Escitalopram Actavis: composition and pharmaceutical form
Escitalopram Actavis comes as film-coated tablets containing 5 mg, 10 mg, 15 mg or 20 mg of escitalopram as the oxalate.
The four strengths are not there for variety: treatment starts at a low dose that is raised step by step, and on withdrawal it is lowered just as gradually. Having 5 mg tablets makes both a gentle start and a smooth exit from the medicine possible.
How Escitalopram Actavis works
Escitalopram is a selective serotonin reuptake inhibitor with high affinity for the primary binding site of the serotonin transporter. To the allosteric site of the same transporter it binds a thousand times more weakly.
The key property of the medicine is its selectivity. Escitalopram binds practically not at all to 5-HT1A and 5-HT2 receptors, dopamine D1 and D2, adrenergic α1, α2 and β, histamine H1, muscarinic cholinergic, benzodiazepine and opioid receptors. It is precisely the inhibition of serotonin reuptake that is considered the only likely mechanism explaining both the pharmacological and the clinical action of the medicine.
Indications
Escitalopram Actavis is prescribed for major depressive episodes, panic disorder with or without agoraphobia, social phobia, generalised anxiety disorder and obsessive-compulsive disorder.
A separate caveat concerns social phobia: it is a strictly defined diagnosis that should not be confused with marked shyness. Drug treatment is indicated here only when the disorder substantially interferes with work and with relating to others, and it remains part of a comprehensive approach rather than its only element.
Method of use and dosage
The medicine is taken once a day, with or without food. The safety of daily doses above 20 mg has not been proven, so this ceiling is not exceeded. The starting dose and the pace of increase are matched to the diagnosis and to tolerance.
| Indication or situation | Dose |
|---|---|
| Major depressive episode | 10 mg a day, if needed up to 20 mg; the effect usually comes in 2–4 weeks and treatment continues for at least 6 months after symptoms disappear |
| Panic disorder | 5 mg in the first week, then 10 mg, if needed up to 20 mg; maximum effect at about 3 months |
| Social phobia | 10 mg a day, then 5–20 mg; for a stable response therapy continues for 12 weeks |
| Generalised anxiety disorder, OCD | 10 mg a day, if needed up to 20 mg |
| Age over 65 | start at 5 mg, if needed up to 10 mg |
| Mild or moderate hepatic impairment, slow CYP2C19 metabolisers | 5 mg for the first 2 weeks, then if needed up to 10 mg |
| Withdrawal of the medicine | the dose is lowered gradually, over at least 1–2 weeks |
The medicine is not prescribed to children and adolescents under 18. With mild or moderate reduction of renal function the dose is unchanged; with severe reduction (creatinine clearance below 30 ml/min) caution is required. Abrupt withdrawal is unacceptable: if distressing symptoms appear as the dose is lowered, the pace of the reduction is slowed.
Contraindications
Some of the prohibitions relate to the risk of serotonin syndrome and some to the effect on heart rhythm.
- hypersensitivity to escitalopram or to any excipient;
- concomitant use of non-selective irreversible MAO inhibitors — the combination threatens serotonin syndrome with agitation, tremor and hyperthermia;
- concomitant use of reversible MAO-A inhibitors, for example moclobemide;
- concomitant use of linezolid — this antibiotic is a reversible non-selective MAO inhibitor;
- established prolongation of the QT interval or congenital long QT syndrome;
- concomitant use of other medicines that prolong the QT interval.
Special warnings and precautions
Depression itself raises the risk of suicidal thoughts, self-harm and suicide, and that risk persists until noticeable clinical improvement arrives. Since improvement may take several weeks, the patient must be watched closely throughout that time. Experience shows the risk may rise in the early phase of recovery. A meta-analysis of placebo-controlled trials showed an increased risk of suicidal behaviour in patients under 25. 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.
In whom the medicine demands particular caution
- it is not indicated in children and adolescents under 18: in trials suicidal behaviour and hostility occurred in them more often than on placebo, and there are no long-term data on the effect on growth and development;
- in panic disorder anxiety may increase at the start of treatment — a paradoxical reaction that usually passes within two weeks, which is why a low dose is used to begin with;
- if the first seizures appear or attacks become more frequent in a patient with epilepsy, the medicine is withdrawn; in unstable epilepsy medicines of this group 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 both hypoglycaemia and hyperglycaemia are possible — doses of insulin or of oral agents may need adjusting;
- akathisia — a distressing inner restlessness with a need to move — is more likely in the first weeks of treatment, and the dose should not be raised when it appears;
- combination with medicines that prolong the QT interval and states with hypokalaemia raise the risk of ventricular arrhythmias;
- in patients over 50 epidemiological data point to an increased risk of bone fractures.
