Cipramil

/ Lundbeck

Depression: Citalopram should be administered as a single oral dose of 20 mg daily. Dependent on individual patient response this may be increased to a maximum of 40 mg daily.
Duration of treatment: The antidepressant effect usually sets in after 2 to 4 weeks. Treatment with antidepressants is symptomatic and must therefore be continued for an appropriate length of time, usually up to 6 months after recovery in order to prevent relapse. In patients with recurrent depression (unipolar) maintenance therapy may need to be continued for a number of years to prevent new episodes.
Panic Disorder: A single oral dose of 10 mg daily is recommended for the first week before increasing the dose to 20 mg daily. Dependent on individual patient response, the dose may be further increased, up to a maximum of 40 mg daily.
Duration of treatment: Maximum effectiveness of citalopram in treating panic disorder is reached after about 3 months and the response is maintained during continued treatment.
Elderly patients (>65 years of age): For elderly patients the dose should be decreased to half the recommended dose, e.g. 10-20mg daily. The recommended maximum dose for the elderly is 20mg daily.
Children and adolescents (<18 years): Cipramil should not be used in the treatment of children and adolescents under the age of 18 years.
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.
Reduced renal function: Dosage adjustment is not required if the patient has mild or moderate renal impairment. Caution is advised in patients with severe renal impairment.
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.
Withdrawal symptoms seen on discontinuation of SSRI: 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 reactions. 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.

For the treatment of states of Depression & Panic disorder.

Hypersensitivity to citalopram or to any of the excipients. MAOIs (monoamine oxidase inhibitors) Citalopram should not be given to patients receiving Monoamine Oxidase Inhibitors (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) as stated in the prescribing text of the RIMA. MAOIs should not be introduced for seven days after discontinuation of citalopram. Citalopram is contraindicated in the combination with linezolid unless there are facilities for close observation and monitoring of blood pressure. Concomitant treatment with pimozide. Citalopram is contraindicated in patients with known QT-interval prolongation or congenital long QT syndrome.

Treatment of elderly patients and patients with reduced kidney and liver function.
Use in children and adolescents under 18 years of age: Antidepressants should not be used in the treatment of children and adolescents under age of 18 years. Suicide related behaviors (suicide attempt and suicidal thoughts), and hostility (predominately 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.
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.
Hyponatraemia: Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported as a rare adverse reaction with the use of SSRIs and generally reverse on discontinuation of therapy. Elderly female patients seem to be at higher risk.
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 are 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.
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.
Mania: In patients with manic-depressive illness a change towards the manic phase may occur. Should the patient enter a manic phase citalopram should be discontinued.
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.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
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. Treatment with citalopram should be discontinued immediately and symptomatic treatment initiated.
Serotonergic medicines: Citalopram should not be used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan, and tryptophan.
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. Caution is advised in patients taking SSRIs, particularly with concomitant use of oral anticoagulants; drugs 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.
ECT (electroconvusive therapy): There is limited clinical experience of concurrent administration of SSRIs and ECT; therefore caution is advisable.
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.
Withdrawal symptoms seen on discontinuation of SSRI treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. 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), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. 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.
Psychosis: Treatment of psychotic patients with depressive episodes may increase psychotic symptoms.
QT interval prolongation: Citalopram has been found to cause a dose-dependent prolongation of the QTinterval. 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 hypokalemia, or with pre-existing QT prolongation or other cardiac diseases. 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. 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.
Excipients: The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp deficiency or glucose-galactose malabsorption should not receive this medicine.
For full details see prescribing information.

Metabolism and nutrition disorders: Common: Appetite decreased, weight decreased.
Psychiatric disorders: Common: Agitation, libido decreased, anxiety, nervousness, confusional state, abnormal orgasm (female), abnormal dreams.
Nervous system disorders: Very common: Somnolence, insomnia. Common: Tremor, paraesthesia, dizziness, disturbance in attention.
Ear and labyrinth disorders: Common: Tinnitus.
Gastrointestinal disorders: Very common: Dry mouth, nausea. Common: Diarrhoea, vomiting, constipation.
Skin and subcutaneous tissue disorders: Very common: Sweating increased. Common: Pruritus.
Musculoskeletal, connective tissue & bone disorders: Common: Myalgia, arthralgia.
Reproductive system & breast disorders: Common: Impotence, ejaculation disorder, ejaculation failure.
General disorders & administration site conditions: Common: Fatigue.
For full details see prescribing information.

Pharmacodynamic interactions: At the pharmacodynamic level cases of serotonin syndrome with citalopram, moclobemide and buspirone have been reported.
Contraindicated combinations: MAO-inhibitors The simultaneous use of citalopram and MAO-inhibitors can result in severe undesirable effects, including the serotonin syndrome. 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 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. Symptoms of an active substance interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma.
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.
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 drugs should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual. Co administration with serotonergic medicinal products (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects. Until further information is available, the simultaneous use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is not recommended.
St. John’s Wort: Dynamic interactions between SSRIs and herbal remedy St John’s wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects. Phrmacokinetic interactions have not been investigated.
Haemorrhage: Caution is warrented for patients who are being treated simultaneously with anticoagulants, medicinal products that affect platelet function, such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamol, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants) ) that can increase the risk of haemorrhage. ECT (electroconvusive therapy) There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and citalopram.
Alcohol: No pharmacodynamic or pharmacokinetic interactions have been demonstrated between citalopram and alcohol. However, the combination of citalopram and alcohol is not advisable.
For full details see prescribing information.

Pregnancy: Published data on pregnant women (more than 2500 exposed outcomes) indicate no malformative feto-/ neonatal toxicity. However, citalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of 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 SSRIs/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, hypoglycaemia, hypotona, hyperreflexia, jitteriness, irritability, lethargy, constant crying, somnolence, tremor, hypertonia, increased muscle tone, difficulty in 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, particularly 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. 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.
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.

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, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, and mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation and atrial and ventricular arrhythmia.
Management: There is no specific antidote to citalopram. Treatment should be symptomatic and supportive. Activated charcoal, osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered. If consciousness is impaired the patient should be intubated. ECG and vital signs should be monitored. 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.