indication

Desvenlafaxine is indicated for the treatment of major depressive disorder in adults.

pharmacology

Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H₁-histaminergic, or α₁-adrenergic receptors in vitro. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity again the cardiac potassium channel, hERG, in vitro. Compared to other SNRIs, desvenlafaxine undergoes simple metabolism, has a low risk of drug-drug interactions and does not have to be extensively titrated to reach a therapeutic dose. Some of the limitations of desvenlafaxine include moderate efficacy in the treatment of major depressive disorder, similar safety and tolerability profile to other SNRIs and possible transient discontinuation symptoms upon cessation of therapy.

mechanism of action

Desvenlafaxine, the major active metabolite of venlafaxine, is a selective serotonin and norepinephrine reuptake inhibitor. The clinical effect of desvenlafaxine is thought to occur via potentiation of serotonin and norepinephrine in the central nervous system. Unlike venlafaxine, desvenlafaxine is thought to have a differential serotonergic and noradrenergic activity profile.

toxicity

The safety and tolerability of desvenlafaxine is similar to other SNRIs. Common side effects upon initiation or dose increase include increased blood pressure and heart rate, agitation, tremor, sweating, nausea, headache, and sleep disturbances. May cause sexual dysfunction and weight loss in some patients. May cause increases in fasting serum total cholesterol, LDL cholesterol, and triglycerides. Withdrawal effects may occur and thus, the dose of desvenlafaxine should be titrated down prior to discontinuation.

biotransformation

The primary route of metabolism is via conjugation mediated by UGT isoforms. Desvenlafaxine also undergoes oxidative N-demethylation via cytochrome P450 3A4 to a minor extent.

absorption

Absolute bioavailability is ~ 80% and is unaffected by food.

half life

The mean terminal half life is 11.1 hours and may be prolonged in patients with renal and/or moderate to severe hepatic impairment.

route of elimination

Excreted in the urine. Approximately 45% of the total oral dose is excreted unchanged in urine. Approximately 19% of the total oral dose is excreted as the glucuronide metabolite and < 5% is excreted as the oxidative metabolite, N,O-didesmethylvenlafaxine. Excreted in human milk.

drug interactions

Almotriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Amitriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Amoxapine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Bromocriptine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Buspirone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Citalopram: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Clomipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Desipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dextromethorphan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroergotamine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dipivefrin: Desvenlafaxine may increase the tachycardic and vasopressor effects of dipivefrin. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Doxepin: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Duloxetine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Eletriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ephedrine: Desvenlafaxine may increase the tachycardic and vasopressor effects of ephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Epinephrine: Desvenlafaxine may increase the tachycardic and vasopressor effects of epinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Ergoloid mesylate: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ergonovine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ergotamine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Escitalopram: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Fluoxetine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Fluvoxamine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Frovatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Imipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Isocarboxazid: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Isometheptene: Desvenlafaxine may increase the tachycardic and vasopressor effects of isometheptene. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

L-Tryptophan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Levonordefrin: Desvenlafaxine may increase the tachycardic and vasopressor effects of levonordefrin. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Linezolid: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Lithium: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Maprotiline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Meperidine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Methylergonovine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Milnacipran: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Mirtazapine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Moclobemide: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Naratriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Nefazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Norepinephrine: Desvenlafaxine may increase the tachycardic and vasopressor effects of norepinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Nortriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Paroxetine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Phenelzine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Procarbazine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Promethazine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Protriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Pseudoephedrine: Desvenlafaxine may increase the tachycardic and vasopressor effects of pseudoephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Rasagiline: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Rizatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

S-Adenosylmethionine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Selegiline: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Sertraline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Sibutramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

St. John's Wort: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Sumatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Zolmitriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.