desvenlafaxine (Rx)

Brand and Other Names:Pristiq, Khedezla
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet, extended release

  • Pristiq
    • 25mg (contains 38 mg of desvenlafaxine succinate)
    • 50mg (contains 76 mg of desvenlafaxine succinate)
    • 100mg (contains 152 mg of desvenlafaxine succinate)
  • Khedezla
    • 50mg
    • 100mg

Major Depressive Disorder

50 mg PO qDay

Higher dosages, up to 400 mg/day, have been used but have not been proved more efficacious; increased side effects have been reported

Assess periodically to determine need for continued treatment

Dosing Modifications

Renal impairment

  • Pristiq
    • Moderate-to-severe (CrCl <50 mL/min), or end-stage renal disease (ESRD): Adjust maximum recommended dosage
  • Khedezla
    • Mild (CrCl ≥50 mL/min): Dosage adjustment not necessary
    • Moderate (CrCl 30-50 mL/min): Not to exceed 50 mg PO qDay
    • Severe (CrCl <30 mL/min) and ESRD, requiring hemodialysis: Not to exceed 25 mg PO once daily or 50 mg PO qDay
    • Do not administer supplemental dose after hemodialysis

Hepatic impairment

  • Pristiq
    • Moderate-to-severe (Child-Pugh score 7-15): Adjust maximum recommended dosage
  • Khedezla
    • Moderate-to-severe (Child-Pugh score 7-15): 50 mg PO qD; dosages >100 mg/day not recommended

Dosing Considerations

Gradually reduce dose rather than stopping therapy abruptly whenever possible; if intolerable effects still occur, resume therapy at previously prescribed dosage and then decrease even more gradually

Switching to or from a monoamine oxidase inhibitor (MAOI) to treat psychiatric disorders

  • Wait at least 14 days between discontinuance of monoamine oxidase inhibitor (MAOI) and initiation of desvenlafaxine; wait at least 7 days between discontinuance of desvenlafaxine and initiation of MAOI
  • Periodically reassessed to determine the need for continued treatment

Using desvenlafaxine with other MAOIs such as linezolid or methylene blue

  • Do not start desvenlafaxine in a patient who is being treated with linezolid or IV methylene blue because there is increased risk of serotonin syndrome; patients who require more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered
  • If acceptable alternatives to linezolid or IV methylene blue treatment are not available and the potential benefits of linezolid or IV methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, promptly discontinue desvenlafaxine, and linezolid or IV methylene blue can be administered

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and desvenlafaxine

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            Contraindicated (11)

            • iobenguane I 123

              desvenlafaxine decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

              isocarboxazid and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • linezolid

              linezolid and desvenlafaxine both increase serotonin levels. Contraindicated. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first

            • methylene blue

              methylene blue and desvenlafaxine both increase serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first

            • phenelzine

              phenelzine and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • procarbazine

              procarbazine and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • rasagiline

              rasagiline and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • safinamide

              desvenlafaxine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • selegiline transdermal

              selegiline transdermal and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            • tranylcypromine

              tranylcypromine and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drug

            Serious - Use Alternative (72)

            • alfentanil

              desvenlafaxine and alfentanil both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • almotriptan

              almotriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • amitriptyline

              amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • amoxapine

              amoxapine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • apixaban

              desvenlafaxine and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

            • buspirone

              buspirone and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • clomipramine

              clomipramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • cocaine

              cocaine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • cyclobenzaprine

              desvenlafaxine and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desipramine

              desipramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dexfenfluramine

              dexfenfluramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dextroamphetamine

              dextroamphetamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dextromethorphan

              dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dihydroergotamine

              dihydroergotamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              doxepin and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • eletriptan

              eletriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • ergotamine

              ergotamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • fentanyl

              desvenlafaxine and fentanyl both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • fluoxetine

              fluoxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • frovatriptan

              frovatriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • granisetron

              granisetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • imipramine

              imipramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • iobenguane I 131

              desvenlafaxine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • isoniazid

              isoniazid and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • L-tryptophan

              L-tryptophan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • levodopa

              levodopa and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • levomilnacipran

              levomilnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • levorphanol

              desvenlafaxine and levorphanol both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • lithium

