Active ingredients: Citalopram
CITALOPRAM ABC - 40 mg / ml oral drops, solution
Package inserts of Citalopram - Generic Drug are available for pack sizes:- CITALOPRAM ABC - 40 mg / ml oral drops, solution
- CITALOPRAM ABC 20 mg film-coated tablets CITALOPRAM ABC 40 mg film-coated tablets
Why is Citalopram used - Generic Drug? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Selective serotonin reuptake inhibitor antidepressants.
THERAPEUTIC INDICATIONS
Endogenous depressive syndromes and in the prevention of relapses and recurrences. Anxiety disorders with panic attacks, with or without agoraphobia.
Contraindications When Citalopram - Generic Drug should not be used
Hypersensitivity to the active substance or to any of the excipients.
Age under 18.
MAOIs (monoamine oxidase inhibitors).
There have been some cases with features similar to serotonin syndrome.
Citalopram should not be administered to patients receiving monoamine oxidase inhibitors (MAOIs), including selegiline, in daily doses greater than 10 mg / day.
Citalopram should not be administered for fourteen days after stopping an irreversible MAOI or for the specified time after stopping a reversible MAOI (RIMA), as indicated in the RIMA prescribing text. MAOIs should not be introduced for seven days after citalopram is stopped (see "Special warnings" and "Interactions").
Citalopram is contraindicated in combination with linezolid, unless facilities for close surveillance and monitoring of blood pressure are available (see "Special Warnings" and "Interactions").
Furthermore, CITALOPRAM ABC is contraindicated:
- in patients who present from birth or who have had an episode of abnormal heart rhythm (identified with an ECG; a test conducted to evaluate the function of the heart)
- In patients taking medications for heart rhythm problems or which can affect the heart's rhythm (See section "Interactions")
Generally contraindicated in pregnancy and lactation (See "Special warnings")
Precautions for use What you need to know before taking Citalopram - Generic Drug
Patients with hepatic insufficiency should start treatment with a low dose and be carefully monitored (See "Dose, Method and Time of Administration")
In patients with severely reduced renal function it is advisable to adhere to the minimum recommended dosage (See "Dose, Method and Time of Administration")
Mania
In patients with manic-depressive illness, a shift towards the manic phase may arise. If the patient enters a manic phase, citalopram should be discontinued and appropriate treatment with neuroleptics instituted.
Hyponatremia
Hyponatremia, possibly due to inadequate secretion of antidiuretic hormone (SIADH), which usually recedes on discontinuation of therapy, has been reported as a rare adverse reaction with SSRIs. particularly high risk.
Serotonin syndrome
In rare cases, serotonin syndrome has been reported in patients taking SSRIs. A combination of symptoms such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this disorder. Treatment with citalopram should be discontinued immediately and symptomatic treatment initiated.
Serotonergic drugs
Citalopram should not be used concomitantly with medicinal products with serotonergic effects, such as sumatriptan or other triptans, tramadol, oxitriptan, tryptophan, nefazodone and trazodone.
St. John's wort
Undesirable effects may be more common during concomitant use of citalopram and herbal preparations containing St. John's wort (Hypericum perforatum). Therefore citalopram and St. John's wort preparations should not be taken concomitantly (see " Interactions ").
Hemorrhages
There have been reports of prolonged bleeding time and / or bleeding abnormalities such as bruising, gynecological bleeding, gastrointestinal bleeding and other cutaneous or mucosal bleeding with SSRIs (see "Undesirable Effects"). Caution is advised in patients taking SSRIs, particularly in the case of concomitant use of active substances known to affect platelet function (NSAIDs, acetylsalicylic acid, ticlopidine, etc.) or other active substances that may increase the risk of bleeding, thus as in patients with a history of bleeding disorders (see Interactions).
Convulsions
Seizures pose a potential risk with antidepressant medications. Citalopram should be discontinued in patients experiencing seizures. Citalopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Citalopram should be discontinued if an increase in the frequency of seizures is observed.
Diabetes.
In patients with diabetes, SSRI treatment can alter glycemic control; this could be a consequence of the improvement in depression.
The dosage of insulin and / or oral hypoglycaemics may require adjustment.
ECT (electroconvulsive therapy)
There is limited clinical experience with the concomitant administration of SSRIs and ECTs, therefore caution is advised.
Use in subjects under the age of 18.
Antidepressants should not be used to treat children and adolescents under 18 years of age. It should also be known that, when taking this class of medicines, patients under 18 years of age have an increased risk of side effects such as suicide attempts, suicidal thoughts and hostility (essentially aggression, oppositional behavior and anger) Notwithstanding the foregoing, your doctor may prescribe CITALOPRAM ABC to patients under the age of 18 if he deems it strictly necessary. If your doctor has prescribed CITALOPRAM ABC to a patient under the age of 18 and you wish to have For more information, contact your doctor again. It will be advisable to inform your doctor if any of the above symptoms appear or worsen while a patient under the age of 18 is taking CITALOPRAM ABC. Furthermore, the long-term safety effects of CITALOPRAM ABC related to growth, maturation and cognitive and behavioral development have not yet been demonstrated.