Drug interactions
Absolutely incompatible with escitalopram are MAO inhibitors. It may be started 14 days after an irreversible MAO inhibitor is withdrawn and at least a day after moclobemide; between withdrawal of escitalopram itself and the start of treatment with a non-selective MAO inhibitor at least 7 days are left. Just as strictly excluded are medicines that prolong the QT interval: class IA and III antiarrhythmics, antipsychotics (phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antibacterials (sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine), antimalarials, in particular halofantrine, as well as astemizole and mizolastine.
Caution is required with serotonergic agents — tramadol, sumatriptan and other triptans: the combination may lead to serotonin syndrome. Medicines that lower the seizure threshold (tricyclic antidepressants, neuroleptics, mefloquine, bupropion, tramadol again) add to that effect. Lithium and tryptophan enhance the action of the medicine, and St John's wort increases the frequency of adverse reactions. Bleeding is a separate topic: with oral anticoagulants the clotting parameters need checking at the start of treatment and on withdrawal, and non-steroidal anti-inflammatory drugs by themselves raise the risk of bleeding.
Pregnancy and breastfeeding
Clinical data on use in pregnancy are scarce. Studies in rats showed toxic effects on the embryo and foetus, but no increase in the frequency of congenital malformations was detected. The medicine is not used in pregnancy unless there is unconditional need and only after careful weighing of the risks against the expected benefit.
If the mother took it late in pregnancy, especially in the third trimester, the newborn needs monitoring: breathing disorders, cyanosis, apnoea, convulsions, temperature swings, feeding difficulties, vomiting, hypoglycaemia, changes in muscle tone, tremor, irritability, lethargy, continuous crying and sleep disturbances are possible. These usually appear immediately or within the first day after delivery. Epidemiological data point to an increased risk of persistent pulmonary hypertension of the newborn — about 5 cases per 1000 pregnancies against 1–2 in the general population. During breastfeeding the medicine is not recommended: it is assumed to pass into the milk.
Adverse effects
Adverse reactions appear more often in the first or second week of treatment and usually ease as it continues. Headache and nausea are recorded very often.
- common: insomnia, drowsiness, dizziness, paraesthesia, tremor, diarrhoea, constipation, vomiting, dry mouth, increased sweating, fatigue, fever, sinusitis, yawning;
- common in the psychic and sexual sphere: restlessness, nervousness, unusual dreams, reduced libido, anorgasmia in women, ejaculation disorders and impotence in men;
- common, other: decreased or increased appetite, weight gain, arthritis, myositis;
- uncommon: bruxism, agitation, panic attack, confusion, fainting, taste and sleep disturbances, mydriasis, visual disturbances, tinnitus, tachycardia, nosebleeds, gastrointestinal bleeding, urticaria, rash, hair loss;
- rare: aggression, depersonalisation, hallucinations, bradycardia, anaphylactic reaction, serotonin syndrome;
- frequency not known but clinically important: mania, suicidal thoughts and behaviour, seizures, akathisia, dyskinesia;
- frequency not known: hyponatraemia, impaired secretion of antidiuretic hormone, hepatitis and abnormal liver tests, urinary retention, angioedema;
- frequency not known, cardiac: prolongation of the QT interval on the ECG and ventricular arrhythmias including torsade de pointes, predominantly in women and with hypokalaemia.
Withdrawal symptoms deserve separate attention: when the medicine is stopped abruptly, dizziness, sensory disturbances, anxiety and sleep disorders are common. That is precisely why the dose is lowered gradually rather than the medicine dropped in a single day.
Overdose
Clinical data are limited, and in most cases several medicines had been taken together. As a rule the symptoms were mild or absent; fatal outcomes from an overdose of escitalopram alone are rare. Taking 400–800 mg of the medicine without other agents caused no severe symptoms.
Possible manifestations are dizziness, tremor, agitation, less often serotonin syndrome, seizures and coma; nausea and vomiting; a fall in blood pressure, tachycardia, prolongation of the QT interval and arrhythmias; disturbance of water and electrolyte balance with hypokalaemia and hyponatraemia. There is no specific antidote. The airway is kept patent and oxygenation sufficient, gastric lavage is performed as early as possible, activated charcoal is considered, and cardiac activity and vital signs are monitored. In heart failure, bradyarrhythmias, use of QT-prolonging medicines or impaired liver function, ECG monitoring is recommended.
How to get a prescription for Escitalopram Actavis online
Escitalopram Actavis is a prescription-only medicine: choosing the dose, the pace of increase and the length of the course is the doctor's task, as is deciding on compatibility with other medicines. During the online consultation the doctor will clarify the diagnosis, go through the medicines you take and assess contraindications, including heart rhythm disorders.
If the medicine is suitable, the doctor will issue an electronic prescription and explain how to start taking it, what to expect in the first weeks and how to finish the course properly so as to avoid withdrawal symptoms.
