Celexa (Citalopram) Interactions
Anti-retroviral protease inhibitors
- Aprepitant
- Aripiprazole
- Aspirin, ASA
- Atomoxetine
Barbiturates
- Buspirone
- Carbamazepine
- Carvedilol
- Cevimeline
- Cimetidine
- Clarithromycin
- Clozapine
- Cocaine
- Cyproheptadine
- Darifenacin
- Dexamethasone
- Dexfenfluramine
- Dextroamphetamine
- Dextromethorphan
- Diltiazem
- Doxercalciferol
- Encainide
- Erythromycin
- Ethanol
- Fenfluramine
- Flecainide
- food
- Furazolidone
- grapefruit juice
- Haloperidol
- Isoniazid, INH
- Itraconazole
- Kava Kava, Piper methysticum
- Ketoconazole
- Linezolid
- Lithium
- Metoclopramide
- Metoprolol
- Mexiletine
- Modafinil
Monoamine oxidase inhibitors (MAOIs)
Nonsteroidal antiinflammatory drugs (NSAIDs)
Opiate agonists
Phenothiazines
- Phentermine
- Phenytoin
- Primidone
- Procarbazine
- Propafenone
- Propranolol
- Rifabutin
- Rifampin
- Risperidone
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-Receptor Agonists
- Sibutramine
- St. John’s Wort, Hypericum perforatum
- Thiothixene
- Timolol
- Tramadol
- Trazodone
Tricyclic antidepressants
- Troglitazone
- Troleandomycin
- Tryptophan, 5-Hydroxytryptophan
- Valerian, Valeriana officinalis
- Venlafaxine
- Verapamil
- Voriconazole
- Warfarin
- Zolpidem
Celexa (Citalopram) Interactions
NOTE: The primary isoenzymes involved in the metabolism of citalopram are CYP3A4 and CYP2C19. Also, citalopram inhibits the hepatic CYP450 isoenzymes CYP1A2, -2D6, and -2C19 mildly in vitro, potentially inhibiting the metabolism of drugs that are substrates for these enzymes in vivo. Increased serum concentrations and possible toxicity may occur. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. Citalopram does not appear to inhibit other CYP hepatic isoenzymes (e.g., 3A4, 2C9, or 2E1), based on in vitro studies, to any clinically significant degree.
Citalopram did not affect the pharmacokinetics of theophylline in multiple-dose studies. In addition, the coadministration of citalopram with digoxin did not significantly affect the pharmacokinetics of either citalopram or digoxin.
Citalopram selectively inhibits the reuptake of serotonin, resulting in elevated levels of serotonin in the CNS. Because of the potential severity of the serotonin syndrome, caution should be observed when administering citalopram with other drugs that have CNS serotonergic properties. Examples of these drugs include: buspirone ; cocaine ; lithium ; nefazodone ; trazodone; other selective serotonin reuptake inhibitors (SSRIs) (duplication of therapy); venlafaxine ; tryptophan, 5-HT ; and St. John’s wort, Hypericum perforatum . The manufacturer reports no pharmacokinetic interaction between lithium and citalopram. However, patients receiving citalopram together with any of these serotonergic agents should be monitored closely for excessive adverse effects.
Citalopram potentiates serotonin by inhibiting its neuronal reuptake. Since serotonin is deaminated by monoamine oxidase type A, administration of drugs that inhibit this enzyme concurrently with SSRIs can lead to a serious reaction known as ‘serotonin syndrome’. This reaction may include confusion, seizures, and severe hypertension as well as less severe symptoms. Most monoamine oxidase inhibitors (MAOIs) (e.g., isocarboxazid, phenelzine, tranylcypromine) are non-specific inhibitors of MAO and, thus, affect MAO type A. Traditional MAOIs should not be used with SSRIs. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of citalopram therapy, and there should be at least 2 weeks between the discontinuation of citalopram therapy and commencement of MAOI therapy. In addition, selegiline, although selective for MAO type B at usual doses, may inhibit MAO type A at higher doses and should also be avoided in patients receiving selected SSRIs. However, a clinical trial performed in Finland reported no evidence of a clinically relevant pharmacokinetic or pharmacodynamic interaction between selegiline and citalopram at usual dosages. Finally, isoniazid, INH (antituberculosis drug), furazolidone and linezolid (antibiotics) and procarbazine (chemotherapy agent) also possess weak non-selective MAO-inhibiting activity and should be combined with any serotonergic agent with caution.