Interactions Which drugs or foods can modify the effect of Citalopram - Generic Drug
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 citalopram and moclobemide and buspirone.
Contraindicated associations
MAO inhibitors
Co-administration of MAO-inhibitors, including reversible MAO-inhibitors (RIMA) such as moclobemide, can cause severe and sometimes fatal adverse reactions, such as hypertensive crisis or a serotonin syndrome (see section 4.3 "Contraindications" and section 4.4 "Warnings special "use" precautions).
Cases of serious and sometimes fatal reactions have been reported in patients treated with an SSRI in combination with a monoamine oxidase (MAO) inhibitor, including irreversible MAOIs selegiline and reversible MAOIs linezolid and moclobemide, and in patients who had recently discontinued an SSRI and had started treatment with a MAOI.
Some cases have presented with features similar to serotonin syndrome. Symptoms of an interaction of the active substance with a MAOI include: agitation, tremor, myoclonus and hyperthermia.
Prolongation of the QT interval
An additive effect of citalopram with other drugs that prolong the QT interval 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 derivatives) is contraindicated. phenothiazines, 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
Co-administration of a single 2 mg dose of pimozide to subjects treated with racemic citalopram 40 mg / day for 11 days resulted in a mean increase in the QTc interval of approximately 10 msec. Due to the interactions observed with a low dose of pimozide, concomitant administration of citalopram and pimozide is contraindicated.
Combinations that require precautions for use
Selegiline (selective MAO-B inhibitor)
The concomitant use of citalopram and selegiline (in doses above 10 mg per day) is not recommended (see section "Contraindications").
Serotonergic medicines
Lithium and tryptophan
There have been reports of increased effects when SSRIs have been co-administered with lithium or tryptophan and therefore concomitant use of citalopram with these drugs should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual.
Co-administration with serotonergic drugs (e.g. tramadol, sumatriptan) may result in increased 5-HT associated effects.
Until further information is available, the concomitant use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is not recommended (see "Precautions for use").
St. John's wort
Dynamic interactions can occur between SSRIs and St. John's wort remedies (Hypericum perforatum), resulting in increased side effects (see "Precautions for use").
Hemorrhages
Caution is warranted in patients being treated concomitantly with anticoagulants, drugs that affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole and ticlopidine, or other drugs (e.g. atypical antipsychotics) that may increase risk of bleeding (see "Precautions for use" section).
ECT (electroconvulsive therapy)
There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and citalopram (see section "Precautions for use").
Alcohol
The combination of citalopram and alcohol is not recommended.
Medicinal products inducing hypokalaemia / hypomagnesaemia
Caution should be exercised in concomitant use of drugs that induce hypokalaemia / hypomagnesaemia, as these conditions increase the risk of malignant arrhythmias (see section "Precautions for use").
Medicines that lower the seizure threshold
SSRIs can lower the seizure threshold. Caution is advised when using citalopram concomitantly with other drugs capable of lowering the seizure threshold (eg antidepressants [tricyclics, SSRIs], neuroleptics [thioxanthenes and butyrophenones]), mefloquine, bupropion and tramadol).
Pharmacokinetic interactions
Food
No reports have been received that the absorption and other pharmacokinetic properties of citalopram are affected by food.
Effects of other medicinal products on the pharmacokinetics of citalopram
Cimetidine
Caution is advised when administering citalopram in combination with citmethidine. Co-administration of escitalopram with omeprazole 30 mg once daily resulted in a moderate (approximately 50%) increase in plasma concentrations of escitalopram. Caution should be exercised when citalopram is used concomitantly with medicinal products such as omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine or cimetidine. A dose reduction of citalopram may be required.
Metoprolol
Caution is advised when citalopram is co-administered with medicines such as flecainide, propafenone and metoprolol (when used for heart failure) or with certain CNS-acting medicines, for example antidepressants such as desipramine, clomipramine and nortriptyline or the antipsychotics such as risperidone, thioridazine and haloperidol. Dose adjustment may be warranted. Co-administration with metoprolol resulted in a doubling of plasma levels of metoprolol but did not statistically significantly increase the effect of metoprolol on blood pressure and rhythm cardiac.
Effects of citalopram on other medicinal products
Levomepromazine, digoxin, carbamazepine
When citalopram was administered with clozapine, theophylline, warfarin, imipramine and mephenytoin, sparteine, imipramine, amitriptyline, risperidone, carbamazepine and triazolam) no changes were observed, or only very mild changes of no clinical significance were observed.
