desvenlafaxine

Indications
 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.
CrCl (ml/min)Dosage Recommendation
30-50 mL/min50 mg once daily.
<30 mL/min or ESRD50 mg every other day. Additional doses should not be given after dialysis.
Hepatic impairment: 50 mg once daily. Doses >100 mg/day are not advised.
Contraindications
 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.
Warnings / 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.
Adverse Reactions
 Dizziness, nausea, vomiting, dry mouth, headache, tinnitus, insomnia, abnormal dreams, fatigue, constipation, diarrhoea, somnolence, decreased appetite, irritability, anxiety, tremor, paresthesia, male sexual function disorders (e.g. decreased libido, delayed ejaculation, erectile dysfunction), urinary hesitancy, hyperhidrosis, blurred vision, mydriasis, palpitations, hypertension, orthostatic hypotension, dyslipidemia, proteinuria, and abnormal liver function test.
Potentially Fatal: Serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Overdose Reactions
 Symptoms may include: Headache, agitation, dizziness, nausea, vomiting, constipation, diarrhoea, dry mouth, paresthesia, and tachycardia (reported within 5 days of an overdose >600 mg). Management: Treatment is supportive and symptomatic. Activated charcoal may be administered. Induction of emesis is not recommended. Forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be useful.
Drug 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.
See Below for More desvenlafaxine Drug Interactions
Food Interactions
 Avoid alcohol and St. John's wort.
Mechanism of Actions
 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, α-adrenergic, dopaminergic, γ-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.
Absorption: Absolute oral bioavailability: About 80%. Mean Tmax: About 7.5 hr.
Distribution: Plasma protein binding: About 30%; independent of drug concentration. Vd: About 3.4 L/kg.
Metabolism: Hepatic via conjugation (via disphosphoglucuronosyltransferase (UGT) isoforms); and to a lesser extent by oxidation via CYP3A4 isozyme.
Excretion: Excreted in urine (about 45% as unchanged drug, 19% as the glucuronide metabolite, and <5% as the oxidative metabolite). Mean elimination half-life: About 11 hr, prolonged in renal failure.
Administration
 Extended-release: May be taken with or without food. (Take at the same time each day. Swallow whole, do not divide/crush/chew/dissolve tab.)
Storage Conditions
 Oral: Store at 20- 25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F).
ATC Classification
 N06AX23 - desvenlafaxine ; Belongs to the class of other antidepressants.
Storage
 Oral: Store at 20- 25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F).
Available As
  • desvenlafaxine 100 mg
  • desvenlafaxine 150 mg
  • desvenlafaxine 50 mg

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