Vortioxetine

Oral
Major depressive disorder

Patient taking strong CYP2D6 inhibitor (e.g. bupropion, quinidine, fluoxetine, paroxetine): Reduce to half of the usual dose. May increase to usual dose when CYP2D6 inhibitor is discontinued.

Patient taking CYP450 inducer (e.g. rifampicin, carbamazepine, phenytoin) for >14 days: Max dose should not exceed 3 times the original dose. May reduce to usual dose within 14 days when CYP450 inducer is discontinued.

Pharmacogenomics:

CYP2D6 is the main enzyme involved in the metabolism of vortioxetine to its major, inactive, carboxylic acid metabolite. CYP2D6 gene polymorphism may affect the safety and effectiveness of vortioxetine.

CYP2D6 poor metabolisers, individuals who lack CYP2D6 enzymes have approx twice the plasma concentration of vortioxetine than normal metabolisers. Product guidelines recommend max daily dose of 10 mg in CYP2D6 poor metabolisers. Concomitant use of strong CYP3A4/2C9 inhibitors in poor metabolisers may also result in higher vortioxetine plasma concentration.

May be taken with or without food.

Concomitant or within 14 days of discontinuing MAOI therapy (e.g. linezolid, IV methylene blue).

Patient with history of suicide-related events or pre-existing suicidal ideation; family history of bipolar disorder, mania or hypomania; seizure disorders or unstable epilepsy; bleeding disorders, cirrhosis, narrow-angle glaucoma (without undergoing iridectomy). Elderly. Pregnancy and lactation. CYP2D6 poor metabolisers. Patient taking strong CYP2D6 inhibitors or strong CYP450 inducers.

Significant: Worsening of depression, mania or hypomania, angle-closure glaucoma, seizures, fractures, hyponatraemia.
Gastrointestinal disorders: Nausea, diarrhoea, constipation, vomiting, flatulence, dry mouth.
Nervous system disorders: Dizziness.
Psychiatric disorders: Abnormal dreams.
Skin and subcutaneous tissue disorders: Pruritus.
Potentially Fatal: Neuroleptic malignant syndrome, serotonin syndrome, haemorrhage, suicidal ideation and behaviour.

PO: Z (Risk of postpartum haemorrhage, persistent pulmonary hypertension in infant and neonatal withdrawal/toxicity in late pregnancy use. Monitor closely.)

This drug may cause dizziness, if affected, do not drive or operate machinery.

Monitor for clinical worsening, emergence of suicidal thoughts or behaviours and unusual changes in behaviour. Monitor for signs and symptoms of serotonin syndrome and hyponatraemia.

Symptoms: Nausea, vomiting, postural dizziness, diarrhoea, abdominal discomfort, generalised pruritus, somnolence, flushing, seizure, serotonin syndrome. Management: Symptomatic treatment and relevant monitoring.

Increased serum concentration with strong CYP2D6 inhibitors (e.g. bupropion, quinidine, fluoxetine, paroxetine). May increase risk of bleeding with anticoagulants (e.g. warfarin), antiplatelet drugs (e.g. aspirin) or NSAIDs. Concomitant use of drugs with potential of lowering seizure threshold e.g. antidepressants (tricyclics, SNRI), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol may increase risk of seizure.
Potentially Fatal: Increased risk of serotonin syndrome with serotonergic agents (e.g. triptans, TCAs, fentanyl, lithium, tramadol, buspirone, tryptophan) or agents that impair the metabolism of serotonin (e.g. MAO inhibitors including linezolid and IV methylene blue).

May increase risk of adverse reactions (e.g. serotonin syndrome) with St. John’s wort.

Description:
Mechanism of Action: Vortioxetine is an antidepressant that inhibits reuptake of serotonin (5-HT) leading to enhanced serotonergic activity in the CNS. It also has antagonist activity at the 5-HT₃ and agonist activity at 5-HT_1A receptors.
Pharmacokinetics:
Absorption: Bioavailability: 75%. Time to peak plasma concentration: 7-11 hours.
Distribution: Volume of distribution: 2,600 L. Plasma protein binding: 98%.
Metabolism: Extensively metabolised in the liver by CYP450 isoenzymes, mainly CYP2D6, via oxidation and further metabolised via glucuronic acid conjugation to an inactive carboxylic acid metabolite.
Excretion: Via urine (59%); faeces (26%) as metabolites. Elimination half-life: Approx 66 hours.

Source: National Center for Biotechnology Information. PubChem Database. Vortioxetine, CID=9966051, https://pubchem.ncbi.nlm.nih.gov/compound/Vortioxetine (accessed on Jan. 24, 2020)

Store below 30°C.

Antidepressants

N06AX26 - vortioxetine ; Belongs to the class of other antidepressants.

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Annotation of Swissmedic Label for Vortioxetine and CYP2D6. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 27/12/2019.

Anon. CYP2D6-Vortioxetine (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/12/2019.

Anon. Vortioxetine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/12/2019.

Buckingham R (ed). Vortioxetine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/12/2019.

Joint Formulary Committee. Vortioxetine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/12/2019.

Trintellix Tablet (Takeda Pharmaceuticals America, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/12/2019.