(and dosage form):
ASPEN ESCITALOPRAM 5 mg (film-coated tablet)
ASPEN ESCITALOPRAM 10 mg (film coated tablet)
ASPEN ESCITALOPRAM 15 mg (film coated tablet)
ASPEN ESCITALOPRAM 20 mg (film-coated tablet)
ASPEN ESCITALOPRAM 5 mg (film-coated tablet)
Each film-coated tablet contains Escitalopram Oxalate corresponding to 5 mg Escitalopram.
ASPEN ESCITALOPRAM 10 mg (film-coated tablet)
Each film-coated tablet contains Escitalopram Oxalate corresponding to 10 mg Escitalopram.
ASPEN ESCITALOPRAM 15 mg (film-coated tablet)
Each film-coated tablet contains Escitalopram Oxalate corresponding to 15 mg Escitalopram.
ASPEN ESCITALOPRAM 20 mg (film-coated tablet)
Each film-coated tablet contains Escitalopram Oxalate corresponding to 20 mg Escitalopram.
A 1.2 Psychoanaleptics (antidepressants)
Mechanism of action
Escitalopram is selective inhibitor of serotonin (5-HT)-uptake.
Escitalopram has minimal effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake. Escitalopram has no or very low affinity for a series of receptors including 5-HT1A, 5-HT2, DA D1 and D2 receptors, alpha1-,alpha2-,(beta-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors.
Absorption is independent of food intake (mean Tmax is 4 hours after multiple dosing).
The apparent volume of distribution (Vd,beta/F) after oral administration is about 12 to 26 L/kg. The plasma protein binding of escitalopram is approximately 55%.
Escitalopram is metabolised in the liver to the demethylated and didemethylated metabolites. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent and metabolites are partly excreted as glucuronides. Unchanged escitalopram is the predominant compound in plasma. After multiple dosing the mean concentrations of the demethyl and didemethyl metabolites are usually 28-31% and <5% of the escitalopram concentration, respectively. Biotransformation of escitalopram to the demethylated metabolite is mediated by a combination of CYP2C19, CYP3A4 and CYP2D6.
The elimination half-life after multiple dosing is about 30 hours and the oral plasma clearance (Cloral) is about 0.60 L/min. Escitalopram and major metabolites are - like racemic citalopram - assumed to be eliminated both by the hepatic (metabolic) and the renal routes with the major part of the dose excreted as metabolites in urine.
Hepatic clearance is mainly by the P450 enzyme system. CYP2C19 is the primary isoenzyme involved in the demethylation of escitalopram, followed by CYP3A4 and CYP2D6. 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.
Elderly patients (> 65 years of age)
A longer half-life (about 50%) and decreased clearance values, due to a reduced rate of metabolism, have been demonstrated in the elderly.
Reduced hepatic function
Escitalopram is eliminated more slowly in patients with reduced hepatic function. The half-life of escitalopram is approximately twice as long in patients with hepatic impairment and steady state escitalopram concentrations at a given dose will be approximately twice as high as in patients with normal liver function.
Reduced renal function
Escitalopram is eliminated more slowly in patients with mild to moderate reduction of renal function with no major impact on the escitalopram concentrations in serum. At present no information is available for the treatment of patients with severely reduced renal function (creatinine clearance < 30 mL/min).
Based on in vitroresults with escitalopram and in vivo results with the racemic citalopram, genetic polymorphism with respect to CYP2D6 is not known, with respect to CYP2C19, it may be of clinical relevance, as shown in limited numbers.
Treatment of major depressive episodes.
Hypersensitivity to escitalopram or to any of the excipients.
Children; as safety and efficacy have not been established in this population.
Monoamine Oxidase Inhibitors- Cases of serious reactions have been reported in patients receiving an SSRI such as ASPEN ESCITALOPRAM in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued an SSRI and have been started on an MAOI. (see "Interactions").
Some cases presented with features resembling serotonin syndrome (see "SIDE-EFFECTS AND SPECIAL PRECAUTIONS": Class reactions).
ASPEN ESCITALOPRAM should not be used in combination with an MAOI. ASPEN ESCITALOPRAM may be started 14 days after discontinuing treatment with an MAOI. At least 7 days should elapse after discontinuing ASPEN ESCITALOPRAM treatment before starting an MAOI.
WARNINGS AND SPECIAL PRECAUTIONS:
Mania- ASPEN ESCITALOPRAM should be discontinued in any patient entering a manic phase. ASPEN ESCITALOPRAM should be used with caution in patients with a history of mania/hypomania.
Paradoxical anxiety- Some patients with panic disorder may experience increased anxiety symptoms at the start of treatment with antidepressants. This paradoxical reaction usually subsides within two weeks during continued treatment. A low starting dose is advised to reduce the likelihood of a paradoxical anxiogenic effect.
