indication

Vilazodone is approved for treatment of acute episodes of major depression. Labeling of vilazodone describes an increased risk of suicidal thoughts in children, adolescents and young adults. The use of vilazodone in pediactrics is not indicated. Its use with monoamine oxidase inhibitors (MAOI) is contraindicated due to increased risk of serotonin syndome. Once the MAOI is discontinued, a 14-day washout period must pass before starting vilazodone.

pharmacology

Vilazodone increases serotonin levels in the brain by inhibiting the reuptake of serotonin while acting as a partial agonist on serotonin-1A receptors. It has therefore been coined by scientists as a selective partial agonist and reuptake inhibitor (SPARI). Because of its partial agonist activity for serotonin-1A, vilazodone helps to reduce anxiety.

mechanism of action

Since serotonin is believed to be one of the three main neurotransmitters that is low or imbalanced in patients with depression, pathways seeking to increase serotonin levels are targeted by pharmaceutical companies. As a selective serotonin reuptake inhibitor, vilazodone prevents serotonin from re-entering cell bodies. Hence, they will remain longer in the synapse. Vilazodone also has an inherent selectivity for serotonin-1A receptors, acting as a partial agonist which stimulates the production of serotonin. The end result is increased serotonin in the synaptic cleft, allowing serotonin to resume its action on nearby cells.

toxicity

Vomiting, serotonin syndrome

biotransformation

• Major: CYP3A4
• Minor: CYP2C19 and CYP2D6

absorption

Its absorption is improved when taken with food to 72%

half life

25.4h

route of elimination

• 1% recovered in urine
• 2% unchanged in feces

drug interactions

Amitriptyline: Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.

Atazanavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Carbamazepine: Carbamazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors (SSRI). Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Carbamazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes.

Celecoxib: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). To minimize the risk of bleeding associated with this combination, consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent, such as a proton pump inhibitor for the time that combined selective serotonin reuptake inhibitor (SSRIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) is necessary.

Cimetidine: Cimetidine may decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Consider using an alternative H2-antagonist to avoid the risk of selective serotonin reuptake inhibitor (SSRI) toxicity. Monitor for increased therapeutic or toxic effects of SSRI if cimetidine is initiated/dose increased, or decreased effects if cimetidine is discontinued/dose decreased.

Clarithromycin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Clozapine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of clozapine. If concurrent use of these agents is employed, monitor for increased toxic effects of clozapine if a selective serotonin reuptake inhibitor (SSRI) is initiated/dose increased, or decreased effects if a SSRI is discontinued/dose decreased.

Conivaptan: CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Vilazodone. Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Desipramine: Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.

Dextromethorphan: Consideration should be given to avoiding the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors (SSRI). Monitor for toxic effects of dextromethorphan (eg, CNS, Cardiovascular) if an SSRI is initiated or the dose is increased. SSRIs, other than fluoxetine and paroxetine, may be safer alternatives due to lesser CYP2D6 inhibition; however, the mechanism for the interaction is not fully understood, and caution is still advised.

Diclofenac: Increased risk of bleeding with concomitant use of NSAIDs with vilazodone.

Drotrecogin alfa: Increase monitoring for signs/symptoms of bleeding during concomitant therapy. If possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents.

Ibuprofen: Increased risk of bleeding with concomitant use of non-steroidal anti-inflammatory drugs with vilazodone.

Isocarboxazid: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Ketoconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Ketorolac: Increased risk of bleeding with concomitant use of vilazodone and ketorolac

L-Tryptophan: Due to risks of enhanced serotonin activity and/or adverse reactions (e.g., serotonin syndrome), concomitant use of selective serotonin reuptake inhibitors (SSRIs) and tryptophan is not recommended. Avoid combination.

Linezolid: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Metoclopramide: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.

Mexiletine: Monitor for increased serum concentrations/toxic effects of mexiletine if a selective serotonin reuptake inhibitor (SSRI) is initiated/dose increased, or decreased concentrations/effects if an SSRI is discontinued/dose decreased.

Naproxen: Increased risk of bleeding with concomitant use of NSAIDs with vilazodone.

Naratriptan: Increased risk of serotonin syndrome

Nortriptyline: Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.

Phenelzine: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.

Piroxicam: Increased risk of bleeding with concomitant use of NSAIDs and vilazodone

Quinidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Selegiline: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Sibutramine: Sibutramine may enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Avoid combination.

Sumatriptan: Increased risk of serotonin syndrome

Thioridazine: Thioridazine prescribing information contraindicates the concomitant use of agents that inhibit CYP2D6 isoenzymes. Avoid combination.

Tranylcypromine: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.

Voriconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.

Warfarin: Increased risk of bleeding with concomitant use of warfarin and vilazodone.