Citalopram Film Coated Tablets USP 40mg Taj Pharma

1. Name of the medicinal product
a) Citalopram Film Coated Tablets USP 10mg Taj Pharma
b) Citalopram Film Coated Tablets USP 20mg Taj Pharma
c) Citalopram Film Coated Tablets USP 40mg Taj Pharma

2. Qualitative and quantitative composition
a) Each tablet contains:
Citalopram Hydrobromide USP
equivalent to 10mg of Citalopram.
Excipients              q.s.

b) Each tablet contains:
Citalopram Hydrobromide USP
equivalent to 20mg of Citalopram.
Excipients              q.s.

c) Each tablet contains:
Citalopram Hydrobromide USP
equivalent to 40mg of Citalopram.
Excipients                   q.s.

3. Pharmaceutical form
Film-coated tablet
A white, oval, normal convex film-coated tablet.The tablet can be divided into equal doses.

4. Clinical particulars
4.1 Therapeutic indications
Treatment of major depressive episodes.
Treatment of panic disorder with or without agoraphobia.

4.2 Posology and method of administration
Posology
Major depressive episodes

Adults:
Citalopram should be administered as a single oral dose of 20 mg daily.

Dependent on individual patient response, the dose may be increased to a maximum of 40 mg daily. In general, improvement in patients starts after 2-4 weeks.

As with all antidepressant medicinal products, dosage should be reviewed and adjusted, if necessary, within 3 to 4 weeks of initiation of therapy and thereafter as judged clinically appropriate. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen, some patients may benefit from having their dose increased up to a maximum of 40 mg a day (see section 5.1). Dosage adjustments should be made carefully on an individual patient basis, to maintain the patient at the lowest effective dose.

Following treatment initiation, an antidepressant effect should not be expected for at least two weeks. Treatment should continue until the patient has been free of symptoms for 4-6 months to give adequate protection against the possibility of a relapse.

Panic disorder
Adults:
A single oral dose of 10 mg is recommended for the first week before increasing the dose to 20 mg daily. Dependent on individual patient response, the dose may be increased to a maximum of 40 mg daily.

Patients should be started on 10 mg/day and the dose gradually increased in 10 mg steps according to the patient’s response up to the recommended dose. A low initial starting dose is recommended to minimise the potential worsening of panic symptoms, which is generally recognised to occur early in the treatment of this disorder. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen some patients may benefit from having their dose increased gradually up to a maximum of 40 mg/day (see section 5.1). Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose.

The maximum efficacy of citalopram in the treatment of panic disorder is achieved after approximately 3 months. Depending on the patient’s individual response, it may be necessary to continue treatment for several months or more. There is insufficient data on efficacy from clinical studies lasting more than 6 months.

Elderly (> 65 years of age)
|For elderly patients the dose should be decreased to half of the recommended dose, e.g. 10-20 mg daily. The recommended starting dose is 10 mg daily. The recommended maximum dose is 20 mg daily.

Paediatric population
The safety and efficacy of citalopram has not been established in the treatment of children and adolescents under the age of 18 years. Thus, citalopram should not be used in this population (see section 4.4).

Reduced hepatic function:
An initial dose of 10 mg daily for the first two weeks of treatment is recommended in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function These patients should be clinically monitored (see section 5.2).

Reduced renal function:
Dosage adjustment is not necessary for patients with mild to moderate renal dysfunction. No information is available for case of severe impairment of renal function (creatinine clearance <30 mL/minute). Particular caution is therefore advised with patients with severe renal impairment (see section 5.2).

Poor metabolisers of CYP2C19:
An initial dose of 10 mg daily during the first two weeks of treatment is recommended for patients who are known to be poor metabolisers with respect to CYP2C19. The dose may be increased to a maximum of 20 mg daily depending on individual patient response (see section 5.2).

Withdrawal symptoms seen on discontinuation of citalopram:
Abrupt discontinuation should be avoided. When stopping treatment with citalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal symptoms (see section 4.4 and section 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

Method of administration
For oral use.

Citalopram should be administered as a single dose, either in the morning or in the evening. The tablets can be taken with or without food, but with fluid.

4.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

  • Monoamine Oxidase Inhibitors (MAOIs)(see sections 4.4 and 4.5):

Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with monoamine oxidase inhibitors (MAOI), including the selective MAOI selegiline and the reversible MAOI (RIMA), moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome.

  • Citalopram should not be given to patients receiving MAOIs including selegiline in daily doses exceeding 10 mg/day. Citalopram should not be given for fourteen days after discontinuation of an irreversible MAOI or for the time specified after discontinuation of a reversible MAOI (RIMA), e.g. moclobemide, as stated in the prescribing text of the RIMA. MAOIs should not be introduced for seven days after discontinuation of citalopram (see section 4.5).
  • 5-HT agonists:

Sumatriptan’s serotonergic effects are suspected to be enhanced by SSRIs. Until further evidence is available it is advised not to use citalopram simultaneously with 5-HT agonists eg. Sumatriptan.

  • Citalopram is contraindicated in combination with linezolid unless there are facilities for close observation and monitoring of blood pressure (see section 4.5).
  • Citalopram should not be used concomitantly with pimozide (see also section 4.5).
  • Citalopram is contraindicated in patients with known QT-interval prolongation or congenital long QT syndrome.
  • Citalopram is contraindicated together with medicinal products that are known to prolong the QT-interval (see section 4.5).

4.4 Special warnings and precautions for use
Elderly patients and patients with renal or hepatic impairment

Treatment of elderly patients and patients with reduced kidney and liver function, see section 4.2.

Paediatric population under 18 years of age

Citalopram should not be used in the treatment of children and adolescents under the age of 18 years (see section 4.2). Suicide-related behaviours (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which citalopram is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

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

Seizures
Seizures are a potential risk with antidepressant drugs. Citalopram should be discontinued in any patient who develops seizures. Citalopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Citalopram should be discontinued if there is an increase in seizure frequency.