No pharmacokinetic interaction was observed between citalopram and levomepromazine or digoxin.
Desipramine, imipramine
When desipramine is combined with citalopram, an increase in the plasma concentration of desipramine has been observed. A dose reduction of desipramine may be required.
Contact your doctor if you have any other questions
Warnings It is important to know that:
Do not administer to patients under the age of 18
The risk of suicide in depressed patients persists until significant remission is achieved, as inhibitory blockade may be removed before effective antidepressant action is established. It is important to closely monitor the patient during the initial period.
The concomitant administration of citalopram and MAO inhibitors can cause hypertensive crisis. Therefore citalopram should not be administered to patients receiving MAO inhibitors and in any case not earlier than at least 14 days after their suspension.
MAO inhibitor treatment can be started 7 days after citalopram is stopped (SEE "Contraindications" and "Interactions")
Paradoxical anxiety
Some patients with panic disorders may report an "accentuation of anxiety symptoms" upon initiation of antidepressant therapy. This paradoxical ration generally decreases within the first two weeks of initiation of treatment. It is advisable to administer a low initial dose, to reduce the likelihood of a paradoxical anxiogenic effect (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 or immediate weeks of treatment, patients should be monitored closely until improvement occurs.
It is generally clinical experience that the risk of suicide may increase in the early stages of improvement. Other psychiatric conditions for which citalopram is prescribed may also be associated with an increased risk of suicidal behavior. Furthermore, these conditions can be associated with major depressive disorder. Therefore, the same precautions followed when treating patients with other psychiatric disorders should be observed when treating patients with other major depressive disorders.
Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. Placebo clinical trials conducted with antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Drug therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Patients (or caregivers) should be advised of the need to monitor and report immediately to their physician any worsening of clinical picture, the onset of suicidal behavior or thoughts or unusual behavioral changes and to seek immediate medical attention. if these symptoms occur.
Akathisia / psychomotor restlessness
The use of SSRIs / SNRIs has been associated with the development of akathisia, characterized by a subjectively unpleasant or painful restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to happen within the first few weeks of treatment. In patients who develop these symptoms, increasing the dosage can be harmful.
Prolongation of the QT interval
Particular attention must be paid:
- for patients who suffer or have suffered from heart problems or have recently had a heart attack
- For patients who have a low resting heart rate and / or if they know they have saline deficiencies following severe and prolonged diarrhea or vomiting or who use diuretics (drugs to urinate)
- In patients who have a rapid or irregular heart rhythm on standing up, faint, collapse or feel dizzy which could indicate an abnormal heart rhythm.
Withdrawal symptoms observed following discontinuation of SSRI treatment
Discontinuation symptoms seen when treatment is stopped are common, particularly if stopped abruptly (see "Undesirable Effects").
In a clinical study on the prevention of recurrences, adverse events occurred in 40% of patients after discontinuation of citalopram treatment compared with 20% of patients who did not discontinue treatment.
The risk of withdrawal symptoms may be dependent on several factors, including the duration of therapy, the dose and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea have been reported most commonly , palpitations, emotional instability, irritability and visual disturbances. Generally, the intensity of these symptoms is mild to moderate, however in some patients they may be severe. They usually appear within the first few days of stopping treatment, but there have been very rare cases in which they have appeared in patients who inadvertently skipped. one dose.
Generally these symptoms are self-limiting, and usually resolve within two weeks, although in some individuals they may last longer (2 to 3 months or more). It is therefore recommended that the dose of CITALOPRAM ABC be gradually reduced when treatment is discontinued, over a period of several weeks or months, depending on the patient's needs (see "Withdrawal Symptoms Observed After Discontinuation of Treatment with SSRIs "and" Dose, method and time of administration ").
Psychosis
Treatment of psychotic patients with depressive episodes can increase psychotic symptoms.
Closed-angle glaucoma
SSRIs including citalopram can have an effect on pupil size resulting in mydriasis. This mydriatic effect is able to reduce the angle of the eye with a consequent increase in intraocular pressure and to cause angle-closure glaucoma, especially in predisposed patients. Citalopram should therefore be used with caution in patients with narrow-angle glaucoma or a history of glaucoma.
Fertility, pregnancy and lactation
Ask your doctor or pharmacist for advice before taking any medicine.
Although animal studies have shown no signs of teratogenic potential, nor effects on reproduction or perinatal conditions, since citalopram with its metabolites cross the placental barrier and a small amount is found in breast milk, its use is not recommended. during pregnancy and breastfeeding (see "Contraindications").
Pregnancy
The safety of citalopram in pregnancy has not been established. A large amount of data on pregnant women (over 2500 exposed results) does not indicate any malformative fetal / neonatal toxicity. If clinically necessary, citalopram can be used during pregnancy, taking into account of the factors mentioned below.
