Arrow Citalopram Tablets

ARROW CITALOPRAM is indicated for the treatment of:

• Depression and prevention of relapse.
• Panic disorder with or without agoraphobia.
• Obsessive-compulsive disorder (OCD).

Posology

Depression: 20mg a day as a single dose. Dosage may be increased by 20mg a day at intervals of at least one week to a maximum of 60 mg depending on the patient's response.

Obsessive Compulsive Disorder: 20 mg a day as a single dose. This dose can be increased by 20 mg increments to a maximum of 60 mg a day depending on the patient's response.

If the decision is made to discontinue treatment with ARROW CITALOPRAM, it is recommended that the dose should be decreased gradually to prevent the possibility of withdrawal symptoms (see section 4.4).

Special populations:

Renal impairment: Dose adjustment is not necessary in cases of mild or moderate renal impairment. The onset of action is seen within 2 to 4 weeks. Treatment should be continued for an appropriate length of time (up to six months) after recovery in order to prevent relapse. The medicine should be gradually withdrawn during a couple of weeks when stopping therapy.

Method of administration

For oral use. ARROW CITALOPRAM may be taken with or without food in the morning or evening.

• Hypersensitivity to citalopram or any of the ingredients in the formulation.
• MAOIs (monoamine oxidase inhibitors): Cases of serious and sometimes fatal reactions have been reported in patients receiving as SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the selective MAO-B inhibitor selegiline and the reversible MAOI (RIMA), moclobemide and in patients who have recently discontinued as SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome. ARROW CITALOPRAM must not be used in combination with MAOI, including selegiline in doses above 10 mg daily. Concurrent use with a monoamine oxidase inhibitor (MAOI). At least 14 days should lapse between discontinuing the MAOI and initiating therapy with ARROW CITALOPRAM. MAOIs should not be introduced for 7 days after discontinuation of ARROW CITALOPRAM (see section 4.5).
• Severe renal impairment (creatinine clearance less than 20 ml/min).
• Safety and efficacy in pregnancy and lactation has not been established.
• Children under the age of 18 years (See section 4.4 and 4.8).
• Concomitant treatment with pimozide (See section 4.5).
• ARROW CITALOPRAM is contraindicated in combination with linezolid (See section 4.5).
• ARROW CITALOPRAM is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome (See section 4.4, 4.8 and 5.1).

Warnings

ARROW CITALOPRAM should be used with caution in:

Use in children and adolescents under 18 years of age - Safety and efficacy in children under 18 years of age have not been established. In clinical trials in Major Depressive Disorder, there were increased reports of hostility (predominantly aggression, oppositional behaviour and anger) and suicide u2013 related adverse events such as suicidal ideation and self-harm. In addition, long-term safety data in children and adolescents concerning growth, maturation and concerning growth, maturation and cognitive and behavioural development are lacking.

Elderly patients - longer half-life and decreased clearance due to a reduced rate of metabolism. A lower dose is recommended in the elderly.

Hepatic impairment - clearance of ARROW CITALOPRAM is reduced. Cautious dosage titration and a lower maximum dose are recommended.

Renal impairment - elimination is decreased. If creatine clearance is less than 20 ml/min, ARROW CITALOPRAM should not be used. (See section 4.3).

Seizures or history thereof u2013 there is an increased risk of seizures. ARROW CITALOPRAM should be discontinued in any patient who develops seizures. ARROW CITALOPRAM should be used with caution in patients with controlled epilepsy and avoided in patients who are poorly controlled epileptics. ARROW CITALOPRAM should be discontinued if there is an increase in seizure frequency.

ECT (electroconvulsive therapy) - Care is advised in patients receiving electroconvulsive therapy.

Mania or history of mania u2013 condition may be re-activated. ARROW CITALOPRAM should be discontinued if the patient enters the manic phase.

ARROW CITALOPRAM may cause a reduction in heart rate. Caution is advised in patients with pre-existing slow heart rates.

Diabetes mellitus u2013 rare occurrences of hypoglycaemia have been reported. In patients with diabetes, treatment with an SSRI, including ARROW CITALOPRAM may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Use with other medicines - ARROW CITALOPRAM should not be used with monoamine oxidase inhibitors, imipramine, other serotonergic medicines, moclobemide, alcohol, warfarin, and cimetidine (see section 4.5).

Risk of serotonin syndrome, a rare but potentially hyperserotonergic state, if combined with other serotonin medicines (see section 4.5).