ECT (electroconvulsive therapy)
There is limited clinical experience of concurrent administration of SSRIs and ECT, therefore caution is advisable.

Mania
Citalopram should be used with caution in patients with a history of mania/hypomania. In patients with manic-depressive illness a change towards the manic phase may occur. Citalopram should be discontinued in any patient entering a manic phase.

Psychosis
Treatment of psychotic patients with depressive episodes may increase psychotic symptoms.

Haemorrhage
There have been reports of prolonged bleeding time and/or bleeding abnormalities such as ecchymosis, purpura, gynaecological haemorrhages, gastrointestinal bleedings and other cutaneous or mucous bleedings with SSRIs (see section 4.8). Caution is advised in patients taking citalopram, particularly in concomitant use with oral anticoagulants, active substances known to affect platelet function or other active substances that may increase the risk of haemorrhage (e.g. atypical antipsychotics, acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), ticlopidine and dipyridamole) as well as in patients with a history of bleeding disorders (see section 4.5).

Serotonin syndrome
In rare cases serotonin syndrome has been reported in patients using SSRIs. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition (see section 4.5). Treatment with citalopram should be discontinued immediately and symptomatic treatment initiated.

Serotonergic medicinal products
Concomitant use of citalopram with medicinal products with serotonergic effects such as tramadol, tryptophan, oxitriptan, sumatriptan or other triptans is contraindicated (see section 4.3).

Reversible, selective MAO-A inhibitors
The combination of citalopram with MAO-A inhibitors is not recommended due to the risk of onset of a serotonin syndrome (see section 4.5). For information on concomitant treatment with non-selective, irreversible MAO-inhibitors see section 4.5.

Hyponatraemia
Hyponatraemia, probably due to inappropriate anti-diuretic hormone secretion (SIADH), has been reported as a rare adverse reaction with the use of SSRIs and generally reverses on discontinuation of therapy. Elderly female patients seem to be at particularly high risk.

St. John’s wort
Undesirable effects may be more common during concomitant use of citalopram and herbal preparations containing St. John’s wort (Hypericum perforatum). Therefore citalopram and St. John’s wort preparations should not be taken concomitantly (see section 4.5).

Akathisia/psychomotor restlessness
The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Withdrawal symptoms seen on discontinuation of SSRI treatment
Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.2 and 4.8). In a recurrence prevention clinical trial with citalopram, adverse events after discontinuation of active treatment were seen in 40% of patients versus 20% in patients continuing citalopram.

The risk of withdrawal 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 following discontinuation of SSRIs/SNRIs. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that citalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient’s needs (see section 4.2 “Withdrawal Symptoms Seen on Discontinuation”).

QT interval prolongation
Citalopram has been found to cause a dose-dependent prolongation of the QT-interval. 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 prolongation or other cardiac diseases (see sections 4.3, 4.5, 4.8, 4.9 and 5.1).

Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure.

Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for malignant arrhythmias and should be corrected before treatment with citalopram is started.

ECG monitoring may be advisable in case of overdose or conditions of altered metabolism with increased peak levels, e.g. liver impairment.

If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started.

If signs of cardiac arrhythmia occur during treatment with citalopram, the treatment should be withdrawn and an ECG should be performed.

Angle-closure glaucoma
SSRIs including citalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Citalopram should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

Paradoxical anxiety
Some patients with panic disorder may experience intensified anxiety symptoms at the start of treatment with antidepressants. This paradoxical reaction usually subsides within the first two weeks of starting treatment. A low starting dose is advised to reduce the likelihood of a paradoxical anxiogenic effect (see section 4.2).

Excipients
Citalopram tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction
Pharmacodynamic interactions
At the pharmacodynamic level cases of serotonin syndrome with citalopram and moclobemide and buspirone have been reported.

Contraindicated combinations
Monoamine Oxidase Inhibitors (MAOIs)

The simultaneous use of citalopram and MAO-inhibitors can result in severe undesirable effects, including serotonin syndrome (see section 4.3).

Cases of serious, and sometimes fatal reactions, have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the selective irreversible MAOI, selegiline, the selective reversible MAOIs linezolid and moclobemide, and in patients who have recently discontinued a SSRI and have been started on a MAOI.

Some cases presented with features resembling serotonin syndrome. Symptoms of an active substance interaction with a MAOI include: extreme agitation, rigidity, tremor, myoclonus, hyperthermia, vegetative instability with rapid fluctuations of the vital signs, changes in mental state, confusion, irritability and even delirium and coma (see section 4.3).

QT interval prolongation
Pharmacokinetic and pharmacodynamic studies between citalopram and other medicinal products that prolong the QT interval have not been performed. An additive effect of citalopram and these medicinal products cannot be excluded. Therefore, co-administration of citalopram 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 (astemizole, mizolastine) etc., is contraindicated.

Pimozide
Co administration of a single dose of pimozide 2 mg to subjects treated with racemic citalopram 40 mg/day for 11 days caused an increase in AUC and Cmax of pimozide, although not consistently throughout the study. The co-administration of pimozide and citalopram resulted in a mean increase in the QTc interval of approximately 10 msec. Due to the interaction noted at a low dose of pimozide, concomitant administration of citalopram and pimozide is contraindicated.

Combinations requiring precaution for use

Selegiline (selective MAO-B inhibitor)
A pharmacokinetic / pharmacodynamic interaction study with concomitantly administered citalopram (20 mg daily) and selegiline (10 mg daily) (a selective MAO-B inhibitor) demonstrated no clinically relevant interactions. The concomitant use of citalopram and selegiline (in doses above 10 mg daily) is contraindicated (see section 4.3).

