Zoloft Interactions
Zoloft (Sertraline) Interactions
- Amphetamine
- Aripiprazole
- Aspirin, ASA
- Astemizole
- Atomoxetine
Barbiturates
- Bosentan
- Bupropion
- Carbamazepine
- Cevimeline
- Cimetidine
- Cocaine
- Codeine
- Cyclosporine
- Cyproheptadine
- Darifenacin
- Delavirdine
- Dexfenfluramine
- Dextroamphetamine
- Dextromethorphan
- Diazepam
- Disulfiram
- Donepezil
- Doxercalciferol
- Encainide
- Fenfluramine
- Flecainide
- food
- Fosphenytoin
- Furazolidone
- Galantamine
- grapefruit juice
- Haloperidol
- Hydrocodone
- Imatinib, STI-571
- Isoniazid, INH
- Kava Kava, Piper methysticum
- Linezolid
- Lithium
- Loxapine
- Meperidine
- Methadone
- Metoclopramide
- Mexiletine
- Molindone
Monoamine oxidase inhibitors (MAOIs)
- Morphine
- Oxycodone
- Pentazocine
Phenothiazines
- Phentermine
- Phenytoin
- Pimozide
- Procarbazine
- Propafenone
- Rifabutin
- Rifampin
- Rifapentine
- Ritonavir
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-Receptor Agonists
- Sibutramine
- St. John’s Wort, Hypericum perforatum
- Terfenadine
- Thiothixene
- Tolbutamide
- Tramadol
- Trazodone
Tricyclic antidepressants
- Tryptophan, 5-Hydroxytryptophan
- Valerian, Valeriana officinalis
- Warfarin
- Zolpidem
Zoloft (Sertraline) Interactions
NOTE: Sertraline is a substrate for the CYP isoenzymes 3A4, 2D6 and 2C19. Sertraline mildly inhibits the hepatic CYP450 isoenzyme CYP2D6 in vivo, thereby inhibiting the metabolism of a number of drugs. Increased serum concentrations and possible toxicity may occur. Sertraline appears to have little effect, if any, on the metabolic capacity of other CYP450 hepatic isoenzymes (e.g., CYP1A2, CYP2C9/10, CYP2C19 or CYP3A3/4), based on in vitro studies and drug interaction studies performed by the manufacturer of sertraline. Sertraline is unlikely to be a clinically significant inhibitor of CYP3A4 based on these studies; however, sertraline is contraindicated for co-administration with certain CYP3A4 substrates with a narrow therapeutic index (e.g., drugs associated with QT prolongation and proarrhythmias).
Due to possible additive effects on serotonin concentrations, it is advisable to avoid combinations of sertraline with other selective serotonin reuptake inhibitors (SSRIs) (duplicative therapy). This interaction can lead to a reaction known as ‘serotonin syndrome’. The syndrome may include symptoms of confusion, nausea, sweating, agitation, or more severe symptoms, like hypertension and unresponsiveness.
Due to the narrow therapeutic index of pimozide, both the manufacturer of sertraline and pimozide state that concomitant administration of sertraline and pimozide is contraindicated. Pimozide is noted to cause QT prolongation when the serum concentrations of the drug are elevated. Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death, when known and potent inhibitors of pimozide’s metabolism are coadministered. In a controlled study of a single dose (2 mg) of pimozide, 200 mg/day of sertraline co-administration to steady state was associated with a mean increase in pimozide AUC and Cmax of roughly 40%, but was not associated with any EKG changes. Although sertraline is considered a weak CYP3A4 inhibitor, this mechanism may contribute to the elevated pimozide serum concentrations during sertraline coadministration.
Astemizole is metabolized by CYP3A4; elevated astemizole serum concentrations may result in QT prolongation. Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death, when known and potent inhibitors of CYP3A4 are coadministered with astemizole. At the time of US market removal, the labeling for astemizole warned against use of selected SSRIs concomitantly. However, according to the manufacturer of sertraline, sertraline has little, if any, effect on CYP3A4 in vivo. Given the narrow therapeutic index of astemizole, however, co-use is best avoided; consider an alternative non-sedating antihistamine.