Suicide/suicidal thoughts or clinical worsening - Patients with major depressive disorder, both adults and children may experience worsening of their depression and or the emergence of suicidal ideation and behavior, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. A causal role, however, for antidepressant medicines in inducing such behavior has not been established. Patients being treated with ARROW CITALOPRAM should, nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning or a course of therapy, or at any time of dose changes, either increases or decreases.

Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders.

The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing ARROW CITALOPRAM, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patientu2019s presenting symptoms.

If the decision is made to discontinue treatment with ARROW CITALOPRAM, it is recommended that the dose should be decreased gradually to prevent the possibility of withdrawal symptoms (see section 4.4 and 4.8)

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 of ARROW CITALOPRAM is advised to reduce the likelihood of a paradoxical anxiogenic effect (see section 4.2).

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

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 of ARROW CITALOPRAM may be detrimental.

Serotonin syndrome - Serotonin syndrome has been reported in patients using SSRIs. Serotonin syndrome is more likely to occur after an increase in dose. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. Treatment with ARROW CITALOPRAM should be discontinued immediately and symptomatic treatment initiated.

Serotonergic medicines u2013 ARROW CITALOPRAM should not be used concomitantly with medicines with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan, and tryptophan (see section 4.5).

Haemorrhage - There have been reports of cutaneous bleeding time and/or bleeding abnormalities such as ecchymoses, gynaecological haemorrhages, gastrointestinal bleedings, and other cutaneous or mucous bleedings with SSRIs (see section 4.8). Caution is advised in patients taking ARROW CITALOPRAM, particularly with concomitant use of active substances known to affect platelet function or other active substances that can increase the risk of haemorrhage, as well as in patients with a history of bleeding disorders (see section 4.5).

Post-partum haemorrhage u2013 There has been evidence of an association between antidepressants [particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin non-selective reuptake inhibitors (SNRIs)] and post-partum haemorrhage (PPH). Observational data indicate an increased risk (less than 2 u2013 fold) of postpartum haemorrhage PPH following SSRI/SNRI exposure within the month prior to birth. Healthcare professionals should be aware of the potential risk of PPH while making treatment decisions for prescribing SSRI/SNRI towards the end of pregnancy. Patients should be advised to inform their doctors before taking SSRI/SNRI if they have history of bleeding disorders, such as van Willebrand disease (VWD) or haemophilia or if they are pregnant.

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

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

QT interval prolongation u2013 ARROW CITALOPRAM has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular dysrhythmia 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 dysrhythmias and should be corrected before treatment with ARROW CITALOPRAM is started. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started. If signs of cardiac dysrhythmia occur during treatment with ARROW CITALOPRAM, the treatment should be withdrawn, and an ECG should be performed.

Withdrawal symptoms - After prolonged administration, abrupt cessation of ARROW CITALOPRAM may produce withdrawal symptoms such as dizziness, sensory disturbances (including paraesthesia), 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 in some patients. These symptoms are not indicative of addiction. It is recommended that withdrawal of treatment should proceed by gradually tapering off the dosage over a period of several weeks or months, according to the patient's needs to avoid occurrence of discontinuation symptoms.

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.

Special precautions

Patients should be monitored during early therapy until improvement in depression is observed because suicide is an inherent risk in depressed patients.

Alcohol - Avoid alcohol (see section 4.5).

ARROW CITALOPRAM contains lactose which may have an effect on the glycaemic control of patients with diabetes mellitus. ARROW CITALOPRAM contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take ARROW CITALOPRAM.