An interaction may occur between citalopram and either fenfluramine or dexfenfluramine. Dexfenfluramine stimulates the release of serotonin and inhibits its reuptake. Citalopram also inhibits the reuptake of serotonin. In addition, citalopram is a weak inhibitor of CYP2D6, an isoenzyme involved in the metabolism of dexfenfluramine. Thus, due to several mechanisms, serotonin excess and/or the serotonin syndrome may be possible if citalopram and dexfenfluramine are used together. Due to the potential severity of the serotonin syndrome, citalopram should not be used with dexfenfluramine. Since dexfenfluramine is the S-enantiomer of the racemic compound fenfluramine, a similar interaction may occur between citalopram and fenfluramine.
Sibutramine is a serotonin reuptake inhibitor. Concomitant use of two serotonin-augmenting drugs has been associated with serotonin syndrome , so concurrent use of citalopram with sibutramine is not recommended.
Concomitant administration of the SSRIs and serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) has resulted in increased plasma concentrations of SSRIs and rare reports of weakness, hyperreflexia and incoordination. If concomitant treatment with 5-HT1 receptor agonists and a SSRI is clinically warranted, the patient should be advised of potential drug interaction symptoms and appropriate actions to take should they occur. All centrally-acting serotonergic agents should be used cautiously in patients receiving SSRIs.
Amphetamine and dextroamphetamine may stimulate the release of serotonin in the CNS and thus may interact with other serotonergic agents, such as the SSRIs, venlafaxine or nefazodone. These interactions could lead to serotonin excess and, potentially, the ‘serotonin syndrome’ (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behaviors, nausea, abdominal cramps, diarrhea, palpitations, or chills). If serotonin syndrome is suspected, offending agents should be discontinued. In addition, the MAOI activity of amphetamines may be of concern with SSRI use. The concurrent use of amphetamines with medications that inhibit serotonin reuptake should be approached with caution. While the SSRI-type medications have occasionally been prescribed for the treatment of ADHD, the concurrent use of amphetamines with medications that inhibit serotonin reuptake should be approached with caution.
Clinicians should be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) class of antidepressants. The SSRIs are known to inhibit isozymes of the cytochrome P-450 mixed function oxidase system including CYP2D6 and/or CYP3A4, the isoenzymes responsible for metabolism of many of the tricyclic antidepressants. In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6, relative to the other SSRIs. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
Food interactions with citalopram may theoretically occur with grapefruit juice. Clinicians should advise patients that are therapeutically stable on citalopram not to alter their consumption of grapefruit juice. Patients who are newly started on citalopram should not consume grapefruit juice. The inhibition of CYP3A4 via grapefruit juice may lead to elevated serum concentrations of citalopram, but the clinical significance of this interaction is not known.
Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists (i.e., methadone, morphine, and oxycodone). In addition, impairment of CYP2D6 metabolism by citalopram may reduce the conversion of the opiates codeine and hydrocodone to their active forms, thus reducing analgesic efficacy. Citalopram should also be used cautiously in conjunction with meperidine, as meperidine blocks the neuronal reuptake of serotonin. A 42 year-old man became agitated, restless, diaphoretic, tachycardiac, and hypertensive immediately after receipt of meperidine 50 mg intravenously. Two weeks before the incident, the patient had stopped a regimen of the SSRI, fluoxetine. Serotonin syndrome was suspected, as fluoxetine and norfluoxetine have long half-lives, and previous meperidine receipt during a time when the patient had not been taking fluoxetine was uneventful.
Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some beta-blockers (carvedilol , metoprolol , propranolol , timolol ). Concomitant administration of citalopram and metoprolol resulted in a two-fold increase in the plasma concentrations of metoprolol, however, the coadministration of metoprolol and citalopram did not produce any clinically significant effects on blood pressure or heart rate. However, increased serum levels of the beta-blockers could result in alterations in cardioselectivity or other clinical effects.
Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some antiarrhythmics (encainide , flecainide , mexiletine , and propafenone ).
Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of some drugs metabolized via the same pathway, including certain antipsychotic agents (clozapine, haloperidol, phenothiazines, risperidone, and thiothixene).
