Ciloram 20 Mg Film-Coated Tablets

CILORAM is indicated for the treatment of:

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

Posology

Depression
20 mg a day as a single dose. Dosage may be increased by 20 mg a day at intervals of at least one week to a maximum of 40 mg depending on the patient's response. Duration of treatment - The antidepressant effect usually sets in after 2 to 4 weeks. Treatment with CILORAM 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.

Panic Disorder
10 mg a day as a single dose for the first week then increasing to 20 mg a day. The dose may be increased thereafter as required to a maximum of 40 mg a day depending on the patient's response.

Obsessive-Compulsive Disorder
20 mg a day as a single dose. This dose can be increased by 20 mg increments to a maximum of 40 mg a day depending on the patient's response. Duration of treatment - The onset of action in treating OCD is 2 u2013 4 weeks with further improvement over time.

Special populations

Elderly
10 mg - 20 mg a day as a single dose. Depending on the patient's response, the dose can be increased to a maximum of 20 mg a day.

Reduced hepatic function
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
Dose adjustment is not necessary in cases of mild or moderate renal impairment. CILORAM is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min) (see sections 4.3 and 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
Abrupt discontinuation should be avoided. When stopping treatment with CILORAM the dose should be gradually reduced over a period of at least one or two weeks in order to reduce the risk of withdrawal symptoms (See sections 4.4 and 4.8). 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 medical practitioner may continue decreasing the dose, but at a more gradual rate.

Paediatric population
CILORAM should not be used in the treatment of children and adolescents under the age of 18 years (See sections 4.3 and 4.4).

Method of administration
CILORAM may be taken with or without food in the morning or evening. CILORAM is administered as a single daily dose.

• Hypersensitivity to citalopram or any of the excipients (see section 6.1).
• Concurrent use with monoamine oxidase inhibitors (MAOIs). Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI 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. CILORAM must not be used in combination with a MAOI, including selegiline in doses above 10 mg daily. At least 14 days should elapse between discontinuing the MAOI and initiating therapy with CILORAM, and minimum one day after discontinuation of moclobemide. MAOIs should not be introduced for 7 days after discontinuation of CILORAM (see section 4.5).
• Severe renal impairment (creatinine clearance less than 30 ml/min).
• Safety and efficacy in pregnancy and lactation has not been established.
• Children and adolescents under the age of 18 years (see section 4.4).
• Concomitant use with pimozide (see section 4.5).
• CILORAM is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome (see sections 4.4, 4.8).
• Concomitant use with linezolid (see section 4.5).

Elderly patients
Longer half-life and decreased clearance due to a reduced rate of metabolism. A lower dose is recommended in the elderly.

Hepatic impairment u2013 Clearance of CILORAM is reduced. Cautious dosage titration and a lower maximum dose are recommended (see section 4.2).

Renal impairment u2013 Elimination is decreased. If creatinine clearance is less than 30 ml/min CILORAM should not be used (see section 4.2 and 4.3).

Seizures
Seizures are a potential risk with antidepressant medicines. CILORAM should be used with caution in patients with controlled epilepsy and avoided in patients who are poorly controlled epileptics. CILORAM should be discontinued in any patient who develops seizures or if there is an increase in seizure frequency.

ECT (electroconvulsive therapy)
There is limited clinical experience of concurrent administration of CILORAM and ECT therefore care is advised in patients receiving electroconvulsive therapy.

Mania or history of mania
Condition may be re-activated. In patients with manic-depressive illness a change towards the manic phase may occur. CILORAM should be discontinued if the patient enters the manic phase.

Diabetes mellitus
Rare occurrences of hypoglycaemia have been reported. In patients with diabetes, treatment with an SSRI including CILORAM may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

CILORAM should not be used with monoamine oxidase inhibitors; imipramine; moclobemide; alcohol; warfarin; and cimetidine (see section 4.5).

Serotonin syndrome
Serotonin syndrome has been reported in patients using SSRIs. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. Treatment with CILORAM should be discontinued immediately and symptomatic treatment initiated.

Serotonergic medicines
CILORAM should not be used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan, and tryptophan (see section 4.5).

