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Name of the medicinal product Qualitative and quantitative composition Pharmaceutical form Clinical particulars - 4.1 Therapeutic indications - 4.2 Posology and method of administration - 4.3 Contraindications - 4.4 Special warnings and precautions for use - 4.5 Interaction with other medicinal products and other forms of interaction - 4.6 Fertility, pregnancy and lactation - 4.7 Effects on ability to drive and use machines - 4.8 Undesirable effects - 4.9 Overdose Pharmacological properties - 5.1 Pharmacodynamic properties - 5.2 Pharmacokinetic properties - 5.3 Preclinical safety data Pharmaceutical particulars - 6.1 List of excipients - 6.2 Incompatibilities - 6.3 Shelf life - 6.4 Special precautions for storage - 6.5 Nature and contents of container - 6.6 Special precautions for disposal and other handling Marketing authorisation holder Marketing authorisation number(s) Date of first authorisation/renewal of the authorisation Date of revision of the text - Legal category Excipients with known effect:LactoseFor the full list of excipients, see section 6.1. Elderly patients (> 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 maximum dose for the elderly is 20 mg daily. Children and adolescents (< 18 years of age)Citalopram should not be used in the treatment of children and adolescents under the age of 18 years (see section 4.4). Reduced hepatic functionAn 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 (see section 5.2). Reduced renal functionDosage adjustment is not necessary in cases of mild or moderate renal impairment. No information is available in cases of severe renal impairment (creatinine clearance <20 mL / min). Poor metabolisers of CYP2C19An 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 citalopramAbrupt 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 (see section 4.4 Special Warnings and Precautions for Use and section 4.8 Undesirable Effects). 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 administrationCitalopram tablets are administered as a single daily dose. Citalopram tablets can be taken at any time of the day without regard to food intake. Suicide/suicidal thoughts or clinical worseningDepression 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 Cipramil 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. Use in children and adolescents under 18 years of ageCipramil should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt 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. Elderly patientsCaution should be used in the treatment of elderly patients (see section 4.2). Reduced kidney and liver functionCaution should be used in the treatment of patients with reduced kidney and liver function (see section 4.2). Paradoxical anxietySome 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). HyponatraemiaHyponatraemia, probably due to inappropriate antidiuretic 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. Akathisia/psychomotor restlessnessThe 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. ManiaIn patients with manic-depressive illness a change towards the manic phase may occur. Should the patient enter a manic phase citalopram should be discontinued. SeizuresSeizures 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. DiabetesIn patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted. Angle-closure GlaucomaSSRIs 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. Serotonin syndromeIn 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 medicinesCitalopram should not be used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan and tryptophan. HaemorrhageThere have been reports of prolonged bleeding time and /or bleeding abnormalities such as ecchymoses, gynaecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucous bleedings with SSSRIs (see section 4.8). Caution is advised in patients taking SSRIs, 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).ECT (electroconvulsive therapy)There is limited clinical experience of concurrent administration of SSRIs and ECT; therefore caution is advisable. Reversible, selective MAO-A inhibitorsFor information on concomitant treatment with non-selective, irreversible MAO-inhibitors see section 4.5. St. John's wortUndesirable 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). Withdrawal symptoms seen on discontinuation of SSRI treatmentWithdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8 Undesirable effects). In a recurrence prevention clinical trial with citalopram, adverse events after discontinuation of active treatment were seen in 40% 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, diarrhoea, 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 (see Withdrawal symptoms seen on discontinuation of citalopram, Section 4.2) PsychosisTreatment of psychotic patients with depressive episodes may increase psychotic symptoms. QT-interval prolongationCitalopram 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. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment 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 signs of cardiac arrhythmia occur during treatment with citalopram, the treatment should be withdrawn and an ECG should be performed. ExcipientsThe tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not receive this medicine. Pharmacodynamic interactionsAt the pharmacodynamic level cases of serotonin syndrome with citalopram and moclobemide and buspirone have been reported. Contraindicated combinations MAO-inhibitorsThe 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 irreversible MAOI selegiline and the reversible MAOIs linezolid and 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. Symptoms of an active substance interaction with a MAOI include: agitation, tremor, myoclonus, and hyperthermia. QT interval prolongationPharmacokinetic 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. PimozideCo-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 productsLithium and tryptophanNo 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 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 (see section 4.4). St. John's wortDynamic 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. HaemorrhageCaution 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) that can increase the risk of haemorrhage (see section 4.4). ECT (electroconvusive 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). AlcoholNo 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/hypomagnesaemiaCaution is warranted for concomitant use of hypokalaemia- / hypomagnesaemia-inducing medicinal products as these conditions increase the risk of malignant arrhythmias. Medicinal products lowering the seizure thresholdSSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g. antidepressants [SSRIs], neuroleptics [thioxanthenes and butyrophenones]), mefloquine, bupropion and tramadol). Pharmacokinetic interactionsBiotransformation of citalopram to demethylcitalopram is mediated by CYP2C19 (approx. 38%), CYP3A4 (approx. 31%) and CYP2D6 (approx. 31%) isozymes of the cytochrome P450 system. The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation is less likely as inhibition of one enzyme may be compensated by another. Therefore co-administration of citalopram with other medicinal products in clinical practice has very low likelihood of producing pharmacokinetic medicinal product interactions. FoodThe 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 citalopramCo-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). CimetidineCimetidine (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. 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). A reduction in the dose of citalopram may be necessary based on monitoring of undesirable effects during concomitant treatment. MetoprololEscitalopram (the active enantiomer of citalopram) is an inhibitor of the enzyme CYP2D6. Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, 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. Co-administration with metoprolol resulted in a twofold increase in the plasma levels of metoprolol, but did not statistically significant increase the effect of metoprolol on the blood pressure and cardiac rhythm. Effects of citalopram on other medicinal productsA pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a twofold increase in metoprolol concentrations, but no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers. 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. Levomepromazine, digoxin, carbamazepineNo change or only very small changes of 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, imipramineIn 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. PregnancyPublished 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 risk/benefit. Neonates should be observed if maternal use of citalopram continues into the later stages of pregnancy, particular 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, 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-feedingCitalopram 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. If treatment with citalopram is considered necessary, discontinuation of breast feeding should be considered. FertilityAnimal 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. Class effectsEpidemiological 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), 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. 