Citalopram is metabolized by CYP2C19 and CYP3A4. Several drugs can induce the metabolism of various CYP 450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking any of the following enzyme-inducing drugs: barbiturates , carbamazepine , dexamethasone , phenytoin , primidone , rifabutin , rifampin , and troglitazone . Combined administration of citalopram and carbamazepine did not significantly affect the pharmacokinetics of either drug. However, given the enzyme-inducing properties of carbamazepine and the other drugs listed, the possibility that any one of them might increase the clearance of citalopram should be considered if they are coadministered.
Citalopram is metabolized by CYP3A4 and CYP2C19. Several drugs can inhibit the metabolism of CYP 450 isoenzymes, including those that are responsible for the metabolism of citalopram. Although clinical studies have not been done to determine the clinical significance of such an interaction, the potential for increased adverse effects and toxicity associated with elevated plasma levels of citalopram theoretically exists. When ketoconazole , a potent inhibitor of CYP3A4 was coadministered with citalopram, significant inhibition of citalopram metabolism did not occur. In clinical trial subjects, combined administration of cimetidine and citalopram for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. The clinical relevance of these findings is unknown as the combination was not associated with significant adverse effects. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. The following drugs might impair the metabolism of citalopram when administered concomitantly: anti-retroviral protease inhibitors , aprepitant, clarithromycin , diltiazem , erythromycin , itraconazole , modafinil , nefazodone , nicardipine , troleandomycin , verapamil or voriconazole. . This list may not be inclusive of all drugs that inhibit CYP3A4.
Citalopram is a weak inhibitor of the hepatic isoenzyme CYP2D6, and could potentially interfere with dextromethorphan metabolism via this pathway. More potent inhibitors of 2D6, such as fluoxetine and paroxetine, have been noted to cause clinically significant reactions when dextromethorphan was co-administered. Therefore, dextromethorphan may need to be used in lower doses in patients receiving citalopram.
Cyproheptadine is an serotonin antagonist in the CNS, and this pharmacological action opposes the pharmacological actions of SSRIs like citalopram. In addition, cyproheptadine is metabolized through CYP2D6 and citalopram weakly inhibits this hepatic isoenzyme. Cyproheptadine should probably be avoided in patients receiving citalopram whenever possible. Alosetron, granisetron, ondansetron, and methysergide also antagonize serotonin (5-HT) receptors, although no drug-drug interactions have been reported when citalopram was coadministered with any of these agents.
Clinicians should monitor patients for increased anticholinergic effects when darifenacin, a CYP2D6 substrate, is coadministered with citalopram, a mild CYP2D6 inhibitor; the dosage of darifenacin may need to be adjusted.
The combination of SSRIs and tramadol has been associated with serotonin syndrome and an increased risk of seizures. Post-marketing reports implicate the concurrent use of SSRIs with tramadol in some cases of seizures. Several cases of serotonin syndrome have been reported following the administration of tramadol with paroxetine or sertraline. SSRIs inhibit the formation of the active M1 metabolite of tramadol by inhibiting CYP2D6. Although citalopram is a weak inhibitor of CYP2D6, the inhibition of this metabolite may decrease the analgesic effectiveness of tramadol but increase the level of the parent compound, which has more serotonergic activity than the metabolite.
Cevimeline is metabolized by the cytochrome P450 CYP3A4 and CYP2D6 isoenzymes. Citalopram is a weak inhibitor of CYP2D6 and could lead to an increase in cevimeline plasma concentrations. Clinical interactions have not been documented at this time.
In some patients taking SSRIs, zolpidem has been associated with rare reports of disorientation, delusions, or hallucinations when administered concomitantly. In most cases the visual hallucinations were short lived (i.e., 30 minutes) but in some patients the symptoms persisted up to 7 hours in duration. The mechanism for the interaction has not been established, but is thought to be pharmacodynamic in nature. In one study, inhibition of zolpidem CYP2D6 metabolism occurred when sertraline was chronically co-administered, indicating that SSRIs that inhibit this isoenzyme may also exhibit a pharmacokinetic interaction with zolpidem. Citalopram is a weak inhibitor of CYP2D6 and theoretically could lead to elevated serum concentrations of zolpidem.
Patients receiving concurrent pentazocine and SSRIs are at increased risk for developing serotonin syndrome; pentazocine should be used cautiously, if at all, in these patients.
