Active ingredients: Citalopram
Elopram 20-40 mg film-coated tablets
Elopram package inserts are available for pack sizes:- Elopram 20-40 mg film-coated tablets
- Elopram 40 mg / ml oral drops, solution
- Elopram 40 mg / ml concentrate for solution for infusion
Why is Elopram used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antidepressants, selective serotonin reuptake inhibitors.
THERAPEUTIC INDICATIONS
Elopram is indicated in endogenous depressive syndromes and prevention of relapses and recurrences.
Anxiety disorders with panic attacks with or without agoraphobia.
Contraindications When Elopram should not be used
Hypersensitivity to the active substance or to any of the excipients.
Age under 18.
The concomitant administration of Serotonin Reuptake Inhibitors (SSRIs) and MAO inhibitors can cause severe and sometimes fatal adverse reactions. Some cases present with features similar to serotonin syndrome.
Elopram should not be administered to patients treated with Monoamine Oxidase Inhibitors (MAOIs) including selegiline in daily doses greater than 10 mg / day. Elopram should not be administered earlier than 14 days after stopping an irreversible MAOI or for the specified time after stopping a reversible MAOI (RIMA) as indicated in the RIMA package insert.
MAOIs should not be administered earlier than 7 days after stopping Elopram (see "Special Warnings" and "Interactions").
Elopram is contraindicated in combination with linezolid unless there are machinery for careful observation and monitoring of blood pressure (see "Interactions").
Elopram is contraindicated for patients with known QT interval prolongation or congenital long QT syndrome.
Elopram is contraindicated in co-administration with medicinal products known to cause prolongation of the "QT interval" (see "Interactions").
Elopram must not be used concomitantly with pimozide (see "Interactions").
Precautions for use What you need to know before taking Elopram
Treatment of elderly patients and patients with impaired renal and hepatic function, see "Dose, method and time of administration".
Use in children and adolescents under 18 years of age
Antidepressants should not be used to treat children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical need, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms.
Furthermore, long-term safety data for children and adolescents are not available with regard to growth, maturation and cognitive and behavioral development.
Paradoxical anxiety
Some patients with panic disorders may experience symptoms of heightened anxiety upon initiation of antidepressant treatment. These paradoxical reactions generally subside within the first two weeks of initiation of treatment. A lower starting dose is recommended to reduce paradoxical anxiogenic effects (see "Dose, Method and Time of Administration").
Hyponatremia
Hyponatremia, a phenomenon involving a decrease in plasma sodium concentration, is sporadically reported as a rare adverse reaction, probably due to inappropriate secretion of antidiuretic hormone (SIADH). This phenomenon is generally reversible after discontinuation of therapy. Elderly female patients appear to be at particularly high risk.
Mania
In patients with manic-depressive illness there may be a shift towards the manic phase. Elopram should be discontinued if the patient enters a manic phase.
Seizures
Seizures are a potential risk with the use of antidepressant drugs. Elopram should be discontinued in all patients experiencing seizures. Elopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored. Elopram should be discontinued if there is an increase in the frequency of seizures.
Diabetes
In diabetic patients, SSRI treatment can impair glycemic control. The dosage of insulin or oral hypoglycaemics may need to be adjusted.
Serotonin syndrome
In rare cases, a serotonin syndrome has been reported in patients treated with SSRIs. An association of symptoms such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. Treatment with Elopram should be stopped immediately and symptomatic therapy initiated.
Serotonergic medicines
Elopram must not be used in combination with medicinal products with a serotonergic effect such as sumatriptan or other triptans, tramadol, oxytryptan and tryptophan (see "Interactions").
Hemorrhage
Prolonged clotting times and / or clotting abnormalities such as ecchymosis, gynecological haemorrhages, gastrointestinal bleeding and other forms of cutaneous or mucosal bleeding have been reported with SSRIs (see "Side Effects"). Caution is advised in patients taking SSRIs particularly in the case of concomitant use of active substances that may affect platelet function or other substances that may increase the risk of bleeding, as well as in patients with a history of bleeding disorders (see "Interactions") .
Electroconvulsive Therapy (ECT)
Clinical experience with the concomitant administration of ECT and citalopram is limited, therefore caution is recommended.
Reversible selective MAO-A inhibitors
The combination of Elopram with MAO-A inhibitors is generally not recommended due to the risk of developing serotonin syndrome (see "Interactions"). For more information on concomitant treatment with irreversible non-selective MAO inhibitors, see "Interactions".
St. John's wort
Undesirable effects may be more common during concomitant use of Elopram and herbal preparations containing St John's wort (Hypericum perforatum). Therefore Elopram and preparations containing St. John's wort should not be taken at the same time (see "Interactions").
Psychosis
Treatment of psychotic patients with depressive episodes can increase psychotic symptoms.
Prolongation of the QT interval
Elopram has been found to cause dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported in post-marketing experience, predominantly in female patients with hypokalaemia or with pre-existing QT interval prolongation or other heart conditions (see "Contraindications", "Interactions", "Undesirable Effects" and "Overdose").
Caution is advised in patients with significant bradycardia, in patients with recent acute myocardial infarction or with uncompensated heart failure. Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before starting treatment with Elopram.
If treating patients with stable cardiac disease, an ECG check should be considered before starting treatment.
If signs of cardiac arrhythmia occur during treatment with Elopram, the treatment should be discontinued and an ECG performed.
Insomnia and agitation may occur at the start of treatment. In such cases, dosage adjustment may help.
Interactions Which drugs or foods can change the effect of Elopram
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Pharmacodynamic interactions
At the pharmacodynamic level, cases of serotonin syndrome have been reported with Elopram and moclobemide and buspirone.
Contraindicated associations
MAO inhibitors
The concomitant use of Elopram and MAO inhibitors can cause serious side effects, including serotonin syndrome (see "Contraindications" and "Special Warnings"). Cases of serious, and sometimes fatal, reactions have been reported in patients undergoing treatment. with SSRIs associated with a monoamine oxidase (MAO) inhibitor, including selegiline, a selective MAOI, and linezolid, a reversible (non-selective) MAOI and moclobemide (selective for type IA), and in patients who had recently stopped treatment with an SSRI and had started therapy with a MAOI.
Some cases presented with features similar to those of serotonin syndrome. Symptoms of serotonin syndrome include: hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, confusion, irritability and agitation. If this condition progresses without any intervention, it can be fatal following rhabdomyolysis, central hyperthermia with acute multi-organ failure, delirium and coma (see "Contraindications").
