Chemical formula: C₂₀H₂₁FN₂O Molecular mass: 324.392 g/mol PubChem compound: 2771
Citalopram interacts in the following cases:
Dynamic interactions between citalopram and the herbal remedy St. John’s Wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects. Pharmacokinetic interactions have not been investigated.
Co administration with serotonergic medicinal products (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects.
Until further information is available, the simultaneous use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is not recommended.
Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram. Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine or cimetidine). A reduction in the dose of citalopram may be necessary based on monitoring of undesirable effects during concomitant treatment.
Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure) or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted. Co-administration with metoprolol resulted in a twofold increase in the plasma levels of metoprolol, but did not statistically significantly increase the effect of metoprolol on blood pressure and cardiac rhythm.
An initial dose of 10 mg daily for the first two weeks of treatment is recommended in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function.
The combination of citalopram and alcohol is not advisable. However clinical studies have revealed no adverse pharmacodynamic or pharmacokinetics interactions between citalopram and alcohol.
Caution is warranted for patients who are being treated simultaneously with anticoagulants, medicinal products that affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamol and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic depressants) that can increase the risk of haemorrhage.
Serotonergic syndrome may occur when citalopram is co-administered with macrolides.
Animal data have shown that citalopram may affect sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Citalopram may increase the bradycardic effect of carvedilol.
Cimetidine (potent CYP2D6, 3A4 and 1A2 inhibitor), caused a slight rise in the average steady-state citalopram levels. Caution is therefore recommended when administering citalopram in combination with cimetidine. Dose adjustment may be warranted.
Citalopram increases the energy/activity of clozapine.
In a pharmacokinetic study no effect was demonstrated on either citalopram or imipramine levels, although the level of desipramine, the primary metabolite of imipramine, was increased. When desipramine is combined with citalopram, an increase of the desipramine plasma concentration has been observed. A reduction of the desipramine dose may be needed.
The risk of serotoninergic syndrome is increased when citalopram is co-administered with desvenlafaxine.
There is no pharmacokinetic interaction between lithium and citalopram. However, there have been reports of enhanced serotonergic effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of citalopram with these drugs should be undertaken with caution. Routine monitoring of lithium levels should be continued as usual.
A pharmacokinetic/pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a twofold increase in metoprolol concentrations, but no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers.
Co-administration of citalopram with tiaprofenic acid, due to its additional antiplatelet activity, increases the risk of bleeding.
Ticlopidine may reduce the metabolism and clearance of citalopram.
Co-administration of citalopram with tolmetine increases the risk of bleeding due to the additional antiplatelet activity.
Co-administration of citalopram with tramadol may produce serotonergic syndrome.
Co-administration of citalopram with treprostinil, due to its additional antiplatelet activity, increases the risk of bleeding.
Citalopram may reduce the metabolism and clearance of trimipramine.
Voriconazole can increase serum citalopram levels by reducing its metabolism.
In rare cases, serotonin syndrome has been reported in patients using citalopram. A combination of symptoms such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. Treatment with citalopram should be discontinued immediately and symptomatic treatment initiated.
SSRIs including citalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Citalopram should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.
Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure.
In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Seizures are a potential risk with antidepressant drugs. The drug should be discontinued in any patient who develops seizures. Citalopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Citalopram should be discontinued if there is an increase in seizure frequency.
Published data on pregnant women (more than 2500 exposed outcomes) indicate no malformative feto/neonatal toxicity. However, citalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit.
Neonates should be observed if maternal use of citalopram continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy.
The following symptoms may occur in neonates after maternal SSRI/ SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.
Epidemiological data have suggested that the use of SSRIs in pregnancy, particular in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.
Citalopram is known to be excreted in breast milk. It is estimated that the suckling infant will receive about 5% of the weight related maternal daily dose (in mg/kg). No or only minor events have been observed in the infants. However, the existing information is insufficient for assessment of the risk to the child. Caution is recommended. If treatment with citalopram is considered necessary, discontinuation of breast-feeding should be considered.
