Pharmacodynamic interaction
The cases of the development of serotonin syndrome with simultaneous application of citalopram with moclobemide and buspirone are described.
Contraindicated combinations
MAO inhibitors
Simultaneous use of citalopram and MAO inhibitors can lead to serious undesirable consequences, including serotonin syndrome.
Cases of serious and sometimes lethal reactions in patients simultaneously receiving SSRIs and a monoamine oxidase inhibitor (MAOI), including irreversible MAOI selegiline and reversible MAOIs linezolid and moclobemide, as well as in patients who recently stopped taking SSRIs and started taking MAOI.
In some of the cases presented, there were signs resembling serotonin syndrome.
Symptoms of interaction between citalopram and MAOI included: hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations in vital signs, changes in mental status, which included confusion, irritability and excessive agitation that progressed to delirium and to whom.
Pimozide
In the study, a single dose of pimozide 2 mg with citalopram at a dose of 40 mg / day for 11 days resulted in an increase in the values AUC and CmOh pimozide, although not always. Simultaneous use of pimozide and citalopram led to lengthening of the interval QTc medium degree (approximately 10 ms). Given the development of interaction with a low dose of pimozide, simultaneous administration of citalopram and pimozide is contraindicated.
Drugs that extend the interval QT
Studies of pharmacokinetic and pharmacodynamic interactions between citalopram and drugs extending the interval QT, was not carried out. Do not exclude the additivity of the effects of citalopram and these drugs. For this reason, simultaneous use of citalopram and drugs that extend the interval QT, such as class antiarrhythmics IA and III, neuroleptics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobials (for example, sparfloxacin, moxifloxacin, erythromycin iv, pentamidine, drugs for the treatment of malaria, especially halofantrine), some blockers H1-gistaminovyh receptors (astemizole, misolastine) is contraindicated.
Combinations that require caution
Selegiline (selective MAO B inhibitor)
Studies of pharmacokinetic and pharmacodynamic interaction with concurrent use of citalopram (20 mg per day) and selegiline (10 mg / day) (dose selective for MAO B) revealed no clinically significant interactions. The simultaneous use of citalopram and selegiline (in a dose exceeding 10 mg per day) is not recommended.
Lithium and tryptophan
In clinical trials of simultaneous use of lithium and citalopram, no pharmacodynamic interactions were identified. However, there has been a reported increase in action with simultaneous use of SSRIs with lithium or tryptophan, so the use of such combinations should be done with caution. Monitoring of the concentration of lithium in the blood is carried out as usual.
Serotonergic drugs
Simultaneous use with such serotonergic drugs as tramadol and sumatriptan, can lead to an increase in serotonergic effects.Until there is accurate data on possible interactions, the combination of citalopram with 5-HT receptor agonists, such as sumatriptan and other triptans, is not recommended.
St. John's wort perforated
Pharmacodynamic interaction of SSRI with plant preparations containing St. John's wort (Hypericum perforatum), can lead to an increase in the frequency of undesirable reactions. Pharmacokinetic interaction has not been studied.
Anticoagulants and agents that affect blood coagulability
Caution should be exercised in appointing citalopram to patients receiving anticoagulant therapy, drugs that affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid, dipyridamole and ticlopidine, or other drugs (eg, atypical antipsychotics, phenothiazine derivatives, tricyclic antidepressants) that may increase the risk of bleeding.
Electroconvulsive therapy (ECT)
Data from clinical studies that indicate the risks or benefits of concurrent use of ECT and citalopram are not available.
Alcohol
There were no pharmacodynamic or pharmacokinetic interactions between citalopram and alcohol. However, simultaneous administration of citalopram and alcohol is not recommended.
Drugs that reduce the threshold of convulsive readiness
SSRIs can reduce the threshold of convulsive alertness. It is advisable to use caution when used simultaneously with other drugs that can reduce the threshold of convulsive readiness (eg, antidepressants [tricyclics, SSRIs], neuroleptics [phenothiazines, thioxanthenes and butyrophenones], mefloquine, bupropion and tramadol).
Desipramine, imipramine
In pharmacokinetic studies, no changes in the concentration of either citalopram or imipramine were found, although the concentration of desipramine, the main metabolite of imipramine, was increased. With the simultaneous use of citalopram and desipramine, the concentration of the latter in plasma was increased. You may need to reduce the dose of desipramine.
Neuroleptics
The experience of using citalopram did not reveal clinically significant interactions with neuroleptics. However, as in the case of other SSRIs, the possibility of pharmacodynamic interaction is not excluded.
Pharmacokinetic interactions
Biotransformation of citalopram to desmethylcitalopram is mediated by isoenzymes of the cytochrome P450 system: CYP2C19 (about 38%), CYP3A4 (about 31%) and CYP2D6 (about 31%). The fact that citalopram is metabolized by more than one isoenzyme, suggests that inhibition of its biotransformation is unlikely, since the degree of inhibition of one of the enzymes can be compensated by others. Therefore, the simultaneous use of citalopram with other drugs has a very low probability of pharmacokinetic interactions.
Food
It has not been reported that eating influences the absorption and other pharmacokinetic properties of citalopram.
The effect of other drugs on the pharmacokinetics of citalopram
With simultaneous application ketoconazole (potent inhibitor of isoenzyme CYP3A4) did not change the pharmacokinetics of citalopram.
Pharmacokinetic studies of the interaction of lithium and citalopram did not reveal any interactions.
Cimetidine (a potent inhibitor of isoenzymes CYP2D6, 3A4 and 1A2) caused a moderate increase in the equilibrium concentration of citalopram.Caution is advised when using citalopram in combination with cimetidine. Dose adjustment may be required.
Effect of citalopram on the pharmacokinetics of other drugs
Studies of the pharmacokinetic / pharmacodynamic interaction of citalopram and metoprolol (substrate of isoenzyme CYP2D6) showed a twofold increase in the concentration of metoprolol, but there was no statistically significant increase in the effect of metoprolol on blood pressure and heart rhythm in healthy volunteers.
Care should be taken when using metoprolol and citalopram at the same time. Dose adjustment may be required.
Citalopram and desmethyl citalopram are moderate inhibitors of isoenzymes CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors CYP1A2, CYP2C19 and CYP2D6 in comparison with other SSRIs considered to be potent inhibitors.
Levomepromazine, digoxin, carbamazepine
No changes or only very small clinically significant changes were observed with simultaneous application of citalopram with isozyme substrates CYP1A2 (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline, risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine-epoxide) and triazolam).
No pharmacokinetic interaction between citalopram and levomepromazine or digoxin was observed (indicating that citalopram does not induce or inhibit P-glycoprotein).