Prolongation of the QT interval
Pharmacokinetic and pharmacodynamic studies on the combination of Elopram and other medicinal products that prolong the QT interval have not been conducted. An additive effect of Elopram with such medicinal products cannot be excluded. Consequently, co-administration of Elopram with medicinal products that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (such as phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (such as sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial treatments, in particular halofantrine), some antihistamines (astemizole, mizolastine) etc.
Pimozide
Concomitant use of Elopram and pimozide is contraindicated (see "Contraindications"). Concomitant administration of a single 2 mg dose of pimozide to healthy volunteers, who were treated with Elopram 40 mg / day for 11 days, caused only a minor increase in pimozide AUC and Cmax of approximately 10%, not statistically significant. Despite the smaller increase in plasma pimozide levels, the QT interval was more prolonged after concomitant administration of Elopram and pimozide (mean 10 ms) compared to single dose administration of pimozide alone (mean 2 ms). Since this interaction had already been observed after single-dose administration of pimozide, concomitant treatment with Elopram is contraindicated.
Associations requiring precautions for use
A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of Elopram (20 mg per day) and selegiline (10 mg per day) (a selective MAO-B inhibitor) demonstrated interactions that are not clinically relevant. The concomitant use of Elopram and selegiline (at doses greater than 10 mg per day) is not recommended.
Serotonergic medicinal products
Lithium and Tryptophan
No pharmacodynamic interactions were found between lithium and Elopram; however, an increase in the serotonergic effect has been reported when SSRIs are administered in combination with lithium or tryptophan. Caution is advised when using Elopram with these active ingredients at the same time. Routine monitoring of lithium levels must be continued as usual.
Sumatriptan and tramadol
The serotonergic effect of sumatriptan and tramadol can be enhanced by selective serotonin reuptake inhibitors (SSRIs); until further information is available, the concomitant use of Elopram and serotonin (or 5-HT) agonists, such as sumatriptan and other triptans, as well as tramadol is not recommended (see "Precautions for use").
St. John's wort
Undesirable effects may be more frequent during concomitant administration of Elopram and herbal preparations containing St. John's wort (Hypericum perforatum) (see "Precautions for use"). Pharmacokinetic interactions have not been investigated.
Hemorrhage
Particular caution is needed for those patients who are being treated concomitantly with anticoagulants, drugs that can affect platelet function, such as non-steroidal anti-inflammatory drugs (or NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine or other drugs (for example atypical antipsychotics, phenothiazines, tricyclic antidepressants) which may increase the risk of bleeding (see "Precautions for use").
Electroconvulsive Therapy (ECT)
There are no clinical studies establishing the risk or benefit of the combined use of electroconvulsive therapy (ECT) and Elopram (see "Precautions for use").
Alcohol
No pharmacodynamic or pharmacokinetic interactions of Elopram with alcohol have been demonstrated; however, the association between Elopram and alcohol is not recommended.
Medicinal products that lower the seizure threshold
SSRIs can lower the seizure threshold. Caution is advised when concomitant drugs capable of lowering the seizure threshold, antidepressants (SSRIs, tricyclics), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol are used.
Desipramine, Imipramine
In a pharmacokinetic study, no effect on either Elopram or imipramine levels was demonstrated, although the levels of desipramine, the major metabolite of imipramine, were increased. When desipramine is combined with citalopram, it is observed an increase in the plasma concentration of the first substance; therefore it may be necessary to reduce its dosage.
Neuroleptics
The use of Elopram did not reveal any clinically relevant interaction with neuroleptics; however, as with other SSRIs, the possibility of a pharmacodynamic interaction cannot be excluded a priori.
Pharmacokinetic interactions
The biotransformation of citalopram to demethylcitalopram is mediated by isoenzymes of the cytochrome P450 system, CYP2C19 (approximately 38%), CYP3A4 (approximately 31%) and CYP2D6 (approximately 31%). The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation is less likely since inhibition of one enzyme can be compensated for by another. Therefore, co-administration of citalopram with other medicinal products in clinical practice has a very low probability of producing pharmacokinetic interactions with medicinal products.
Food
No effects of food on the absorption and other pharmacokinetic properties of Elopram have been reported.
Influence of other medicinal products on the pharmacokinetics of citalopram
Co-administration with ketoconazole (potent CYP3A4 inhibitor) does not change the pharmacokinetics of citalopram.
A pharmacokinetic interaction study of lithium and citalopram reveals no pharmacokinetic interaction.
Cimetidine
Cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor) causes a moderate increase in mean steady-state plasma levels of citalopram. Caution is advised when administering Elopram in combination with cimetidine. Dose adjustments may be needed.
Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole (a CYP2C19 inhibitor) 30 mg once daily resulted in a moderate (approximately 50%) increase in plasma concentrations of escitalopram. concomitant use of CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine.
Based on the control of undesirable effects during concomitant administration of other therapy, a reduction in the dose of citalopram may be necessary.
Metoprolol
Escitalopram (the active enantiomer of citalopram) is an inhibitor of the CYP2D6 enzyme. Caution is advised when citalopram is co-administered with medicinal products which are mainly metabolised by this enzyme, and which have a narrow therapeutic index, eg flecainide , propafenone and metoprolol (when used in heart failure), or some medicinal products which act on the central nervous system and which are mainly metabolised by CYP2D6, eg. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics such as risperidone, thioridazine and haloperidol.
Dosage adjustments may be needed. Co-administration with metoprolol results in a doubling of the plasma levels of the latter. No clinically significant effects on blood pressure or heart rate have been observed.
Effects of citalopram on other medicinal products
A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a doubling of the plasma levels of metoprolol, but no clinically significant effects of metoprolol on blood pressure or heart rate were observed in healthy volunteers.
Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6, compared to other SSRIs known as significant inhibitors.
No changes or only small changes of no clinical relevance were observed when citalopram was administered with clozapine and theophylline (CYP1A2 substrates), warfarin (CYP2C9 substrate), imipramine and mephenytoin (CYP2C19 substrates), sparteine, imipramine, amitriptyline, risperidone (CYP2D6 substrates) and warfarin, carbamazepine (and its metabolite carbamazepine epoxide), triazolam (CYP3A4 substrates).
No pharmacokinetic interactions have been observed between citalopram and levopromazine, or digoxin, (indicating that citalopram neither induces nor inhibits P-glycoprotein).
Warnings It is important to know that:
Paradoxical anxiety
Some patients with panic disorder may experience symptoms of heightened anxiety at the start of treatment with antidepressants.
These paradoxical reactions generally subside within the first two weeks of starting treatment. A lower starting dose is recommended to reduce the likelihood of paradoxical anxiogenic effects (see "Dose, Method and Time of Administration").
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 clinical experience in general that the risk of suicide may increase in the early early stages of improvement.