Suicide/suicidal thoughts or clinical worsening
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. This risk may persist until significant remission occurs. Patients should be monitored during early therapy until improvement in depression is observed because suicide is an inherent risk in depressed patients. A causal role, however, for antidepressant medicines in inducing such behaviour has not been established. Patients being treated with CILORAM 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.

Because of the possibility of co-morbidity between major depressive disorders and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder 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 for major depressive disorders 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 such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing CILORAM in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

If the decision is made to discontinue treatment, CILORAM should be tapered. It is recommended that the dose is decreased gradually in order to prevent the possibility of a withdrawal syndrome (see section 4.2 and 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 in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants such as citalopram compared to placebo in patients less than 25 years old.

Paradoxical anxiety
Some patients with panic disorder may experience intensified anxiety symptoms at the start of treatment with antidepressants. This paradoxical reaction usually subsides within the first two weeks of starting treatment. A low starting dose of CILORAM 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 and generally reverses on discontinuation of therapy. Elderly female patients seem to be at higher risk.

Akathisia/psychomotor restlessness
The use of SSRIs/SNRIs 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 of CILORAM may be detrimental.

Use in children and adolescents under 18 years of age
CILORAM should not be used in the treatment of children and adolescents under the age of 18 years. In clinical trials in Major Depressive Disorder, there were increased reports of hostility (predominantly aggression, oppositional behaviour and anger) and suicide-related adverse events such as suicidal ideation and self-harm (see section 4.3). In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

QT - Prolongation and torsades de pointes
CILORAM causes dose-dependent QT prolongation and should not be used in patients with congenital long QT syndrome. Cases of 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 sections 4.3, 4.5, 4.8, 4.9). 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 CILORAM is started. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started. If signs of cardiac dysrhythmia occur during treatment with CILORAM, the treatment should be withdrawn, and an ECG should be performed.

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

Withdrawal symptoms
After prolonged administration, abrupt cessation of CILORAM may produce withdrawal symptoms such as 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. It is recommended that withdrawal of treatment should proceed by gradually tapering off the dosage over a period of several weeks or months, according to the patientu2019s needs to avoid occurrence of discontinuation symptoms.

Angle - Closure Glaucoma
SSRIs including citalopram 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. CILORAM should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

St. Johnu00b4s Wort
Undesirable effects may be more common during concomitant use of CILORAM and herbal preparations containing St Johnu2019s wort (Hypericum perforatum). Therefore, CILORAM and St Johnu2019s wort preparations should not be taken concomitantly (see section 4.5).

Psychosis
Treatment of psychotic patients with depressive episodes may increase psychotic symptoms.

Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRI.

CILORAM contains lactose and should not be given to patients with rare hereditary problems or a history of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Pharmacodynamic interactions

At the pharmacodynamic level, cases of serotonin syndrome with CILORAM and moclobemide and buspirone have been reported.

Contraindicated combinations:

• Monoamine oxidase inhibitors (MAOI) u2013 Concurrent use is contraindicated. Serious and potentially fatal reactions have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the irreversible MAOI selegiline, the reversible MAOIs linezolid and moclobemide and in patients who have recently discontinued SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome. Symptoms of citalopram interaction with a MAOI include hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuation of vital signs and mental status changes including extreme agitation progressing to delirium and coma (see section 4.3).
• Pimozide u2013 concurrent administration of pimozide with CILORAM has been associated with a mean increase in QTc values compared to when pimozide was given alone (see section 4.3).
• Medicines that prolong the QT Interval u2013 Concomitant use is contraindicated (see section 4.3) with medicine such as Class IA and III antidysrhythmics, antipsychotic (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarial treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine).

Combinations requiring precaution for use:

• Selegiline (selective MAO - B inhibitor) - A interaction study with concomitantly administered citalopram (20 mg daily) and selegiline (10 mg daily) (a selective MAO-B inhibitor) demonstrated no clinically relevant interactions. The concomitant use of CILORAM and selegiline (in doses above 10 mg daily) is not recommended. (See section 4.3).
• Desipramine, Imipramine u2013 An increase in the concentration of desipramine (the active metabolite of imipramine) may occur (see section 4.4). A reduction of the desipramine dose may be needed.
• Serotonergic medicinal products
  Lithium and tryptophan: No pharmacodynamic interactions have been found in clinical studies in which CILORAM has been given concomitantly with lithium. However, there have been reports of enhanced effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of CILORAM with these medicinal products should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual.
• Other serotonergic medicines or medicines with serotonergic activity (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects. The simultaneous use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is not recommended. Increased risk of developing the serotonin syndrome, a rare but potentially fatal hyperserotonergic state, may occur when CILORAM is co-administered with other medicines that may affect the serotonergic neurotransmitter systems such as linezolid (see section 4.3).
• St. Johnu2019s Wort u2013 Pharmacodynamic interactions between SSRIs such as CILORAM and herbal remedy St Johnu2019s wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects (see section 4.4). Pharmacokinetic interactions have not been investigated.
• Alcohol u2013 The effects of alcohol may be increased.
• Haemorrhage - Simultaneous treatment with anticoagulants (e.g. warfarin), medicinal products that affect the platelet function, such as non-steroidal anti-inflammatory medicines (NSAIDs), acetylsalicylic acid, dipyridamol, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) 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 CILORAM (see section 4.4).
• Medicinal products lowering the seizure threshold u2013 CILORAM can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g. antidepressants tricyclics, other SSRIs, neuroleptics phenothiazines, thioxanthenes, and butyrophenones, mefloquine, bupropion and tramadol).
• Neuroleptics - Experience with citalopram has not revealed any clinically relevant interactions with neuroleptics. However, the possibility of a pharmacodynamic interaction cannot be excluded.

Pharmacokinetic interactions

Biotransformation of citalopram to demethylcitalopram is mediated by CYP2C19 (approx. 38 %), CYP3A4 (approx. 31 %) and CYP2D6 (approx. 31 %) isozymes of the cytochrome P450 system. Therefore co-administration of CILORAM with other medicinal products may result in pharmacokinetic medicinal product interactions.

Food u2013 The absorption and other pharmacokinetic properties of citalopram have not been reported to be affected by food.

Influence of other medicinal products on the pharmacokinetics of CILORAM
Co-administration with ketoconazole (potent CYP3A4 inhibitor) did not change the pharmacokinetics of citalopram. A pharmacokinetic interaction study of lithium and citalopram did not reveal any pharmacokinetic interactions (see also above). Cimetidine u2013 Cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor) caused a moderate increase in the average steady state levels of citalopram. The AUC and the maximum plasma concentration of CILORAM are increased when CILORAM is administered concurrently with cimetidine. Dose adjustment may be warranted.

Influence of CILORAM on other medicinal products
A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a twofold increase in metoprolol concentrations, but no statistically significant increase in the effect of metoprolol on blood pressure and cardiac rhythm in healthy volunteers. Caution is recommended when metoprolol and CILORAM are co-administered. Dose adjustment may be warranted.

Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6. No change or only very small changes of clinical importance were observed when CILORAM was given with CYP1A2 substrates (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline, risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine epoxide) and triazolam). No pharmacokinetic interaction was observed between CILORAM and levomepromazine, or digoxin, (indicating that CILORAM neither induces nor inhibits P-glycoprotein).

Pregnancy
Safety and efficacy in pregnancy has not been established (see section 4.3). Neonates should be observed if maternal use of CILORAM 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 SSRI/SNRI (such as CILORAM) 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 CILORAM exposure within the month prior to birth (see sections 4.4, 4.8).

Breastfeeding
Safety and efficacy in lactation has not been established. CILORAM is excreted into the breast milk (see section 4.3).

Fertility
No data on fertility is currently available.

CILORAM may impair performance of skilled tasks. The potential for dizziness, impaired concentration, confusion and headache should be taken into account before patients on CILORAM drive or use machinery.

