Lexapro (Escitalopram) Interactions
- Alosetron
- Amphetamine
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)
- Nefazodone
- Nicardipine
Nonsteroidal Antiinflammatory Drugs (NSAIDs)
Opiate agonists
- Pentazocine
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
Lexapro (Escitalopram) Interactions
NOTE: Escitalopram is extensively metabolized in the liver by the cytochrome P450 isozymes 2C19, 2D6 and 3A4. Contributions to clearance for each enzyme are 37% for CYP2C19, 28% for CYP2D6 and 35% for CYP3A4. Biotransformation is in parallel with each enzyme. Impaired activity by any one of the enzymes due to a drug interaction or genetic polymorphism may not have a large effect on net metabolic clearance. However, due to differing pharmacokinetics in any one patient, potential drug interactions are listed below to aid the clinician in making appropriate therapeutic decisions. In-vitro unpublished studies have noted that escitalopram and S(+)-desmethylcitalopram are weak or negligible inhibitors of CYP 450 isozymes 1A2, 2C19, 2C9, 2E1, and 3A. In-vivo data suggest a modest inhibitory effect of escitalopram on CYP2D6. The secondary metabolite of escitalopram, S(+)-didesmethylcitalopram has an ability inhibit 2C9 and 2C19 isozymes; however, due to low plasma levels of S(+)-didesmethylcitalopram this effect does not appear to be clinically relevant.
Escitalopram 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 escitalopram with other drugs that have CNS serotonergic properties. Examples of these drugs include: buspirone; cocaine; lithium; nefazodone; trazodone; other selective serotonin reuptake inhibitors (SSRIs) (duplicative therapy), venlafaxine; tryptophan, 5-HTP; and St. John’s wort, Hypericum perforatum. Serotonin syndrome may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Currently, data regarding the ability of escitalopram to induce significant pharmacokinetic interactions with other drugs are lacking. Most of the data available is in regard to the effect of citalopram on other medications. According to clinical studies, the coadministration of citalopram with digoxin did not significantly affect the pharmacokinetics of either citalopram or digoxin. Drug interaction data for digoxin are currently unavailable for escitalopram. Although data are not available for escitalopram, when ketoconazole, a substrate and potent inhibitor of CYP3A4 was coadministered with citalopram, the Cmax and AUC of ketoconazole decreased by 21% and 10%, respectively, suggesting CYP3A4 induction by citalopram. Ketoconazole did not alter the pharmacokinetics of citalopram. Citalopram did not affect the pharmacokinetics of theophylline in multiple-dose studies.
Escitalopram 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 escitalopram therapy, and there should be at least 2 weeks between the discontinuation of escitalopram 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 (antibiotic) 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 escitalopram and either fenfluramine or dexfenfluramine. Dexfenfluramine stimulates the release and inhibits the reuptake of serotonin. Escitalopram also inhibits the reuptake of serotonin. In addition, escitalopram 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 escitalopram and dexfenfluramine are used together. Due to the potential severity of the serotonin syndrome, escitalopram should not be used with dexfenfluramine. This reaction may include confusion, seizures, and severe hypertension as well as less severe symptoms. Since dexfenfluramine is the S-enantiomer of the racemic compound fenfluramine, a similar interaction may occur between escitalopram 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 escitalopram with sibutramine is not recommended. Serotonin syndrome may include confusion, seizures, and severe hypertension as well as less severe symptoms.
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. Limited in-vivo data suggests a modest CYP2D6 inhibitory effect for escitalopram. Co-administration of escitalopram and desipramine (a substrate for CYP2D6), resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. 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.
While data are not available for escitalopram, food-drug interactions between citalopram and grapefruit juice have been documented. Grapefruit juice is an inhibitor of the cytochrome P450 isozyme 3A4, a metabolic enzyme utilized by escitalopram. Theoretically, elevated levels of escitalopram may occur. Until further information is available, clinicians should warn patients to avoid consumption of grapefruit juice while taking escitalopram.
Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, 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 escitalopram may reduce the conversion of the opiates codeine and hydrocodone to their active forms, thus reducing analgesic efficacy. Escitalopram 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.
Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including some beta-blockers (e.g., carvedilol, metoprolol, propranolol, timolol). Concomitant administration of escitalopram and metoprolol resulted in a 50% increase in Cmax and a 82% increase in AUC of metoprolol. The coadministration of metoprolol and citalopram did not produce any clinically significant effects on blood pressure or heart rate. Increased serum levels of the beta-blockers could result in reductions in cardioselectivity.
Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including some antiarrhythmics (encainide, flecainide, mexiletine, and propafenone).
Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of some drugs metabolized via the same pathway, including certain antipsychotic agents (clozapine, haloperidol, phenothiazines, risperidone, and thiothixene).
Escitalopram, a modest CYP2D6 inhibitor, may decrease the metabolism of darifenacin, a CYP2D6 substrate. Clinicians should monitor patients for increased anticholinergic effects when CYP2D6 inhibitors are coadministered with darifenacin; dosage adjustments of darifenacin may be necessary.
Escitalopram is metabolized by CYP2C19 and CYP3A4. Several drugs can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram 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. Although data are unavailable for escitalopram, 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 escitalopram should be considered if they are coadministered.
Escitalopram 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 escitalopram. 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 escitalopram theoretically exists. 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 escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease drug clearance. Although not studied, the following drugs might theoretically impair the metabolism of escitalopram when administered concomitantly: anti-retroviral protease inhibitors, aprepitant, clarithromycin, diltiazem, erythromycin, itraconazole, modafinil, nefazodone, nicardipine, troleandomycin, verapamil or voriconazole. This list is not inclusive of all drugs which may inhibit the CYP 450 pathyways involved in the metabolism of escitalopram.
Escitalopram is a modest 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 escitalopram.
Cyproheptadine is a serotonin antagonist in the CNS, and this pharmacological action opposes the pharmacological actions of SSRIs like escitalopram. In addition, cyproheptadine is metabolized through CYP2D6 and escitalopram weakly inhibits this hepatic isoenzyme. Cyproheptadine should probably be avoided in patients receiving escitalopram whenever possible. Alosetron, granisetron, ondansetron, and methysergide also antagonize serotonin (5-HT) receptors, although no drug-drug interactions have been reported yet with escitalopram.
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 escitalopram is a modest 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. Escitalopram is a modest 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 metabolism occurred when sertraline was chronically co-administered, indicating that SSRIs that inhibit this isoenzyme may also exhibit a pharmacokinetic interaction with 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. Serotonin syndrome may include confusion, seizures, and severe hypertension as well as less severe symptoms.
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 escitalopram. Although escitalopram is a weak to modest 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 escitalopram. A dosage adjustment of aripiprazole is necessary when these drugs are used concomitantly, and conversely, when escitalopram is discontinued in a patient taking aripiprazole.
The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or nonsteroidal antiinflammatory drugs (NSAIDs) 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.
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 escitalopram 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; however, studies with escitalopram have not been done.
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, serotonergic agents may increase the risk of bleeding when combined with warfarin or other anticoagulants via inhibition of serotonin uptake by platelets; 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 escitalopram is coadministered with doxercalciferol. Because escitalopram 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 ]
References
. Brannan SK et al. Sertraline and isocarboxazid cause a serotonin syndrome. J Clin Psycopharmacol 1994;14:144.
Related entries
Monthly Archives
Syndicate
Allergies