Other psychiatric conditions for which Elopram is prescribed may also be associated with an increased risk of suicide-related events. Furthermore, there may be coexistence of such pathologies with major depression. The same precautions adopted in the treatment of patients suffering from major depression must therefore be adopted in the treatment of patients suffering from other psychiatric pathologies.
Patients with a positive medical history of suicide-related events or those who exhibit a significant degree of suicidal ideation prior to initiation of therapy are at increased risk for suicidal thoughts or suicide attempts, and should be closely monitored during therapy. Meta-analysis of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Pharmacological therapy with antidepressants, especially in the initial stages of treatment and following dose changes, should always be associated with close surveillance of patients, especially those at high risk. Patients (and their carers) should be advised of the need to monitor for any clinical worsening, suicidal behavior or thoughts and unusual changes in behavior, and if such symptoms occur, seek immediate medical attention.
Akathisia / psychomotor agitation
The use of SSRIs / SNRIs has been associated with the development of akathisia, characterized by subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. These symptoms are more likely to present within the first few weeks of treatment. In patients who develop such symptoms, increasing the dosage can be harmful.
Reversible selective MAO-A inhibitors
The combination of Elopram with MAO-A inhibitors is generally not recommended due to the risk of developing serotonin syndrome (see "Interactions").
For more information on concomitant treatment with irreversible non-selective MAO inhibitors, see "Interactions".
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
A large number of data on pregnant women (more than 2500 published results) indicate no malformative fetal / neonatal toxicity. Elopram can be used during pregnancy, if clinically needed, taking into account the aspects mentioned below.
Newborns should be observed if maternal use of Elopram has continued in the later stages of pregnancy, particularly in the third trimester. Abrupt termination should be avoided during pregnancy.
Following the mother's use of SSRIs / SNRIs during the last stages of pregnancy, the newborn may manifest the following symptoms: respiratory disorders, cyanosis, apnea, convulsions, unstable temperature, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, nervousness, irritability, lethargy, chronic crying, drowsiness and difficulty sleeping. These symptoms may be due to serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately after delivery or within hours. immediately following (less than 24 hours).
Make sure your doctor and / or midwife is aware that you are taking Elopram. When taken during pregnancy, particularly in the last three months, medicines such as Elopram can increase the risk of developing a serious condition in babies, called hypertension. persistent lung disease (PPHN), manifested by increased breathing rate and a bluish skin. These symptoms usually begin within 24 hours after birth. If this happens to your baby, you should contact your midwife and / or nurse. doctor immediately.
Feeding time
Elopram is excreted in breast milk. It is estimated that infants who are breastfed will receive approximately 5% relative to the daily dose taken by the mother (in mg / kg). Only minor events were observed in infants. However, existing information is insufficient to assess the risk in children. Caution is advised.
Fertility
Citalopram has been shown to reduce sperm quality in animal studies. In theory, this could affect fertility but, the impact on human fertility has not yet been observed.
Effects on ability to drive and use machines
Elopram has minor or moderate influence on the ability to drive and use machines.
Psychiatric drugs can reduce judgment and reactivity in emergency situations. Patients should be informed of these effects and warned that their ability to drive a car or use machines may be affected.
Important information about some of the ingredients
Elopram contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Elopram: Dosage
Adults
Endogenous depressive syndromes
Elopram should be administered as a single 20 mg oral daily dose. Based on the individual patient response, the dose can be increased up to a maximum of 40 mg per day.
The antidepressant effect usually occurs within 2-4 weeks of starting therapy; the patient should be followed by the doctor until the depressive state remits.
Since antidepressant treatment is symptomatic, it should be continued for an appropriate period of time, typically 4-6 months in manic-depressive illness. In patients with recurrent unipolar depression it may be necessary to continue maintenance therapy for a long time in order to prevent new depressive episodes.
Anxiety disorders with panic attacks with or without agoraphobia
For the first week of treatment the recommended dose is 10 mg, thereafter the dose is increased to 20 mg per day. Based on the individual patient response, the dose can be increased up to a maximum of 40 mg per day.
The maximum effectiveness is reached after about 3 months of treatment.
In anxiety disorders with panic attacks, treatment is long-term. Maintenance of clinical response has been demonstrated during prolonged treatment (1 year). In case of insomnia or severe restlessness, additional treatment with acute sedatives is recommended. .
Withdrawal symptoms observed following discontinuation of treatment
Abrupt discontinuation of treatment should be avoided. When stopping treatment with Elopram the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions (see "Special Warnings" and "Undesirable Effects" ").
If intolerable symptoms occur following dose reduction or upon discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually.
Elderly (over 65 years of age)
For elderly patients, the dose should be reduced to half the recommended dose, e.g. 10-20 mg per day. The maximum recommended dose for the elderly is 20 mg per day.
Use in children and adolescents under the age of 18
Elopram should not be used to treat children and adolescents under 18 years of age (see "Contraindications").
Hepatic insufficiency
For patients with mild or moderate hepatic impairment, the recommended starting dose for the first two weeks of treatment is 10 mg per day. Based on the individual patient response, the dose can be increased up to a maximum of 20 mg per day.
Kidney failure
In these patients it is advisable to adhere to the minimum recommended dosage.
When a decision is made to discontinue treatment, doses should be reduced gradually to minimize the extent of withdrawal symptoms.
Overdose What to do if you have taken too much Elopram
In case of accidental ingestion / intake of an excessive dose of Elopram, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Elopram, ask your doctor or pharmacist.
Toxicity
Comprehensive clinical data on Elopram overdose are limited and many cases involve concomitant overdoses of other drugs / alcohol. Fatal cases of Elopram alone have been reported; however, most fatal cases are due to overdose when the drug is taken together with other medicines.
Symptoms
The following undesirable effects have been reported in overdose cases: seizures, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, conduction block heart failure, QRS prolongation, hypertension, mydriasis, torsades de pointes, stupor, sweating, cyanosis, hyperventilation and atrioventricular arrhythmia Rhabdomyolysis is rare.
Symptoms possible with a dose up to 600 mg are: fatigue, weakness, sedation, tremor, nausea and tachycardia.
With doses above 600 mg, seizures may occur within hours of taking. ECG changes and, rarely, rhabdomyolysis may also occur. Overdose is rarely fatal. One adult patient survived after ingesting 5,200 mg of citalopram.
Treatment
There is no known specific antidote to citalopram. Treatment should be symptomatic and supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate) and gastric lavage should be considered. In the presence of impaired consciousness, the patient should be intubated. ECG and vital signs should be monitored. Administer oxygen in case of hypoxia and diazepam in case of convulsions. Physician surveillance for approximately 24 hours is recommended, as well as ECG monitoring if the ingested dose exceeds 600 mg. A widening of the QRS complex can be normalized by a hypertonic NaCl infusion.
