Interactions : אינטראקציות

4.5     Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

Contra-indicated combinations:
Irreversible, non-selective, MAOIs
Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non- selective irreversible monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued SSRI treatment and have been started on such MAOI treatment (see section 4.3). In some cases, the patient developed serotonin syndrome (see section 4.8).

Escitalopram is contra-indicated in combination with non-selective irreversible MAOIs. Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI. At least 7 days should elapse after discontinuing escitalopram treatment, before starting a non-selective irreversible MAOI.

Reversible, selective MAO-A inhibitor (Moclobemide)
Due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-A inhibitor such as moclobemide is contraindicated (see section 4.3). If the combination proves necessary, it should be started at the minimum recommended dosage and clinical monitoring should be reinforced.


Reversible, non-selective MAO-A inhibitor (Linezolid)
The antibiotic linezolid is a reversible non-selective MAO-inhibitor and should not be given to patients treated with escitalopram. If the combination proves necessary, it should be given with minimum dosages and under close clinical monitoring (see section 4.3).

Irreversible, selective MAO-B inhibitor (Selegiline)
In combination with selegiline (irreversible MAO B inhibitor), caution is required due to the risk of developing serotonin syndrome. Selegiline doses up to 10 mg/day have been safely co-administered with racemic citalopram.

QT interval prolongation
Pharmacokinetic and pharmacodynamic studies of escitalopram combined with other medicinal products that prolong the QT interval have not been performed. An additive effect of escitalopram ad these medicinal products cannot be excluded. Therefore, co-administration of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics., antipsychotics (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 (e.g.
astemizole, hydroxyzine, mizolastine), is contraindicated.


Combinations requiring precautions for use:
Serotonergic medicinal products
Co-administration with serotonergic medicinal products e.g. opioids (including tramadol), and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

Medicinal products lowering the seizure threshold
SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g. antidepressants (tricyclics, SSRIs) neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol).

Lithium, tryptophan
There have been reports of enhanced effects when SSRIs have been given together with lithium or tryptophan, therefore concomitant use of SSRIs with these medicinal products should be undertaken with caution.


St. John’s Wort
Concomitant use of SSRIs and herbal remedies containing St. John´s Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.4).

Haemorrhage
Altered anti-coagulant effects may occur when escitalopram is combined with oral anticoagulants. Patients receiving oral anticoagulant therapy should receive careful coagulation monitoring when escitalopram is started or stopped (see section 4.4).
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase bleeding-tendency (see section 4.4).

Alcohol
No pharmacodynamic or pharmacokinetic interactions are expected between escitalopram and alcohol.
However, as with other psychotropic medicinal products, the combination with alcohol is not advisable.

Medicinal products inducing hypokalaemia/hypomagnesaemia
Caution is warranted for concomitant use of hypokalaemia/hypomagnesaemia inducing medicinal products as these conditions increase the risk of malignant arrhythmias (see section 4.4).

Pharmacokinetic interactions

Influence of other medicinal products on the pharmacokinetics of escitalopram 
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 with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram.

Co-administration of escitalopram with cimetidine 400mg twice daily(moderately potent general enzyme- inhibitor) resulted in moderate (approximately 70%) increase in the plasma concentrations of escitalopram.
Caution is advised when administering escitalopram in combination with cimetidine. Dose adjustment may be warranted.

Thus, caution should thus be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine.
A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment (see section 4.4).

Effect of escitalopram on the pharmacokinetics of other medicinal products 
Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when escitalopram is co- administered with medicinal products 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 medicinal products 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 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 medicinal products that are metabolised by CYP2C19.