Newborns should be observed if maternal use of citalopram continues into the later stages of pregnancy, especially in the third trimester. Abrupt termination should be avoided during pregnancy.
The following symptoms may occur in the newborn after maternal use of SSRIs / SNRIs in late pregnancy: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, agitation, irritability, lethargy, constant crying, drowsiness and difficulty sleeping. These symptoms may be due to serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately or soon after (<24 hours) childbirth.
Make sure your midwife and / or doctor know you are being treated with Citalopram ABC. When taken during pregnancy, particularly in the last 3 months of pregnancy, drugs such as Citalopram ABC may increase the risk of a serious pediatric condition called persistent pulmonary hypertension in the newborn (IPPN), which leads to rapid breathing in the newborn and the appearance of bluish tint. Usually, these symptoms appear during the first 24 hours after the baby is born. Tell your midwife and / or doctor immediately if your baby develops these symptoms.
Feeding time
Citalopram is excreted in breast milk. It is estimated that the infant will receive approximately 5% of the daily maternal administered dose based on weight (in mg / kg). No or only minor events were observed in neonates. However, the existing information is insufficient for assessing the risk to the child. Caution is advised.
Male 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
Citalopram has little or moderate influence on the ability to drive and use machines.
Psychoactive drugs can reduce the ability to judge and react to emergencies. Patients should be advised of these effects and that their ability to drive a car or use machines may be impaired
Important information about some of the ingredients
CITALOPRAM ABC contains methyl parahydroxybenzoate and propyl parahydroxybenzoate. They can cause allergic reactions (even delayed).
CITALOPRAM ABC contains 9 vol% ethanol. One dose can contain up to 0.09 g of ethanol (maximum dose). Harmful for those patients suffering from liver disease, alcoholism, epilepsy, brain injury or disease or for pregnant women and children. It may change or increase the effect of other medicines.
For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.
Dosage and method of use How to use Citalopram - Generic Drug: Dosage
Adults:
Depression
The usual dose is 16 mg (8 drops) / (0.4 ml) per day.
This can be increased by your doctor up to a maximum of 32 mg (16 drops) / (0.8 ml) 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 long-term maintenance therapy in order to prevent new depressive episodes.
Panic Disorder
The starting dose is 8 mg (4 drops) / (0.2 ml) per day for the first week, before increasing the dose to 16-24 mg (8-12 drops) / (0.4-0.6 ml) per day. The dose may be increased by your doctor up to a maximum of 32 mg (16 drops) / (0.8 ml) per day.
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
When a decision is made to discontinue treatment, doses should be reduced gradually to minimize the extent of withdrawal symptoms.
Elderly patients (over 65 years of age)
The starting dose should be reduced to half the recommended dose, e.g. 8-16 mg per day.
Elderly patients should normally not receive more than 16 mg (8 drops) / (0.4 ml) per day.
Use in children and adolescents under the age of 18.
Normally CITALOPRAM ABC should not be taken by children and adolescents under 18 years of age
Patients with particular risk factors
Patients with liver problems should not receive more than 16 mg (8 drops) / (0.4 ml) per day. In patients with renal insufficiency it is advisable to adhere to the minimum recommended dosage.
Withdrawal symptoms observed following discontinuation of treatment
"Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with CITALOPRAM ABC the dose should be reduced gradually over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions (see sections" Special warnings "and" Side 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 gradual.
Method of Administration:
the drops can be mixed with water, orange juice or apple juice. 1 drop = 2 mg of citalopram.
Overdose What to do if you have taken an overdose of Citalopram - Generic Drug
In case of accidental ingestion / intake of an excessive dose of CITALOPRAM ABC, notify your doctor immediately or contact the nearest hospital.
If you have any questions about the use of CITALOPRAM ABC, ask your doctor or pharmacist.
Toxicity
Comprehensive clinical data on Citalopram overdose are limited and many cases involve concomitant overdoses of other drugs / alcohol. Fatal cases have been reported from overdose of citalopram alone; however, most fatal cases are due to overdose with concomitant medications.
Symptoms
The following undesirable effects have been reported in cases of overdose: fatigue, weakness, sedation, dizziness, convulsions within hours of taking, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea , serotonin syndrome, agitation, bradycardia, dizziness, electrical conduction block in the heart, QRS prolongation, hypertension, mydriasis, torsades de pointes, stupor, sweating, cyanosis, atrioventricular hyperventilation and arrhythmia, rarely rhabdomyolysis.
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 sulphate) and gastric lavage should be considered as soon as possible after oral ingestion and a patent airway should be maintained. 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. Medical surveillance for approximately 24 hours as well as ECG monitoring is recommended if the ingested dose exceeds 600 mg.
In the event of overdose, ECG monitoring is advisable in patients with congestive heart failure / bradyarrhythmias in patients using concomitant QT-prolonging medications or in patients with impaired metabolism, eg hepatic insufficiency.
