of 18 years (see section 4.4 and section 4.8).
• Combination with monoamine oxidase inhibitors (MAOIs): Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI, such as citalopram, as in CILIFT 20 mg TABLET, in combination with a monoamine oxidase inhibitor (MAOI), including the selective MAO-B inhibitor selegiline and the reversible MAOI (RIMA), moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome. CILIFT 20 mg TABLET must not be used in combination with a MAOI, including selegiline in doses above 10 mg daily. Treatment with CILIFT 20 mg TABLET may be instituted 14 days after discontinuation of non-selective MAOIs and minimum of one day after discontinuation of moclobemide. Treatment with MAOIs may be introduced 7 days after discontinuing CILIFT 20 mg TABLET (see section 4.5).
• Patients with known QT interval prolongation or congenital long QT syndrome (see section 4.4, section 4.8 and section 5.1).
• Combination with medicines that are known to prolong the QT interval (see section 4.4 and section 4.5).
• Combination with linezolid (see section 4.5).
• Concomitant treatment with pimozide (see section 4.5).

Suicide/suicidal thoughts or clinical worsening Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. Patients with major depressive disorder, both adults and children, may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines, such as CILIFT 20 mg TABLET. This risk may persist until significant remission occurs. A causal role however, for antidepressant medicine, such as CILIFT 20 mg TABLET, in inducing such behaviour, has not been established. Patients being treated with CILIFT 20 mg TABLET should nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy or at any time of dose changes, either increases or decreases. Other psychiatric conditions for which CILIFT 20 mg TABLET is prescribed can also be associated with an increased risk of suicide related events. Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorders should be observed when treating patients with other psychiatric and non-psychiatric disorders. The following symptoms have been reported in patients being treated with antidepressants, such as CILIFT 20 mg TABLET, for major depressive disorder, as well as for other indications both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia, hypomania, and mania. Although a causal link between the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing CILIFT 20 mg TABLET, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patientu2019s presenting symptoms. If the decision is made to discontinue treatment, CILIFT 20 mg TABLET should be tapered (see section 4.4 and section 4.8).

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant medicines, such as CILIFT 20 mg TABLET, in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany medicine therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Withdrawal symptoms seen on discontinuation of CILIFT 20 mg TABLET Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8). The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. After prolonged administration, abrupt cessation of CILIFT 20 mg TABLET may produce withdrawal symptoms such dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances in some patients. These symptoms are not indicative of addiction. Generally these symptoms are mild to moderate however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but this was also reported in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2 to 3 months or more). It is therefore advised that the dosage of CILIFT 20 mg TABLET should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patientu2019s needs to avoid occurrence of discontinuation symptoms (see section 4.2).

ECT (electroconvulsive therapy) There is little clinical experience of concurrent use of CILIFT 20 mg TABLET and electroconvulsive treatment, therefore caution is advisable.

Mania In patients with manic-depressive illness, a change towards the manic phase may occur. Should the patient enter a manic phase CILIFT 20 mg TABLET should be discontinued.

QT interval prolongation CILIFT 20 mg TABLET has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular dysrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see section 4.3, section 4.5, section 4.8, section 4.9 and section 5.1). Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure. Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for malignant dysrhythmias and should be corrected before treatment with CILIFT 20 mg TABLET is started. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started. ECG monitoring may be advisable in case of overdose or conditions of altered metabolism with increased peak levels, e.g. liver impairment. If signs of cardiac dysrhythmia occur during treatment with CILIFT 20 mg TABLET, the treatment should be withdrawn and an ECG should be performed.

Elderly patients Caution should be used in the treatment of elderly patients (see section 4.2).

Reduced kidney and liver function Caution should be used in the treatment of patients with reduced kidney and liver function (see section 4.2).

Paradoxical anxiety Some patients with panic disorder may experience intensified anxiety symptoms at the start of treatment with antidepressants, such as CILIFT 20 mg TABLET. This paradoxical reaction usually subsides within the first two weeks of starting treatment. A low starting dose of CILIFT 20 mg TABLET is advised to reduce the likelihood of a paradoxical anxiogenic effect (see section 4.2).

Hyponatraemia Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported as an adverse reaction with the use of SSRIs, such as CILIFT 20 mg TABLET (see section 4.8). Hyponatraemia generally reverses on discontinuation of therapy. Elderly female patients seem to be at particularly high risk.

Akathisia or psychomotor restlessness The use of CILIFT 20 mg TABLET has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Seizures Seizures are a potential risk with antidepressant medicines, such as CILIFT 20 mg TABLET. CILIFT 20 mg TABLET should be discontinued in any patient who develops seizures. CILIFT 20 mg TABLET should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. CILIFT 20 mg TABLET should be discontinued if there is an increase in seizure frequency.