The German Commission E and other groups warn that any substances that act on the CNS, including psychopharmacologic agents, may interact with the phytomedicinals kava kava, Piper methysticum or valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action.
Until more data are available, the combined use of phentermine and SSRIs should be avoided. While the combined use of phentermine with certain SSRIs (e.g., fluoxetine) has been of interest for the treatment of obesity, studies have generally not supported combined treatment due to a risk of significant weight-regain after discontinuation of use. Additionally, a few case reports suggest potential adverse effects from the combination. In vitro data suggest that fluoxetine potentiates the anorectic and neurotoxic effects of phentermine; similar effects may occur with the use of other SSRIs, although the mechanism of the interaction is uncertain. As a drug related to the amphetamines, phentermine should additionally be combined with SSRIs with caution due to the potential for excessive serotonin activity (i.e., ‘serotonin syndrome’). The slight MAOI activity of phentermine may also be of concern with SSRI use, since serotonin is deaminated by monoamine oxidase type A and increased serotonin activity may result from MAO inhibition. However, some experts have debated phentermine’s effect on MAO at therapeutic doses. Thus, while a mechanism of interaction between phentermine and SSRIs is unclear at this time, the potential for interaction exists based on current evidence.
Atomoxetine is primarily a substrate for the cytochrome P450 (CYP) isozyme CYP2D6. A dosage adjustment of atomoxetine may be needed in normal populations (also known as extensive metabolizers) when atomoxetine is administered with inhibitors of the CYP2D6 enzyme, such as citalopram. Although citalopram is a weak inhibitor of 2D6, the potential for an interaction exists. In vitro studies suggest that coadministration of CYP inhibitors to poor metabolizers will not further increase the plasma concentrations of atomoxetine.
Increased aripiprazole blood levels are expected when aripiprazole is coadministered with inhibitors of CYP2D6, such as citalopram. A dosage adjustment of aripiprazole is necessary when these drugs are used concomitantly, and conversely, when citalopram is discontinued in a patient taking aripiprazole.
The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in >26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate. Patients should be cautioned of the risk of bleeding when any SSRI or serotonin-norepinephrine reuptake inhibitor (i.e., duloxetine, venlafaxine) is combined with aspirin, NSAIDs , or other drugs that affect coagulation.
There may be a potential for rare drug interactions between metoclopramide and selective serotonin reuptake inhibitors (SSRIs) and selected other drugs that inhibit serotonin reuptake (i.e., venlafaxine). The few published case reports of possible interactions have resulted in either ‘serotonin-syndrome’ type events and/or movement disorders (e.g., dystonia). The mechanism of the interactions is elusive but is thought to be a pharmacodynamic interaction; the interactions do not appear common. In most of the cases reported, a singular drug effect was not ruled out; however, the time course of the events are enough to raise suspicion that a drug interaction might be possible. Patients receiving metoclopramide concomitantly with an SSRI or venlafaxine should report any unusual movements or other unusual side effects to their health care professionals promptly.
The use of ethanol by patients taking citalopram is not recommended due to the potential for additive effects on the CNS. Also, pharmacologically ethanol is a CNS depressant, which may interfere with psychotropic therapies. Citalopram has not been shown to potentiate the cognitive and motor effects of ethanol.
Although data are limited, SSRIs may exhibit pharmacodynamic interactions with warfarin. The coadministration of citalopram with warfarin did not significantly affect the pharmacokinetics of either citalopram or warfarin. The combination of warfarin and citalopram did result in a small increase in prothrombin time that was felt to be clinically unimportant. Although pharmacokinetic interactions may be unlikely. pharmacodynamically, via inhibition of serotonin uptake by platelets, serotonergic agents may increase the risk of bleeding when combined with warfarin or other anticoagulants; however, the absolute risk is not known. It would be prudent for clinicians to monitor the INR and patient’s clinical status closely if a SSRI is added to or deleted from the regimen of a patient stabilized on warfarin.
Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including selective serotonin reuptake inhibitors may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if citalopram is coadministered with doxercalciferol. Because citalopram is a mild cytochrome P450 isozyme inhibitor, this interaction is less likely with doxercalciferol than other more potent cytochrome P450 isozyme inhibitors.
[ Last revised: 8/31/2005 3:01:00 PM ]
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