In the event of overdose, ECG monitoring is advisable in patients with congestive heart failure / bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with impaired metabolism, eg hepatic insufficiency.
EFFECTS DUE TO THE SUSPENSION OF THE TREATMENT
Discontinuation symptoms observed following discontinuation of SSRI treatment
Discontinuation symptoms are common upon discontinuation of treatment, particularly if discontinuation is sudden (see "Undesirable Effects"). In a clinical study on the prevention of recurrences, adverse events occurred in 40% of patients after treatment. "discontinuation of treatment, compared with 20% of patients who continued treatment with Elopram.
The risk of withdrawal symptoms may be dependent on various factors, including the duration and dose of therapy and the rate of dose reduction. The most commonly reported adverse reactions are: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. Generally these symptoms are mild to moderate; however, in some patients they can be severe in intensity. They usually appear within the first few days of stopping treatment; however, very rare cases of withdrawal symptoms have been reported in patients who inadvertently missed a dose.
Generally these symptoms resolve spontaneously without the necessary use of drugs, within 2 weeks, although in some patients they may be prolonged (2-3 months or more).
If treatment is to be discontinued, it is therefore recommended to gradually reduce the dosage of Elopram over a period of several weeks or months, according to the patient's needs (see "Dose, Method and Time of Administration").
Side Effects What are the side effects of Elopram
Like all medicines, Elopram can cause side effects, although not everybody gets them.
The side effects seen with citalopram are generally mild and transient in nature. They occur mainly in the first or second week of therapy, and then subside later. Adverse reactions are listed in the MedDRA classification (Medical Dictionary for Regulatory Activities). A dose-response relationship was found for the following reactions: increased sweating, dry mouth, insomnia, somnolence, diarrhea, nausea and fatigue.
The table below shows the rate of adverse reactions associated with SSRIs and / or citalopram occurring in both ≥1% of patients in double-blind placebo-controlled clinical trials and in post-marketing experience.
Frequency categories are defined as follows: very common (≥1 / 10), common (≥1 / 100 to <1/10), uncommon (≥1 / 1000 to <1/100), rare (≥1 / 10,000, <1/1000), very rare (<1 / 10,000), not known (frequency cannot be estimated from the available data).
Number of patients: Citalopram / placebo = 1346/545
1 Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported during post-marketing experience, predominantly in female patients, with hypokalaemia or with pre-existing QT interval prolongation or other cardiac diseases. (see "Contraindications", "Usage Precautions", "Interactions" and "Overdose").
2 Cases of suicidal ideation and suicidal behaviors have been reported during citalopram therapy or soon after treatment discontinuation (see "Special Warnings").
An increased risk of fractures has been observed in patients taking this type of medicine.
Withdrawal symptoms observed following discontinuation of treatment
Discontinuation of citalopram treatment (especially if abrupt) usually leads to withdrawal symptoms.
The most commonly reported side effects were 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.
Generally these events are mild to moderate and self-limiting, however in some patients they may be severe and / or prolonged. It is therefore recommended that, if treatment with citalopram is no longer required, a "gradual discontinuation, conducted by a gradual decrease in dose, is implemented (see" Dose, Method and Time of Administration "and" Special Warnings ").
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious or if you notice a side effect not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Store at a temperature not exceeding 30 ° C in the original container in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
COMPOSITION
Each 20 mg film-coated tablet contains:
Citalopram hydrobromide 24.98 mg
equal to citalopram 20 mg
Excipients
Corn starch, Lactose monohydrate, Microcrystalline cellulose, Copovidone, Glycerin (85%), Croscarmellose sodium, Magnesium stearate, Titanium dioxide, Hypromellose, Macrogol 400.
Each 40 mg film-coated tablet contains:
Citalopram hydrobromide 49.96 mg
equal to citalopram 40 mg
Excipients
Corn starch, Lactose monohydrate, Microcrystalline cellulose, Copovidone, Glycerin (85%), Croscarmellose sodium, Magnesium stearate, Titanium dioxide, Hypromellose, Macrogol 400.
PHARMACEUTICAL FORM AND CONTENT
Box of 28 film-coated tablets of 20 mg
Carton of 14 film-coated tablets of 20 mg
Carton of 14 film-coated tablets of 40 mg
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ELOPRAM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
ELOPRAM 20 mg film-coated tablets
Each tablet contains:
Active principle:
Citalopram 20 mg (equivalent to 24.98 mg of citalopram hydrobromide)
Excipients: Lactose monohydrate
ELOPRAM 40 mg film-coated tablets
Each tablet contains:
Active principle:
Citalopram 40 mg (equivalent to 49.96 mg of citalopram hydrobromide)
Excipients: Lactose monohydrate
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
The 20 mg and 40 mg tablets can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Endogenous depressive syndromes and prevention of relapses and recurrences.
Anxiety disorders with panic attacks with or without agoraphobia.
04.2 Posology and method of administration
Adults
Endogenous depressive syndromes:
Citalopram should be administered as a single 20 mg oral daily dose.
Based on the individual patient response, the dose can be increased up to a maximum of 40 mg per day.
The antidepressant effect usually occurs within 2-4 weeks of starting therapy; the patient should be followed by the doctor until the depressive state remits.
As antidepressant treatment is symptomatic, it should be continued for an appropriate period of time, typically 4-6 months in manic-depressive illness.
In patients with recurrent unipolar depression it may be necessary to continue maintenance therapy for a long time in order to prevent new depressive episodes.
Anxiety disorders with panic attacks with or without agoraphobia:
For the first week of treatment the recommended dose is 10 mg, thereafter the dose is increased to 20 mg per day. Based on the individual patient response, the dose can be increased up to a maximum of 40 mg per day.
The maximum effectiveness is reached after about 3 months of treatment.
In panic disorder, treatment is long-term. Maintenance of clinical response was demonstrated during prolonged treatment (1 year).
In case of insomnia or severe restlessness, additional treatment with acute sedatives is recommended.
Hepatic insufficiency:
For patients with mild or moderate hepatic impairment, the recommended starting dose for the first two weeks of treatment is 10 mg per day. Based on the individual patient response, the dose can be increased up to a maximum of 20 mg per day. Caution and increased attention in dose titration is advised in patients with severely reduced hepatic function (see section 5.2).
Kidney failure:
In these patients it is advisable to adhere to the minimum recommended dosage.