• Monoamine oxidase inhibitors (MOAI) - concurrent use is contra-indicated. Serious and potentially fatal reactions have occurred in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the irreversible MAOI selegiline, the reversible MAOIs linezolid and moclobemide and in patients who have recently discontinued SSRI and have been started on a MAOI. Some cases presented with features resembling serotonin syndrome.
• Moclobemide - serotonin syndrome has developed after taking overdoses of moclobemide and ARROW CITALOPRAM. Symptoms of citalopram interaction with MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuation of vital signs and mental status changes including extreme agitation progressing to delirium and coma (see section 4.3).
• Serotonergic medicines Lithium and tryptophan: However, there have been reports of enhanced effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of ARROW CITALOPRAM with these medicines should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual.
• Co-administration with serotonergic medicines (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects. The simultaneous use of ARROW CITALOPRAM and 5-HT agonists, such as sumatriptan and other triptans, is not recommended (see section 4.4).
• St. Johnu2019s Wort u2013 Pharmacodynamic interactions between SSRIs such as ARROW CITALOPRAM and herbal remedy St. Johnu2019s wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects (see section 4.4).
• Medicines lowering the seizure threshold ARROW CITALOPRAM can lower the seizure threshold. Caution is advised when concomitantly using other medicines capable of lowering the seizure threshold (e.g. antidepressants [tricyclic, other SSRIs], neuroleptics [phenothiazines, thioxanthenes, and butyrophenones], mefloquine, bupropion and tramadol).
• Imipramine u2013 an increase in the concentration of desimipramine (the active metabolite of imipramine) may occur. It appears that ARROW CITALOPRAM does not cause a marked increase in plasma levels of some tricyclic antidepressants.
• QT interval prolongation u2013 An additive effect of ARROW CITALOPRAM and these medicines cannot be excluded. Therefore, co-administration of ARROW CITALOPRAM with medicines that prolong the QT interval, such as a Class IA and III antidysrhythmics, antipsychotic (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimalarial treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine), should only be prescribed after careful consideration.
• Other serotonergic medicines or medicines with serotonergic activity u2013 increased risk of developing the serotonin syndrome, a rare but potentially fatal hyperserotonergic state.
• Alcohol u2013 the effects of alcohol may be increased.
• Warfarin u2013 the anticoagulant activity of warfarin may be increased. Simultaneous treatment with anticoagulants, medicines that affect the platelet function, such as non-steroidal anti-inflammatory medicines (NSAIDs), acetylsalicylic acid, dipyridamol, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) can increase the risk of haemorrhage (see section 4.4).
• Cimetidine - the AUC and the maximum plasma concentration of ARROW CITALOPRAM are increased when ARROW CITALOPRAM is administered concurrently with cimetidine.

PREGNANCY AND LACTATION: Safety and efficacy in pregnancy and lactation has not been established. ARROW CITALOPRAM is excreted into the breast milk.

Pregnancy

Safety and efficacy in pregnancy has not been established. The following symptoms may occur in neonates after maternal SSRI 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 such as ARROW CITALOPRAM in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Neonates should be observed if maternal use of ARROW CITALOPRAM continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy.

Breastfeeding

Safety and efficacy in lactation has not been established. ARROW CITALOPRAM is excreted into the breast milk.

Fertility

Animal data have shown that citalopram may affect sperm quality. 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.

ARROW CITALOPRAM may impair performance of skilled tasks. If affected these patients should not operate machinery or drive.

a. Summary of the safety profile

Adverse events observed with ARROW CITALOPRAM are most frequent during the first one or two weeks of treatment, and usually decrease in intensity and frequency as the depressive state improves. For the following reactions a dose-response was discovered: Sweating increased, dry mouth, insomnia, somnolence, diarrhoea, nausea and fatigue.

b. Tabulated list of adverse reactions

c. Description of selected adverse reactions

Suicide/suicidal thoughts or clinical worsening Cases of suicidal ideation and suicidal behaviour have been reported during citalopram therapy or early after treatment discontinuation (see section 4.4).

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 the risk is unknown.

QT interval prolongation Cases of QT prolongation and ventricular dysrhythmia 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 interval prolongation of other cardiac diseases (see section 4.3, 4.4, 4.5, 4.9 and 5.1).

Withdrawal symptoms seen on discontinuation of citalopram treatments Discontinuation of citalopram commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor and headache 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 (see section 4.). It is therefore advised that when ARROW CITALOPRAM treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

Children and adolescents under 18 years of age Hostility, suicidal ideation and self-harm have been reported in children under 18 years of age (see section 4.3).

*This event has been reported for the therapeutic class of SSRIs/SNRIs (see section 4.4 and 4.6).

Overdose

Symptoms of overdose: Tiredness. weakness, sedation, dizziness, tremor, nausea, somnolence and sinus tachycardia, sedation, convulsion, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, bundle branch block, QRS prolongation, hypertension, and mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, and atrial- and ventricular dysrhythmia.

Treatment of overdose: Treatment is symptomatic and supportive. There is no specific antidote to ARROW CITALOPRAM. Monitoring of cardiac and vital signs is necessary and medical surveillance is advisable for about 24 hours.