Escitalopram Unicorn 5 mg/10 mg/15 mg/20 mg Film-Coated Tablets

ESCITALOPRAM UNICORN is indicated for the treatment of

• Major depressive episodes.
• Panic disorder with or without agoraphobia.

Posology

Major depressive episodes

A single oral dose of 10 mg per day in otherwise healthy adults. Dosage may be increased to a maximum of 20 mg per day, depending on the patientu2019s response. A treatment period of 2 to 4 weeks is usually required for an antidepressant effect.

Panic disorder with or without agoraphobia

A single oral dose of 5 mg per day for the first week, before increasing it to a 10 mg daily dose. The dose may be further increased thereafter as required to a maximum of 20 mg per day depending on the patientu2019s response. The onset of action is seen within 2 to 4 weeks. Treatment should be continued for an appropriate length of time (up to six months) after recovery in order to prevent relapse. ESCITALOPRAM UNICORN should be gradually withdrawn during a couple of weeks when stopping therapy (see sections 4.4, 4.8).

Special populations

Elderly: In view of a decreased metabolism, clearance and longer half-life, the initial and maximum dose should be lower than the adult recommended dose.

Reduced hepatic function: Dose should be halved to the lower end of the dosage range.

Reduced renal function: Dose adjustment is not necessary in cases of mild or moderate renal impairment. No information is available on the treatment of patients with severely reduced renal function (creatinine clearance < 30 ml/min).

Paediatric population: Safety and efficacy in children under 18 years of age have not been established. In clinical trials in major depressive disorder, there were increased reports of hostility and suicide-related adverse events, such as suicidal ideation and self-harm (see sections 4.4, 4.8).

Method of administration

ESCITALOPRAM UNICORN may be taken with or without food in the morning or evening.

• Hypersensitivity to escitalopram or any of the ingredients in the formulation (see sections 2, 6.1).
• Patients with known QT interval prolongation or congenital long QT syndrome.
• Concurrent use with medicines such as pimozide that are known to prolong the QT interval (see section 4.5).
• Concurrent use with a monoamine oxidase inhibitor (MAOI). At least 14 days should elapse between discontinuing the MAOI and initiating therapy with ESCITALOPRAM UNICORN. MAOIs should not be introduced for 7 days after discontinuation of ESCITALOPRAM UNICORN (see section 4.5).
• Safety and efficacy in pregnancy and lactation have not been established.
• Children under the age of 18 years (see sections 4.4, 4.8).

ESCITALOPRAM UNICORN should be used with caution in:

