Vortioxetine (Trintellix) - Uses, Dosage, Side effects, MOA, brands

Vortioxetine (Trintellix) is an antidepressant medicine that has almost similar efficacy as the other antidepressants. It is recommended in patients who have failed treatment with two antidepressants in the past.

  • Patients with serious depressive disorder are treated with it.

Vortioxetine (Trintellix) Dose in Adults

Vortioxetine (Trintellix) Dosage used  in  the treatment of major depressive disorder:

  • Initially 10 mg orally once daily is given
  • Once tolerated, it is then increased to 20 mg once daily; for individuals who cannot handle greater dosages, 5 mg once daily is used.
  • 5–20 mg used once daily is the maintenance dose.
  • Dosage adjustment done for CYP2D6 poor metabolizers:

    • Maximum dose is 10 mg/day.
  • Dosage adjustment done for concomitant therapy with strong CYP2D6 inhibitors:

    • Reduce total daily dose by 50 % when a strong CYP2D6 inhibitor (eg, quinidine, bupropion, fluoxetine, paroxetine) is also given.
    • Increase the dose to original level if the CYP2D6 inhibitor is stopped.
  • Dosage adjustment is done for concomitant therapy with strong CYP inducers:

    • Increase the dose when a strong CYP inducer (eg, phenytoin, rifampin, carbamazepine) is coadministered for more than 14 days.
    • The maximum dose is not exceeded three times the original dose.
    • Dosage is reduced to the original level within 2 weeks of stopping the CYP inducer.

  • Discontinuing therapy:

    • Reduce the dose gradually (e.g., over 2 to 4 weeks) after quitting antidepressant medication if it has lasted more than 3 weeks in order to reduce withdrawal symptoms and spot reemerging symptoms.
    • When using an antidepressant with a half-life of less than 24 hours, such as paroxetine or venlafaxine, experiencing antidepressant withdrawal symptoms in the past, or using large doses of the medication, a slower titration is used (for example, over a month).
    • If uncomfortable withdrawal symptoms develop, you should either resume taking the previously suggested amount or reduce it more gradually.
    • Some individuals, such as those on long-term medication (>6 months), with a history of discontinuation syndrome, benefit most from tapering over >3 months.
    • In order to prevent withdrawal symptoms, vortioxetine dosages of 15 mg once daily or more should be reduced to 10 mg once daily for one week before being completely discontinued.

MAO inhibitor recommendations:

  • Switching from or to an MAO inhibitor intended to treat psychiatric disorders:

    • After stopping an MAO inhibitor used to treat psychiatric disorders, wait two weeks before commencing vortioxetine.
    • Vortioxetine should be stopped 3 weeks before starting an MAO inhibitor for the treatment of mental disorders.

Use in Children:

Not recommended for use in children.

Vortioxetine (Trintellix) Pregnancy Risk Category: B3

 

  • Late in the third trimester, SSRI/SNRI may have non-teratogenic effects on the infant.
  • Symptoms include difficulty breathing, cyanosis, convulsions, and fluctuating body temperature. vomiting; low blood sugar. both hypo- and hypertonia. Hyperreflexia. Unsteadiness, jitters, and irritation.
  • A discontinuation syndrome or SSRI/SNRI toxicity may be to blame for symptoms. This may be related to SSRI treatment-related serotonin dysfunction.
  • It has also been demonstrated that SSRIs can make neonates develop persistent pulmonary hypertension.
  • Individualized SSRI and SNRI treatment during pregnancy is advised by ACOG.
  • For the management of depression in pregnancy, the main physician, the paediatrician, and the mental health expert should all be contacted.
  • In comparison to other available treatment options and untreated depression, the advantages of pharmaceutical therapy should be considered.
  • Women who have stopped taking antidepressant medication during pregnancy are at risk of postpartum depression. The medications can be restarted after delivery.

Use of vortioxetine while breastfeeding

  • It is unknown if vortioxetine can be found in breast milk.
  • When deciding whether to breastfeed during treatment, you should consider the risks to infants, the benefits to the mother, and the benefits to the mother.

Dose in Renal Disease:

  • No dosage adjustment required.

Dose in Liver disease:

  • No dosage adjustment required.