Terfenadine is metabolized by CYP3A4; elevated terfenadine serum concentrations may result in QT prolongation. Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death, when known and potent inhibitors of CYP3A4 are coadministered with terfenadine. At the time of US market removal, the labeling for terfenadine warned against use of sertraline concomitantly based on in vitro data indicating that sertraline inhibited terfenadine metabolism. However, according to the manufacturer of sertraline, sertraline has little, if any, effect on CYP3A4 and an in vivo interaction study reports that sertraline does not increase plasma concentrations of terfenadine. Given the narrow therapeutic index of terfenadine, however, co-use is best avoided; consider an alternative non-sedating antihistamine.
Sertraline 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 sertraline therapy, and there should be at least 2 weeks between the discontinuation of sertraline 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. Finally, isoniazid, INH, furazolidone, linezolid (antibiotic) and procarbazine (chemotherapy agent) also possess weak non-selective MAO-inhibiting activity and should be combined with any serotonergic agent with caution.
Clinicians should be alert for pharmacokinetic interactions between tricyclic antidepressants 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 isozymes responsible for metabolism of many of the tricyclic antidepressants. Cytochrome CYP2D6 is impaired most by fluoxetine and least by sertraline and is the isozyme most responsible for metabolism of tricyclic antidepressants. In several cases, symptoms of toxicity, including seizures, were reported when drugs from these 2 categories were used together. At least one case report exists of a death thought to be due to impaired clearance of amitriptyline by fluoxetine. The CYP2D6 isozyme is a common pathway for both of these drugs and norfluoxetine also inhibits this enzyme. Patients receiving a tricyclic antidepressant should be monitored closely for toxicity if a SSRI-type drug is added. Clinicians should be particularly cautious in patients with fluoxetine due to the extremely long elimination half-life of its metabolite, norfluoxetine (7—9 days). The American Heart Association has published guidelines regarding cardiovascular monitoring of certain psychotropic drug combinations in children. Sertraline inhibits the metabolism of the CYP2D6 (cytochrome P-450 isoenzyme 2D6) pathway at therapeutic doses. This can cause substantial increases in concentrations of benzodiazepines metabolized via the same pathway. The manufacturer reports a 32% decrease in the clearance of diazepam and a 23% increase in Tmax for desmethyldiazepam vs. a 19% decrease and a 20% decrease, respectively for placebo. These pharmacokinetic changes were statistically significant, but the clinical importance is not known. Fluoxetine, a related agent, has also been reported to affect the clearance and plasma concentrations of alprazolam (also metabolized by CYP3A4), but not the pharmacodynamics. An in-vivo study demonstrated that sertraline (50—150 mg/day) does not effect the pharmacokinetics or pharmacodynamics of alprazolam; studies suggest that the two agents may be coadministered with limited risk of alprazolam toxicity. The In general, when prescribing a SSRI in combination with a benzodiazepine, select medications to avoid metabolic interactions, if possible, and observe the patient more closely for increased CNS adverse effects.
An interaction may occur between sertraline and either fenfluramine or dexfenfluramine. Dexfenfluramine stimulates the release of serotonin and inhibits its reuptake. Sertraline also inhibits the reuptake of serotonin. Serotonin excess may occur if these two drugs are used together. Due to the potential severity of the serotonin syndrome, sertraline should not be used with dexfenfluramine. Since dexfenfluramine is the S-enantiomer of the racemic compound fenfluramine, a similar interaction may occur between sertraline and fenfluramine.