Diabetes In patients with diabetes, treatment with an SSRI, such as CILIFT 20 mg TABLET, can alter glycaemic control, possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Glaucoma SSRIs, including CILIFT 20 mg TABLET, may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. CILIFT 20 mg TABLET should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

Serotonin syndrome Serotonin syndrome has been reported in patients using SSRIs, such as CILIFT 20 mg TABLET. A combination of symptoms such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition (see section 4.5). Treatment with CILIFT 20 mg TABLET should be discontinued immediately and symptomatic treatment initiated.

Serotonergic medicines CILIFT 20 mg TABLET should not be used concomitantly with medicines with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan and tryptophan (see section 4.5). Concomitant administration of citalopram, as in CILIFT 20 mg TABLET, and buprenorphine may result in serotonin syndrome, a potentially life-threatening syndrome (see section 4.5). If concomitant treatment with buprenorphine is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.

Haemorrhage There have been reports of prolonged bleeding time and/or bleeding abnormalities such as ecchymoses, gynaecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucous bleedings with SSRIs, such as CILIFT 20 mg TABLET (see section 4.8). Caution is advised in patients taking CILIFT 20 mg TABLET, particularly with concomitant use of active medicines known to affect platelet function or other active medicines that can increase the risk of haemorrhage, as well as in patients with a history of bleeding disorders (see section 4.5). SSRIs/SNRIs, such as CILIFT 20 mg TABLET, may increase the risk of postpartum haemorrhage (see section 4.6 and section 4.8).

Reversible, selective MAO-A inhibitors The combination of CILIFT 20 mg TABLET with MAO-A inhibitors is generally not recommended due to the risk of onset of a serotonin syndrome (see section 4.5). For information on concomitant treatment with non-selective, irreversible MAO-inhibitors, see section 4.3 and section 4.5.

St. Johnu2019s wort Undesirable effects may be more common during concomitant use of CILIFT 20 mg TABLET and herbal preparations containing St. Johnu2019s wort (Hypericum perforatum). Therefore CILIFT 20 mg TABLET and St. Johnu2019s wort preparations should not be taken concomitantly (see section 4.5).

Pharmacodynamic interactions At the pharmacodynamic level cases of serotonin syndrome with CILIFT 20 mg TABLET and moclobemide and buspirone have been reported.

Contraindicated combinations MAO-Inhibitors The simultaneous use of CILIFT 20 mg TABLET and MAO-inhibitors can result in severe undesirable effects, including serotonin syndrome (see section 4.3 and 4.4). Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI, such as CILIFT 20 mg TABLET, in combination with a MAOI, including the irreversible MAOI selegiline and the reversible MAOIs linezolid and moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome. Symptoms of an active medicine interaction with a MAOI include: tremor, myoclonus hyperthermia, rigidity, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma (see section 4.3).

QT interval prolongation Pharmacokinetic and pharmacodynamic studies of citalopram, as in CILIFT 20 mg TABLET, combined with other medicines that prolong the QT interval have not been performed. An additive effect of citalopram and these medicines cannot be excluded. Therefore, co-administration of CILIFT 20 mg TABLET with medicines that prolong the QT interval, such as Class IA and III antidysrhythmics (e.g. amiodarone, quinidine), antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial medicines (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarial treatment particularly halofantrine), certain antihistamines (e.g. astemizole, mizolastine) and anti-retrovirals (e.g. ritonavir, saquinavir, lopinavir), is contraindicated (see section 4.3).

Pimozide Co-administration of a single dose of pimozide 2 mg to patients treated with racemic citalopram 40 mg/day for 11 days caused an increase in AUC and C max of pimozide, although not consistently throughout the study. The co-administration of pimozide and CILIFT 20 mg TABLET resulted in a mean increase in the QTc interval of approximately 10 msec. Due to the interaction noted at a low dose of pimozide, concomitant administration of citalopram, as in CILIFT 20 mg TABLET, and pimozide is contraindicated (see section 4.3).

Combinations requiring precaution for use Selegiline (selective MAO-B inhibitor) A pharmacokinetic / pharmacodynamic interaction study with concomitantly administered citalopram (20 mg daily), as in CILIFT 20 mg TABLET, and selegiline (10 mg daily) (a selective MAO-B inhibitor) demonstrated no clinically relevant interactions. The concomitant use of CILIFT 20 mg TABLET and selegiline (in doses above 10 mg daily) is contraindicated (see section 4.3).