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 reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard ToxicityComprehensive 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. Fatal dose is not known. Patients have survived ingestion of more than 2 g citalopram. The effects may be potentiated by alcohol taken at the same time. Potential interaction with TCAs, MAOIs and other SSRIs. SymptomsThe following symptoms have been seen in reported overdose of citalopram: convulsion, tachycardia, somnolence, QT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, hyperpyrexia, and atrial and ventricular arrhythmia.ECG changes including nodal rhythm, prolonged QT intervals and wide QRS complexes may occur. Fatalities have been reported. Prolonged bradycardia with severe hypotension and syncope has also been reported. Rarely, features of the "serotonin syndrome" may occur in severe poisoning. This includes alteration of mental status, neuromuscular hyperactivity and autonomic instability. There may be hyperpyrexia and elevation of serum creatine kinase. Rhabdomyolysis is rare. TreatmentThere is no known specific antidote to citalopram. Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of ECG and vital signs until stable. 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. Consider oral activated charcoal in adults and children who have ingested more than 5 mg/kg body weight within 1 hour. Activated charcoal given ½ hour after ingestion of citalopram has been shown to reduce absorption by 50%. Osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered. If consciousness is impaired the patient should be intubated. Control convulsions with intravenous diazepam if they are frequent or prolonged. Pharmacotherapeutic group: antidepressants, selective serotonin reuptake inhibitors ATC-code: N 06 AB 04 Mechanism of actionBiochemical and behavioural studies have shown that citalopram is a potent inhibitor of the serotonin (5-HT)-uptake. Tolerance to the inhibition of 5-HT-uptake is not induced by long-term treatment with citalopram. Citalopram is a very 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-HT 1A, 5-HT2, DA D1 and D2 receptors, a1-, a2-, B-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors. A series of functional in vitro tests in isolated organs as well as functional in vivo tests have confirmed the lack of receptor affinity. 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 many of the newer SSRIs. The metabolites do not contribute to the overall antidepressant effect. Pharmacodynamic effectsSuppression of rapid eye movement (REM) sleep is considered a predictor of antidepressant activity. Like tricyclic antidepressants, other SSRIs and MAO inhibitors, citalopram suppresses REM-sleep and increases deep slow-wave sleep. 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. 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). AbsorptionAbsorption is almost complete and independent of food intake (T maxaverage/mean 3.8 hours). Oral bioavailability is about 80%. DistributionThe apparent volume of distribution (Vd)B is about 12.3 L/kg. The plasma protein binding is below 80% for citalopram and its main metabolites. BiotransformationCitalopram is metabolized to the active demethylcitalopram, didemethylcitalopram, citalopram-N-oxide and an inactive deaminated propionic acid derivative. All the active metabolites are also SSRIs, although weaker than the parent compound. Unchanged citalopram is the predominant compound in plasma. EliminationThe elimination half-life (T½B) is about 1.5 days and the systemic citalopram plasma clearance (Cls) is about 0.33 L/min, and oral plasma clearance (Cl oral) 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 about 0.068 L/min. The kinetics are linear. Steady state plasma levels are achieved in 1-2 weeks. Average concentrations of 250 nmol/L (100-500 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) Longer half-lives and decreased clearance values due to a reduced rate of metabolism have been demonstrated in elderly patients. Reduced hepatic functionCitalopram is eliminated more slowly in 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. Reduced renal functionCitalopram 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 <20 mL/min). Acute toxicityCitalopram has low acute toxicity. Chronic toxicityIn chronic toxicity studies there were no findings of concern for the therapeutic use of citalopram. Reproduction studiesBased on data from reproduction toxicity studies (segment I, II and III) there is no reason to have special concern for the use of citalopram in women of child-bearing potential. Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in the implantation number and abnormal sperm at exposure well in excess of human exposure. Mutagenic and carcinogenic potentialCitalopram has no mutagenic or carcinogenic potential. Lundbeck Limited Building K1, Timbold Drive, Kents Hill, Milton Keynes, MK7 6BZ Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why? Active ingredients Legal categories This site uses cookies. 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Seroxat tablete (20/30mg) – Uputa o lijeku Proizvođač: Belupo Samo na recept? DA Skoči na: » opis » primjena » doziranje » mjere opreza » napomene Opis SASTAV 1 SEROXATTM 20 mg tableta sadržava 20 mg paroksetina u obliku paroksetin-klorid hemihidrata. Pomoćne tvari: boja E171. 1 SEROXATTM 30 mg tableta sadržava 30 mg paroksetina u obliku paroksetin-klorid hemihidrata. Pomoćne tvari: boje E 171 i E132. FARMACEUTSKI OBLIK I VELIČINA PAKIRANJA Filmom obložena tableta. Blister s 10 tableta, 3 blistera u kutiji. FARMAKOTERAPIJSKA SKUPINA Paroksetin je antidepresiv iz skupine selektivnih inhibitora ponovne pohrane serotonina. NAČIN I MJESTO IZDAVANJA Na recept , u ljekarnama. ROK VALJANOSTI Otisnut je na pakiranju. Lijek se ne smije primijeniti nakon isteka roka valjanosti! NAČIN ČUVANJA LIJEKA Lijek treba čuvati pri temperaturi do 25°C. Lijek treba čuvati izvan dohvata djece! Primjena Terapijske indikacije Odrasli SEROXAT se primjenjuje u liječenju: - teške depresivne epizode - opsesivno kompulzivnog poremećaja - paničnog poremećaja sa ili bez agorafobije - socijalnog anksioznog poremećaja / socijalne fobije - posttraumatskog stresnog poremećaja - generaliziranog anksioznog poremećaja. Djeca/Adolescenti SEROXAT nije namijenjen za liječenje djece i adolescenata do 18 godina. Naime, kontrolirana klinička ispitivanja nisu dokazala djelotvornost i ne podupiru primjenu paroksetina u liječenju velikog depresivnog poremećaja kod djece i adolescenata do 18 godina. Primjena paroksetina u djece mlađe od 7 godina nije ispitivana. Doziranje Doziranje i način primjene Preporuča se primjenjivati SEROXAT jednom dnevno, ujutro, uz jelo. Bolesnike s depresijom ili opsesivno kompulzivnim poremećajem treba liječiti dovoljno dugo kako bi osigurali nestanak simptoma bolesti. To može biti razdoblje od nekoliko mjeseci za depresiju, a još dulje za opsesivno kompulzivni i panični poremećaj. Teška depresivna edpizoda Preporučena doza je 20 mg paroksetina na dan. Poboljšanje obično nastupa nakon tjedan dana liječenja, ali u nekim slučajevima su potrebna i 2 tjedna. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se povećava za po 10 mg u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Tri do četiri tjedna od početka liječenja doziranje se mora nadgledati i, ovisno o kliničkom odgovoru, korigirati. Opsesivno kompulzivni poremećaj Preporučena doza je 40 mg paroksetina na dan. Liječenje započinje s 20 mg paroksetina na dan, a doza se može postupno povećavati za po 10 mg u skladu s terapijskim učinkom lijeka, do postizanja preporučene dnevne doze. Najviša dnevna doza je 60 mg paroksetina. Panični poremećaj Preporučena doza je 40 mg paroksetina na dan. Liječenje započinje s 10 mg paroksetina na dan i doza se povećava za po 10 mg paroksetina, u skladu s terapijskim učinkom. Doza se može povećavati do najviše 60 mg paroksetina na dan. Niska početna doza se preporuča zbog izbjegavanja mogućeg pogoršanja simptoma panike do kojih općenito dolazi u ranoj fazi liječenja ovog poremećaja. Socijalni anksiozni poremećaj / Socijalna fobija Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Posttraumatski stresni poremećaj Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Generalizirani anksiozni poremećaj Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Prestanak primjene paroksetina Kao i kod drugih psihoaktivnih lijekova, općenito treba izbjegavati nagli prestanak primjene. U nedavno provedenim kliničkim ispitivanjima kod odraslih i djece primijenjen je režim postupnog smanjivanja doze za po 10 mg paroksetina na dan