Seizures- ASPEN ESCITALOPRAM should be discontinued in any patient who develops seizures. ASPEN ESCITALOPRAM should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. ASPEN ESCITALOPRAM should be discontinued if there is an increase in seizure frequency.
Diabetes mellitus- In patients with diabetes mellitus treatment with ASPEN ESCITALOPRAM may alter glycaemic control, possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Suicide- As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored during this period. The possibility of a suicide attempt is inherent in depression and may persist until significant therapeutic effect is achieved.
Haemorrhage- There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, with ASPEN ESCITALOPRAM. Caution is advised in patients taking ASPEN ESCITALOPRAM, particularly in concomitant use with medicines known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin and non-steroidal anti-inflammatory medicines (NSAIDs), as well as in patients with a history of bleeding disorders.
ECT (electroconvulsive therapy) - There is limited published clinical experience of concurrent administration of ASPEN ESCITALOPRAM and ECT, therefore caution is advisable.
Effects on ability to drive and use machines
ASPEN ESCITALOPRAM does not impair intellectual function or psychomotor performance. Nevertheless, patients who are depressed and require treatment may have an impaired ability to drive or operate machinery. They should be warned of the possibility and advised to avoid such tasks if so affected. Risk of Serotonin syndrome (see INTERACTIONS)
When stopping ASPEN ESCITALOPRAM therapy, gradual dose reduction should be considered.
Escitalopram has a low potential for clinically significant medicine interactions. In vitro studies have shown that the biotransformation of escitalopram to its demethylated metabolites depends on three parallel pathways (cytochrome P450 (CYP) 2C19, 3A4 and 2D6). Escitalopram is a very weak inhibitor of isoenzyme CYP1A2, 2C9, 2C19, 2E1, and 3A, and weak inhibitor of 2D6.
Effects of other medicinal products on ASPEN ESCITALOPRAM in vivo
The pharmacokinetics of single doses of ASEN ESCITALOPRAM was not changed by co-administration with a single dose of ritonavir (CYP3A4 inhibitor).
Co-administration with ketoconazole (potent CYP3A4 inhibitor) did not change the pharmacokinetics of racemic citalopram.
Co-administration of racemic citalopram with cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor) resulted in increased plasma concentrations of the racemate (43% increase in AUC, 39% increase in Cmax). Thus, caution should be exercised at the upper end of the dose range of ASPEN ESCITALOPRAM when used concomitantly with high doses of cimetidine.
Monoamine Oxidase inhibitors (MAOI), Sumatriptan & Tramadol:
Co-administration with MAO inhibitors may cause serotonin syndrome. Co-administration with other serotonergic medicines (e.g. tramadol, sumatriptan) as well as other antidepressants with serotonergic properties may lead to an enhancement of serotonin associated effects, e.g. the serotonin syndrome.
There have been reports of enhanced effects when ASPEN ESCITALOPRAM has been given with lithium or tryptophan and therefore concomitant use of ASPEN ESCITALOPRAM with these medicines should be undertaken with caution.(see WARNINGS)
Effects of ASPEN ESCITALOPRAM on other medicinal products in vivo
Co-administration with a single dose of desipramine (a CYP2D6 substrate) resulted in a twofold increase in plasma levels of desipramine. Therefore, caution is advised when ASPEN ESCITALOPRAM and desipramine are co-administered. A similar increase in plasma levels of desipramine, after administration of imipramine, was seen when given together with racemic citalopram.
Co-administration with a single dose of metoprolol 100 mg (a CYP2D6 substrate) resulted in a twofold increase in the Cmax and a 52% increase of the AUC of metoprolol. However, the combination had no clinically significant effects on blood pressure and heart rate.
Racemic citalopram increased the AUC of selegiline by 29%.
Pharmacokinetic interaction studies with racemic citalopram have demonstrated no clinically important interactions with carbamazepine (CYP3A4 substrate), triazolam (CYP3A4 substrate), theophylline (CYP1 A2 substrate) (single dose), warfarin (CYP3A4 and CYP2C9 substrate), levomepromazine (CYP2D6 inhibitor), lithium and digoxin. However, prothrombin time was slightly increased after a single dose of 25 mg warfarin. The International Normalised Ratio (INR) needs to be carefully monitored in patients on the combination.
PREGNANCY AND LACTATION:
The safety of ASPEN ESCITALOPRAM in pregnant and lactating women has not been established.
DOSAGE AND DIRECTIONS FOR USE:
Major depressive episodes
ASPEN ESCITALOPRAM should be administered as a single oral dose of 10 mg daily in otherwise healthy adults. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily.