A widening of the QRS complex can be normalized by a hypertonic NaCl infusion.
Side Effects What are the side effects of Citalopram - Generic Drug
Like all medicines, CITALOPRAM ABC can cause side effects, although not everybody gets them.
The secondary reactions observed are generally mild and transient.
They are most common during the first or first two weeks of treatment and usually subside thereafter. Adverse reactions are presented at the MedDRA Preferred Term Level
A dose-response relationship was found for the following reactions: increased sweating, dry mouth, insomnia, somnolence, diarrhea, nausea and fatigue.
The table shows the percentage of adverse reactions associated with SSRIs and / or citalopram observed in ≥ 1% of patients in double-blind placebo-controlled studies or in the post-marketing period. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100,
1 Cases of suicidal ideation and suicidal behaviors have been reported during citalopram therapy or soon after treatment discontinuation (see "Precautions for use" and "Special Warnings").
Bone fractures
An increased risk of bone fractures has been observed in patients taking this type of medicine.
Prolongation of the QT interval
Stop taking CITALOPRAM ABC and seek immediate medical attention if you experience the following symptoms: Rapid, irregular heartbeat, feeling faint, which may be symptoms of a life-threatening condition known as Torsade de Pointes.
Withdrawal symptoms observed following discontinuation of treatment
Discontinuation of citalopram treatment (especially if abrupt) usually leads to withdrawal symptoms.
The most commonly reported reactions are dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, 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 ABC is no longer required, there is a gradual interruption, conducted by a gradual decrease of the dose (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 indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored
Warning: do not use the medicine after the expiry date indicated on the package.
Store at a temperature not exceeding 25 ° C protected from light in the original container.
The product must be used within 4 months of first opening the bottle, the excess product must be discarded.
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.
Keep this medicine out of the reach and sight of children.
COMPOSITION
One ml (= 20 drops) of solution contains:
Active principle:
Citalopram hydrochloride 44.48 mg
equal to citalopram 40 mg
Excipients:
Methyl parahydroxybenzoate, propyl parahydroxybenzoate, ethanol, hydroxyethylcellulose, purified water.
PHARMACEUTICAL FORM AND CONTENT
Oral drops, solution. 15 ml bottle of 40 mg / ml solution.
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
CITALOPRAM ABC 40 mg / ml oral drops, solution
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Oral drops 40 mg / ml, solution
One ml (= 20 drops) of solution contains:
Active ingredient: citalopram hydrochloride 44.48 mg equal to citalopram 40 mg
Excipients: methyl parahydroxybenzoate, propyl parahydroxybenzoate, ethanol
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Oral drops, solution.
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
Depression
Adults
Citalopram should be administered as a single daily oral dose of 16 mg (8 drops).
Based on the individual patient response, the dose can be increased up to a maximum of 32 mg (16 drops) 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 long-term maintenance therapy in order to prevent new depressive episodes.
Panic Disorders
Adults
For the first week of treatment the recommended dose is 8 mg (4 drops), thereafter the dose is increased to 16 mg (8 drops) per day. Based on the individual patient response, the dose can be increased up to a maximum of 32 mg (16 drops) per day.
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.
When a decision is made to discontinue treatment, doses should be reduced gradually to minimize the extent of withdrawal symptoms.
Elderly patients (> 65 years of age)
For elderly patients, the dose should be reduced to half the recommended dose, e.g. 8 mg (4 drops) to 16 mg (8 drops) per day. The maximum recommended dose for the elderly is 16 mg (8 drops) per day.
For use by children and adolescents under the age of 18
CITALOPRAM ABC should not be used for the treatment of children and adolescents under 18 years of age.
Reduced liver function
For patients with mild or moderate hepatic impairment, the recommended starting dose for the first two weeks of treatment is 8 mg (4 drops) per day. Based on the individual patient response, the dose can be increased up to a maximum of 16 mg (8 drops) per day. Caution and increased attention in dose titration is advised in patients with severely reduced hepatic function (see section 5.2).
Poor metabolisers of CYP2C19
For patients known to be CYP2C19 poor metabolisers, a starting dose of 8 mg (4 drops) daily during the first two weeks of treatment is recommended. Based on the individual patient response, the dose can be increased up to a maximum of 16 mg (8 drops) per day. (see section 5.2).
Kidney failure
In these patients it is advisable to adhere to the minimum recommended dosage.
Withdrawal symptoms observed following discontinuation of treatment
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with CITALOPRAM ABC the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions (see section 4.4 "Special warnings and precautions" of use "and section 4.8" 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 gradual.
Method of administration
The drops can be mixed with water, orange juice or apple juice.
1 drop = 2 mg of citalopram.
Citalopram oral drops, solution has a higher bioavailability than tablets by approximately 25%. Consequently, the correspondences between the doses of the tablets and those of the drops are as follows:
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Age under 18.