• Elderly patients u2013 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 ESCITALOPRAM UNICORN is reduced. Cautious dosage titration and a lower maximum dose are recommended.
• Seizures or history thereof u2013 There is an increased risk of seizures. ESCITALOPRAM UNICORN should be used with caution in patients with controlled epilepsy and avoided in patients who are poorly controlled epileptics. ESCITALOPRAM UNICORN should be discontinued in any patient who develops seizures.
• Electroconvulsive therapy u2013 Caution is advised in patients receiving electroconvulsive therapy as there is limited clinical experience of concurrent administration of ESCITALOPRAM UNICORN and electroconvulsive therapy.
• Mania or history of mania u2013 Condition may be re-activated. ESCITALOPRAM UNICORN should be used with caution in patients with a history of mania/hypomania. ESCITALOPRAM UNICORN should be discontinued if the patient enters the manic phase.
• Coronary heart disease u2013 ESCITALOPRAM UNICORN may cause a reduction in heart rate. Caution is advised in patients with pre-existing slow heart rates or in patients with acute myocardial infarction or uncompensated heart failure.
• Diabetes mellitus u2013 Hypoglycaemia has been reported. Insulin and/or hypoglycaemic dosage may need to be adjusted.
• Suicide/suicidal thoughts or clinical worsening u2013 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. A causal role, however, for antidepressant medicines in inducing such behaviour has not been established. Patients being treated with ESCITALOPRAM UNICORN 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 disorder 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 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 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 ESCITALOPRAM UNICORN, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patientu2019s presenting symptoms.
• Haemorrhage u2013 There have been reports of cutaneous bleeding time increases and/or bleeding abnormalities, such as ecchymoses, gynaecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucous bleeding with ESCITALOPRAM UNICORN. SSRIs/SNRIu2019s may increase the risk of postpartum haemorrhage, and this risk could potentially apply also to ESCITALOPRAM UNICORN (see sections 4.6, 4.8).
• Discontinuation symptoms seen when stopping ESCITALOPRAM UNICORN treatment u2013 If the decision is made to discontinue treatment, ESCITALOPRAM UNICORN should be tapered (see section 4.2) in order to prevent the possibility of a withdrawal syndrome.
• Paediatric population u2013 Safety and efficacy in children under 18 years of age have not been established. In clinical trials in major depressive disorder, there were increased reports of hostility and suicide-related adverse events, such as suicidal ideation and self-harm (see sections 4.3, 4.8).
• Paradoxical anxiety u2013 Some patients with panic disorder may experience increased anxiety symptoms at the beginning of treatment with ESCITALOPRAM UNICORN. This paradoxical reaction usually subsides within two weeks during continued treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect (see section 4.2).
• Akathisia/psychomotor restlessness u2013 The use of ESCITALOPRAM UNICORN 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 can be detrimental.
• Hyponatraemia u2013 Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion, has been reported with the use of selective serotonin re-uptake inhibitors (SSRIs) and generally resolves on discontinuation of therapy. Caution should be exercised in patients at risk, such as the elderly, or patients with cirrhosis, or if used in combination with other medications which may cause hyponatraemia.
• Serotonin syndrome u2013 Caution is advisable if ESCITALOPRAM UNICORN is used concomitantly with medicines with serotonergic effects, such as sumatriptan or other triptans, tramadol or tryptophan. Serotonin syndrome has been reported in patients using SSRIs concomitantly with serotonergic medicines and is more likely to occur after an increase in dose. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. If this occurs, treatment with the SSRI and the serotonergic medicine should be discontinued immediately and symptomatic treatment initiated.
• QT interval prolongation u2013 ESCITALOPRAM UNICORN may cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular dysrhythmia, including torsades de pointes have been reported during the post-marketing period, predominantly in female patients with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see sections 4.3, 4.5, 4.8). 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 ESCITALOPRAM UNICORN 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 ESCITALOPRAM UNICORN, the treatment should be withdrawn and an ECG should be performed.
• St Johnu2019s wort u2013 Concomitant use of SSRIs and herbal remedies containing St Johnu2019s wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.8).
• Angle-closure glaucoma u2013 ESCITALOPRAM UNICORN 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. ESCITALOPRAM UNICORN should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

• Monoamine oxidase inhibitors (MAOI) e.g., linezolid, selegiline, moclobemide u2013 Concurrent use is contra-indicated. Serious and potentially fatal reactions resembling serotonin syndrome have occurred, such as 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).
• Imipramine u2013 An increase in the concentration of desimipramine (the active metabolite of imipramine) may occur.
• Other serotonergic medicines or medicines with serotonergic activity e.g., tramadol, sumatriptan and other triptans u2013 Increased risk of developing serotonin syndrome, a rare but potentially fatal hyper serotonergic state.
• Alcohol u2013 The effects of alcohol may be increased and should be avoided.
• Anticoagulants, e.g., warfarin u2013 The anticoagulant activity of warfarin may be increased.
• Cimetidine u2013 The AUC and the maximum plasma concentration of ESCITALOPRAM UNICORN are increased when ESCITALOPRAM UNICORN is administered concurrently with cimetidine.
• QT interval prolongation u2013 Co-administration of ESCITALOPRAM UNICORN with medicines that prolong the QT interval, such as class IA and III antidysrhythmics, antipsychotics (e.g., phenotiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.
• Medicines lowering the seizure threshold u2013 SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicines capable of lowering the seizure threshold (e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquin, bupropion and tramadol).
• Lithium, tryptophan u2013 There have been reports of enhanced effects when SSRIs have been given together with lithium or tryptophan. Concomitant use of SSRIs with these medicines should therefore be undertaken with caution.
• St John's wort u2013 Concomitant use of SSRIs and herbal remedies containing St Johnu2019s wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.4).
• Nonsteroidal anti-inflammatory drugs (NSAIDs) u2013 Concomitant use of NSAIDs may increase bleeding-tendency (see section 4.4).
• Medicines inducing hypokalaemia/hypomagnesaemia u2013 Caution is warranted for concomitant use of hypokalaemia/hypomagnesaemia inducing medicines, as these conditions increase the risk of malignant dysrhythmias (see section 4.4).
• Influence of other medicines on the pharmacokinetics of escitalopram u2013 The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 may also contribute to the metabolism, although to a smaller extent. The metabolism of the major metabolite S-DCT (demethylated escitalopram) seems to be partly catalysed by CYP2D6. Co-administration of ESCITALOPRAM UNICORN with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in a moderate increase in the plasma concentration of escitalopram.
• Effect of ESCITALOPRAM UNICORN on the pharmacokinetics of other medicines u2013 Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when ESCITALOPRAM UNICORN is co-administered with medicines that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g., flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicines that are mainly metabolised by CYP2D6, e.g., antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.
• Co-administration with desipramine or metoprolol resulted in both cases in a twofold increase in the plasma levels of these two CYP2D6 substrates. In vitro studies have demonstrated that escitalopram may also cause weak inhibition of CYP2C19. Caution is recommended with concomitant use of medicines that are metabolised by CYP2C19.