u tjednim razmacima. Kada se dostigne doza paroksetina od 20 mg paroksetina na dan, bolesnik treba nastaviti uzimati lijek u toj dozi tijekom jednog tjedna prije potpunog prestanka terapije. Ukoliko se tijekom smanjivanja ili nakon prestanka terapije pojave simptomi koje bolesnik teško podnosi, treba razmotriti ponovnu primjenu prethodno propisane doze. Nakon toga liječnik može nastaviti smanjivati dozu, ali u još duljim vremenskim razmacima. Djeca i adolescenti (do 18 godina) Paroksetin nije namijenjen za liječenje djece i adolescenata mlađih od 18 godina. Primjena paroksetina u djece mlađe od 7 godina nije ispitivana. Stariji bolesnici U starijih bolesnika dolazi do povećanja koncentracije paroksetina u plazmi, ali raspon koncentracija poklapa se s onim u mlađih bolesnika. Liječenje treba početi s početnom dozom SEROXATA za odrasle koja se može povećavati do maksimalne doze od 40 mg paroksetina na dan. Bolesnici s poremećenom funkcijom bubrega / jetre U plazmi bolesnika s teško poremećenom funkcijom bubrega (klirens kreatinina manji od 30 ml/min) ili jetre javljaju se povećane koncentracije paroksetina. Stoga dozu SEROXATA treba svesti na donju granicu preporučenog raspona doziranja. Predoziranje Prema dostupnim podacima o predoziranju paroksetinom, očit je njegov povoljan profil neškodljivosti. Simptomi predoziranja paroksetinom uključuju, osim simptoma opisanih u poglavlju NUSPOJAVE, povraćanje, proširene zjenice, povišenu temperaturu, promjene krvnog tlaka, glavobolju, nevoljne mišićne kontrakcije, nemir, anksioznost i tahikardiju. Oporavak obično prolazi bez ozbiljnih posljedica čak i u slučaju uzimanja do 2000 mg paroksetina (bez kombinacije s drugim lijekovima). Stanje kome ili promjene u EKG-u su rijetko zabilježeni. Vrlo rijetko je zabilježen smrtni ishod, obično ako je paroksetin uziman istodobno s drugim psihotropnim lijekovima, sa ili bez alkohola. Nije poznat nikakav specifični antidot. Liječenje bi trebalo obuhvaćati općenite mjere koje se primjenjuju u liječenju predoziranja bilo kojim antidepresivom. Ako je moguće, treba isprazniti želudac izazivanjem povraćanja, ispiranjem, ili na oba načina. Nakon pražnjenja, može se dati 20 do 30 grama aktivnog ugljena svakih 4 do 6 sati tijekom prva 24 sata nakon uzimanja lijeka. Preporuča se dodatna njega s čestim kontrolama vitalnih funkcija i pažljivim promatranjem. Mjere opreza Liječenje SEROXATOM može se oprezno započeti 2 tjedna nakon završetka liječenja ireverzibilnim MAO inhibitorima odnosno najmanje jedan dan nakon završetka liječenja reverzibilnim MAO inhibitorom. Dozu SEROXATA treba postupno povećavati do postizanja optimalnog odgovora. Mogućnost pokušaja samoubojstva predstavlja nerazdvojni dio velikog depresivnog poremećaja i može biti prisutna sve do postignuća značajnije remisije. Budući da do poboljšanja ne mora doći tijekom prvih nekoliko tjedana liječenja ili više, bolesnike treba strogo nadzirati tijekom liječenja i pratiti do nastupa poboljšanja. Ostala psihijatrijska stanja za koja se paroksetin propisuje, također mogu biti povezana s povećanim rizikom suicidalnog ponašanja. Mjere opreza koje se poduzimaju prilikom liječenja bolesnika s velikim depresivnim poremećajem treba poduzimati i kod liječenja bolesnika s ostalim duševnim poremećajima. U bolesnika u kojih su i prije početka liječenja zabilježena suicidalna ponašanja ili misli, odnosno u bolesnika s izraženim suicidalnim idejama te u mlađih bolesnika (u dobi 18 – 29 godina) postoji povećani rizik pojave suicidalnih misli i pokušaja samoubojstva te ih je potrebno strogo nadzirati tijekom liječenja. Bolesnike (i osobe koje o njima brinu) treba uputiti u potrebu praćenja pojavljivanja suicidalnih misli/ponašanja ili razmišljanja o samoozljeđivanju kako bi na vrijeme zatražili stručnu pomoć. Rijetko su tijekom liječenja paroksetinom, i obično ukoliko se primjenjivao istodobno s drugim serotoninergičkim i/ili neuroleptičkim lijekovima, zabilježeni slučajevi serotoninskog sindroma ili sindroma nalik neuroleptičkom malignom sindromu. U tim slučajevima, liječenje SEROXATOM treba odmah prekinuti te započeti sa simptomatskim liječenjem. U bolesnika sa srčanim smetnjama treba se držati uobičajenih mjera opreza. U bolesnika sa šećernom bolesti terapija inhibitorima ponovne pohrane serotonina može utjecati na kontrolu glikemije, stoga može biti potrebna prilagodba doze inzulina i/ili oralnih hipoglikemika. Kao i sve antidepresive, SEROXAT treba primjenjivati s oprezom u bolesnika s epilepsijom. U slučaju pojave epileptičkih