Vortioxetine Hydrobromide

Vortioxetine is indicated for the treatment of major depressive disorder (MDD) in adults.

The mechanism of the antidepressant effect of Vortioxetine is not fully understood, but it is thought to be related to its enhancement of serotonergic activity in the central nervous system through inhibition of the reuptake of serotonin (5-HT). It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism.

Recommended dose: The recommended starting dose is 10 mg administered orally once daily without regard to meals. The dosage should then be increased to 20 mg/day, as tolerated. The efficacy and safety of doses above 20 mg/day have not been evaluated in controlled clinical trials. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses. The lowest effective dose of 5 mg/day should always be used as the starting dose for elderly patients (>65 years of age).

Maintenance dose: For MDD, Vortioxetine can be administered for several months or longer. For a long period use patients should be re-evaluated to assess the usefulness of the drugs for individual patients.

Discontinuation treatment: Although Vortioxetine can be abruptly discontinued, in placebo-controlled trials patients experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation of Vortioxetine 15 mg/day or 20 mg/day. To avoid these adverse reactions, it is recommended that the dose should be decreased to 10 mg/day for one week before full discontinuation of Vortioxetine 15 mg/day or 20 mg/day.

Switching a patient to or from a Monoamine Oxidase Inhibitor (MAOI) intended to treat Psychiatric Disorders: At least 14 days must elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Vortioxetine to avoid the risk of Serotonin Syndrome. Conversely, at least 21 days must elapse after stopping Vortioxetine before starting an MAOI intended to treat psychiatric disorders.

Monoamine Oxidase Inhibitors: Adverse reactions, some of which are serious or fatal, can develop in patients who use MAOIs or who have recently been discontinued from an MAOI and started on a serotonergic antidepressant(s) or who have recently had SSRI or SNRI therapy discontinued prior to initiation of an MAOI.

Serotonergic drugs: Co-administration of Vortioxetine with other drugs that may affect the serotonergic neurotransmitter systems (e.g. SSRIs, SNRIs, Triptans, Buspirone, Tramadol, and Tryptophan products etc.) may potentially increase serotonin toxicity or serotonin syndrome. Closely monitor symptoms of serotonin syndrome if Vortioxetine is co-administered with other serotonergic drugs. Treatment with Vortioxetine and any concomitant serotonergic agents should be discontinued immediately if serotonin syndrome occurs.

Other CNS active agents: No clinically relevant effect was observed on steady-state Lithium exposure following co-administration with multiple daily doses of Vortioxetine.

Potential for other drugs to affect Vortioxetine: Reduce Vortioxetine dose by half when a strong CYP2D6 inhibitor (e.g. Bupropion, Fuoxetine, Paroxetine, Quinidine) is co-administered. Consider increasing the Vortioxetine dose when a strong CYP inducer (e.g. Rifampin, Carbamazepine, Phenytoin) is co-administered.

Vortioxetine Hydrobromide is contraindicated in Patients with known hypersensitivity to Vortioxetine or any of the excipients of the drug product & concomitant use of Monoamine Oxidase Inhibitors (MAOIs).

Patients taking Vortioxetine may experience some adverse events such as Hypersensitivity, Clinical worsening and suicide risk, Serotonin syndrome, Abnormal bleeding, activation of Mania/Hypomania, Angle closure Glaucoma, Hyponatremia.

The safety of Vortioxetine in human pregnancy has not been established. Therefore, Vortioxetine should not be used during pregnancy or in women intending to become pregnant, unless the benefits outweigh the possible risks to the fetus. Available data in animals have shown the excretion of Vortioxetine metabolites in milk. It is expected that Vortioxetine will be excreted into human milk. Because risks to the nursing child cannot be excluded, breastfeeding is not recommended during treatment with Vortioxetine.

Clinical Worsening and Suicide Risk: All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants including Vortioxetine, when used alone but more often when used concomitantly with other serotonergic drugs (including Triptans, Tricyclic Antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone & St. John's Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as Linezolid and intravenous methylene blue).

Abnormal Bleeding: The use of drugs that interfere with serotonin reuptake inhibition, including Vortioxetine, may increase the risk of bleeding events. Concomitant use of Aspirin, Nonsteroidal
Anti-inflammatory drugs (NSAIDs), Warfarin, and other Anticoagulants may add to this risk. Activation of

Mania/Hypomania: As with all Antidepressants, use Vortioxetine cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.

Angle Closure Glaucoma: The pupillary dilation that occurs following the use of many Antidepressant drugs, including Vortioxetine, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Hyponatremia: Hyponatremia occurrs because of treatment with serotonergic drugs.

Pediatric use (<18 years of age): The safety and effectiveness of Vortioxetine in the pediatric population have not been established.

Geriatrics use (>65 years of age): No dose adjustment is recommended on the basis of age. Results from a single-dose pharmacokinetic study in elderly (>65 years old) vs young (24 to 45 years old) subjects demonstrated that the pharmacokinetics were generally similar between the two age groups.

Renal impairment: No dose adjustment is needed.

Hepatic impairment: No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Vortioxetine is not recommended in patients with severe hepatic impairment.

CYP2D6 poor metabolizers: The plasma concentration of Vortioxetine was approximately two times higher in CYP2D6 poor metabolizers than in extensive metabolizers. In the presence of strong CYP3A4/2C9 inhibitors, the exposure could potentially be higher, and a dosage adjustment may be required.

Use in other patient populations: No dose adjustment of Vortioxetine is needed on the basis of race, gender and ethnicity.

There is limited data available on Vortioxetine overdose. Medical follow-up in a specialized environment is recommended.

Serotonin-norepinephrine reuptake inhibitor (SNRI)

Store at 30°C or below in a dry place. Keep away from light. Keep out of the reach of the children.