Serotonergic medicines No pharmacodynamic interactions have been found in clinical studies in which citalopram, as in CILIFT 20 mg TABLET, has been given concomitantly with lithium. However, there may be enhanced effects when SSRIs, including CILIFT 20 mg TABLET, are given with lithium, sumatriptan or tryptophan. Therefore, the concomitant use of CILIFT 20 mg TABLET with these medicines should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual. Co-administration with serotonergic medicines (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects. Until further information is available. The simultaneous use of CILIFT 20 mg TABLET and 5-HT agonists, such as sumatriptan and other triptans, is not recommended (see section 4.4).

Buprenorphine Citalopram, as in CILIFT 20 mg TABLET, should be used cautiously when co-administered with buprenorphine, as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).

Medicines lowering the seizure threshold CILIFT 20 mg TABLET can lower the seizure threshold. Caution is advised when concomitantly using other medicines capable of lowering the seizure threshold (e.g. antidepressants (tricyclics, other SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol).

St. Johnu2019s wort Pharmacodynamic interactions between CILIFT 20 mg TABLET and the herbal remedy St. Johnu2019s wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects (see section 4.4 and section 4.8). Pharmacokinetic interactions have not been investigated.

Haemorrhage Caution is warranted for patients who are being treated simultaneously with anticoagulants (e.g warfarin), medicines that affect the platelet function, such as non-steroidal anti-inflammatory medicines (NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) that can increase the risk of haemorrhage (see section 4.4).

ECT (electroconvulsive therapy) There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and citalopram, as in CILIFT 20 mg TABLET (see section 4.4).

Safety in pregnancy and lactation has not been established.

Pregnancy Data on pregnant women (more than 2 500 exposed outcomes) indicate no malformative foeto / neonatal toxicity, however CILIFT 20 mg TABLET should not be used during pregnancy. Neonates should be observed if maternal use of CILIFT 20 mg TABLET continues into the later stages of pregnancy, particular in the third trimester. Abrupt discontinuation should be avoided during pregnancy. The following symptoms may occur in the neonates after maternal CILIFT 20 mg TABLET use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (< 24 hours) after delivery. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI, such as citalopram as in CILIFT 20 mg TABLET, exposure within the month prior to birth (see section 4.4 and section 4.8). Epidemiological data have suggested that the use of SSRIs, such as citalopram, as in CILIFT 20 mg TABLET, in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1 000 pregnancies. In the general population 1 to 2 cases of PPHN per 1 000 pregnancies occur.

Breastfeeding CILIFT 20 mg TABLET is excreted into breast milk. Mothers breastfeeding their infants should not be treated with CILIFT 20 mg TABLET.

Fertility Animal data have shown that citalopram, as in CILIFT 20 mg TABLET, may affect sperm quality. Human case reports with some SSRIs, such as citalopram, as in CILIFT 20 mg TABLET, have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.

CILIFT 20 mg TABLET has minor influence on the ability to drive and use machines. Since adverse reactions such as dizziness, drowsiness and amnesia have been reported in patients taking CILIFT 20 mg TABLET, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that CILIFT 20 mg TABLET does not adversely affect their ability to do so (see section 4.8).

a) Summary of the safety profile Undesirable effects observed with citalopram, as in CILIFT 20 mg TABLET, are in general mild and transient. They are most prominent during the first one or two weeks of treatment and usually attenuate as the depressive state improves. For the following reactions, a dose-response was discovered: sweating increased, dry mouth, insomnia, somnolence, diarrhoea, nausea, and fatigue.

b) Tabulated list of adverse reactions

System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data) Blood and the lymphatic system disorders Thrombocytopenia Immune system disorders Hypersensitivity, anaphylactic reaction Endocrine disorders Inappropriate ADH secretion Metabolism and nutrition disorders Weight loss, weight gain, decreased appetite Hyponatraemia (particularly in the elderly), appetite increased Hypokalaemia Psychiatric disorders Anxiety, decreased libido, agitation, nervousness, confusional state, abnormal orgasm (female), abnormal dreams, sleep disorder, apathy. Mania, aggression, depersonalisation, hallucination, panic attack, bruxism, restlessness, increased libido, suicidal ideation, suicidal behaviour 2 , in children: hostility, suicidal ideation, self-harm Parasomnia Nervous system disorders Insomnia, somnolence, drowsiness, paraesthesia, headache, tremor, dizziness, disturbance in attention, migraine, amnesia Convulsions, convulsion grand mal, extrapyramidal side effects, confusion, syncope, serotonin syndrome, akathisia, dyskinesia movement disorder, taste disturbance Eye disorders Accommodation disturbances Mydriasis (which may lead to acute narrow angle glaucoma) Visual disturbance Ear and labyrinth disorders Tinnitus Cardiac disorders Decrease in pulse rate, bradycardia, tachycardia, palpitations Electrocardiogram QT prolongation 1 , ventricular dysrhythmia including torsade de pointes Vascular disorders Haemorrhage, orthostatic hypotension Respiratory, thoracic and mediastinal disorders Yawning, rhinitis Nasal congestion, epistaxis, coughing