MedDRA System Organ Class Frequency Undesirable Effects

Psychiatric disorders Frequent Female and male: libido decreased, sleep disorder, agitation, anxiety, nervousness, confusional state, abnormal orgasm (female), sleep disturbances including abnormal dreams, apathy Less frequent Aggression, depersonalisation, hallucination, mania, libido increased Frequency unknown Panic attack, bruxism, restlessness, suicidal ideation, suicidal behaviour

1) Immune system disorders Frequency unknown Anaphylaxis, hypersensitivity Endocrine disorders Frequency unknown Inappropriate ADH secretion Nervous system disorders Frequent Sleep disturbances, somnolence. insomnia, tremor, headache, paraesthesia, dizziness, disturbance in attention, migraine, amnesia Less frequent Serotonin syndrome, syncope, convulsion grand mal, dyskinesia, taste disturbance Frequency unknown Neuroleptic malignant syndrome, extrapyramidal disorder, akathisia, movement disorder Eye disorders Less frequent Mydriasis (which may lead to acute narrow angle glaucoma), see section 4.4 Frequency unknown Accommodation disturbances, visual disturbances Ear and labyrinth disorders Frequent Tinnitus Cardiac disorders Frequent Palpitations Less frequent Bradycardia, tachycardia. Frequency unknown QT prolongation, ventricular arrhythmia including torsades de pointes Vascular disorders Less frequent Haemorrhage Frequency unknown Orthostatic hypotension Respiratory, thoracic and mediastinal disorders Frequent Yawning, rhinitis, nasal congestion Less frequent Coughing Frequency unknown Epistaxis Gastrointestinal disorders Frequent Nausea, dry mouth, diarrhoea, constipation, dyspepsia, vomiting, abdominal pain, flatulence, salivary hypersecretion Frequency unknown Gastrointestinal haemorrhage (including rectal haemorrhage) Hepatobiliary disorders Less frequent Hepatitis Frequency unknown Liver function test abnormal Skin and subcutaneous tissue disorders Frequent Sweating increased, pruritis Less frequent Rash, urticaria, alopecia, purpura, photosensitivity reaction Frequency unknown Ecchymosis, angioedema Musculoskeletal, connective tissue and bone disorders Frequent Myalgia, arthralgia Less frequent Asthenia Renal and urinary disorders Less frequent Micturition disorders, urinary retention Reproductive system and breast disorders Frequent Sexual dysfunction including ejaculation disorder, decreased libido, anorgasmia, impotence, ejaculation failure Less frequent Female: Menorrhagia Frequency Female: Metrorrhagia, postpartum haemorrhage 2), unknown Male: Priapism Galactorrhoea General disorders and administration site conditions Frequent Fatigue, asthenia Less frequent Hostility, suicidal ideation and self-harm have been reported in children, oedema, pyrexia, malaise, neuroleptic malignant syndrome Blood and lymphatic disorders Frequency unknown Thrombocytopenia Metabolism and nutrition disorders Frequent Appetite decreased, weight decreased Less frequent Increased appetite, weight increased, hyponatraemia Frequency unknown Hypokalaemia

1) Cases of suicidal ideation and suicidal behaviours have been reported during citalopram therapy or early aftertreatment discontinuation (see section 4.4). 2) This event has been reported for the therapeutic class of SSRIs/SNRIs (see section 4.4 and 4.6). QT interval prolongation - Cases of QT-prolongation and ventricular arrhythmia 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 sections 4.3, 4.4, 4.5, 4.9 and 5.1). 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 and TCAs. The mechanism leading to this risk is unknown. Withdrawal symptoms seen on discontinuation
Discontinuation of CILORAM (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. In some patients they may be severe and/or prolonged. It is therefore advised that when CILORAM treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

Toxicity
Fatal cases of overdose have been reported with citalopram alone; however, the majority of fatal cases have involved overdose with concomitant medication/alcohol.

Symptoms of overdose
Tiredness, weakness, sedation, dizziness, tremor, nausea, somnolence, sinus tachycardia, convulsion, QT interval prolongation, coma, vomiting, hypotension, cardiac arrest, serotonin syndrome, agitation, bradycardia, bundle branch block, QRS prolongation, hypertension, and mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, and atrial- and ventricular dysrhythmia.

Treatment of overdose
Treatment is symptomatic and supportive. There is no specific antidote to CILORAM. The stomach should be emptied as soon as possible by emesis or gastric lavage. Activated charcoal and osmotically working laxative (such as sodium sulphate) should be considered. If the consciousness is impaired the patient should be intubated. Monitoring of cardiac and vital signs is necessary and medical surveillance is advisable for about 24 hours. ECG monitoring should be considered in all cases of overdose especially in congestive heart failure.