Common Side Effects of Vortioxetine (trintellix):

  • Central Nervous System:

    • Female Sexual Disorder
    • Male Sexual Disorder
  • Gastrointestinal:

    • Nausea

Less Common Side Effects of Vortioxetine (Trintellix):

  • Central Nervous System:

    • Dizziness
    • Abnormal Dreams
  • Dermatologic:

    • Pruritus
  • Gastrointestinal:

    • Diarrhea
    • Xerostomia
    • Constipation
    • Vomiting
    • Flatulence

Contraindications to Vortioxetine (Trintellix):

 

  • Hypersensitivity to vortioxetine or any other formulation ingredient (eg. angioedema).
    concomitant use of an MAO inhibitor for psychiatric illnesses. After stopping vortioxetine, you can do this within 3 weeks or within 2 weeks.
  • Start vortioxetine for patients who have received intravenous methyleneblue or linezolid.

Warnings and precautions

  • Bleeding Risk:
    • It can cause platelet aggregation to be impaired, which could increase the risk of bleeding events, particularly if taken with warfarin, aspirin, NSAIDs or other anticoagulants.
    • Antidepressant use can cause bleeding that ranges from minor bruising and epistaxis, to life-threatening hemorhage.
  • Depression in the CNS:
    • It can lead to CNS depression, which can impair mental or physical abilities.
    • It is important to warn patients about tasks that require mental alertness.
  • Fractures
    • Antidepressant treatment has been shown to reduce bone fractures.
    • If an antidepressant-treated person experiences unexplained bone pain or tenderness, swelling, or bruising, there is a possibility of a fragility injury.
  • Ocular effects
    • It can cause mild pupillary dilation, which can result in an episode of narrow angle glaucoma in those who are susceptible.
    • You should monitor patients who have not undergone an iridectomy to reduce narrow-angle glaucoma risks.
  • Serotonin syndrome
    • Serotonergic antidepressants such as SSRIs and SNRIs can be used to treat potentially life-threatening serotonin Syndrome (SS).
    • This is especially true when it is combined with other serotonergic drugs (eg TCAs and fentanyls, lithium, triptans or tramadols, buspirones, St John's worts, tryptophan, tramadol, tramadol, tramadol, tramadol, triptans, buspirones, buspirones, tryptophan, TCAs) or agents that alter the metabolism of serotonin [iemethylene blue intravenous methylene]
    • Carefully inspect patients for indications of serotonin syndrome, such as:
      • Mental status changes (eg: agitation, hallucinations and coma),
      • Autonomic instability (eg diaphoresis or tachycardia or labile blood pressure).
      • Neuromuscular changes (eg, tremors, rigidity, myoclonus, etc.)
      • GI symptoms (eg nausea, diarrhea, vomiting).
      • Seizure
    • If you notice any signs or symptoms, stop taking any serotonergic agents immediately.
  • SIADH and Hyponatremia
    • SIADH is often associated with serotonergic drugs
    • Hyponatremia was seen in severe cases (e.g., with serum sodium of less than 110 mg/L).
    • Volume depletion and simultaneous use of diuretics can increase the risk for seniors.
    • Patients with hyponatremia symptomatic should be stopped.
  • Hypomania and mania:
    • Patients at high risk of developing bipolar disorder may experience a mixed/manic episode.
    • Patients with a family history or bipolar disorder, hypomania, or mania should be cautious.
    • Bipolar disorder should be considered for patients who have depressive symptoms.
    • The FDA has not approved Vortioxetine for treatment of bipolar disorder.
  • Seizure disorders
    • Patients with seizure disorders, a history of seizure disorder or other conditions that can cause seizures should be cautious.
    • Patients without any history of seizures have reported experiencing seizures.'

 

Vortioxetine: Drug Interaction

Risk Factor C (Monitor therapy)

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)

Other agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ajmaline

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Anticoagulants

The anticoagulant impact of anticoagulants may be strengthened by agents with antiplatelet properties. Exceptions: Heparin, Bemiparin, and Enoxaparin.

Antiemetics (5HT3 Antagonists)

Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.

Antipsychotic Agents

Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Apixaban

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.

Aspirin

Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin.

Beta-Blockers

Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Sotalol.

Blood Glucose Lowering Agents

Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents.