Sertraline inhibits metabolism of the CYP2D6 (cytochrome P-450 isoenzyme 2D6) pathway at therapeutic doses. This can cause substantial increases in concentrations of antipsychotics metabolized via the same pathway. Sertraline can increase the possible risk of adverse effects if used with haloperidol , loxapine, molindone, the phenothiazines , or thiothixene. Thioridazine is generally contraindicated for use with sertraline. Serum concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, may increase by up to three-fold because sertraline impairs the CYP2D6 isoenzyme metabolic pathway. Substantial increases in serum thioridazine concentrations may lead to prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes-type arrhythmias and sudden death. Sertraline decreases tolbutamide clearance by approximately 16%. Protein binding of tolbutamide is not affected. Due to the minimal change in clearance, this interaction is not expected to be clinically important. Monitor blood glucose during tolbutamide therapy.
Atenolol’s beta-adrenergic blocking activity was not altered by the addition of sertraline. The effect of atenolol on sertraline was not evaluated.
Sertraline should be used with caution with other highly protein-bound drugs because it also is a highly protein-bound drug (98%); one highly protein-bound drug can displace the other from their binding sites, leading to increased plasma levels and possible toxicity. However, at up to 300 and 200 ng/mL concentrations, respectively, sertraline and N-desmethylsertraline did not alter the plasma protein binding of two other highly protein bound drugs (e.g., warfarin and propranolol). Because sertraline is a base, however, it is more likely to bind to alpha1-acid glycoprotein than to albumin. Sertraline may potentiate the pharmacodynamic effects of warfarin in some patients. In one study of healthy volunteers, the mean hypoprothrombinemic response to warfarin was slightly affected by sertraline (prothrombin time prolonged by 8%). The mechanism of this interaction is uncertain, however other SSRI antidepressants are known to inhibit specific hepatic isozymes involved in warfarin metabolism. Sertraline appears to exert less of an effect on warfarin pharmacodynamics than other SSRIs, although more data are necessary to confirm this generalization. In addition, SSRI treatment may result in impaired platelet aggregation, which may result from platelet serotonin depletion and may contribute to abnormal bleeding. It would be prudent for clinicians to closely monitor the INR and the patient’s clinical status during coadministration of sertraline with warfarin.
In a study assessing sertraline (100 mg) on the second of 8 days of cimetidine administration (800 mg daily), there were significant increases in sertraline mean AUC (50%), Cmax (24%) and half-life (26%) compared to the placebo group. The clinical significance of these changes is unknown. A significant interaction with cimetidine has been identified for paroxetine, a related agent. Cimetidine should be used cautiously in patients receiving sertraline.
While another SSRI (fluoxetine) can increase or decrease lithium concentrations, two doses of sertraline have been shown not to significantly alter lithium concentrations or clearance . Close monitoring of lithium concentrations is advisable, particularly before steady-state has been achieved. Inadequate lithium concentrations (<0.6 mEq/L) can precipitate a conversion to mania in bipolar patients.
Since tryptophan is converted to serotonin (5-hydroxytryptamine), the use of tryptophan in patients receiving SSRIs 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). Discontinuation of tryptophan usually resolves 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.
Cyproheptadine is an antagonist of serotonin in the CNS, and this pharmacologic action opposes the pharmacologic actions of sertraline . Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine. Clinically, cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine, an agent related to paroxetine, but more data are needed to confirm a direct drug-drug interaction. Ondansetron, granisetron, and methysergide also antagonize serotonin (5-HT) receptors, although no drug-drug interactions have been reported with sertraline.
Due to possible additive effects on serotonin concentrations, it is advisable to avoid combinations of St. John’s wort, Hypericum perforatum with SSRIs. This interaction can lead to a reaction known as ‘serotonin syndrome’. The syndrome may include symptoms of confusion, nausea, sweating, agitation, or more severe symptoms, like hypertension and unresponsiveness. Several cases of serotonin-syndrome reactions have been documented when SSRIs were used concurrently with St. John’s wort.