Serotonergic medicinal products

Lithium and tryptophan
No pharmacodynamic interactions have been found in clinical studies in which citalopram has been given concomitantly with lithium. However there have been reports of enhanced effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of citalopram with these medicinal products should be undertaken with caution. Routine monitoring of lithium levels should be continued as normal.

Co-administration with serotonergic medicinal products (e.g. tramadol, tryptophan, oxitriptan, sumatriptan and other triptans) may lead toenhancement of 5-HT associated effects.

In combination with triptans, there is a potential risk of coronary vasoconstriction and hypertension too. Until further information is available, the simultaneous use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is contraindicated (see section 4.3 and 4.4).

St. John’s wort
Dynamic interactions between SSRIs and the herbal remedy St. John´s wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects (see section 4.4). Pharmacokinetic interactions have not been investigated.

Haemorrhage
Caution is warranted for patients who are being treated simultaneously with anticoagulants, medicinal products that affect the platelet function, such as non steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) that can increase the risk of haemorrhage (see section 4.4).

ECT (electroconvulsive therapy)
There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and citalopram (see section 4.4).

Alcohol
No adverse pharmacodynamic or pharmacokinetic interactions have been demonstrated between citalopram and alcohol. However, the combination of citalopram and 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).

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 such as antidepressants (tricyclic antidepressants (SSRIs), neuroleptics, (phenothiazine, thioxanthenes and butyrophenones), mefloquin, bupropion and tramadol. (see section 4.4).

Pharmacokinetic interactions
Biotransformation of citalopram to demethylcitalopram is mediated by CYP2C19 (approx. 38%), CYP3A4 (approx. 31%) and CYP2D6 (approx. 31%) isozymes of the cytochrome P450 system.

Food
The absorption and other pharmacokinetic properties of citalopram have not been reported to be affected by food.

Effect of other medicinal products on the pharmacokinetics of citalopram
Co-administration with ketoconazole (potent CYP3A4 inhibitor) did not change the pharmacokinetics of citalopram.

A pharmacokinetic interaction study of lithium and citalopram did not reveal any pharmacokinetic interactions (see also above).

Cimetidine
Cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor) caused a moderate increase in the average steady state levels of citalopram. Caution is advised when administering citalopram in combination with cimetidine. Dose adjustment may be warranted.

Omeprazole and other CYP2C19 inhibitors
Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram. Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) cimetidine. A reduction in the dose of citalopram may be necessary based on monitoring of undesirable effects during concomitant treatment.

Effects of citalopram on other medicinal products
Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6 as compared to other SSRIs established as significant inhibitors.

Metoprolol and other CYP2D6 substrates
Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by CYP2D6, 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.

A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a two-fold increase in metoprolol concentrations, but no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers.

Levomepromazine, digoxin, carbamazepine
No change or only very small changes of no clinical importance were observed when citalopram was given with CYP1A2 substrates (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline, risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine epoxid) and triazolam).

No pharmacokinetic interaction was observed between citalopram and levomepromazine, or digoxin, (indicating that citalopram neither induces nor inhibits P-glycoprotein).

Desipramine, imipramine
In a pharmacokinetic study no effect was demonstrated on either citalopram or imipramine levels, although the level of desipramine, the primary metabolite of imipramine, was increased. When desipramine is combined with citalopram, an increase of the desipramine plasma concentration has been observed. A reduction of the desipramine dose may be needed.

4.6 Fertility, pregnancy and lactation
Pregnancy
Published data on pregnant women (more than 2500 exposed outcomes) indicate no malformative foeto/ neonatal toxicity. However citalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit.

Neonates should be observed if maternal use of citalopram continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy.

The following symptoms may occur in the neonates after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particular in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Breast-feeding
Citalopram is excreted into breast milk in small quantities. It is estimated that the suckling infant will receive about 5% of the weight related maternal daily dose (in mg/kg). No or only minor events have been observed in the infants. However, the existing information is insufficient for assessment of the risk to the child. Caution is recommended. If treatment with citalopram is considered necessary, discontinuation of breast feeding should be considered.

Fertility
Animal data have shown that citalopram may affect sperm quality (see section 5.3). Human case reports with some SSRIs have shown that an effect on sperm quality is reversible.

Impact on human fertility has not been observed so far.

4.7 Effects on ability to drive and use machines
Citalopram has minor or moderate influence on the ability to drive and use machines. Patients who are prescribed psychotropic medication may be expected to have some impairment of general attention and concentration due to the illness itself and psychoactive medicinal products can reduce the ability to make judgements and to react to emergencies. Patients should be informed of these effects and be warned that their ability to drive a car or operate machinery could be affected.

4.8 Undesirable effects
Adverse effects observed with citalopram are in general mild and transient. They are most frequent during the first one or two weeks of treatment and usually attenuate subsequently. The adverse reactions are presented at the MedDRA Preferred Term Level.

For the following reactions a dose-response was discovered: sweating increased, dry mouth, insomnia, somnolence, diarrhoea, nausea and fatigue, QT prolongation.

The table shows the percentage of adverse drug reactions associated with SSRIs and/or citalopram seen in either ≥ 1% of patients in double-blind placebo-controlled trials or in the post-marketing period. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and not known (cannot be estimated from the available data).

