Escitalopram Actavis - (IR): composition and pharmaceutical form
The medicine comes as film-coated tablets. One tablet contains 5 mg, 10 mg, 15 mg or 20 mg of escitalopram as the oxalate.
The different strengths are there for gradual adjustment: treatment often starts at 5 mg. The whole daily dose is taken at once, with food or independently of it.
How Escitalopram Actavis - (IR) works
Escitalopram is a selective inhibitor of serotonin (5-HT) reuptake with high affinity for the primary binding site of the serotonin transporter. It also binds to the allosteric site of the same transporter, but its affinity for that site is 1000 times lower.
For other receptors — 5-HT1A, 5-HT2, dopamine D1 and D2, adrenergic α1, α2 and β, histamine H1, muscarinic cholinergic, benzodiazepine and opioid — escitalopram has practically no affinity. That is why inhibition of serotonin reuptake is regarded as the only likely mechanism explaining its pharmacological and clinical action.
Indications
The medicine is prescribed for major depressive episodes, panic disorder with or without agoraphobia, social anxiety (social phobia), generalised anxiety disorder and obsessive-compulsive disorder.
Social phobia is a clearly defined diagnosis, not excessive shyness. Drug treatment is justified only when the disorder substantially interferes with work and with relating to others, and it is part of a comprehensive approach alongside psychotherapy.
Method of use and dosage
The medicine is taken once a day. The safety of daily doses above 20 mg has not been proven, so this limit is not exceeded. The dose is chosen individually according to the response, and the time to effect differs by diagnosis.
| Indication | Starting dose | Usual and maximum dose | Timing |
|---|---|---|---|
| Major depressive episode | 10 mg a day | 10 mg, if needed up to 20 mg | Effect usually in 2–4 weeks; after symptoms disappear treatment continues for at least 6 months |
| Panic disorder | 5 mg in the first week | then 10 mg, if needed up to 20 mg | Maximum effect at about 3 months, treatment lasts several months |
| Social phobia | 10 mg a day | from 5 to 20 mg by response | Improvement in 2–4 weeks, a course of at least 12 weeks |
| Generalised anxiety disorder | 10 mg a day | if needed up to 20 mg | Long-term therapy has been studied over at least 6 months |
| Obsessive-compulsive disorder | 10 mg a day | if needed up to 20 mg | Treatment is long-term, benefit and dose are reviewed regularly |
Special patient groups
People over 65 start at 5 mg a day and if needed the dose is raised to 10 mg; in social phobia efficacy in the elderly has not been studied. The medicine is not prescribed to children and adolescents under 18. With mild or moderate impairment of renal function no dose adjustment is needed; with severe impairment (creatinine clearance below 30 ml/min) caution is required. With mild or moderate hepatic impairment 5 mg a day is given for the first two weeks, after which an increase to 10 mg is possible; in severe impairment the dose is chosen with particular care. The same cautious scheme is used in people who are slow metabolisers via the CYP2C19 isoenzyme.
Contraindications
Escitalopram is not prescribed in the following cases:
- hypersensitivity to escitalopram or to any excipient;
- concomitant use of non-selective irreversible MAO inhibitors, because of the risk of serotonin syndrome with agitation, tremor and hyperthermia;
- concomitant use of the reversible MAO-A inhibitor moclobemide or of the reversible non-selective MAO inhibitor linezolid;
- diagnosed prolongation of the QT interval or congenital long QT syndrome;
- concomitant use of other medicines that prolong the QT interval: class IA and III antiarrhythmics, antipsychotics (phenothiazines, pimozide, haloperidol), tricyclic antidepressants, a number of antibacterials (sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials, especially halofantrine), some antihistamines (astemizole, mizolastine);
- age under 18: in children and adolescents on antidepressants, suicidal behaviour and hostility were seen more often.
