Desvenlafaxine

Indications

Desvenlafaxine is used for: Depression

Adult Dose

Oral Depression Adult: 50 mg once daily. Doses up to 400 mg once daily have been studied and shown to be effective, but no additional benefit was observed with doses >50 mg once daily. Hepatic impairment: 50 mg once daily. Doses >100 mg/day are not advised.

Child Dose

Renal Dose

Renal impairment: CrCl (ml/min) 30-50 mL/min 50 mg once daily. <30 mL/min or ESRD 50 mg every other day. Additional doses should not be given after dialysis.

Administration

Take whole with fluid; do not divide, crush, chew, or dissolve Take at approximately the same time every day

Contra Indications

Hypersensitivity to Desvenlafaxine, venlafaxine or any component of the formulation. Concomitant/recent (within preceeding 14 days) use of MAOI. Do not initiate MAOI at least 7 days after discontinuing Desvenlafaxine.

Precautions

May be associated with increased risk of suicidal thinking and behaviour in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Monitor patients for clinical worsening of depression, emergence of suicidality, unusual changes in behaviour particularly during initiation of therapy and during dosage adjustments. Serotonin syndrome or neuroleptic malignant syndrome (NMS) have occurred with selective serotonin reuptake inhibitor (SSRI) or SNRI treatment alone; and particularly with concomitant use of MAOI, serotogenic agents (e.g. triptans), antipsychotics or dopamine antagonists. Gradually taper dose if discontinuing to reduce risk of withdrawal symptoms. May activate mania/hypomania, caution in patients with history or family history of mania or hypomania. Caution in patients with pre-existing glaucoma, hypertension, cardiovascular, cerebrovascular, or lipid metabolism and seizure disorders. Sustained elevations in blood pressure have been reported. May be associated with dose-related increase in serum total cholesterol, LDL, triglycerides. May increase risk of bleeding. May be associated with development of syndrome of inappropriate antidiuretic hormone (SIADH) and Hyponatraemia, elderly and patients who are taking diuretics or with volume depletion may be at greater risk. Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of desvenlafaxine) have been reported. Medications containing venlafaxine should not be used concomitantly. Renal and hepatic impairment. Safety and efficacy have not been established in paediatrics. Elderly. Pregnancy. Not recommended in lactation. Lactation: Drug is excreted in breast milk; discontinue drug, or do not nurse; use only if benefits greatly outweigh risks

Pregnancy-Lactation

Pregnancy 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

Interactions

Desvenlafaxine may diminish the therapeutic effect of Iobenguane I-123. May enhance adverse effects of other CNS depressants. Sibutramine and MAOI may enhance the serotonergic effect of Desvenlafaxine; increase risk of development of serotonin syndrome. Concomitant use with alpha-/beta-agonists may enhance tachycardic and vasopressor effect. Desvenlafaxine may increase concentration of CYP2D6 substrates (e.g. desipramine); decrease exposure of CYP3A4 substrates (e.g. midazolam). CYP3A4 inhibitors (e.g. ketoconazole) may increase concentration of desvenlafaxine. May enhance the antiplatelet effect of nonselective NSAIDs, aspirin; and anticoagulant effect of warfarin. Potentially Fatal: Concurrent use with MAOIs may lead to fatal serotonin syndrome or NMS-like reactions. Do not use within at least 14 days of discontinuing MAOI treatment and start MAOI at least 7 days after stopping desvenlafaxine. Increased risk of serotonin syndrome with sibutramine.

Side Effects

Side effects of Desvenlafaxine : >10% Nausea (22-41%), Headache (20-29%), Dry mouth (11-25%), Hyperhidrosis (10-21%), Dizziness (13-16%), Insomnia (9-15%), Constipation (9-14%), Fatigue (7-11%), Diarrhea (5-11%) 1-10% Decreased appetite (5-10%), Anxiety (0-10%), Elevated cholesterol and triglycerides (0-10%), Insomnia (0-10%), Tremor (2-9%), Proteinuria (5-8%), Mydriasis (2-6%), Male sexual dysfunction (0-6%), Anxiety (3-5%), Vertigo (1-5%), Blurred vision (3-4%), Abnormal dreams (2-4%), Urinary hesitation (2-4%), Yawning (1-4%), Feeling jittery (1-3%), Female sexual dysfunction (0-3%), Irritability (2%) Other (eg, abnormal liver function tests, increased blood prolactin, convulsion, syncope, extrapyramidal disorders, musculoskeletal stiffness, depersonalization, hypomania, bruxism, epistaxis, orthostatic hypotension) (<2%) Asthenia (1-2%), Nervousness (1-2%), Hot flush (1-2%), Rash (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 Potentially Fatal: Serotonin syndrome or neuroleptic malignant syndrome-like reactions.

Mode of Action

Desvenlafaxine, the major active metabolite of venlafaxine, is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI). Clinical efficacy of desvenlafaxine is thought to be related with the drug's potentiation of serotonergic and noradrenergic activity in the CNS. It does not have monoamine oxidase (MAO) inhibitory activity; and has not shown significant affinity for muscarinic cholinergic, H1-histaminergic, alpha-adrenergic, dopaminergic, gama-aminobutyric acid (GABA), glutamate, and opiate receptors in vitro. At concentrations that inhibit serotonin and norephinephrine reuptake, inhibition of dopamine reuptake appears to be unlikely.