Very common Common Uncommon Rare Very rare Not known
Blood and lymphatic system disorders Thrombocytopenia
Immune system disorders Hypersensitivity, anaphylactic reaction
Endocrine disorders Inappropriate ADH secretion
Metabolism and nutrition disorders Appetite decreased, weight decreased Increased appetite, weight increased Hypo-natraemia Hypokalaemia
Psychiatric disorders Sleep disorder impaired concentration, decreased libido, anxiety, , confusional state, abnormal orgasm (female), abnormal dreams, apathy Aggression, depersonalisation, hallucination, euphoria, mania, increased libido Panic attack (these symptoms may be due to the underlying disease), Bruxism, restlessness, suicidal ideation, suicidal behaviour1
Nervous system disorders Somnolence, insomnia, headache, tremor, nervousness, agitation, giddiness Tremor, migraine, paraesthesia, dizziness, disturbance in attention, migraine, taste disturbance amnesia Syncope, extrapyramidal disorder, seizure Convulsion grand mal, dyskinesia, serotonin syndrome, akathisia movement disorder
Eye disorders Visual disturbance, Mydriasis (which may lead to acute narrow angle glaucoma), see section 4.4)
Ear and labyrinth disorders Tinnitus
Cardiac disorders Palpitations tachycardia Bradycardia, QT-prolongation, Ventricular arrhythmia including torsade de pointes
Vascular disorders Orthostatic hypotension Haemorrhage
Respiratory, thoracic and mediastinal disorders Yawning, rhinitis Coughing Epistaxis
Gastrointestinal disorders Dry mouth, nausea, constipation Diarrhoea, dyspepsia, vomiting, dyspepsia, abdominal pain, flatulence, increased salivation Gastrointestinal haemorrhage (including rectal haemorrhage)
Hepatobiliary disorders Liver function test abnormal Hepatitis
Skin and subcutaneous tissue disorders Increased sweating Pruritus Urticaria, alopecia, rash, purpura Ecchymosis angioedema
Musculoskeletal and connective tissue disorders Myalgia, arthralgia
Renal and urinary disorders Urinary retention
Reproductive system and breast disorders Impotence, ejaculation disorder, ejaculation failure Female: Menorrhagia Galactorrhoea Female: Metrorrhagia

Male: Priapism

General disorders and administration site conditions Asthenia Fatigue Oedema, malaise Pyrexia,

Number of patients: citalopram / placebo = 1346 / 545

1 Cases of suicidal ideation and suicidal behaviours have been reported during citalopram therapy or early after treatment discontinuation (see section 4.4).

QT interval prolongation
Cases of QT-prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalemia, or with pre-existing QT prolongation or other cardiac disease (see sections 4.3, 4.4, 4.5, 4.9 and 5.1).

Class effects (bone fractures)
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.

Withdrawal symptoms seen on discontinuation of SSRI treatment:
Discontinuation of citalopram (particularly when abrupt) commonly leads to withdrawal 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, dizziness, 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 citalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 and section 4.4).

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.

4.9 Overdose
Toxicity
Comprehensive clinical data on citalopram overdose are limited and many cases involve concomitant overdoses of other drugs/alcohol. Fatal cases of citalopram overdose have been reported with citalopram alone; however, the majority of fatal cases have involved overdose with concomitant medications.

Symptoms
The following symptoms have been seen in reported overdose of citalopram: convulsion, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, transpiration, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, mydriasis, torsade de pointes, stupor, sweating, giddiness, dystonia, cyanosis, hyperventilation, hyperpyrexia atrial and ventricular arrhythmia, and rhabdomyolysis. Fatal cases have been reported.

Treatment
There is no known specific antidote to citalopram. Treatment should be symptomatic and supportive

If consciousness is impaired, the patient should be intubated. ECG and vital signs should be monitored.

ECG monitoring is advisable in case of overdose in patients with congestive heart failure/bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment (see sections 4.2, 4.4 and 4.5).

Activated charcoal, osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered.

5. Pharmacological properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antidepressants, selective serotonin reuptake inhibitors

Mechanism of action
Biochemical and behavioural studies have shown that citalopram is a potent inhibitor of serotonin (5-HT)-uptake. Long-term treatment with citalopram does not induce tolerance to the inhibition of 5-HT-uptake.

Citalopram is the most Selective Serotonin Reuptake Inhibitor (SSRI) with no, or minimal, effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake.

In contrast to many tricyclic antidepressants and some of the newer SSRIs, citalopram has no or very low affinity for a series of receptors including 5-HT1A, 5-HT2, dopamine D1 and Dreceptors, α1-, α2- and β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors. This is in contrast to many tricyclic antidepressants and some of the other SSRI’s. Lack of receptor affinity has been confirmed using a series of functional in vitro tests in isolated organs as well as functional in vivo tests. This absence of effects on receptors could explain why citalopram produces fewer of the traditional side effects such as dry mouth, bladder and gut disturbance, blurred vision, sedation, cardiotoxicity and orthostatic hypotension.

The main metabolites of citalopram are all SSRIs although their potency and selectivity ratios are lower than those of citalopram. However, the selectivity ratios of the metabolites are higher than those of newer SSRIs. The metabolites do not contribute to the overall antidepressant effect.

Pharmacodynamic effects
Like tricyclic antidepressants, other SSRI’s and MAO inhibitors, citalopram suppresses REM–sleep and increases deep slow-wave sleep. Suppression of rapid eye movement (REM) sleep is considered a predictor of antidepressant activity. Although citalopram does not bind to opioid receptors it potentiates the anti-nociceptive effect of commonly used opioid analgesics. There was potentiation of d-amphetamine-induced hyperactivity following administration of citalopram.

In humans citalopram does not impair cognitive (intellectual function) and psychomotor performance and has no or minimal sedative properties, either alone or in combination with alcohol.

Citalopram did not reduce saliva flow in a single dose study in human volunteers and in none of the studies in healthy volunteers did citalopram have significant influence on cardiovascular parameters. Citalopram has no effect on the serum levels of prolactin and growth hormone.

Clinical efficacy and Safety
In a double-blind, placebo-controlled ECG study in healthy subjects, the change from baseline in QTc (Fridericia-correction) was 7.5 (90%CI 5.9-9.1) msec at the 20 mg/day dose and 16.7 (90%CI 15.0-18.4) msec at the 60 mg day/dose (see sections 4.3, 4.4, 4.5, 4.8 and 4.9).

5.2 Pharmacokinetic properties
Absorption
Absorption is almost complete and independent of food intake (Tmax average/mean 3.8 hours). Oral bioavailability is about 80%.