Safety and efficacy in pregnancy and lactation have not been established (see section 4.3). Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth (see sections 4.4, 4.8). ESCITALOPRAM UNICORN is excreted into the breast milk.

ESCITALOPRAM UNICORN may impair performance of skilled tasks. If affected these patients should not operate machinery or drive.

Blood and the lymphatic system disorders: Frequency unknown: Thrombocytopenia

Immune system disorders: Less frequent: Anaphylactic reaction Frequency unknown: Angioedema

Metabolism and nutrition disorders: Frequent: Decreased appetite, increased appetite, increased mass Less frequent: Decreased mass Frequency unknown: Hyponatraemia, anorexia, hypoglycaemia, inappropriate ADH secretion

Psychiatric disorders: Frequent: Anxiety, restlessness, abnormal dreams, decreased libido, anorgasmia (in females) Less frequent: Bruxism, nervousness, panic attack, aggression, depersonalisation, hallucinations, agitation, confusion, mania Frequency unknown: Suicidal ideation, suicidal behaviour, hostility, self-harm

Nervous system disorders: Frequent: Sleep disturbances, insomnia, somnolence, dizziness, fatigue, headache, paraesthesia, tremor Less frequent: Taste disturbance, sleep disorder, syncope, serotonin syndrome, restlessness, impaired concentration, malaise, convulsions, neuroleptic malignant syndrome, dyskinesia movement disorder, psychomotor restlessness/akathisia

Eye disorders: Less frequent: Accommodation (visual) disturbances, mydriasis

Ear and labyrinth disorders: Less frequent: Tinnitus

Cardiac disorders: Less frequent: Tachycardia, palpitations, bradycardia, prolonged electrocardiogram QT interval, ventricular dysrhythmia (including torsades de pointes)

Vascular disorders: Frequency unknown: Orthostatic hypotension

Respiratory, thoracic and mediastinal disorders: Frequent: Sinusitis, yawning Less frequent: Nasal congestion, epistaxis

Gastrointestinal disorders: Frequent: Nausea, constipation, diarrhoea, dry mouth, dyspepsia, vomiting Less frequent: Gastrointestinal haemorrhage (including rectal haemorrhage) Frequency unknown: Salivation

Hepato-biliary disorders: Frequency unknown: Hepatitis, abnormal liver function tests

Skin and subcutaneous tissue disorders: Frequent: Increased sweating Less frequent: Urticaria, alopecia, pruritus, rash Frequency unknown: Ecchymosis

Musculoskeletal, connective tissue and bone disorders: Frequent: Asthenia, arthralgia, myalgia Frequency unknown: Increased risk of bone fractures (class effect of SSRIs, like ESCITALOPRAM UNICORN)

Renal and urinary disorders: Frequency unknown: Micturition disorders, urinary Retention

Reproductive system and breast disorders: Frequent: Sexual dysfunction (including ejaculation disorder), decreased libido, impotence Less frequent: Metrorrhagia, menorrhagia, galactorrhoea, priapism Frequency unknown: Postpartum haemorrhage* *This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections 4.4, 4.6).

General disorders: Frequent: Pyrexia, oedema

Symptoms of overdose: Tiredness, weakness, sedation, dizziness, tremor, nausea, somnolence and sinus tachycardia (see also sections 4.4, 4.8).

Treatment of overdose: Treatment is symptomatic and supportive. There is no specific antidote to ESCITALOPRAM UNICORN. The stomach should be emptied as soon as possible by emesis or gastric lavage. Monitoring of cardiac and vital signs is necessary, and medical surveillance is advisable for about 24 hours, along with general supportive measures.