Special warnings and precautions
Depression itself carries an increased risk of suicidal thoughts, self-harm and suicide, and that risk persists until noticeable clinical improvement. Since improvement may take several weeks, the patient needs close monitoring at the start of treatment; experience shows the risk may also rise in the period when symptoms begin to recede. A meta-analysis of placebo-controlled trials in adults showed an increased risk of suicidal behaviour in patients under 25. Monitoring is especially attentive at the start of therapy and at every dose change, and the patient and those close to them are warned: if symptoms worsen, suicidal thoughts appear or behaviour changes unusually, a doctor must be contacted immediately.
- at the start of treatment for panic disorder anxiety may paradoxically increase; this usually passes within two weeks, and a low starting dose reduces the likelihood of such a reaction;
- at the first seizures in a patient's life or an increase in attacks in a patient with epilepsy the medicine is withdrawn; in uncontrolled epilepsy SSRIs are not used;
- with mania or hypomania in the history caution is needed, and if a manic phase develops the medicine is withdrawn;
- in diabetes mellitus glycaemic control may shift in either direction, and doses of insulin or of glucose-lowering medicines sometimes need revising;
- hyponatraemia develops rarely, probably linked to the syndrome of inappropriate antidiuretic hormone secretion; at risk are the elderly, patients with liver cirrhosis and those taking other medicines that lower sodium;
- skin haemorrhages have been described — petechiae and purpura; caution is needed with anticoagulants, medicines affecting platelets, non-steroidal anti-inflammatory drugs and in haemorrhagic diathesis;
- akathisia is possible — a distressing inner restlessness with a need to move, more often in the first weeks; the dose must not be raised in that case;
- escitalopram prolongs the QT interval in a dose-dependent way: hypokalaemia and hypomagnesaemia are corrected before treatment starts, in stable heart disease an ECG is worth recording beforehand, and if an arrhythmia appears during treatment it is interrupted.
How to finish treatment
Abrupt withdrawal is unacceptable. Withdrawal symptoms are common: in studies they affected about 25% of those taking escitalopram against 15% on placebo. Most often these are dizziness, sensory disturbances including paraesthesia and a sensation of electric shock, insomnia and vivid dreams, anxiety and agitation, nausea, tremor, confusion, sweating, headache, diarrhoea, palpitations, irritability and visual disturbances. They are usually mild or moderate, appear in the first days after stopping and pass within two weeks, though sometimes they drag on for two or three months. That is why the dose is lowered gradually — over a minimum of one or two weeks and, if needed, several weeks or months; if the reduction is tolerated badly, the doctor returns to the previous dose and lowers it more slowly. Escitalopram can dilate the pupil, so in closed-angle glaucoma, including past episodes, it is used with caution.
Drug interactions
Escitalopram may be started 14 days after an irreversible MAO inhibitor is withdrawn and no earlier than a day after moclobemide is stopped; between withdrawal of escitalopram and the start of a non-selective MAO inhibitor at least 7 days are left. The risk of serotonin syndrome is raised by tramadol, sumatriptan and other triptans, tryptophan, lithium and St John's wort products. The seizure threshold is lowered by tricyclic antidepressants, other SSRIs, neuroleptics, mefloquine, bupropion and tramadol again. With oral anticoagulants, clotting parameters are checked at the start and on withdrawal of escitalopram, and non-steroidal anti-inflammatory drugs additionally raise the risk of bleeding. Alcohol is not recommended during treatment.
Escitalopram is metabolised mainly by the CYP2C19 isoenzyme and to a lesser extent by CYP3A4 and CYP2D6. Omeprazole at 30 mg a day raises its plasma concentration by about 50% and cimetidine at 400 mg twice a day by about 70%, so it is combined cautiously with CYP2C19 inhibitors (omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine, sometimes at a reduced dose. Escitalopram itself inhibits CYP2D6: the concentrations of desipramine and metoprolol doubled with concomitant use, hence the caution with flecainide, propafenone, metoprolol, tricyclic antidepressants, risperidone, thioridazine and haloperidol. Agents causing hypokalaemia or hypomagnesaemia raise the risk of dangerous arrhythmias.
