Escitalpro 5 mg, 10 mg, 15 mg & 20 mg film-coated tablets

6.5 Nature and contents of container

Opaque PVC/PVdC/Aluminium blisters with an outer carton; 10, 14, 20, 28, 30, 49, 50, 56, 60, 90, 100, 180, 200, tablets
Opaque PVC/PVdC/Aluminium perforated unit dose blisters with an outer carton; 28 x 1, 56 x 1 tablets Polypropylene tablet container: 28, 49, 100, 200, 250, 500 tablets
Not all pack sizes may be marketed.

10. DATE OF REVISION OF THE TEXT

December 2016September 2017

6.5 Nature and contents of container

Opaque PVC/PVdC/Aluminium blisters with an outer carton; 10, 14, 20, 28, 30, 49, 50, 56, 60, 90, 100, 180, 200, tablets
Opaque PVC/PVdC/Aluminium perforated unit dose blisters with an outer carton: ; 28 x 1 tablets (not 5 mg tablets).
Polypropylene tablet container: 28, 49, 100, 200, 250, 500 tablets
Not all pack sizes may be marketed.

10. DATE OF REVISION OF THE TEXT

May 2016December 2016

3. PHARMACEUTICAL FORM

Film-coated tablet.
Escitalpro 5 mg film-coated tablets: round, white, film-coated tablet marked with "EC 5" on one side and “G” on the other. The tablets are circular with a diameter of 5.5 mm.                                                                                                                 
Escitalpro 10 mg film-coated tablets: oblong, white, scored, film-coated tablet marked with "EC|10" on one side and “G” on the other. The tablets are oblong with dimensions of 9.5 mm x 5.5 mm. The tablet can be divided into equal doses.

Escitalpro 15 mg film-coated tablets: oblong, white, scored, film-coated tablet marked with "EC|15" on one side and “G” on the other. The tablets are oblong with dimensions of 10.5 mm x 6.0 mm. The tablet can be divided into equal doses.

Escitalpro 20mg film-coated tablets: oblong, white, scored, film-coated tablet marked with "EC|20" on one side and “G” on the other. The tablets are oblong with dimensions of 12.5 mm x 7 mm. The tablet can be divided into equal doses.

4.2 Posology and method of administration

Obsessive-Compulsive disorderDisorder
Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg daily.
As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free. Treatment benefits and dose should be re-evaluated at regular intervals (see section 5.1).

Paediatric population
Escitalpro should not be used in the treatment of Children children and Adolescents adolescents under 18 years of age (see Section section 4.4).

4.3 Contraindications

Hypersensitivity to escitalopram the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Diabetes
In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglaycaemia hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Discontinuation symptoms seen when stopping treatment
Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials adverse events seen on treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and 15% of patients taking placebo.

The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), 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 symptoms are mild to moderate; however, in some patients they may be severe in intensity.

4.6 Fertility, pregnancy and lactation

Pregnancy
For escitalopram only limited clinical data are available regarding exposed pregnancies.

Animal studies have shown reproductive toxicity (see section 5.3). In reproductive toxicity studies performed in rats with escitalopram, embryo-fetotoxic effects, but no increased incidence of malformations, were observed (see section 5.3). The risk for humans is unknown. Therefore, Escitalpro tablets should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit.