Elderly (> 65 years of age):
For elderly patients, the dose should be reduced to half the recommended dose, e.g. 10-20 mg per day. The maximum recommended dose for the elderly is 20 mg per day.
For use by children and adolescents under the age of 18:
Elopram should not be used for the treatment of children and adolescents under 18 years of age (see section 4.4).
Metabolisers CYP2C19 lenses:
For patients known to be CYP2C19 poor metabolisers, a starting dose of 10 mg per day is recommended during the first two weeks of treatment. Based on the individual patient response, the dose can be increased up to a maximum of 20 mg per day (see section 5.2).
Withdrawal symptoms observed following discontinuation of treatment "Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with Elopram the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions. (see sections 4.4 and 4.8).
If intolerable symptoms occur following dose reduction or upon discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
Age under 18.
MAOIs (Monoamine Oxidase Inhibitors):
The concomitant administration of serotonin reuptake inhibitors (SSRIs) and MAO inhibitors can cause severe, sometimes fatal, adverse reactions. Some cases present with features similar to serotonin syndrome. Citalopram should not be administered to patients treated with Monoamine Oxidase Inhibitors (MAOIs) including selegiline in daily doses greater than 10 mg / day. Citalopram should not be administered earlier than 14 days after discontinuation of an irreversible MAOI or for the specified time after discontinuation of a reversible MAOI (RIMA) as indicated in the RIMA package insert. MAOIs should not be administered earlier than 7 days after discontinuation of citalopram (see section 4.5).
Citalopram is contraindicated in combination with linezolid unless there are machinery for careful observation and monitoring of blood pressure (see section 4.5).
Citalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome.
Citalopram is contraindicated in co-administration with medicinal products known to cause prolongation of the QT interval (see section 4.5).
Citalopram should not be used concomitantly with pimozide (see section 4.5).
04.4 Special warnings and appropriate precautions for use
Treatment of elderly patients and patients with impaired renal and hepatic function, see section 4.2.
Use in children and adolescents under 18 years of age:
Antidepressants should not be used to treat children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical need, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms. In addition, long-term safety data for children and adolescents with regard to growth, maturation and cognitive and behavioral development are not available.
Paradoxical anxiety:
Some patients with panic disorder may experience an "accentuation of anxiety symptoms at" initiation of antidepressant treatment.
These paradoxical reactions generally subside within the first two weeks after initiation of treatment. A lower starting dose is recommended to reduce the likelihood of paradoxical anxiogenic effects (see section 4.2).
Hyponatremia:
Hyponatremia, possibly due to inappropriate antidiuretic hormone secretion (SIADH), has been reported as a rare adverse reaction with the use of SSRIs and is generally reversible after discontinuation of therapy.
Elderly female patients appear to be at particularly high 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 clinical experience in general that the risk of suicide may increase in the early early stages of improvement.
Other psychiatric conditions for which citalopram is prescribed may also be associated with an increased risk of suicide-related events. Furthermore, there may be co-morbidities of such pathologies with major depression. The same precautions adopted in the treatment of patients suffering from major depression must therefore be adopted in the treatment of patients suffering from other psychiatric pathologies.
Patients with a history of suicide-related events or those who experience a significant degree of suicidal ideation prior to initiation of therapy are at increased risk for suicidal thoughts or suicide attempts, and should be closely monitored during therapy. One goal -analysis of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Pharmacological therapy with antidepressants, especially in the initial stages of treatment and following dose changes, should always be associated with close surveillance of patients, especially those at high risk. Patients (and their caregivers) should be advised of the need to monitor for any clinical worsening, suicidal behaviors or thoughts, and unusual changes in behavior and to seek immediate medical attention if such symptoms occur.
Akathisia / psychomotor agitation:
The use of SSRIs / SNRIs has been associated with the development of akathisia, characterized by subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. These symptoms are more likely to present within the first few weeks. In patients who develop such symptoms, increasing the dosage can be harmful.
Mania:
In patients with manic-depressive illness there may be a shift towards the manic phase. Citalopram should be discontinued if the patient enters a manic phase.
Seizures:
Seizures are a potential risk with the use of antidepressant drugs. Citalopram should be discontinued in all patients experiencing seizures. Citalopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored. Citalopram should be discontinued if there is an increase in the frequency of seizures.
Diabetes:
In diabetic patients, SSRI treatment can impair glycemic control. The dosage of insulin or oral hypoglycaemics may need to be adjusted.
Serotonin syndrome:
In rare cases, a serotonin syndrome has been reported in patients treated with SSRIs.
An association 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 therapy initiated.
Serotonergic medicines:
Citalopram should not be used in combination with medicinal products with a serotonergic effect such as sumatriptan or other triptans, tramadol, oxytryptan and tryptophan (see section 4.5).
Hemorrhage:
Prolonged clotting times and / or clotting abnormalities such as ecchymosis, gynecological haemorrhages, gastrointestinal bleeding and other forms of cutaneous or mucosal haemorrhage have been reported with SSRIs (see section 4.8). Caution is advised in patients taking SSRIs particularly in the case of concomitant use of active substances that may affect platelet function or other substances that may increase the risk of bleeding, as well as in patients with a history of coagulation disorders (see section 4.5).
Electroconvulsive Therapy (ECT):
Clinical experience with the simultaneous administration of SSRIs and ECTs is limited, therefore caution is recommended.
Reversible selective MAO-A inhibitors:
The combination of citalopram with MAO-A inhibitors is generally not recommended due to the risk of developing serotonin syndrome (see section 4.5).
For more information on concomitant treatment with non-selective irreversible MAO inhibitors, see section 4.5.
Insomnia and agitation may occur at the start of treatment. In such cases, dosage adjustment may help.
St. John's wort / Hypericum:
Undesirable effects may be more common during concomitant use of citalopram and herbal preparations containing St John's wort (Hypericum perforatum). Therefore citalopram and preparations containing St. John's wort should not be taken at the same time (see section 4.5).
Discontinuation symptoms observed following discontinuation of SSRI treatment:
On discontinuation of treatment, the onset of withdrawal symptoms is common, particularly if discontinuation is sudden (see section 4.8). In a recurrence prevention clinical study, adverse events occurred in 40% of patients after discontinuation. of treatment, compared with 20% of patients who continued citalopram treatment.
The risk of withdrawal symptoms may be dependent on various factors, including the duration and dose of therapy and the rate of dose reduction. The most commonly reported adverse reactions are: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. Generally these symptoms are mild to moderate; however, in some patients they can be severe in intensity.
They usually appear within the first few days of stopping treatment; however, very rare cases of withdrawal symptoms have been reported in patients who inadvertently missed a dose. In general, these symptoms are self-limiting and usually resolve within 2 weeks, although in some patients they may be prolonged (2-3 months or more).