Distribution
The apparent volume of distribution (Vd)ß is 12 – 17 L/kg. The plasma protein binding is below 80% for citalopram and its main metabolites.

Biotransformation
Citalopram is metabolised to the active demethylcitalopram, didemethylcitalopram, citalopram-N-oxide and an inactive deaminated proprionic acid derivative. All the active metabolites are also SSRIs, although weaker than the parent compound. Unchanged citalopram is the predominant compound in plasma. The concentration of desmethylcitalopram and didesmethylcitalopram is usually 30 – 50% or 5 – 10% of the citalopram concentration. The biotransformation of citalopram into desmethylcitalopram is mediated by CYP2C19 (approx. 38%), CYP3A4 (approx. 31%) and CYP2D6 (approx. 31%).

Elimination
The elimination half-life (T1/2 ß) is about 1.5 days and the systemic citalopram plasma clearance (CIs) is 0.3 – 0.4 L/min, and oral plasma clearance (CIoral) is about 0.41 L/min.

Citalopram is excreted mainly via the liver (85%) and the remainder (15%) via the kidneys. About 12% of the daily dose is excreted in urine as unchanged citalopram. Hepatic (residual) clearance is about 0.35 L/min and renal clearance approximately 0.05 – 0.08 L/min.

The kinetics is linear. Steady state plasma levels are achieved in 1-2 weeks. Average concentrations of 300 nmol/L (165 – 405 nmol/L) are achieved at a daily dose of 40 mg. There is no clear relationship between citalopram plasma levels and therapeutic response or side effects.

Elderly patients (≥65 years)
In elderly patients, longer half-lives (1.5 – 3.75 days) and lower clearance values (0.08 – 0.3 L/min) have been determined as a result of the reduced metabolism. With the same posology, the steady-state plasma values of citalopram in elderly patients are approximately twice as high as in young patients.

Hepatic impairment
Citalopram is eliminated more slowly for patients with reduced hepatic function. The half-life of citalopram is about twice as long and steady state citalopram concentrations at a given dose will be about twice as high as in patients with normal liver function.

Renal impairment
Citalopram is eliminated more slowly in patients with mild to moderate reduction of renal function, without any major impact on the pharmacokinetics of citalopram. At present no information is available for treatment of patients with severely reduced renal function (creatinine clearance <30 mL/min).

Polymorphism
In vivo examinations of people with reduced activity of the CYP2D6 enzyme have shown no relevant change in the plasma concentration of citalopram. In people with reduced activity of the CYP2C19 enzyme, the plasma concentrations of citalopram observed were twice as high. In known slow CYP2C19 metabolisers, an initial posology of 10 mg should therefore be considered as a precautionary measure (see section 4.2).

5.3 Preclinical safety data
Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenic potential.

Phospholipidosis in several organs was observed in repeated dose toxicity studies in rats. This reversible effect is known for several lipophilic amines and was not connected with morphological and functional effects. The clinical relevance is not clear.

Reproduction toxicity studies in rats have demonstrated skeletal anomalies in the offspring but no increased frequency of malformations.

The effects may be related to the pharmacological activity or could be an indirect effect due to maternal toxicity. Peri- and postnatal studies have revealed reduced survival in offspring during the lactation period. The potential risk for humans is unknown.

Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in number in implantation and abnormal sperm at exposure well in excess of human exposure.

6. Pharmaceutical particulars

6.1 List of excipients
Tablet Core

Lactose monohydrate
Maize starch
Cellulose, microcrystalline
Povidone
Crospovidone
Magnesium stearate

Tablet Coating
Titanium dioxide (E171)
Lactose monohydrate|
Macrogol 4000
Hypromellose (E464)

6.2 Incompatibilities
Not applicable

6.3 Shelf life
2 years

6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container
PVC/PVdC blisters sealed with aluminium foil (also includes unit dose packs). Pack sizes of 10, 12, 14, 20, 28, 30, 49, 50, 56, 60, 98, 100 or 500 tablets.

PVC/PVdC blisters sealed with aluminium foil. Calendar pack size of 28 tablets.

High Density Polyethylene (HDPE) containers with polypropylene (PP) caps. Pack sizes of 12, 14, 20, 28, 50, 100 or 250 tablets.

Polypropylene tablet containers with polyethylene caps. Pack sizes of 12, 14, 20, 28, 50, 100 or 250 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling
No special requirements.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Citalopram Film Coated Tablets USP 40mg Taj Pharma

Package leaflet: Information for the patient

a) Citalopram Film Coated Tablets USP 10mg Taj Pharma
b) Citalopram Film Coated Tablets USP 20mg Taj Pharma
c) Citalopram Film Coated Tablets USP 40mg Taj Pharma

Important things you need to know about citalopram

Read all of this leaflet carefully before you start taking this medicine.

  • Citalopram treats depression and panic disorders but it will not work straight away. Like all medicines, it can have side-effects. It is important that you and your doctor talk about the benefits and the possible unwanted effects of the medicine before you start taking it.
  • Citalopram should not be taken by children or teenagers under 18 (see section 6 on page 4).
  • Citalopram will not work straight away. You may feel worse before feeling better after starting the medicine. Your doctor should ask to see you again 2 or 3 weeks after you first start taking the medicine. Tell your doctor if you feel no better. (see section 3 on page 2).
  • You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour (see section 2 on page 1).
  • If you feel restless or feel like you cannot keep still, go to your doctor. If you keep on taking more citalopram each day, it may make these feelings worse. (see section 5 on page 3).
  • Talk to your doctor before you stop taking citalopram. If you stop taking it suddenly or miss a dose you may get unwanted effects. (see section 4, on page 3).
  • Taking some other medicines with citalopram can cause problems. You may need to talk to your doctor first. (See section 2 on page 1).
  • If you are pregnant or planning to get pregnant, talk to your doctor before taking citalopram. (See section 2 on page 1).