              lithium and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • lonafarnib

              desvenlafaxine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • lorcaserin

              desvenlafaxine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • lsd

              lsd and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • maprotiline

              maprotiline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • meperidine

              meperidine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • metoclopramide

              metoclopramide and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactions

            • metoclopramide intranasal

              desvenlafaxine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • milnacipran

              milnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • mirtazapine

              mirtazapine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • morphine

              morphine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • nalbuphine

              desvenlafaxine and nalbuphine both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • naratriptan

              naratriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • netupitant/palonosetron

              netupitant/palonosetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • ondansetron

              ondansetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • opium tincture

              desvenlafaxine and opium tincture both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • ozanimod

              ozanimod increases toxicity of desvenlafaxine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palonosetron

              palonosetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • pentazocine

              pentazocine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • protriptyline

              protriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • pseudoephedrine

              desvenlafaxine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • remifentanil

              desvenlafaxine and remifentanil both decrease serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • rizatriptan

              rizatriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • SAMe

              SAMe and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • sertraline

              sertraline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • sufentanil

              desvenlafaxine and sufentanil both decrease serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndrome

            • sumatriptan

              sumatriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • sumatriptan intranasal

              sumatriptan intranasal and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • tedizolid

              tedizolid, desvenlafaxine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • tramadol

              tramadol and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • trazodone

              trazodone and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • trimipramine

              trimipramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilazodone

              desvenlafaxine, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              desvenlafaxine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

            • zolmitriptan

              zolmitriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            Monitor Closely (89)

            • aripiprazole

              desvenlafaxine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • atazanavir

              atazanavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • atomoxetine

              desvenlafaxine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • avapritinib

              desvenlafaxine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • axitinib

              desvenlafaxine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • benzhydrocodone/acetaminophen

              desvenlafaxine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              benzhydrocodone/acetaminophen, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • buprenorphine subdermal implant

              desvenlafaxine, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • buprenorphine, long-acting injection

              desvenlafaxine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • captopril

              desvenlafaxine will increase the level or effect of captopril by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • carvedilol

              desvenlafaxine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • cenobamate

              cenobamate, desvenlafaxine. Either increases effects of the other by sedation. Use Caution/Monitor.

            • chlorpromazine

              desvenlafaxine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • clomipramine

              desvenlafaxine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • clopidogrel

              desvenlafaxine increases effects of clopidogrel by pharmacodynamic synergism. Use Caution/Monitor. SNRIs affect platelet activation; coadministration of SNRIs with clopidogrel may increase the risk of bleeding.

            • codeine

              desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • cyproheptadine

              cyproheptadine decreases effects of desvenlafaxine by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.

            • darunavir

              darunavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • desipramine

              desvenlafaxine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • dexfenfluramine

              desvenlafaxine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • dextroamphetamine

              desvenlafaxine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • dextromethorphan

              desvenlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • diazepam intranasal

              diazepam intranasal, desvenlafaxine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • donepezil

              desvenlafaxine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • doxepin

              desvenlafaxine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • doxorubicin

              desvenlafaxine will increase the level or effect of doxorubicin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • doxorubicin liposomal

              desvenlafaxine will increase the level or effect of doxorubicin liposomal by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • duloxetine

              desvenlafaxine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • encainide

              desvenlafaxine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • fenfluramine

              fenfluramine, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fesoterodine

              desvenlafaxine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • finerenone

              desvenlafaxine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of desvenlafaxine by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • flecainide

              desvenlafaxine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • flibanserin

              desvenlafaxine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluoxetine

              desvenlafaxine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • fluphenazine

              desvenlafaxine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • fluvoxamine

              desvenlafaxine will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. With higher desvenlafaxine doses (eg, 400 mg) decrease CYP2D6 substrate dose by up to 50%; dose adjustment not necessary with desvenlafaxine doses <100mg

            • fosamprenavir

              fosamprenavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • gabapentin

              gabapentin, desvenlafaxine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, desvenlafaxine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • galantamine

              desvenlafaxine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • haloperidol

              desvenlafaxine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • hydrocodone

              desvenlafaxine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • hydromorphone

              desvenlafaxine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ibrutinib

              ibrutinib will increase the level or effect of desvenlafaxine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • iloperidone

              desvenlafaxine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • imipramine

              desvenlafaxine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • indinavir

              indinavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • ivacaftor

              desvenlafaxine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • lasmiditan

              lasmiditan, desvenlafaxine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

              desvenlafaxine increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • lemborexant

              desvenlafaxine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

              lemborexant, desvenlafaxine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lisdexamfetamine

              desvenlafaxine, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

            • lomitapide

              desvenlafaxine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lopinavir

              lopinavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.