Therefore, it is recommended to gradually reduce the dosage of citalopram over a period of several weeks or months, according to the patient's needs, when discontinuing treatment (see section 4.2 "Withdrawal symptoms observed following discontinuation of treatment").
Psychosis:
Treatment of psychotic patients with depressive episodes can increase psychotic symptoms.
Prolongation of the QT interval:
Citalopram has been found to cause dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported in post-marketing experience, predominantly in female patients with hypokalaemia or with pre-existing QT interval prolongation or other cardiac disorders (see sections 4.3, 4.5, 4.8, 4.9 and 5.1).
Caution is advised in patients with significant bradycardia, in patients with recent acute myocardial infarction or with uncompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before starting treatment with citalopram.
If treating patients with stable cardiac disease, an ECG check should be considered before starting treatment.
If signs of cardiac arrhythmia occur during treatment with citalopram, the treatment should be discontinued and an ECG performed.
Closed-angle glaucoma:
SSRIs including citalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to reduce the angle of the eye resulting in increased intraocular pressure and closed angle glaucoma, especially in predisposed patients. Citalopram should therefore be used with caution in patients with narrow-angle glaucoma or a history of glaucoma.
Important information about some of the ingredients:
Elopram contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
At the pharmacodynamic level, cases of serotonin syndrome have been reported with the use of citalopram, moclobemide and buspirone.
Contraindicated associations
MAO inhibitors:
The concomitant use of citalopram and MAO inhibitors can cause serious undesirable effects, including serotonin syndrome (see section 4.3).
Cases of serious, and sometimes fatal, reactions have been reported in patients receiving SSRI treatment associated with a monoamine oxidase inhibitor (MAOI), including selegiline, an irreversible MAOI, and linezolid, a reversible MAOI and moclobemide, and in patients who had recently stopped treatment with an SSRI and started therapy with a MAOI.
Some cases presented with features similar to those of serotonin syndrome. Symptoms of interaction of an active substance with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, confusion, irritability, agitation and tremor. If this condition progresses without intervention, it can be fatal following rhabdomyolysis, central hyperthermia with acute multi-organ failure, delirium and coma (see section 4.3).
Prolongation of the QT interval:
Pharmacokinetic and pharmacodynamic studies on the combination of citalopram and other medicinal products that prolong the QT interval have not been conducted. An additive effect of citalopram with such medicinal products cannot be excluded. Consequently, co-administration of citalopram with drugs that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (such as phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (such as sparfloxacin, moxifloxacin IV) is contraindicated. , pentamidine, antimalarial treatments, in particular halofantrine), some antihistamines (astemizole, mizolastine) etc.
Pimozide:
Concomitant use of citalopram and pimozide is contraindicated (see section 4.3). Concomitant administration of a single 2 mg dose of pimozide to healthy volunteers who were treated with racemic citalopram 40 mg / day for 11 days only resulted in an increase in pimozide AUC and Cmax although not consistently across the study. Concomitant administration of pimozide and citalopram caused a mean increase in the QTc interval of approximately 10 msec. As this interaction had already been observed after administration of a low dose of pimozide, concomitant treatment with citalopram and pimozide is contraindicated.
Associations requiring precautions for use
Selegiline (selective MAO-B inhibitor):
A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram (20 mg per day) and selegiline (10 mg per day) (a selective MAO-B inhibitor) showed no clinically relevant interactions. The concomitant use of citalopram and selegiline (at doses above 10 mg per day) is not recommended (see section 4.3).
Lithium and Tryptophan:
No pharmacodynamic interactions were found in clinical studies in which citalopram was administered concomitantly with lithium. However, there have been reports of potentiation of effects when SSRIs are administered in combination with lithium or tryptophan and therefore caution is advised when using citalopram concurrently with these medicinal products. Continuous monitoring of lithium levels should be continued as usual.
Serotonergic medicinal products:
Concomitant administration with serotonergic medicinal products (e.g. tramadol, sumatriptan) may lead to increased 5-HT associated effects.
Until further information is available, the concomitant use of citalopram and serotonin (or 5-HT) agonists, such as sumatriptan and other triptans is not recommended (see section 4.4).
St. John's wort / Hypericum:
Dynamic interactions may occur with concomitant use of SSRIs and herbal preparations containing St. John's wort resulting in increased undesirable effects (see section 4.4). Pharmacokinetic interactions have not been studied.
Hemorrhage:
Particular caution is needed for those patients who are being treated concomitantly with anticoagulants, drugs that can affect platelet function, such as non-steroidal anti-inflammatory drugs (or NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine or other drugs (for example atypical antipsychotics, phenothiazines, tricyclic antidepressants) which may increase the risk of bleeding (see section 4.4).
Electroconvulsive Therapy (ECT):
There are no clinical studies establishing the risk or benefit of the combined use of electroconvulsive therapy (ECT) and citalopram (see section 4.4).
Alcohol:
No pharmacodynamic or pharmacokinetic interactions of citalopram with alcohol have been demonstrated; however, the association between citalopram and alcohol is not recommended.
Medicinal products inducing hypokalaemia / hypomagnesaemia:
Caution is advised in concomitant use of hypokalaemia / hypomagnesaemia inducing medicinal products as these conditions increase the risk of malignant arrhythmias (see section 4.4).
Medicinal products that lower the seizure threshold:
SSRIs can lower the seizure threshold. Caution is advised when concomitantly using medicinal products capable of lowering the seizure threshold (eg antidepressants [SSRI], neuroleptics [butyrophenones, thioxanthenes], mefloquine, bupropion and tramadol).
Neuroleptics:
The use of citalopram did not reveal any clinically relevant interaction with neuroleptics; however, as with other SSRIs, the possibility of a pharmacodynamic interaction cannot be excluded a priori.
Pharmacokinetic interactions
The biotransformation of citalopram to demethylcitalopram is mediated by the isoenzymes of the P450 system: CYP2C19 (approximately 38%), CYP3A4 (approximately 31%) and CYP2D6 (approximately 31%). The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation is less likely since inhibition of one enzyme can be compensated for by another.
Therefore, co-administration of citalopram with other medicinal products in clinical practice has a low probability of producing pharmacokinetic interactions.
Food:
No effects of food on the absorption and other pharmacokinetic properties of citalopram have been reported.
Influence of other medicinal products on the pharmacokinetics of citalopram:
Co-administration with ketoconazole (potent CYP3A4 inhibitor) does not change the pharmacokinetics of citalopram.
A pharmacokinetic interaction study of lithium and citalopram revealed no pharmacokinetic interactions (see also above).