 Read the rest of this leaflet carefully before taking this medicine

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. See section 5.

What is in this leaflet
1. What citalopram is and what it is used for
2. What you need to know before you take citalopram
3. How to take citalopram
4. Stopping citalopram
5. Possible side effects
6. Children and adolescents under 18
7. How to store citalopram
8. Contents of the pack and other information

1. What Citalopram is and what it is used for
Citalopram belongs to a group of antidepressants called SSRIs (selective serotonin reuptake inhibitors).

Citalopram is used to treat:

  • Depression
  • Panic disorders including fear of wide open spaces (agoraphobia) or crowds

Other medicines or psychotherapy can also treat these conditions. Treating your condition properly is important to help you get better. Without treatment your condition may get worse and be more difficult to treat.

2. What you need to know before you take citalopram
Do not take citalopram if:

  • You are allergic (hypersensitive) to citalopram or any of the other ingredients in this medicine (see Section 8: Further Information).
    Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
  • You are taking a MAOI (monoamine oxidase inhibitor) medicine, or have taken them in the last 2 weeks. Examples of MAOIs include: tranylcypromine, phenelzine and isocarboxazid (for depression) or selegiline (for Parkinson’s disease)
  • You are taking a medicine called moclobemide, or have taken it in the last 24 hours
  • You are taking pimozide (an antipsychotic medicine).
  • You are taking linezolid (an antibiotic medicine used to treat pneumonia and infections in skin)
  • You are born with or have had an episode of abnormal heart rhythm (seen at ECG; an examination to evaluate how the heart is functioning)
  • You take medicines for heart rhythm problems or that may affect the heart’s rhythm. Also refer to the section “Taking other medicines” below.

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking citalopram.

Thoughts of suicide and worsening of your depression or anxiety disorder
If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

You may be more likely to think like this:

  • If you have previously had thoughts about killing or harming yourself.
  • If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Warnings and precautions
Take special care and check with your doctor or pharmacist before taking citalopram if:

  • You have epilepsy or have ever had a fit
  • You have diabetes
  • You have or have ever had a history of overactive behaviour or thoughts (mania)
  • You are having ECT (electro-convulsive treatment).
  • You have bleeding disorders or have ever suffered from bleeding in the stomach or intestine or use anticoagulants (for thinning the blood)
  • You are taking this medicine for a panic disorder. You may need to be started on a lower dose.
  • You have problems with your eyes, such as certain kinds of glaucoma or you have in history of glaucoma.
  • You have liver disease.
  • You have severe kidney disease
  • You suffer or have suffered from heart problems or have recently had a heart attack
  • You have a low resting heart-rate and/or you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting (being sick) or usage of diuretics (water tablets)
  • You experience a fast or irregular heartbeat, fainting, collapse or dizziness on standing up which may be signs of an abnormal heart rate.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking citalopram.

Some patients with manic-depressive illness may enter into a manic phase. This is characterized by unusual and rapidly changing ideas, inappropriate happiness and excessive physical activity. If you experience this, contact your doctor.

Symptoms such as restlessness or difficulty in sitting or standing still can also occur during the first weeks of the treatment. Tell your doctor immediately if you experience these symptoms.

Pregnancy, breast-feeding and fertility
Ask your doctor or pharmacist for advice before taking any medicine. If you are pregnant, think you might be pregnant, or are trying to become pregnant, tell your doctor.

Do not take citalopram if you are pregnant unless you and your doctor have discussed the risks and benefits involved.

Make sure your midwife and/or doctor know you are on citalopram. When taken during pregnancy, particularly in the last 3 months of pregnancy, medicines like citalopram may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born. If this happens to your baby you should contact your midwife and/or doctor immediately. Also, if you take citalopram during the last 3 months of your pregnancy and until the date of birth you should be aware that the following effects may be seen in your newborn: trouble with breathing, stiff or loose muscles, jitteriness, a bluish skin or being too hot or cold. If your newborn baby gets any of these symptoms please contact your midwife and/or doctor immediately.

Citalopram may get into breast milk in very small amounts and may affect your baby. Talk to your doctor before you start breast-feeding.

Citalopram has been shown to reduce the quality of sperm in animal studies. Theoretically, this could affect fertility, but impact on human fertility has not been observed as yet.

Taking citalopram with other medicines:
DO NOT TAKE CITALOPRAM
 if you take medicines for heart rhythm problems or medicines that may affect the heart’s rhythm, e.g. such as Class IA and III antiarrhythmics, antipsychotics (e.g. fentiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarian treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine). If you have any further questions about this you should speak to your doctor.

Please tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because citalopram can affect the way some other medicines work. Also some medicines can affect the way citalopram works.

Some medicines should not be taken with citalopram (see Do not take citalopram above).

In particular, tell your doctor if you are taking any of the following:

  • Other medicines for depression (SSRIs, tricyclic antidepressants, such as clomipramine, nortriptyline, imipramine and desipramine, and medicines containing buproprion, oxitriptan and tryptophan)
  • Some medicines for mental illness (such as perphenazine, risperidone and lithium)
  • Medicines for epilepsy (such as phenytoin, sodium valproate, phenobarbital or carbamazepine)
  • Painkillers containing acetylsalicylic acid (such as aspirin) or non-steroidal anti-inflammatory medicines (NSAID’s) such as ibuprofen
  • Medicines for migraine such as sumatriptan (triptans)
  • Herbal products containing St John’s Wort
  • Medicines for pain such as tramadol
  • Medicines known to affect the blood platelets (e.g. anticoagulant drugs used to treat or prevent blood clots; aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and diclofenac used as painkillers and some antipsychotic drugs and tricyclic antidepressants).
  • Metoprolol, a beta blocker used to treat migraine, some heart conditions and high blood pressure.
  • Medicines for early-stage Parkinson’s disease such as selegiline
  • Lithium (used to prevent and treat mania) and tryptophan (an antidepressant)
  • Medicines used to heal active stomach and duodenal ulcers such as cimetidine
  • Antibiotics such as Linezolid
  • Mefloquine (used to treat malaria)
  • Neuroleptics (used in the treatment of schizophrenia)

Taking citalopram with food, drink and alcohol:
Citalopram can be taken with or without food. Do not drink alcohol whilst taking citalopram.