            • loratadine

              desvenlafaxine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • lurasidone

              lurasidone, desvenlafaxine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • methamphetamine

              desvenlafaxine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • metoprolol

              desvenlafaxine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • mexiletine

              desvenlafaxine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • midazolam intranasal

              desvenlafaxine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

              midazolam intranasal, desvenlafaxine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • morphine

              desvenlafaxine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • nebivolol

              desvenlafaxine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • nelfinavir

              nelfinavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • nortriptyline

              desvenlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • oliceridine

              desvenlafaxine, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • oxycodone

              desvenlafaxine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • oxymorphone

              desvenlafaxine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • paroxetine

              desvenlafaxine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • perphenazine

              desvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • pregabalin

              pregabalin, desvenlafaxine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • prochlorperazine

              desvenlafaxine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • promethazine

              desvenlafaxine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • propafenone

              desvenlafaxine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • propranolol

              desvenlafaxine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • remimazolam

              remimazolam, desvenlafaxine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • risperidone

              desvenlafaxine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • ritonavir

              ritonavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              desvenlafaxine, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • sufentanil SL

              sufentanil SL, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • tapentadol

              desvenlafaxine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tazemetostat

              desvenlafaxine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • thioridazine

              desvenlafaxine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • timolol

              desvenlafaxine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • tinidazole

              desvenlafaxine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolterodine

              desvenlafaxine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • tramadol

              desvenlafaxine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • trifluoperazine

              desvenlafaxine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • valerian

              valerian and desvenlafaxine both increase sedation. Use Caution/Monitor.

            • vorapaxar

              desvenlafaxine, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur; SSRIs and SNRIs may cause platelet serotonin depletion .

            Minor (1)

            • ruxolitinib

              desvenlafaxine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Adverse drug reactions (ADRs) shown occur with 50 mg/day dosage at rate higher than seen with placebo

            >10%

            Nausea (22-41%)

            Dry mouth (11-25%)

            Hyperhidrosis (10-21%)

            Dizziness (10-16%)

            Insomnia (9-15%)

            Constipation (9-14%)

            Somnolence (4-12%)

            Fatigue (7-10%)

            1-10%

            Increased total cholesterol of ≥50 mg/dL and an absolute value of ≥261 mg/dL (3-10%)

            Decreased appetite (5-10%)

            Vomiting (3-9%)

            Tremor (2-9%)

            Anorgasmia (3-8%)

            Ejaculation delayed (1-7%)

            Libido decreased (3-6%)

            Triglycerides, fasting ≥327 mg/dL (2-6%)

            Mydriasis (2-6%)

            Vertigo (2-5%)

            Anxiety (3-5%)

            Blurred vision (3-4%)

            Chills (1-4%)

            Yawning (1-4%)

            Abnormal dreams (2-3%)

            Feeling jittery (1-3%)

            Orgasm abnormal (1-3%)

            Nervousness (<2%)

            Tachycardia (<2%)

            Asthenia (<2%)

            Weight increased, liver function test abnormal, blood prolactin increased (<2%)

            Musculoskeletal stiffness (<2%)

            Syncope, convulsion, dystonia (<2%)

            Depersonalization, bruxism (<2%)

            Urinary retention (<2%)

            Rash, alopecia, photosensitivity reaction, angioedema (<2%)

            Urinary hesitation (1-2%)

            Ejaculation failure (1-2%

            Sexual dysfunction (1-3%)

            Tinnitus (1-2%)

            Dysgeusia (1-2%)

            Hot flush (1-2%)

            Blood pressure increased (1-2%)

            Increased LDL ≥50 mg/dL and an absolute value of ≥190 mg/dl (1-2%)