Gastrointestinal disorders Dry mouth, nausea, vomiting, dyspepsia, constipation, diarrhoea, abdominal pain, flatulence, increased salivation Gastrointestinal haemorrhage including rectal haemorrhage) Hepatobiliary disorders Hepatitis, abnormal liver function test Skin and subcutaneous tissue disorders Increased sweating, pruritis Rash, urticaria, alopecia, purpura, photosensitivity reaction, ecchymosis, angioedema Musculoskeletal and connective tissue disorders Myalgia, arthralgia Renal and urinary disorders Micturition disorder Urinary retention Reproductive system and breast disorders Ejaculation disorder, impotence, ejaculation failure Menorrhagia, metrorrhagia, priapism, galactorrhoea Postpartum haemorrhage* General disorders and administrative site conditions Fatigue, asthenia Pyrexia, oedema, malaise Neuroleptic malignant syndrome 1 Cases of QT-prolongation and ventricular dysrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT prolongation or other cardiac diseases (see section 4.3, section 4.4, section 4.5, section 4.9 and section 5.1). 2 Cases of suicidal ideation and suicidal behaviours have been reported during citalopram, as in CILIFT 20 mg TABLET, therapy or early after treatment discontinuation (see section 4.4).

* This event has been reported for the therapeutic class of SSRIs/SNRIs (see section 4.4 and section 4.6).

c) Description of selected adverse reactions Bone fractures Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs, such as CILIFT 20 mg TABLET, and TCAs. The mechanism leading to this risk is unknown. Withdrawal symptoms seen on discontinuation Discontinuation of CILIFT 20 mg TABLET (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally, these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when CILIFT 20 mg TABLET treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 and section 4.4).

d) Paediatric population Children and adolescents under 18 years of age In children reports of hostility and suicidal ideation (see section 4.3 and section 4.4).

Symptoms The fatal dose is not known. Patients have survived ingestion of up to 2 g citalopram, as in CILIFT 20 mg TABLET. The effects will be potentiated by alcohol taken at the same time. Potential interactions with tricyclic antidepressants and MAOIs (see section 4.5). Comprehensive clinical data on citalopram, as in CILIFT 20 mg TABLET, overdose are limited, and many cases involve concomitant overdoses of other medicines/alcohol. Fatal cases of citalopram, as in CILIFT 20 mg TABLET, overdose have been reported with citalopram alone; however, the majority of fatal cases have involved overdose with concomitant medicines/alcohol. The following symptoms have been seen in reported overdose of CILIFT 20 mg TABLET: tiredness, weakness, sedation, convulsion, tachycardia, somnolence, QT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, mydriasis, drowsiness, torsade de pointes, stupor, dystonia, sweating, cyanosis, hyperventilation, hyperpyrexia, nodal rhythm, and atrial and ventricular dysrhythmia.

ECG changes including nodal rhythm, prolonged QT intervals and wide QRS complexes may occur. Fatalities have been reported. Prolonged bradycardia with severe hypotension and syncope has also been reported. Features of the u201cserotonin syndromeu201d may occur in severe poisoning. This includes alteration of mental status, neuromuscular hyperactivity and autonomic instability. There may be hyperpyrexia and elevation of serum creatine kinase.

Treatment There is no known specific antidote to citalopram, as in CILIFT 20 mg TABLET. Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac, ECG and vital signs until stable. ECG monitoring is advisable in all cases of overdose especially in patients with congestive heart failure/bradydysrhythmias, in patients using concomitant medicines that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment. An ECG should be taken. Consider oral activated charcoal in adults and children who have ingested more than 5 mg/kg body weight within 1 hour. Activated charcoal given half an hour (u00bd) hour after ingestion of citalopram, as in CILIFT 20 mg TABLET, has been shown to reduce absorption by 50 %. Osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered. If consciousness is impaired the patient should be intubated. Control convulsions with intravenous diazepam if they are frequent or prolonged. Medical surveillance for about 24 hours is advisable.