napadaja liječenje SEROXATOM treba odmah prekinuti. SEROXAT nije namijenjen za liječenje depresivne epizode u sklopu bipolarnog afektivnog poremećaja. Kao i sve antidepresive, SEROXAT treba primjenjivati s oprezom u bolesnika u kojih je ranije dijagnosticirana manija. Prilikom primjene paroksetina zabilježeni su slučajevi krvarenja u koži (ekhimoze i purpura) i sluznicama (uključujući gastrointestinalno krvarenje). Stoga je nužan oprez pri primjeni SEROXATA kod bolesnika koji istodobno uzimaju lijekove koji povećavaju rizik krvarenja (npr. atipični antipsihotici i fenotijazini, većina tricikličkih antidepresiva, aspirin i nesteroidni protuupalni lijekovi), kao i kod bolesnika s poznatom sklonošću krvarenju ili s predisponirajućim stanjima te kod starijih bolesnika. Kao i ostale selektivne inhibitore ponovne pohrane serotonina, SEROXAT treba s oprezom primjenjivati u bolesnika s glaukomom uskog kuta. Hiponatremija je zabilježena rijetko, uglavnom u starijih osoba. Hiponatremija se obično povlači po prestanku uzimanja SEROXATA. Kontraindikacije SEROXAT se ne smije primjenjivati u bolesnika koji su preosjetljivi na paroksetin ili neki od pomoćnih sastojaka lijeka. SEROXAT se ne smije primjenjivati istodobno s inhibitorima monoaminooksidaze (MAO inhibitorima). Liječenje paroksetinom ne smije započeti unutar 2 tjedna od završetka liječenja ireverzibilnim MAO inhibitorima odnosno najmanje jedan dan nakon završetka liječenja reverzibilnim MAO inhibitorom, moklobemidom. Isto tako, liječenje MAO inhibitorima ne smije započeti unutar 2 tjedna od završetka liječenja paroksetinom (vidi INTERAKCIJE). SEROXAT se ne smije primjenjivati u kombinaciji s tioridazinom (vidi INTERAKCIJE). SEROXAT se ne smije primjenjivati istodobno s pimozidom. Trudnoća SEROXAT se ne smije primjenjivati u trudnica, osim ako prema procjeni liječnika, moguća korist za trudnicu prevladava moguće rizike za plod. Žene koje planiraju trudnoću ili koje zatrudne tijekom liječenja SEROXATOM trebaju se savjetovati sa svojim liječnikom. Nagli prekid primjene SEROXATA tijekom trudnoće treba izbjegavati. Dojenje Poznato je da se male količine paroksetina izlučuju u majčino mlijeko. Učinci paroksetina na dojenče nisu utvrđeni. Stoga se SEROXAT ne smije primjenjivati u dojilja, osim ako očekivana korist za majku prevladava mogući rizik za dojenče. Upravljanje vozilima i strojevima Kliničko iskustvo pokazalo je da liječenje paroksetinom nije povezano s poremećajem kognitivnih ni psihomotoričkih funkcija. Međutim, kao i kod svih psihoaktivnih lijekova, bolesnicima treba savjetovati oprez pri upravljanju vozilom ili strojevima. Djeca i adolescenti (do 18 godina) Liječenje antidepresivima je povezano s povećanim rizikom pojave suicidalnih misli i suicidalnog ponašanja u djece i adolescenata s velikom depresivnom epizodom kao i drugim duševnim poremećajima. Kontrolirana klinička ispitivanja nisu dokazala djelotvornost i dugotrajnu neškodljivost paroksetina te ne podupiru primjenu paroksetina u liječenju teške depresivne epizode kod djece i adolescenata do 18 godina. Djeca (mlađa od 7 godina) Učinkovitost i neškodljivost primjene paroksetina u djece mlađe od 7 godina nije ispitivana. Nuspojave Pri kontinuiranoj primjeni učestalost i intenzitet nekih od dolje navedenih nuspojava može se smanjiti te u većini slučajeva terapiju nije potrebno prekidati. Vrlo učestalo (>1/10) zabilježene nuspojave povezane s primjenom paroksetina bile su: - mučnina - seksualna disfunkcija Učestalo (1/100 – 1/10) su zabilježene: - pospanost, zijevanje - znojenje - tremor - astenija - povećanje tjelesne mase - suha usta - nesanica - omaglica, zamućenje vida - opstipacija - proljev - smanjeni apetit/anoreksija. Neučestalo (1/1000 – 1/100) su se javljala abnormalna krvarenja (uglavnom na koži i sluznicama): - zbunjenost - halucinacije - ekstrapiramidni poremećaji - sinusna tahikardija - osip, svrbež - retencija mokraće Rijetko (1/10000 – 1/100) su zabilježene sljedeće nuspojave: - hiponatrijemija - manične reakcije - uznemirenost - depersonalizacija - napadaji panike - akatizija - konvulzije - bradikardija - trombocitopenija - hiperprolaktinemija/galaktoreja Vrlo rijetko (manje od 1/10000) su zabilježene sljedeće nuspojave: - alergijske reakcije - sindrom neadekvatnog lučenja antidiuretskog hormona - serotoninski sindrom - akutni glaukom - gastroinestinalno krvarenje - periferni edemi - prijapizam - fotosenzitivne reakcije - poremećaji funkcije jetre - artralgija - mijalgija Zabilježene su i povišene vrijednosti jetrenih