            Frequency Not Defined

            Ischemic cardiac events in patients with multiple underlying cardiac risk factors

            Gastrointestinal (GI) bleeding, hallucinations, photosensitivity reactions and severe cutaneous reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have occurred with other serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs)

            Suicidal thoughts and behaviors in adolescents and young adults

            Hyponatremia

            Interstitial lung disease and eosinophilic pneumonia

            Serotonin syndrome

            Elevated blood pressure

            Abnormal bleeding

            Narrow-angle glaucoma

            Activation of mania or hypomania

            Discontinuance syndrome

            Seizure

            Postmarketing Reports

            Cardiac disorders: Tachycardia

            General disorders and administration site conditions: Asthenia

            Investigations: Weight increased, liver function test abnormal, blood prolactin increased

            Musculoskeletal and connective tissue disorders: Musculoskeletal stiffness

            Nervous system disorders: Syncope, convulsion, dystonia

            Psychiatric disorders: Depersonalization, bruxism

            Renal and urinary disorders: Urinary retention

            Skin and subcutaneous tissue disorders: Rash, alopecia, photosensitivity reaction, angioedema.

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            Warnings

            Black Box Warnings

            Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies

            Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years

            In children and young adults, initiate only if benefits greatly outweigh risks

            Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments

            Patient’s family should communicate any abrupt behavioral changes to healthcare provider

            Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

            Not approved for use in pediatric patients

            Contraindications

            Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine formulation

            Coadministration with serotonergic drugs

            • Coadministration with MAOIs increases risk of serotonin syndrome
            • Use of MAOIs concomitantly within 14 days before initiating desvenlafaxine or within 7 days after discontinuing desvenlafaxine
            • Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome (NMS), seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
            • Starting desvenlafaxine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
            • If linezolid or IV methylene blue must be administered, discontinue desvenlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

            Cautions

            Suicidality; monitor for clinical worsening and suicide risk (especially in children, adolescents, and young adults aged 18-24 years), during early phases of treatment and alterations in dosages

            Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

            Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy; avoid use of antidepressants, including desvenlafaxine, in patients with untreated anatomically narrow angles

            Use caution in patients with history of seizure disorders

            Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants

            May precipitate shift to mania or hypomania in patients with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen for bipolar disorder patients presenting with depressive symptoms

            Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders

            Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased

            Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion

            Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

            May impair congnitive abilities; use caution operating heavy machinery

            A gradual reduction in dosage rather than abrupt cessation recommended; monitor for discontinuation symptoms; adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures

            Sexual dysfunction

            • Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider
            • Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction
            • In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm
            • Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported
            • When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder
            • Discuss potential management strategies to support patients in making informed decisions about treatment

            Serotonin syndrome

            • Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort
            • Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors
            • Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
            • Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding
            • Monitor for the emergence of serotonin syndrome
            • Discontinue treatment with desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment
            • If concomitant use of desvenlafaxine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms See Contraindications

            Drug interactions overview

            • Concomitant use of desvenlafaxine increases peak plasma concentration and AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drugs
            • False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine
            • Risk of bleeding
              • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage
              • Concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk
              • For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing therapy
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            Pregnancy & Lactation

            Pregnancy

            Pregnancy exposure registry monitors pregnancy outcomes in women exposed to antidepressants during pregnancy

            Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185

            No published studies on desvenlafaxine in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes

            Exposure to SNRIs in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage

            Exposure to SNRIs or SSRIs in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding; monitor neonates who were exposed to desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome

            Lactation

            Available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants

            There are no data on the effects of desvenlafaxine on milk production

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for desvenlafaxine and any potential adverse effects on the breastfed child from desvenlafaxine or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Potent SNRI; major active metabolite of venlafaxine

            Absorption

            Bioavailability: 80%

            Peak plasma time: 7.5 hr

            Ingestion of a high-fat meal (800-1000 calories) increased desvenlafaxine peak plasma concentration about 16% and had no effect on AUC

            Distribution

            Protein bound: 30%

            Vd: 3.4 L/kg

            Metabolism

            Primary: Conjugation (UDP-glucuronosyltransferase isoform mediated)