Bosentan

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Brexanolone

The CNS depressive action of brexanolone may be enhanced by selective serotonin reuptake inhibitors.

Cephalothin

Substances having antiplatelet properties may intensify cephalothin's harmful or hazardous effects. In particular, there may be an elevated risk of bleeding.

CloBAZam

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

CNS Depressants

May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.

Cobicistat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Collagenase (Systemic)

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.

CYP2D6 Inhibitors (Moderate)

May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).

CYP3A4 Inducers (Moderate)

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Cyproheptadine

May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.

Dabigatran Etexilate

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.

Darunavir

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Dasatinib

May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Deferasirox

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Deoxycholic Acid

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.

Desmopressin

Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin.

Edoxaban

Antiplatelet agents may intensify the toxic/unfavorable effects of edoxaban. In particular, there may be an elevated risk of bleeding.

Erdafitinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Fat Emulsion (Fish Oil Based)

Agents with poisonous or harmful effects may intensify their negative or hazardous effects.

Glucosamine

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ibritumomab Tiuxetan

Antiplatelet agents may intensify the toxic/unfavorable effects of ibritumomab tiuxetan. Both substances may raise the risk of bleeding and compromise platelet function.

Ibrutinib

Agents with poisonous or harmful effects may intensify their negative or hazardous effects.

Imatinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Inotersen

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ioflupane I 123

Ioflupane I 123's ability to diagnose conditions may be diminished by selective serotonin reuptake inhibitors.

Ivosidenib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Limaprost

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Lumefantrine

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Metaxalone

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Methylphenidate

May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased.

MetyroSINE

May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.

Multivitamins/Fluoride (with ADE)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Multivitamins/Minerals (with ADEK, Folate, Iron)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Multivitamins/Minerals (with AE, No Iron)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)

Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.

Nonsteroidal Anti-Inflammatory Agents (Topical)

May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors.

Obinutuzumab

Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.

Omega-3 Fatty Acids

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Opioid Agonists

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Panobinostat

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Peginterferon Alfa-2b

May lower the serum level of CYP2D6 substrates (High risk with Inhibitors).

Pentosan Polysulfate Sodium

The concentration of CYP2D6 Substrates in the serum may rise when using Peginterferon Alfa-2b (High risk with Inhibitors).

Pentoxifylline

Agents with poisonous or harmful effects may intensify their negative or hazardous effects. In particular, the concurrent use of several drugs may raise the risk of bleeding.

Perhexiline

Agents with antiplatelet properties may have an enhanced antiplatelet impact. The serum levels of perhexiline may increase when exposed to CYP2D6 Substrates (High Risk with Inhibitors). The serum concentration of CYP2D6 Substrates may rise in response to perhexiline (High risk with Inhibitors).

Prostacyclin Analogues

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

QuiNINE

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

RisperiDONE

The metabolism of RisperiDONE might be slowed down by selective serotonin reuptake inhibitors.

Rivaroxaban

Rivaroxaban's anticoagulant impact may be increased by substances with antiplatelet properties. Management: Thoroughly weigh the advantages and disadvantages of this combination, and keep a tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.

Salicylates

The harmful or toxic effect of salicylates may be increased by substances with antiplatelet properties. Bleeding risk could rise as a result.

Sarilumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Serotonin Modulators

The negative or hazardous effects of other serotonin modulators might be increased. Serotonin syndrome may start to develop. Nicergoline and Tedizolid are exceptions.

Siltuximab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Tedizolid

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Thiazide and Thiazide-Like Diuretics

Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics.

Thrombolytic Agents

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.

Thyroid Products

Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased.

Tocilizumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

TraMADol

Serotonin modulators may intensify TraMADol's harmful or hazardous effects. Seizures may become more likely. The serotonergic impact of serotonin modulators may be enhanced by TraMADol. Serotonin syndrome might occur from this.

Vitamin E (Systemic)

May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

Vitamin K Antagonists (eg, warfarin)

Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists.

Risk Factor D (Consider therapy modification)

Abiraterone Acetate

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.

Alcohol (Ethyl)

May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors.