Animal data have shown that citalopram may affect sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Citalopram has minor or moderate influence on the ability to drive and use machines.
Patients who are prescribed psychotropic medication may be expected to have some impairment of general attention and concentration due to the illness itself and psychoactive medicinal products can reduce the ability to make judgements and to react to emergencies. Patients should be informed of these effects and be warned that their ability to drive a car or operate machinery could be affected.
Adverse effects observed with citalopram are in general mild and transient. They are most prominent during the first one or two weeks of treatment and usually attenuate as the depressive state improves. Adverse reactions are presented at the MedDRA Preferred Terms level.
For the following reactions a dose-response was discovered: increased sweating, dry mouth, insomnia, somnolence, diarrhoea, nausea and fatigue.
In comparative clinical trials with tricyclic antidepressants the incidence of adverse events occurring with citalopram was found to be lower in all cases.
The table shows the percentage of adverse drug reactions associated with SSRIs and/or citalopram seen in either ≥1% of patients in double-blind placebo-controlled trials or in the post-marketing period. Frequencies are defined as: Very common (≥1/10); Common (≥1/100, <1/10); Uncommon (≥1/1000, ≤1/100); Rare (≥1/10000, ≤1/1000); Very rare (≤1/10000), Not known (cannot be estimated from available data).
Not known: Thrombocytopenia
Not known: Hypersensitivity, anaphylactic reaction
Not known: Inappropriate ADH secretion
Common: Appetite decreased weight decreased
Uncommon: Increased appetite, weight increased
Rare: Hyponatremia
Not known: Hypokalaemia
Very common:
Common: Agitation, libido decreased, anxiety, nervousness, confusional state, abnormal orgasm (female), abnormal dreams, anorexia, apathy
Uncommon: Aggression, depersonalisation, hallucination, mania, increased libido, euphoria
Not known: Panic attack, bruxism, restlessness, suicidal ideation, suicidal behaviour2
Very common: Somnolence, insomnia, headache
Common: Tremor, paraesthesia, dizziness, disturbance in attention, migraine, amnesia
Uncommon: Syncope
Rare: Convulsion grand mal, dyskinesia, taste disturbance
Not known: Convulsions, serotonin syndrome, extrapyramidal disorder, akathisia, movement disorder
Very common: Abnormal accommodation
Uncommon: Mydriasis (which may lead to acute narrow angle glaucoma)
Not known: Visual disturbance
Common: Tinnitus
Common: palpitations
Uncommon: Bradycardia, tachycardia
Not known: Electrocardiogram QT-prolonged1, Ventricular arrhythmia including torsade de pointes
Rare: Haemorrhage
Not known: Orthostatic hypotension
Common: Yawning, rhinitis, sinusitis
Rare: coughing
Not known: Epistaxis
Very common: Dry mouth, nausea
Common: Diarrhoea, vomiting, constipation, dyspepsia, abdominal pain, flatulence, increased salivation
Not known: Gastrointestinal haemorrhage (including rectal haemorrhage)
Rare: Hepatitis
Not known: Liver function test abnormal
Very common: Sweating increased
Common: Pruritus
Uncommon: Urticaria, alopecia, rash, purpura, photosensitivity reaction
Rare: Other forms of skin haemorrhage or bleeding in the mucous membranes
Not known: Ecchymosis, angioedemas
Common: Myalgia, arthralgia
Common: Micturition disorder, polyuria
Uncommon: Urinary retention
Common: Impotence, ejaculation disorder, ejaculation failure dysmenorrhoea
Uncommon: Female: Menorrhagia
Not known: Female: Metrorrhagia. Male: Priapism, galactorrhoea
Very common: asthenia
Common: Fatigue
Uncommon: Oedema
Rare: Pyrexia, malaise
Number of patients: Citalopram/placebo = 1346/545
1 Cases of QT-prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalemia, or with pre-existing QT prolongation or other cardiac diseases.
2 Cases of suicidal ideation and suicidal behaviours have been reported during citalopram therapy or early after treatment discontinuation.
Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.
Discontinuation of citalopram (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when citalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out.
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