            Minor: CYP3A4 oxidative metabolism (N-demethylation)

            Enzymes inhibited: CYP2D6 (minimally)

            Elimination

            Half-life: 11 hr (prolonged in renal or hepatic dysfunction)

            Dialyzable: No

            Excretion, unchanged drug: Urine (45%)

            Excretion, metabolite: 19% (glucuronide); <5% (oxidative metabolite [N,O-didesmethylvenlafaxine])

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            Administration

            Oral Administration

            Take 1 tablet at about the same time each day

            Take either with or without food

            Swallow tablets whole, with fluid

            Do not divide, crush, chew, or dissolve tablets

            Avoid drinking alcohol while taking dose

            Storage

            Tablets: Store at 20- 25°C (68-77°F); excursions permitted to 15-30°C (59- 86°F)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            desvenlafaxine oral
            -
            100 mg tablet
            desvenlafaxine oral
            -
            50 mg tablet
            desvenlafaxine oral
            -
            100 mg tablet
            desvenlafaxine oral
            -
            50 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            desvenlafaxine oral

            DESVENLAFAXINE EXTENDED-RELEASE - ORAL

            (des-VEN-la-FAX-een)

            COMMON BRAND NAME(S): Khedezla, Pristiq

            WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

            USES: Desvenlafaxine is used to treat depression. It may improve your mood, feelings of well-being, and energy level. Desvenlafaxine is known as a serotonin-norepinephrine reuptake inhibitor (SNRI). It works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain.

            HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking desvenlafaxine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. The dosage is based on your medical condition and response to treatment.Do not crush, chew, or dissolve this medication in water. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day.Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as mood swings, headache, tiredness, sleep changes, and brief feelings similar to electric shock. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.If you are switching from another antidepressant to desvenlafaxine, your doctor should slowly reduce the dose of your old antidepressant to prevent withdrawal reactions from the other antidepressant. Ask your doctor or pharmacist for more details.It may take several weeks before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: See also Warning section.Drowsiness, dizziness, nausea, dry mouth, constipation, loss of appetite, weight loss, blurred vision, nervousness, trouble sleeping, or excessive sweating may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.An empty tablet shell may appear in your stool. This effect is harmless because your body has already absorbed the medication.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: severe/pounding headache, shakiness (tremor), decreased interest in sex, changes in sexual ability, easy bruising/bleeding.Get medical help right away if you have any very serious side effects, including: cough that doesn't go away, shortness of breath, chest pain, black stools, vomit that looks like coffee grounds, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night), seizures.This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking desvenlafaxine, tell your doctor or pharmacist if you are allergic to it; or to venlafaxine; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of psychiatric disorders (such as bipolar/manic-depressive disorder), personal or family history of suicide attempts, bleeding problems, personal or family history of glaucoma (angle-closure type), high blood pressure, heart problems (such as chest pain, heart failure, heart attack), history of stroke, high cholesterol, kidney disease, liver disease, seizure disorder, low sodium in the blood (hyponatremia).This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially dizziness when standing. Older adults may also be more likely to develop a type of salt imbalance (hyponatremia), especially if they are taking "water pills" (diuretics). Dizziness and salt imbalance can increase the risk of falling. Older adults may also be at greater risk for bleeding while using this drug.Based on information for a similar drug (venlafaxine), children may be more sensitive to the side effects of this drug, especially loss of appetite and weight loss. Monitor height and weight in children who are taking this drug. Consult your doctor or pharmacist for more details.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Also, babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.Since untreated mental/mood problems (such as depression, anxiety, and panic attacks) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, "blood thinners" such as dabigatran/warfarin).Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and at least 7 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including other SNRIs such as duloxetine/milnacipran, SSRIs such as fluoxetine/paroxetine), tryptophan, among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.Desvenlafaxine is very similar to venlafaxine. Do not use medications containing venlafaxine while using desvenlafaxine.This medication may interfere with certain lab tests (including urine tests for amphetamines), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness, seizures, fast/irregular heartbeat.

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as blood pressure, cholesterol, growth monitoring in children) should be done periodically to monitor your progress or check for side effects. Consult your doctor for more details.Keep all regular medical and psychiatric appointments.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.