enzima. Treba razmotriti prekid terapije paroksetinom u slučaju dugotrajnije povišenih vrijednosti jetrenih enzima. Simptomi povezani s prestankom primjene paroksetina u odraslih Nagli prekid primjene često može izazvati pojavu sljedećih simptoma: - vrtoglavicu, poremećaje osjeta, poremećaje spavanja, tjeskobu, glavobolju. Neučestalo se mogu javiti: - uznemirenost, mučnina, znojenje, tremor, zbunjenost, proljev. U većine bolesnika opisane nuspojave su uglavnom bile blage do umjereno teške naravi te su prestale same od sebe. Međutim u nekih bolesnika mogu biti ozbiljne i/ili produljenog trajanja. Stoga se, u slučaju da primjena paroksetina više nije potrebna, preporuča prekid terapije uz postupno smanjivanje doze. Nuspojave zabilježene u kliničkim ispitivanjima u djece i adolescenata U kratkotrajnim kliničkim ispitivanjima u djece i adolescenata zabilježene su sljedeće nuspojave koje su se javljale u najmanje 2% bolesnika s najmanje dvostruko većom učestalošću u odnosu na placebo: - emocionalna labilnost (uključujući suicidalne misli, pokušaje samoubojstva, plačljivost i promjene raspoloženja), neprijateljsko ponašanje, smanjeni apetit, tremor, znojenje, hiperkinezija i uznemirenost. Suicidalne misli i pokušaji samoubojstva bili su uglavnom zabilježeni u kliničkim ispitivanjima u adolescenata s velikim depresivnim poremećajem. Pojačano neprijateljsko ponašanje obično se pojavljivalo u djece, najčešće mlađe od 12 godina, s opsesivnim kompulzivnim poremećajem. Simptomi povezani sa prestankom primjene paroksetina u djece i adolescenata. Po prestanku primjene paroksetina u djece i adolescenata češće su zabilježeni sljedeći simptomi: - emocionalna labilnost (uključujući suicidalne misli, pokušaje samoubojstva, promjene raspoloženja i plačljivost), nervoza, omaglice, mučnina i bol u trbuhu. U slučaju nuspojave treba se obratiti liječniku ili ljekarniku! Interakcije Ne preporuča se istodobno uzimanje SEROXATA i alkohola. Istodobna primjena paroksetina i serotoninergičkih lijekova (npr. MAO inhibitora, L-triptofana, triptana, tramadola, linezolida, inhibitora ponovne pohrane serotonina, litija i pripravaka gospine trave – Hypericum perforatum) može dovesti do povećanja pojave učinaka povezanih sa serotoninom. Na metabolizam i farmakokinetiku paroksetina mogu utjecati lijekovi koji induciraju ili inhibiraju jetrene enzime. Ako se paroksetin treba primjenjivati zajedno s nekim poznatim inhibitorom jetrenih enzima, treba razmotriti doziranje na donjoj granici raspona. Nije potrebno početno prilagođavanje doze ako će se lijek primjenjivati zajedno s nekim poznatim induktorom jetrenih enzima (kao npr. karbamazepinom, rifampicinom, fenobarbitonom i fenitoinom). Istodobna primjena paroksetina i antikonvulziva (karbamazepin, natrij-valproat i fenitoin) u bolesnika s epilepsijom ne utječe na njihov farmakokinetički/farmakodinamički profil. Svakodnevna primjena paroksetina značajno povisuje plazmatske razine prociklidina. Kao i ostali antidepresivi, uključujući i druge inhibitore ponovne pohrane serotonina, paroksetin inhibira jetreni enzim CYP2D6 što može dovesti do povećanih koncentracija u plazmi istodobno primijenjenih lijekova. To su neki triciklički antidepresivi (npr. imipramin, nortriptilin i dezipramin), fenotijazinski neuroleptici (npr. perfenazin i tioridazin), risperidon, atomoksetin, određeni antiaritmici iz skupine 1c (npr. propafenon i flekainid) i metoprolol (posebno u bolesnika sa zatajivanjem srca). Istodobna primjena paroksetina i oralnih antikoagulansa može dovesti do povećanja antikoagulantne aktivnosti i povećanja rizika krvarenja. Stoga, paroksetin treba primjenjivati s oprezom u bolesnika na terapiji oralnim antikoagulansima. Potreban je oprez prilikom istodobne primjene inhibitora ponovne pohrane serotonina i oralnih antikoagulansa te ostalih lijekova koji utječu na funkciju trombocita ili povećavaju rizik krvarenja (npr. atipični antipsihotici kao što je klozapin, fenotijazini, većina tricikličkih antidepresiva, acetilsalicilna kiselina, nesteroidni antireumatici, COX-2 inhibitori) kao i u bolesnika s prethodnim poremećajima zgrušavanja ili sklonosti krvarenju. Napomene IME I ADRESA NOSITELJA ODOBRENJA BELUPO lijekovi i kozmetika d.d., Ulica Danica 5, 48000 Koprivnica,Hrvatska IME I ADRESA PROIZVOĐAČA BELUPO lijekovi i kozmetika d.d.,Ulica Danica 5, 48000 Koprivnica, Hrvatska u suradnji s GlaxoSmithKline, Brentford, Velika Britanija. Amantilla Relax Značajno ublažava stres i tjeskobu. Tensilen Prirodno rješenje za stres, umor i iscrpljenost.