4.8 Undesirable effect

	Very common	Common	Uncommon	Rare	Very rare	Not known
Blood and lymphatic system disorders						Thrombocytopenia
Immune system disorders				Anaphylactic reaction
Endocrine disorders						Inappropriate ADH secretion
Metabolism and nutrition disorders		Decreased appetite, increased appetite Weight increased	Weight decreased			Hyponatraemia, anorexia2 anorexia1
Psychiatric disorders		Anxiety, restlessness, abnormal dreams Female and male: libido decreased female: anorgasmia	Bruxism, agitation, nervousness, panic attack, confusional state	Aggression, depersonalisation hallucination		Mania, suicidal ideation, suicidal behaviour2behaviour1
Nervous system disorders	Headache	Insomnia, somnolence, dizziness, paraesthesia, tremor	Taste disturbance, sleep disorder, syncope	Serotonin syndrome		Dyskinesia, movement disorder, convulsion, psychomotor restlessness/akathisia1akathisia2
Eye disorders			Mydriasis, visual disturbance
Ear and labyrinth disorders			Tinnitus
Cardiac disorders			Tachycardia	Bradycardia		Electrocardiogram QT prolonged, ventricular arrhythmia including torsade de pointes
Vascular disorders						Orthostatic hypotension
Respiratory, thoracic and mediastinal disorders		Sinusitis, yawning	Epistaxis
Gastro-instestinal disorders	Nausea	Diarrhoea, constipation, vomiting, dry mouth	Gastrointestinal haemorrhages (including rectal haemorrhage)
Hepatobiliary disorders						Hepatitis, Liver function test abnormal
Skin and subcutaneous tissue disorders		Sweating increased	Urticaria, alopecia, rash, pruritus			Ecchymosis, angioedemas
Musculo-skeletal and connective tissue disorders		Arthralgia, myalgia
Renal and urinary disorders						Urinary retention
Reproductive system and breast disorders		Male: ejaculation disorder, impotence	Female: metrorrhagia, menorrhagia			Galactorrhoea Male: priapism,
General disorders and administration site conditions		Fatigue, pyrexia	Oedema

¹ These events have been reported for the therapeutic class of SSRIs.
^{1 2} Cases of suicidal ideation and suicidal behaviours have been reported during escitalopram therapy or early after treatment discontinuation (see section 4.4)
² These events have been reported for the therapeutic class of SSRIs.

QT interval prolongation
Cases of QT interval 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 interval prolongation or other cardiac diseases (see sections 4.3, 4.4, 4.5, 4.9 and 5.1).

Class effects
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.

Discontinuation symptoms seen when stopping treatment
Discontinuation of SSRIs/SNRIs (particularly when abrupt) commonly leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), 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 escitalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

QT interval prolongation
Cases of QT interval 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 interval prolongation or other cardiac diseases (see sections 4.3, 4.4, 4.5, 4.9 and 5.1).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance

5.1  Pharmacodynamic properties

Generalised Anxiety anxiety Disorderdisorder
Escitalopram in doses of 10 and 20 mg/day was effective in four out of four placebo-controlled studies.

5.2 Pharmacokinetic properties

Linearity
There is linear pharmacokinetics. Steady-state plasma levels are achieved in about 1 week. Average steady-state concentrations of 50 nmol/L (range 20 to 125 nmol/L) are achieved at a daily dose of 10 mg.

5.3 Preclinical safety data

No complete conventional battery of preclinical studies was performed with escitalopram since the bridging toxicokinetic and toxicological studies conducted in rats with escitalopram and citalopram showed a similar profile. Therefore, all the citalopram information are expected can to be extrapolated to escitalopram.

In comparative toxicological studies in rats, escitalopram and citalopram caused cardiac toxicity, including congestive heart failure, after treatment for some weeks, when using dosages that caused general toxicity. The cardiotoxicity seemed to correlate with peak plasma concentrations rather than to systemic exposures (AUC). Peak plasma concentrations at no-effect-level were in excess (8-fold) of those achieved in clinical use, while AUC for escitalopram was only 3- to 4-fold higher than the exposure achieved in clinical use. For citalopram AUC values for the S-enantiomer were 6- to 7-fold higher than exposure achieved in clinical use. The findings are probably related to an exaggerated influence on biogenic amines i.e. secondary to the primary pharmacological effects, resulting in hemodynamic effects (reduction in coronary flow) and ischemia. However, the exact mechanism of cardiotoxicity in rats is not clear. Clinical experience with citalopram, and escitalopram, together with the clinical trial experience with escitalopram, do not indicate that these findings have a clinical correlate.

 

In section 6.5, clear to opaque blisters:

ClearOpaque PVC/PVdC/Aluminium blisters with an outer carton; 10, 14, 20, 28, 30, 49, 50, 56, 60, 90, 100, 180, 200, tablets.

ClearOpaque PVC/PVdC/Aluminium perforated unit dose blisters with an outer carton: 28 x 1 tablets (not 5 mg tablets).

Sections 4.1, 4.2 and 5.1 updated to include information relating to the indication "Treatment of generalized anxiety disorder".

None provided