Driving and using machines
Citalopram has a minor or moderate influence on the ability to drive and use machines. You should be careful when driving, operating machinery or performing jobs that need you to be alert. Do not drive or use machines if you feel you are affected.

3. How to take citalopram
Always take Citalopram exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Your doctor will tell you how much to take when you first start taking it. Most people start to feel better after 2 to 3 weeks. If you do not feel any better after this time, talk to your doctor. He or she may tell you to take more of the medicine each day.

Taking citalopram:

  • Take your medicine at the same time every day
  • Swallow the tablets with a glass of water

How much to take:
Depression

  • The usual dose is 20 mg per day. This may be increased by your doctor to a maximum of 40mg per day.
  • The exact dose will depend on how your condition responds to treatment
  • You will normally be asked to keep taking this medicine for at least 6 months

Panic disorder (panic attacks):

  • The starting dose is 10mg per day for the first week before increasing the dose to 20-30mg per day. The dose may be increased by your doctor to a maximum of 40mg per day.
  • The exact dose will depend on how your condition responds to treatment.

Older people (above 65 years of age)
The starting dose should be decreased to half of the recommended dose, e.g. 10-20mg per day. Older people should not usually receive more than 20mg per day.

People with liver problems
Patients with liver complaints should not receive more than 20mg per day.

If you take more citalopram than you should:
If you think that you or anyone else may have taken too many citalopram tablets, contact your doctor or go to the nearest hospital straight away. Do this even if there are no signs of discomfort or poisoning. Signs could include: feeling sick (nausea), being sick (vomiting), dizziness, sweating, fits, being very sleepy, passing out or going into a coma, tremor, having a blue colour to the skin, fast short breathing, changes in blood pressure, a staring or fixed look on the face, changes in heart rhythm, a fast or irregular heartbeat, agitation, enlarged eye pupils or serotonin syndrome (see Section 5)

Take the carton and any tablets left with you. This is so that the doctor knows what you have taken.

If you forget to take citalopram:

  • If you forget a tablet and you remember before you go to bed, take it straight away. Carry on as usual the next day.
  • If you only remember during the night, or the next day, leave out the missed tablet. You may possibly feel different, but this should go away after you take your next tablet at the usual time.

If you have any further question on the use of this product, ask your doctor or pharmacist.

4. Stopping citalopram
Do not stop taking citalopram until your doctor tells you to.

When stopping citalopram, your doctor will help you to gradually take less of the medicine. This will be over a period of weeks or months. As you take less citalopram you may notice some side effects. If you notice any effects when you are stopping citalopram, tell your doctor. Your doctor may then ask you to start taking it again and reduce the dose more slowly.

Possible effects when stopping: feeling dizzy, feelings like pins and needles, feeling sick (nausea) or vomiting, feeling agitated or being anxious or having headaches, difficulty in falling asleep or staying asleep, vivid dreams, nightmares, tremor, confusion or disorientation, sweating, diarrhoea, palpitations, emotional instability, irritability and visual disturbances.

5. Possible side effects
Like all medicines, citalopram can cause side effects, although not everybody gets them.

Stop taking citalopram and see a doctor or go to a hospital straight away if:

  • Difficulty in breathing
  • You get swelling of the hands, feet, ankles, face, lips or throat which may cause difficulty in swallowing or breathing. You could also notice an itchy, lumpy rash (hives) or nettle rash (urticaria).
    This may mean you are having an allergic reaction to citalopram. This affects less than 1 in every 100 people who take citalopram.
  • You have thoughts of harming or killing yourself
  • You have a fit (seizure). This affects less than 1 in every 1000 people who take citalopram
  • Fast, irregular heartbeat, fainting which could be symptoms of a life-threatening condition known as Torsades de Pointes.

Talk to a doctor straightaway if:

  • You have unpleasant or distressing restlessness accompanied by inability to sit or stand.
  • You feel confused, restless, agitated, sweaty, shaky, shiver, high fever, confusion, see or hear things which are not there (hallucinations), jerking muscles, muscle spasm (which may also affect the jaw and tongue) or a fast heartbeat. You may have something called serotonin syndrome. This happens in only a very few people who take this medicine.
  • You notice changes in the way your heart beats, it may beat much faster or slower than normal
  • You have unusual bruising or bleeding. This affects less than 1 in 1000 people who take citalopram
  • You notice blood in your vomit or stools (motions)
  • You cannot pass water
  • You notice yellowing or your skin or eyes and your urine becomes darker in colour. This could be a liver problem, such as jaundice or hepatitis
  • You notice any of the following symptoms: trembling, muscle stiffness or spasm, slow movement, producing more saliva than usual or feeling restless. This affects less than 1 in every 100 people who take citalopram.
  • You start having fits for the first time or fits that you have suffered from in the past become more frequent
  • Your behaviour changes because you feel elated or over excited
  • You experience tiredness, confusion and twitching of your muscles. These may be signs of a low blood level of sodium (hyponatraemia).