Citalopram must not be administered to patients treated with MAO inhibitors and in any case not earlier than 14 days after their suspension (see section 4.4 "Special warnings and precautions for use" and section 4.5 "Interactions with other medicinal products and other forms of interaction ").
Citalopram is contraindicated for 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).
Generally contraindicated in pregnancy and during lactation.
04.4 Special warnings and appropriate precautions for use
The concomitant administration of SSRIs and MAO-inhibitors can cause serious adverse reactions, sometimes fatal and the onset of hypertensive crises. Therefore citalopram should not be administered to patients receiving MAO inhibitors and in any case not earlier than at least 14 days after their suspension.
MAO inhibitor treatment can be started 7 days after citalopram is stopped.
If the patient enters a manic phase, treatment should be discontinued and appropriate treatment with neuroleptics instituted.
Some anxiety disorder patients with panic attacks may report an "accentuation of anxiety symptoms" upon initiation of antidepressant therapy. This paradoxical increase in anxiety symptoms is most marked during the first days of therapy and disappears as treatment continues (usually within two weeks).
When treatment with serotonin reuptake inhibitors is stopped abruptly, insomnia, dizziness, sweating, palpitations, nausea, anxiety, irritability, paraesthesia and headache may occur, therefore, when deciding to stop treatment, doses should be gradually decreased to minimize the extent of these symptoms. Be careful not to interpret these symptoms by attributing them to a worsening of the psychiatric illness being treated.
Undesirable effects may be more frequent during concomitant use of the serotonin reuptake inhibitors (SSRIs) nefazodone, trazodone, triptans and Hypericum perforatum preparations.
The drugs belonging to the class of serotonin reuptake inhibitors antidepressants should be administered with caution in patients receiving concomitant anticoagulants, drugs that affect platelet aggregation (NSAIDs, acetylsalicylic acid, ticlopidine, etc. ..) or other drugs that can increase the risk of bleeding.
In addition, these drugs should be administered with caution to patients with a history of coagulation disorders.
Patients with hepatic insufficiency should start treatment with a low dose and be closely monitored.
In patients with severely impaired renal function it is advisable to adhere to the minimum recommended dosage.
Although animal studies have not shown potential epileptogenic effects for citalopram as for other antidepressants, citalopram should be used with caution in patients with a history of seizures.
The drug should be discontinued if an increase in the frequency of seizures is observed.
In patients with diabetes, SSRI-based therapy can alter glycemic control; this could be a consequence of the improvement in depression. Your insulin and / or oral antidiabetic dosage may need to be adjusted.
The medicine contains para-hydroxybenzoates which can cause allergic reactions, usually of the delayed type.
The product contains 9 vol% ethanol. One dose can contain up to 0.09 g of ethanol (maximum dose). Harmful for those patients suffering from liver disease, alcoholism, epilepsy, brain injury or disease or for pregnant women and children. It may change or increase the effect of other medicines.
For use by children and adolescents under the age of 18.
CITALOPRAM ABC should not be used for the treatment of 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.
Suicide / Suicidal ideation
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 or immediate weeks of treatment, patients should be monitored closely until improvement occurs. & EGRAVE; Clinical experience in general that the risk of suicide may increase in the early stages of improvement.
Other psychiatric conditions for which CITALOPRAM ABC is prescribed may also be associated with an increased risk of suicidal behavior. Furthermore, these conditions can be associated with major depressive disorder. Therefore, the same precautions followed when treating patients with other psychiatric disorders should be observed when treating patients with major depressive disorders.
Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. 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.
Drug therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Patients (or caregivers) should be advised of the need to monitor and report immediately to their physician any clinical worsening, the onset of suicidal behavior or thoughts, or changes in behavior.
Akathisia / psychomotor restlessness
The use of citalopram has been associated with the development of akathisia, characterized by an internal feeling of restlessness and psychomotor agitation such as an inability to sit or stand still, usually associated with subjective malaise. This is most likely to happen within the first few weeks of treatment. In patients who develop these symptoms, increasing the dosage can be harmful.
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.
Withdrawal symptoms observed following discontinuation of treatment.
Discontinuation symptoms observed when treatment is stopped are common, particularly in the event of abrupt discontinuation (see section 4.8 "Undesirable effects").
In a clinical study on the prevention of recurrences, adverse events occurred in 40% of patients after discontinuation of citalopram treatment compared with 20% of patients who did not discontinue treatment.
The risk of withdrawal symptoms may be dependent on several factors, including the duration of therapy, the dose and the rate of dose reduction.
Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations have been reported , emotional instability, irritability and visual disturbances. Generally, the intensity of these symptoms is mild to moderate, however in some patients they may be severe. They usually appear within the first few days of stopping treatment, but there have been very rare cases in which they have appeared in patients who inadvertently skipped. Generally these symptoms are self-limiting, and usually resolve within two weeks, although in some individuals they may last longer (2 to 3 months or more). It is therefore recommended that the dose of CITALOPRAM be gradually reduced. ABC when discontinuing treatment over a period of several weeks or months, as needed by the patient (see "Withdrawal Symptoms Observed Upon Discontinuation", Section 4.2 "Posology and Method of Administration").
Important information about some of the ingredients
CITALOPRAM ABC contains methyl parahydroxybenzoate and propyl parahydroxybenzoate. They can cause allergic reactions (including delayed type).
CITALOPRAM ABC contains 9% vol ethanol. One dose can contain up to 0.09 g of ethanol (maximum dose). Harmful for those patients suffering from liver disease, alcoholism, epilepsy, brain injury or disease or for pregnant women and children. It may change or increase the effect of other medicines.
04.5 Interactions with other medicinal products and other forms of interaction
The biotransformation of citalopram to demethylcitalopram is mediated by isoenzymes of the cytochrome P450 system, CYP2C19 (approximately 60%), CYP3A4 (approximately 30%) and CYP2D6 (approximately 10%). The inhibition of the isoenzymes CYP2C9, CYP2E1 and CYP3A4 by citalopram and demethylcitalopram is negligible and the two compounds are only weak inhibitors of isoenzymes CYP1A2, CYP2C19 and CYP2D6 compared to other SSRIs, with which significant inhibition has been demonstrated. that citalopram inhibits P450-mediated drug metabolism at therapeutic doses.
Contraindicated associations
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 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.
Co-administration of MAO inhibitors, including reversible MAO inhibitors (RIMA), such as moclobemide, may cause serious and sometimes fatal adverse reactions, such as hypertensive crisis or a serotonin syndrome (see section 4.3 "Contraindications" and section 4.4 " Special warnings and precautions for "use").
No interactions related to concomitant alcohol intake have been reported.
Effects of other medicinal products on the pharmacokinetics of citalopram
Cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor) causes a moderate increase in mean steady-state plasma levels of citalopram. Caution is advised when administering citalopram in combination with cimetidine. Dose adjustments may be needed.
There have been reports of potentiation of effects when SSRIs are co-administered with lithium or tryptophan; therefore, caution should be exercised when these drugs are used concurrently.
Drugs belonging to the serotonin reuptake inhibitor class of antidepressants may increase the risk of bleeding when administered concomitantly with anticoagulants or drugs that affect platelet aggregation (NSAIDs, acetylsalicylic acid, ticlopidine, etc.) (see section 4.4 " Special warnings and precautions for "use").
A pharmacodynamic and pharmacokinetic interaction study between citalopram and metoprolol (a CYP2D6 substrate) showed a doubling of metoprolol concentrations, but no significant increase in the effects of metoprolol on blood pressure and heart rate in healthy volunteers.
Concomitant administration of other serotonergic drugs, such as tramadol and sumatriptan, may potentiate the associated 5HT effects.
Pharmacokinetic interaction studies have been performed with levomepromazine (an inhibitor of the CYP2D6 isoenzyme and prototype of phenothiazines) and with imipramine (a partial inhibitor of CYP2D6, a prototype of tricyclic antidepressants). No pharmacokinetic interactions were detected. having clinical importance.
04.6 Pregnancy and lactation
Pregnancy and breastfeeding
The safety of citalopram in pregnancy has not been established. Although animal studies have shown no signs of teratogenic potential or effects on reproduction or perinatal conditions, as citalopram with its metabolites cross the placental barrier and a small amount is found in breast milk, its use during pregnancy and lactation is not recommended (see section 4.3 "Contraindications").
Epidemiological data show that the use of selective serotonin reuptake inhibitors (SSRIs) in pregnancy, especially towards the end of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (IPPN). The observed risk was approximately 5 cases. per 1000 pregnancies In the general population, 1-2 cases of IPPN occur per 1000 pregnancies.
Fertility
Animal data have shown that citalopram can 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 little effect on psychomotor performance. However, given the possible onset of drowsiness, due caution should be exercised by those who are about to drive or operate machinery.
04.8 Undesirable effects
The secondary reactions observed are generally mild and transient.
They manifest themselves mainly in the first or second week of therapy, and then disappear with the improvement of the depressive state.
Frequent side effects (> 1/100 -
• metabolic and nutrition disorders: reduced appetite.
• psychiatric disorders: decreased libido and abnormal orgasm (women).
• nervous system disorders: agitation, insomnia, somnolence, dizziness.
• respiratory, thoracic and mediastinal diseases: yawning.
• gastrointestinal pathologies: nausea, dry mouth, diarrhea, constipation.
• skin and subcutaneous tissue disorders: increased sweating.