The German Commission E warns that any substances that act on the CNS, including psychotropic agents, may interact with kava kava. In addition, substances that act on the CNS, including psychoactive drugs and drugs used as anesthetic adjuvants, may theoretically interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. Persons taking medications such as anticonvulsants, skeletal muscle relaxants, tricyclic antidepressants, MAOIs, and SSRIs should discuss the use of herbal supplements with their health care professional prior to consuming these herbs. Patients should not abruptly stop taking their prescribed psychoactive medication.
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 cytochrome P450 2D6. 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.
The ingestion of ethanol by patients receiving disulfiram causes an extremely unpleasant reaction that can last from 30 minutes to several hours. Oral sertraline solution contains a high percentage of alcohol (12%) and should not be co-administered with disulfiram.
Amphetamine, cocaine , dexfenfluramine , 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. While fluoxetine, sertraline, or venlafaxine 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.
Cevimeline is metabolized by CYP3A4 and CYP2D6. Sertraline is an mild to moderate inhibitor of CYP2D6 and could theoretically 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 with sertraline, inhibition of zolpidem metabolism occurred when sertraline was chronically co-administered, indicating that some SSRIs may also exhibit a pharmacokinetic interaction with zolpidem.
SSRI-type antidepressants have been shown to interfere with dextromethorphan metabolism leading to clinical toxicity mimicking the serotonin syndrome. Dextromethorphan should be used in lower doses in patients receiving SSRIs (e.g., fluoxetine, paroxetine) which are potent inhibitors of CYP2D6, the hepatic isoenzyme responsible for metabolism of dextromethorphan. Sertraline is a weak to moderate inhibitor of CYP2D6 and could potentially interact with dextromethorphan; although no clinical drug interactions have been reported.
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.
Sertraline is a weak inhibitor of CYP3A4 and a mild to moderate inhibitor of CYP2D6 Hepatic CYP3A4 and 2D6 are each partially responsible for the metabolism of galantamine. The bioavailability of galantamine may be theoretically increased when co-administered with inhibitors of these enzymes, including the SSRIs.
Sibutramine is a serotonin reuptake inhibitor. Concomitant use of two serotonin-augmenting drugs has been associated with serotonin syndrome, so concurrent use of sertraline with sibutramine is not recommended.
Trazodone inhibits serotonin reuptake, although, it is less potent than the SSRIs in this regard. However, because of this similarity in mechanism of action, patients receiving sertraline concomitantly with trazodone should be monitored closely for adverse effects related to excessive serotonergic stimulation (’serotonin syndrome’).
Sertraline is a substrate for CYP3A4 and CYP2C19. Drugs that induce hepatic isoenzymes (e.g., barbiturates , bosentan , carbamazepine , phenytoin or fosphenytoin , rifabutin , rifampin , rifapentine ) could decrease sertraline plasma concentrations, potentially causing decreased effectiveness of this SSRI. A few case reports have described reduced antidepressant effect or withdrawal symptoms when sertraline was combined with carbamazepine, phenytoin , or rifampin. In addition, two case reports describe potential for sertraline to increase serum phenytoin concentrations; however, the mechanism of this interaction has not been established.
Sertraline is a substrate for the CYP isoenzymes 3A4, 2D6 and 2C19. Imatinib, STI-571 , ritonavir , and delavirdine are potent inhibitors of cytochrome P450 2D6 and 3A4 and might decrease sertraline metabolism leading to increased adverse reactions.
Sertraline is a mild to moderate inhibitor of drug metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via CYP2D6, including some opiate agonists (i.e., methadone , morphine, and oxycodone ). Clinicians should be alert for increased opiate effects if these drugs are used concurrently. In addition, impairment of CYP2D6 metabolism by sertraline may reduce the conversion of codeine and hydrocodone to their active forms, thus potentially reducing analgesic efficacy of these two opiates. Sertraline 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.