Usually 2-4 weeks are necessary for an antidepressant response.
A single oral dose of 5 mg is recommended for the first week before increasing the dose to 10 mg daily. The dose may be further increased, up to a maximum of 20 mg daily, dependent on individual patient response.
Elderly patients (> 65 years of age)
A longer half-life and a decreased clearance have been demonstrated in the elderly, therefore a lower initial and maximum dose should be considered.
Reduced renal function (see WARNINGS)
Dosage adjustment is not necessary in patients with mild or moderate renal impairment. No information is available on the treatment of patients with severely reduced renal function (creatinine clearance < 30 mL/min.).
Reduced hepatic function (see WARNINGS)
Dosages should be halved to the lower end of the dose range in patients with hepatic insufficiency. ASPEN ESCITALOPRAM is administered as a single daily dose. ASPEN ESCITALOPRAM may be taken without regard to food intake
Adverse reactions observed with ASPEN ESCITALOPRAM are most frequent during the first one or two weeks of treatment and may decrease in intensity and frequency with continued treatment.
After prolonged administration abrupt cessation of ASPEN ESCITALOPRAM may produce withdrawal reactions in some patients.
Common (>1/100, <1/10)
Nausea, insomnia, somnolence, sweating increased, diarrhoea, constipation, dizziness, fatigue, appetite decreased, sinusitis, libido decreased, pyrexia, yawning.
Ejaculation disorder, impotence, abnormal orgasm (female).
Uncommon (>1/1000, <1/100)
Sleep disorder, taste disturbance
SSRI - Class Reactions
The following adverse reactions apply to the therapeutic class of SSRIs.
Cardiovascular disorders - Postural hypotension
Disorders of metabolism and nutrition - Hyponatraemia, inappropriate ADH secretion.
Disorders of the eye - Abnormal vision
Gastrointestinal disorders - Nausea, vomiting, dry mouth, diarrhoea, anorexia.
General disorders - Insomnia, dizziness, fatigue, drowsiness, anaphylactoid reactions.
Hepato-biliary disorders - Abnormal liver function tests.
Musculoskeletal disorders - Arthralgia, myalgia.
Neurological disorders - Seizures, tremor, movement disorders, serotonin syndrome (typically characterized by a rapid onset of changes in mental state, with confusion, mania, agitation, hyperactivity, shivering, fever, tremor, ocular movements, myoclonus, hyperreflexia, and incoordination).
Psychiatric disorders - Hallucinations, mania, confusion, agitation, anxiety, depersonalisation, panic attacks, nervousness.
Renal and urinary disorders - Urinary retention.
Reproductive disorders - Galactorrhoea, sexual dysfunction such as ejaculation disorder and anorgasmia.
Skin disorders - Rash, ecchymoses, pruritus, angioedema, sweating.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Doses of 190 mg have been taken without any symptoms being reported.
There is no specific antidote. Treatment is supportive and symptomatic. Gastric lavage should be carried out as soon as possible after oral ingestion. Cardiac and vital signs monitoring are recommended along with general symptomatic supportive measures.
ASPEN ESCITALOPRAM 5 MG: 5.5 mm normal convex, white film-coated tablet debossed "EC" 5 on one side and "G" on the other.
ASPEN ESCITALOPRAM 10 MG: 9.5 mm x 5.5 mm oblong normal convex, white film-coated tablet debossed "EC"/10"on one side and "G" on the other. The tablets have a breakline and are intended to be breakable.
ASPEN ESCITALOPRAM 15 MG: 10.5 mm x 6 mm ellipse normal convex, white film-coated tablet debossed "EC"/15"on one side and "G" on the other.
ASPEN ESCITALOPRAM 20 MG: 12.5 mm x 7 mm oblong normal convex, white film-coated tablet debossed "EC"/20"on one side and "G" on the other.
Aluminium/Clear PVC/PVDC blister strips packed in 28's or 30's in cardboard cartons or
Polypropylene containers with polyethylene tamper evident lids and optional polyethyleneullage filler (Securitainers) packed in 28's or 30's.
Store below 30ºC.
Keep the tablets in the outer carton until required for use.
KEEP OUT OF REACH OF CHILDREN.
ASPEN ESCITALOPRAM 5 MG: 41/1.2/0896
ASPEN ESCITALOPRAM 10 MG: 41/1.2/0897
ASPEN ESCITALOPRAM 15 MG: 41/1.2/0898
ASPEN ESCITALOPRAM 20 MG: 41/1.2/0899
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
DATE OF PUBLICATION OF THE PACKAGE INSERT:
9 December 2008
New addition to this site: February 2010
Source: Pharmaceutical Industry
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