• reproductive system and breast pathologies: ejaculation disorders, impotence.
• systemic diseases and conditions relating to the site of administration: fatigue.
Rare side effects (> 1 / 10,000, ≤ 1/1000):
• psychiatric disorders: suicidal ideation / behavior (see section 4.4 "Special warnings and precautions for use")
• psychomotor restlessness / akathisia (see section 4.4 "Special warnings and precautions for use").
Very rare side effects (
• endocrine pathologies: inappropriate ADH secretion (especially in elderly women).
• metabolic and nutrition disorders: hyponatremia.
• pathologies of the nervous system: convulsions, extrapyramidal disorders.
• pathologies of the skin and subcutaneous tissue: ecchymosis, purpura.
• general disorders and administration site conditions: hypersensitivity reactions, serotonin syndrome, withdrawal symptoms (dizziness, nausea and paraesthesia).
Frequency not known: ventricular arrhythmias, including Torsade de Pointes.
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).
Rarely, following the administration of serotonin reuptake inhibitor antidepressants, haemorrhagic manifestations such as ecchymosis, gynecological haemorrhages, haemorrhagic manifestations affecting the gastrointestinal tract, mucous membranes or even other parts of the body may occur.
Withdrawal symptoms observed following discontinuation of treatment
Discontinuation of treatment with CITALOPRAM ABC (especially if abrupt) usually leads to withdrawal symptoms.
Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations have been reported , 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 ABC is no longer required, there is a gradual interruption, conducted by a gradual decrease in the dose (see section 4.2 "Posology and method of administration" and section 4.4 "Special warnings and precautions for use. ").
Other side effects that have been seen with SSRI medications are:
• cardiac pathologies: postural hypotension.
• eye diseases: abnormal vision.
• gastrointestinal pathologies: vomiting.
• hepatobiliary disorders: changes in liver function tests.
• pathologies of the musculoskeletal system and connective tissue: arthralgia, myalgia.
• psychiatric disorders: hallucinations, mania, confusion, anxiety, depersonalization, panic attacks, nervousness.
• kidney and urinary disorders: urinary retention.
• reproductive system and breast disorders: galactorrhea.
• skin and subcutaneous tissue disorders: itching.
Hyponatremia, possibly due to inappropriate antidiuretic hormone secretion, has been reported as a rare adverse reaction to SSRI use. Elderly women appear to be a particularly at risk group. "Serotonin syndrome" has rarely been reported in patients under treatment. with SSRIs The onset of a range of symptoms, including agitation, confusion, tremor, myoclonus and hyperthermia, may be the prodrome of the syndrome.
Epidemiological studies conducted mainly in patients aged 50 and over show an increased risk of bone fractures in patients taking SSRIs and TCAs. The mechanism underlying this effect is unknown.
04.9 Overdose
Symptoms possible with a dose up to 600 mg are: fatigue, weakness, sedation, dizziness, tremor, nausea and tachycardia.
At 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 of overdose is symptomatic and supportive as there is no specific antidote; gastric lavage should be performed as soon as possible after oral ingestion and a patent airway maintained, if necessary with intubation.
Administer oxygen in case of hypoxia and diazepam in case of convulsions. Medical surveillance for approximately 24 hours as well as ECG monitoring is recommended if the ingested dose exceeds 600 mg
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.
A widening of the QRS complex can be normalized by a hypertonic NaCl infusion.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antidepressants; selective serotonin-reuptake inhibitors
ATC code: N06AB04
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 in most tricyclic antidepressants and with the most 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 by deamination, to a deaminated derivative of propionic acid, while the inactive propionic acid derivative, demethylcitalopram, didemethylcitalopram and citalopram N-oxide, are also selective inhibitors of N-oxide. serotonin, 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 between steady-state plasma concentrations and administered dose has been demonstrated, and 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); concentrations plasma levels at steady state 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; biological half-life doubles and steady-state plasma concentrations are approximately twice as high as in patients with normal liver 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
Methyl parahydroxybenzoate, propyl parahydroxybenzoate, ethanol, hydroxyethylcellulose, purified water.
06.2 Incompatibility
The drops should only be mixed with water, orange juice or apple juice.
06.3 Period of validity
3 years.
Use the product within 4 months of first opening the bottle.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C protected from light in the original packaging.
Keep this medicine out of the reach and sight of children.
06.5 Nature of the immediate packaging and contents of the package
Cardboard box containing a 15 ml glass bottle fitted with a dropper cap.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
ABC Farmaceutici S.p.A.
C.so Vittorio Emanuele II, 72
10121 Turin
08.0 MARKETING AUTHORIZATION NUMBER
CITALOPRAM ABC 40 mg / ml oral drops, solution - bottle 15 ml - AIC n. 036043014
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
27/06/2005
10.0 DATE OF REVISION OF THE TEXT
Aife determination of September 2012