Some SSRIs may interact with certain antiarrhythmics. Sertraline is a mild to moderate inhibitor of the hepatic CYP2D6 isoenzyme. Inhibition of CYP2D6 can result in increased concentrations of antiarrhythmic drugs metabolized via the same pathway, including encainide, flecainide, mexiletine, and propafenone. Clinical data are not always available to document interactions. Increased plasma concentrations may increase the risk of proarrhythmias.
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. 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 sertraline. In vitro studies suggest that coadministration of CYP2D6 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 sertraline . A dosage adjustment of aripiprazole is necessary when these drugs are used concomitantly, and conversely, when sertraline 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.
Some selective serotonin reuptake inhibitors are CYP3A4 inhibitors (e.g., fluoxetine, fluvoxamine, sertraline) and may decrease the clearance of cyclosporine, with the potential to cause cyclosporine toxicity (e.g., nephrotoxicity or seizures) or require the downward dosage adjustment of cyclosporine. In 1 patient, the addition of fluoxetine to a stabilized cyclosporine regimen resulted in an increase in cyclosporine concentrations that were noted 10 days after fluoxetine initiation. A decrease in cyclosporine concentrations occurred after fluoxetine was discontinued. During both phases, the dosage of cyclosporine required adjustment. Until more data are available, cyclosporine concentrations should be monitored very carefully any time one of these SSRIs is prescribed. Although a causal relationship has not been established, the combination of cyclosporine and sertraline is also suspected of causing serotonin syndrome in a renal transplant patient. Sertraline serum concentrations may have increased due to possible CYP3A4 inhibition by cyclosporine.
Clinicians should be aware that sertraline might interact with selected foods, although, in general, the drug may be administered with or without food. Grapefruit juice has been reported to inhibit the metabolism of sertraline and formation of desmethylsertraline in a dose-dependent manner, elevating sertraline trough concentrations. The theorized mechanism is the inhibition of sertraline metabolism via CYP3A4. The clinical significance of this interaction is not certain and requires more data. Until more data are available, sertraline oral solution should not be mixed in grapefruit juice, and in general patients should not significantly alter their grapefruit juice or grapefruit intake while receiving sertraline.
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.
Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Co-administration of bupropion with medications that are metabolized by the CYP2D6 hepatic isoenzyme, such as sertraline, should be approached with caution. Plasma concentrations of sertraline may be increased if bupropion is added; dosage reduction of sertraline may be needed. Conversely, if bupropion therapy is discontinued, dosages of sertraline may need to be adjusted upward.
Clinicians should be aware of the potential for inhibition of donepezil metabolism via CYP2D6 by selected SSRIs, which may result in the need for dosage adjustment or selection of alternative therapy should side effects occur. Fluoxetine , paroxetine , and sertraline , are potent inhibitors of the hepatic CYP2D6 isoenzyme, and concurrent use of these drugs with donepezil may lead to increased plasma levels of donepezil. An increased incidence of cholinergic-related side effects may occur. At least 2 case reports of an interaction with paroxetine have been published; the patients exhibited cholinergic-induced GI side effects and/or the appearance of insomnia, agitation, confusion and combativeness when paroxetine was added to donepezil therapy. The side effects subsided with the downward titration of the donepezil dosage or the discontinuation of both treatments. Both fluoxetine and fluvoxamine another SSRI, inhibit the hepatic CYP3A4 isoenzyme and may decrease the metabolism of donepezil through this pathway. Citalopram and escitalopram do not appear to inhibit other CYP hepatic isoenzymes (e.g., 3A4, 2C9, or 2E1), based on in vitro studies, to any clinically significant degree and appear least likely of the SSRIs to decrease donepezil metabolism.
Sertraline, an inhibitor of CYP3A4, may decrease the metabolism of darifenacin and increase serum concentrations. Patients should be monitored for increased anticholinergic effects if these drugs are used concomitantly; dosage adjustments of darifenacin may be necessary.
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 sertraline 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 sertraline is coadministered with doxercalciferol.
[ Last revised: 8/31/2005 3:00:00 PM ]
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