Pregnancy and breastfeeding
Clinical data on the use of escitalopram in pregnancy are scarce. In reproductive toxicity studies in rats a toxic effect on the embryo and foetus was seen, but the frequency of congenital malformations did not rise. In pregnancy the medicine is used only where there is unconditional need and after careful assessment of the risk-benefit balance; an SSRI should not be withdrawn abruptly during pregnancy.
If the mother takes escitalopram late in pregnancy, especially in the third trimester, the newborn needs monitoring: breathing disorders, cyanosis, apnoea, convulsions, fluctuations in body temperature, feeding difficulties, vomiting, hypoglycaemia, raised or lowered muscle tone, hyperreflexia, tremor, irritability, lethargy, constant crying and sleep disturbances have been described. These symptoms usually appear immediately or within the first day after delivery. Epidemiological data point to a possible increase in the risk of persistent pulmonary hypertension of the newborn — about 5 cases per 1000 pregnancies against 1–2 per 1000 in the general population. Escitalopram is assumed to pass into breast milk, so it is not recommended for breastfeeding women.
Adverse effects
Adverse reactions occur more often in the first or second week of use and, as treatment continues, usually become weaker and less frequent.
- very common — headache and nausea;
- common — insomnia, drowsiness, dizziness, paraesthesia, tremor, restlessness, nervousness, unusual dreams;
- common — reduced libido in men and women, anorgasmia in women, ejaculation disorders and impotence in men;
- common — diarrhoea, constipation, vomiting, dry mouth, decreased or increased appetite, weight gain;
- common — increased sweating, fatigue, raised temperature, sinusitis, yawning;
- uncommon — bruxism, agitation, panic attack, confusion, fainting, taste and sleep disturbances, pupil dilation and visual disturbances, tinnitus, tachycardia, nosebleeds, bleeding from the gastrointestinal tract, urticaria, rash, hair loss, oedema;
- rare — anaphylactic reaction, aggression, depersonalisation, hallucinations, bradycardia, serotonin syndrome;
- frequency not known — hyponatraemia and impaired secretion of antidiuretic hormone, mania, suicidal thoughts and behaviour, seizures, akathisia, prolongation of the QT interval and ventricular arrhythmias of the torsade de pointes type, hepatitis, angioedema, urinary retention, galactorrhoea.
Ventricular arrhythmias, including torsade de pointes, were recorded mainly in women, with hypokalaemia, with an already prolonged QT interval or with other heart diseases. Epidemiological studies, conducted mostly in patients aged 50 and over, show an increased risk of bone fractures with SSRIs and tricyclic antidepressants; the mechanism has not been established.
Overdose
Data on escitalopram overdose are limited, and in many described cases other medicines had been taken at the same time. More often the symptoms were mild or absent; taking 400–800 mg of escitalopram alone caused no severe manifestations, and fatal outcomes from an isolated overdose were recorded rarely. Dizziness, tremor and agitation are possible, less often serotonin syndrome, seizures and coma, nausea and vomiting, a fall in blood pressure, tachycardia, prolongation of the QT interval and arrhythmias, as well as electrolyte disturbances — hypokalaemia and hyponatraemia.
There is no specific antidote. Help comes down to maintaining a patent airway and sufficient oxygenation, gastric lavage as soon as possible after intake, possible use of activated charcoal and symptomatic supportive therapy with monitoring of cardiac activity. ECG monitoring is especially important in congestive heart failure, bradyarrhythmias, concomitant use of QT-prolonging medicines and in impaired liver function.
How to get a prescription for Escitalopram Actavis - (IR) online
Escitalopram is a prescription-only medicine, and prescribing it requires medical assessment: of the diagnosis, of concomitant heart disease, of the medicines being taken and of the risk of interactions.
During the online consultation the doctor will discuss your symptoms with you, choose the dose and the scheme for raising it gradually and, if there are no contraindications, issue an electronic prescription — the medicine can be collected at a pharmacy with its code.