Asunaprevir

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Bemiparin

Bemiparin's anticoagulant impact may be strengthened by substances with antiplatelet properties. Management: Avoid taking bemiparin at the same time as antiplatelet medications. If concurrent use is unavoidable, keep a cautious eye out for bleeding signs and symptoms.

BuPROPion

May intensify Vortioxetine's negative or hazardous effects. Serotonin syndrome and seizures in particular may be at higher risk. Vortioxetine's serum levels may rise as a result of BuPROPion. Management: When taken with bupropion, the dosage of vortioxetine needs to be halved. The dosage of vortioxetine should be increased once bupropion use has been discontinued.

BusPIRone

May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.

CYP2D6 Inhibitors (Strong)

May increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level.

CYP3A4 Inducers (Strong)

May decrease the serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer.

Dabrafenib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Where possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).

Dacomitinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). Management: Steer clear of using dacomitinib at the same time as CYP2D6 subtrates with a limited therapeutic index.

Dextromethorphan

Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine.

Enoxaparin

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.

Enzalutamide

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.

Gilteritinib

May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor.

Heparin

Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)

May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.

Linezolid

May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid.

Linezolid

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.

Lithium

May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.

Lorlatinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.

Metoclopramide

The negative or hazardous effects of selective serotonin reuptake inhibitors might be increased. Management: When possible, look for substitutions for this combination. Serotonin syndrome, neuroleptic malignant syndrome, and extrapyramidal symptoms should all be watched out for in individuals taking metoclopramide along with selective serotonin reuptake inhibitors.

Mitotane

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.

Nonsteroidal Anti-Inflammatory Agents (Nonselective)

Nonsteroidal Anti-Inflammatory Drugs may have a stronger antiplatelet impact when used with Selective Serotonin Reuptake Inhibitors (Nonselective). Selective serotonin reuptake inhibitors' therapeutic effects may be lessened by nonsteroidal anti-inflammatory drugs (Nonselective). Management: Take NSAID substitutes into account. Keep an eye out for any signs of bleeding and decreased antidepressant effects. NSAIDs that are COX-2 selective may lessen risk, however this is unknown. Diclofenac (Topical), Ibuprofen (Topical), and Piroxicam are exceptions (Topical).

Pitolisant

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Pitolisant should not be used in conjunction with a CYP3A4 substrate that has a limited therapeutic index. When administered with pitolisant, other CYP3A4 substrates need to be checked more carefully.

Serotonin Reuptake Inhibitor/Antagonists

Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity.

St John's Wort

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Certain contraindications may apply to some combinations. the relevant manufacturer's label.

Risk Factor X (Avoid combination)

Bromopride

May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.

Dapoxetine

May enhance the adverse/toxic effect of Serotonin Modulators.

Dothiepin

Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dothiepin.

Methylene Blue

Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.

Methylene Blue

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Monoamine Oxidase Inhibitors

May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid.

Tryptophan

The serotonergic effects of selective serotonin reuptake inhibitors might be improved. It might result in serotonin syndrome.

Urokinase

Urokinase's anticoagulant impact may be strengthened by substances with antiplatelet properties.

Monitor:

  • Mental status for depression
  • Suicidal ideation (particularly at the beginning of therapy or when doses are increased or decreased),
  • anxiety
  • mania
  • social functioning
  • panic attacks
  • akathisia
  • signs of serotonin syndrome
  • hyponatremia
  • Baseline hepatic function .

How to administer Vortioxetine (Trintellix)?

  • Give without regard to meals.

Mechanism of action of Vortioxetine (Trintellix):

  • It inhibits serotonin reuptake (5-HT3)
  • It has antagonist activity at 5-HT-1D and 5-HT-1A receptors.

Distribution: V: 2600 L

Protein binding: 98%

Metabolism:

  • Mainly via the hepatic route, primarily through oxidation via CYP450 enzymes, mostly CYP2D6 and subsequent glucuronic acids conjugation to an active carboxylic acid metabolite

Bioavailability75%

Eliminating half-life: Almost 66 hours

Time to reach peak: 7-11 hours

Excretion:

  • By Urine (59%)
  • By feces (26%).

International Brands of Vortioxetine:

  • Brintellix
  • Vortiocyrl
  • Brintellix
  • Trintellix

Vortioxetine Brand Names in Pakistan:

Brintellix