The following side-effects may also occur:
Very common
 (may affect more than 1 in 10 people):

  • Feeling sick (nausea),
  • Being sleepy or drowsy, or finding it difficult to sleep
  • Headaches, dry mouth
  • Feeling weak, dizzy or shaky
  • Sweating more than usual
  • Changes in your sleeping pattern

Common (may affect up to1 in 10 people):

  • Diarrhoea, constipation
  • Feeling agitated or nervous
  • Feeling anxious
  • Feeling shaky or dizziness
  • Ringing in your ears (Tinnitus)
  • Strange or vivid dreams
  • Finding it hard to concentrate, forgetting things or feeling confused
  • Decreased or loss of appetite (anorexia), or losing weight
  • Becoming less interested or bothered by things
  • Lowered sex drive
  • Migraines
  • Muscles pain
  • Joint pain
  • Unusual skin sensations such as numbness, tingling, pricking, burning or creeping on the skin (paraesthesia), ‘pins and needles’. These could be signs of paraesthesia
  • Indigestion, being sick (vomiting), stomach ache, passing wind, or having more saliva than usual
  • Problems passing water or passing water more often than usual
  • A runny or itchy nose, blocked or painful sinuses
  • A rash or itching
  • Feeling tired or yawning
  • Painful period cramps
  • Sexual problems including being unable to get an erection, having delayed or no ejaculation, or being unable to have an orgasm, abnormal orgasm (female)
  • Very fast, uneven or forceful heartbeat (palpitations)
  • Loss of memory (amnesia)
  • Loss of weight
  • Tremor

Uncommon (may affect up to 1 in 100 people):

  • Feeling unusually happy (euphoria)
  • Increased appetite, putting on weight
  • Feeling detached from yourself (depersonalisation)
  • Seeing or hearing things that aren’t there (hallucinations)
  • Overactive behaviour or thoughts (mania)
  • Being more sensitive to sunlight
  • Aggression
  • Fainting
  • Menstrual periods which are heavier or last longer than usual
  • Water retention which may cause swollen arms or legs (Oedema)
  • Large pupils (the dark centre of eye)
  • Severe itching of the skin (with raised lumps)
  • Loss of hair, balding
  • Redness of the skin with blood spots
  • Bruising easily
  • Fast or slow heartbeat
  • Rash
  • Difficulties urinating

Rare (may affect up to 1 in 1000 people):

  • Tired, weak, confused and have muscles that ache, are stiff or do not work well. This may be due to low sodium levels in your blood
  • Increased sex drive
  • Changes in the way things taste
  • Fits or seizure
  • Coughing
  • Fever
  • Bleeding under skin or mucous membrane
  • Involuntary movements
  • Hepatitis
  • Feeling generally unwell

Not known (frequency cannot be estimated from the available data):

  • Panic attacks
  • Abnormal production of breast milk in men and women
  • Feeling dizzy when you stand up (postural hypotension)
  • Blurred vision
  • Clenching or grinding the teeth (Bruxism)
  • You may bruise more easily than usual. This could be because of a blood disorder (thrombocytopenia)
  • Liver problems shown by blood tests
  • An increased risk of bone fractures has been observed in patients taking this type of medicines.
  • Feeling unwell, confused or weak, feeling sick (nausea), loss of appetite, feeling irritable. This could be an illness called ‘syndrome of inappropriate anti-diuretic hormone secretion’ (SIADH). This rare side effect is more likely to happen if you are elderly.
  • Tiredness, confusion, and muscle weakness and muscle cramps. This may be due to low levels of potassium in your body (hypokalaemia)
  • Nose bleed (Epistaxis)
  • Wide spreading of bruising (Ecchymosis)
  • Bleeding between menstrual periods
  • A persistent or painful erection that lasts for several hours (priapism).
  • Rash (hypersensitivity)
  • Restlessness
  • Unusual movements or stiffness
  • Involuntary movements of the muscles (akathisia)
  • Low blood pressure
  • Sudden swelling of skin or mucosa
  • Abnormal heart rhythm

SSRIs can, very rarely increase the risk of bleeding, including stomach or intestinal bleeding. Let your doctor know if you vomit blood or develop black or blood stained stools.

Also let your doctor know if you continue to have other symptoms associated with your depression. This might include hallucinations, anxiety, mania or confusion.

Any side effects that do occur will usually disappear after a few days. If they are troublesome or persistent, or if you develop any other unusual side effects while taking Citalopram, please tell your doctor.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

6. Children and adolescents under 18
Use in children and adolescents under 18 years of age

Citalopram should normally not be used for children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side-effects such as suicide and suicidal behaviour when they take this type of medicine. Despite this, your doctor may prescribe citalopram for patients under 18 because he/she decides that this is in their best interests. If your doctor has prescribed citalopram for a patient under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the symptoms listed below start or get worse when patients under 18 are taking citalopram.

Among children and teenagers under 18 given citalopram, these side effects are common

  • Increased thoughts about suicide and suicide attempts
  • Being hostile, aggressive or unfriendly
  • Being agitated

7. How to store citalopram
Keep out of the sight and reach of children.
Store in the original packaging
Do not use after the expiry date stated on the pack.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

8. Contents of the pack and other information

What Citalopram film-coated Tablets contains:
The active substance is: citalopram hydrobromide
a) Each tablet contains: Citalopram Hydrobromide USP (equivalent to 10mg of Citalopram)
b) Each tablet contains: Citalopram Hydrobromide USP (equivalent to 20mg of Citalopram)
c) Each tablet contains: Citalopram Hydrobromide USP (equivalent to 40mg of Citalopram)
The other ingredients are: mannitol, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate. The film-coating contains hypromellose, titanium dioxide (E171) and macrogol 6000.

What Citalopram 10mg, 20mg and 40mg film-coated Tablets look like and contents of the pack:
This medicine comes in blister packs of 28 film-coated tablets.

  • Citalopram 10 mg tablets are round, biconvex, white film coated tablets, diameter 6 mm.
  • Citalopram 20 mg tablets are round biconvex, white film coated tablets, diameter 8 mm, with a score line.
  • Citalopram 40 mg tablets are round biconvex, white film coated tablets, diameter 10 mm, with a score line.

9. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.