Cimetidine:
Cimetidine, a known enzyme inhibitor, causes a moderate increase in the mean steady-state plasma levels of citalopram. Therefore, caution is recommended when administering citalopram in combination with cimetidine. Dose adjustments may be needed.
Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole (a CYP2C19 inhibitor) 30 mg once daily resulted in a moderate (approximately 50%) increase in plasma concentrations of escitalopram.
Therefore, caution should be exercised in concurrent use of CYP2C19 inhibitors (eg omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A dose adjustment of citalopram may be required.
Metoprolol:
Escitalopram (the active enantiomer of citalopram) is an inhibitor of the CYP2D6 enzyme. Caution is advised when citalopram is co-administered with medicinal products which are mainly metabolised by this enzyme, and which have a narrow therapeutic index, eg flecainide. , propafenone and metoprolol (when used in heart failure), or some medicinal products which act on the CNS and which are mainly metabolised by CYP2D6, eg. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics such as risperidone, thioridazine and haloperidol. Dosage adjustments may be needed. Co-administration with metoprolol resulted in a doubling of the plasma levels of the latter but did not statistically significantly increase the effect of metoprolol on blood pressure and heart rate.
Effects of citalopram on other medicinal products:
A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a doubling of the plasma levels of metoprolol, but not a 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, compared to other SSRIs known as significant inhibitors.
Levomepromazine, digoxin, carbamazepine:
No changes were observed or only small changes of no clinical relevance were observed when citalopram was administered with CYP1A2 (clozapine and theophylline) CYP2C9 (warfarin) and CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline) substrates , risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine epoxide) and triazolam.
No pharmacokinetic interactions have been 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 shown on either citalopram or imipramine levels, although levels of desipramine, the major metabolite of imipramine, were increased. When desipramine is combined with citalopram, a increase in plasma concentration of desipramine, therefore it may be necessary to reduce its dosage.
04.6 Pregnancy and lactation
Pregnancy:
A large number of data on pregnant women (more than 2500 published results) indicate no malformative fetal / neonatal toxicity. However, citalopram should not be used during pregnancy, unless strictly necessary, and only after a "careful risk / benefit assessment".
Newborns should be observed if maternal use of citalopram has continued in the later stages of pregnancy, particularly in the third trimester. Abrupt termination should be avoided during pregnancy.
Following the mother's use of SSRIs / SNRIs during the last stages of pregnancy, the newborn may manifest the following symptoms: respiratory disorders, cyanosis, apnea, convulsions, unstable temperature, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, nervousness, irritability, lethargy, chronic crying, drowsiness and difficulty sleeping. These symptoms may be due to serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately after delivery or within hours. immediately following (less than 24 hours).
Epidemiological data have suggested that the use of SSRIs in pregnancy, especially towards the end of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 in 1000 pregnancies. there are 1-2 cases of PPHN per 1000 pregnancies.
Feeding time:
Citalopram is excreted in breast milk. It is estimated that infants who are breastfed receive about 5% relative to the daily dose taken by the mother (in mg / kg). Only minor events were observed in infants. However, existing information is insufficient to assess the risk in children. Caution is advised.
Male fertility:
Animal data have shown that citalopram may affect sperm quality (see section 5.3).
In humans, reports from patients treated with SSRIs have shown that the effect on sperm quality is reversible.
No impact on fertility has been observed so far.
04.7 Effects on ability to drive and use machines
Citalopram has minor or moderate influence on the ability to drive and use machines.
Psychiatric drugs can reduce judgment and reactivity in emergency situations. Patients should be informed of these effects and warned that their ability to drive a car or use machines may be affected.
04.8 Undesirable effects
The side effects seen with citalopram are generally mild and transient in nature. They occur mainly in the first or second week of therapy, and then subside later.
Adverse reactions follow the MedDRA Preferred Terms classification.
A dose-response relationship was found for the following reactions: increased sweating, dry mouth, insomnia, somnolence, diarrhea, nausea and fatigue.
The table below shows the rate of adverse reactions associated with SSRIs and / or citalopram occurring in both ≥1% of patients in double-blind placebo-controlled clinical trials and in post-marketing experience.
Frequency classes are defined as follows: very common (≥1 / 10), common (≥1 / 100 to
1 Cases of suicidal ideation and suicidal behaviors have been reported during citalopram therapy or early after treatment discontinuation (see section 4.4).
Fracture of bones Epidemiological studies, conducted mainly in patients over 50 years of age, have shown an increased risk of fractures in patients treated with SSRIs and TCAs. The main mechanism leading to this risk is unknown.
Prolongation of the QT interval:
Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported during post-marketing experience, predominantly in female patients, with hypokalaemia or with pre-existing QT interval prolongation or other cardiac conditions ( see sections 4.3, 4.4, 4.5, 4.9 and 5.1).
Withdrawal symptoms observed following discontinuation of treatment:
Discontinuation of citalopram treatment (especially if abrupt) usually leads to withdrawal symptoms.
The most frequently reported reactions are: 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.
Generally these events are mild or moderate and self-limiting, however in some patients they may be severe and / or prolonged in duration. It is therefore recommended when treatment with citalopram is no longer necessary, to gradually discontinue treatment by progressively reducing the dose (see section 4.2 Posology and method of administration and 4.4 Special warnings and precautions for use).
04.9 Overdose
Toxicity:
Comprehensive clinical data on citalopram overdose are limited and in many cases are associated with concomitant drug / alcohol overdose. Fatal cases have been reported from overdose of citalopram alone; however, most fatal cases are due to overdose with multiple concomitant medications.
Symptoms:
The following symptoms have been reported in cases of citalopram overdose: seizures, tachycardia, somnolence, QT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, conduction block heart failure, QRS prolongation, hypertension, mydriasis, torsades de pointes, stupor, sweating, cyanosis, hyperventilation and atrioventricular arrhythmia Rhabdomyolysis is rare.
Symptoms possible with a dose up to 600 mg are: fatigue, weakness, sedation, tremor, nausea and tachycardia. With doses above 600 mg, seizures may occur within hours of taking. ECG changes and, rarely, rhabdomyolysis may also occur. Overdose is rarely fatal. One adult patient survived after ingesting 5,200 mg of citalopram.
Treatment:
There is no known specific antidote to citalopram. Treatment should be symptomatic and supportive. Activated charcoal, osmotic laxatives (such as sodium sulfate) and gastric lavage should be considered. In the presence of impaired consciousness, the patient should be intubated. ECG and vital signs should be monitored.
Administer oxygen in case of hypoxia and diazepam in case of convulsions. Physician surveillance for approximately 24 hours is recommended, as well as ECG monitoring if the ingested dose exceeds 600 mg. A widening of the QRS complex can be normalized by a hypertonic NaCl infusion.
In the event of overdose, ECG monitoring is advisable in patients with congestive heart failure / bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with impaired metabolism, eg hepatic insufficiency.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antidepressants; selective serotonin-reuptake inhibitors. ATC code: N06 AB 04.
Citalopram is a new bicyclic phthalene derivative with antidepressant effect.
Biochemical and behavioral studies have shown that the pharmacodynamic effect of citalopram is closely related to a potent inhibition of 5-HT (5-hydroxytryptamine = serotonin) uptake.
Citalopram has no effect on NA (noradrenaline) uptake and is therefore the most selective serotonin uptake inhibitor described so far, as demonstrated by the ratio of 5,000 NA to serotonin uptake inhibitor concentrations.
Citalopram has no influence on the uptake of DA (dopamine) or GABA (gamma-aminobutyric acid). Furthermore, neither citalopram nor its metabolites have antidopaminergic, antiadrenergic, antiserotonergic, antihistaminergic or anticholinergic properties and do not inhibit MAO (monoamine oxidase). .
Citalopram does not bind to benzodiazepine, GABA or opioid receptors.
After prolonged treatment, the inhibitory efficacy on 5-HT uptake is unchanged; moreover, citalopram does not induce changes in neuroreceptor density as occurs with most tricyclic antidepressants and with the more recent atypical antidepressants.
The effects on muscarinic cholinergic receptors, histamine receptors and alpha-adrenoreceptors are absent, with consequent failure to onset of the side effects related to the inhibition of these receptors: dry mouth, sedation, orthostatic hypotension, present after treatment with many antidepressant drugs.
Citalopram is unique for its extreme selectivity to block uptake and the absence of agonist or antagonist activity on the receptors.
In a double-blind, placebo-controlled ECG study in healthy volunteers, the change from baseline in QTc (Fridericia's correction) was 7.5 msec (90% CI 5.9-9.1) at the dose of 20 mg / day and 16.7 msec (90% CI 15.0-18.4) at a dose of 60 mg / day (see sections 4.3, 4.4, 4.5, 4.8 and 4.9).
05.2 Pharmacokinetic properties
Absorption:
Citalopram is rapidly absorbed after oral administration (mean T of 2 hours after taking drops and mean T of 3 hours after taking tablets). The bioavailability of the tablet formulation is 80%. The relative bioavailability of the drop formulation is approximately 25% higher than the tablet formulation.
Distribution:
The apparent volume of distribution is approximately 14 l / kg (range 12-16 l / kg).
Plasma protein binding is less than 80%.
Like other psychotropic drugs, citalopram is distributed throughout the body; the highest concentrations of the drug and of demethylated metabolites are found in the lungs, liver, kidneys, lower concentrations in the spleen, heart and brain.
The drug and its metabolites pass the placental barrier and are distributed in the fetus in a similar way to what is seen in the mother.
A very small amount of citalopram and its metabolites are secreted into breast milk.
Biotransformation:
Citalopram is metabolised to demethylcitalopram, didemethylcitalopram, citalopram-N-oxide and, by deamination, to a deaminated derivative of propionic acid.
While the propionic acid derivative is inactive, demethylcitalopram, didemethylcitalopram and citalopram-N-oxide are also selective serotonin uptake inhibitors although weaker than the parent compound.
In patients, unmetabolized citalopram is the predominant compound in plasma.
The steady-state citalopram / demethylcitalopram concentration ratio in plasma is on average 3.4 after 15 hours and 2 after 24 hours after administration.
Plasma levels of didemethylcitalopram and citalopram-N-oxide are generally very low.
Elimination:
The biological half-life is approximately one and a half days.
Systemic plasma clearance is approximately 0.4 l / min.
Excretion occurs with urine and faeces.
Linearity:
A linear relationship has been demonstrated between steady-state plasma concentrations and administered dose; steady state is achieved within the first week of therapy in most patients.
Steady state levels are in the range of 100-400 nM for a daily dose of 40 mg in most patients.
Elderly patients (> 65 years):
In elderly patients, following a reduction in the rate of metabolism, the half-life is lengthened (1.5-3.75 days) and the clearance values are reduced (0.08-0.3 l / min); steady-state plasma concentrations are twice as high as in young patients treated with the same dose.
Reduced liver function:
In patients with impaired hepatic function, citalopram is eliminated more slowly; the biological half-life doubles and steady-state plasma concentrations are approximately twice as high as in patients with normal hepatic function.
Reduced renal function:
Citalopram is eliminated more slowly in patients with mild to moderate renal impairment, but the phenomenon has no major influence on the pharmacokinetics of the drug. There is currently no information on the pharmacokinetics of citalopram in severe renal insufficiency (creatinine clearance
Pharmacokinetic / pharmacodynamic relationship:
An evaluation of plasma concentration and effect was not performed; even the side effects do not seem related to the plasma concentrations of the drug.
The conversion factor from nM to ng / ml (based on the base) is 0.32 for citalopram and 0.31 for demethylcitalopram.
05.3 Preclinical safety data
The drug has no teratogenic power and does not affect reproduction or perinatal conditions, has no mutagenic or carcinogenic effect.
Animal data have shown that citalopram induces a reduction in the fertility index and pregnancy index, a reduction in the number of implants, abnormal spermatozoa at exposure levels well above human exposure.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Cornstarch;
Lactose monohydrate;
Microcrystalline cellulose;
Copovidone;
Glycerin (85%);
Croscarmellose sodium;
Magnesium stearate;
Titanium dioxide;
Hypromellose;
Macrogol 400.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C in the original container in order to protect from light.
06.5 Nature of the immediate packaging and contents of the package
The 20 mg and 40 mg tablets are packed in opaque PVC / PVDC and aluminum blisters.
Box of 28 tablets of 20 mg
Box of 14 tablets of 20 mg
Box of 14 tablets of 40 mg
06.6 Instructions for use and handling
No particular precautions.
Unused medicine and waste from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
beck Italia S.p.A. - Via della Moscova, 3 - 20121 Milan
08.0 MARKETING AUTHORIZATION NUMBER
ELOPRAM "20 mg film-coated tablets" 28 tablets - AIC: 028681017
ELOPRAM "20 mg film-coated tablets" 14 tablets - AIC: 028681031
ELOPRAM "40 mg film-coated tablets" 14 tablets - AIC: 028681029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: November 1994
Renewal of the authorization: November 2009
10.0 DATE OF REVISION OF THE TEXT
June 2013
