Vortioxetine Hydrobromide

Registered South African indications:

• Major depressive disorder and to reduce the risk of relapse

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with nonselective monoamine oxidase inhibitors (MAOIs) or selective MAO-A inhibitors

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Porphyria
• History of suicide-related events or those exhibiting a significant degree of suicidal ideation 
• History of seizures  
• Unstable epilepsy
• Liver cirrhosis  
• Patients with known bleeding disorders
• History of mania/hypomania
• Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)
• Hyponatraemia
• Concurrent administration with electroconvulsive therapy (ECT)

Forms avail. in SA and covered in this monograph: fct

South African registered indications and dosages

Major depressive disorder and to reduce the risk of relapse

• Oral (fct): Initial: 10mg, dly; Depending on patient response titration can be considered; Titrate at intervals of 1 week; Maintenance: 5-20mg, dly

After the depressive symptoms resolve, treatment for at least 6 months is recommended for consolidation of the antidepressive response

A dose decrease may be considered for patients who do not tolerate higher doses

Can be taken with or without food

Patients being treated with vortioxetine can abruptly stop taking vortioxetine without the need for a gradual reduction in dose  

See Additional Prescribing Points

Not established for use in children below 18 years

Pregnancy

• Caution
• There are limited data from the use of vortioxetine in pregnant women. Studies in animals have shown reproductive toxicity
• The following symptoms may occur in the newborn after maternal use of a serotonergic medicinal product in the later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either discontinuation effects or excess serotonergic activity. In the majority of instances, such complications began immediately or soon (<24 hours) after delivery
• Epidemiological data suggest that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN with vortioxetine treatment, this potential risk cannot be ruled out taking into account the related mechanism of action (increase in serotonin concentrations)
• Vortioxetine should only be administered to pregnant women if the expected benefits outweigh the potential risk to the foetus

Breastfeeding

• Caution; not recommended
• Available data in animals have shown excretion of vortioxetine/ vortioxetine metabolites in milk. It is expected that vortioxetine will be excreted into human milk 
• A risk to the breastfeeding child cannot be excluded
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from vortioxetine treatment taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility 

• Fertility studies in male and female rats showed no effect of vortioxetine on fertility, sperm quality or mating performance
• Human case reports with medicinal products from the related pharmacological class of antidepressants (SSRIs) have shown an effect on sperm quality that is reversible. Impact on human fertility has not been observed so far

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; dose adjustment recommended
  Initial: 5mg, once daily; May increase to 10mg, once daily; Max: 20mg/day
  Caution is advised at doses >10 mg once daily

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Serotonin syndrome
• Abnormal dreams
• Bruxism

Cardiovascular Disorders

• Flushing

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Constipation
• Epistaxis
• Gastrointestinal bleeding

Genitourinary Disorders

• Vaginal bleeding
• Sexual dysfunction
  - Difficulties with satisfaction of orgasm
  - Ease of sexual arousal

Endocrine and Metabolic Disorders

• Hyponatraemia
• Decreased appetite

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Night sweats
• Ecchymosis
• Rash
• Contusion

Musculoskeletal Disorders

• Increased risk of bone fractures in older patients (>50 years of age)

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reaction
• Haemorrhage
• Angioedema

• Serotonergic agents
• Anticoagulants
• Antiplatelet agents
• Acetylsalicylic acid
• Lithium
• Tryptophan
• Sodium-depleting agents
• Monoamine oxidase inhibitors
• Selective MAO-A inhibitors
• St. John's wort
• Agents which decrease seizure threshold
• Tricyclic antidepressants
• Selective serotonin reuptake inhibitor
• Serotonin-norepinephrine reuptake inhibitor
• Neuroleptics
• Phenothiazines
• Thioxanthenes
• Butyrophenones
• Alcohol
• CYP2D6 inhibitors
• CYP3A4 inhibitors
• CYP2C9 inhibitors
• CYP450 inducers
• CYP450 substrates
• Moclobemide
• Linezolid
• Selegiline
• Rasagiline
• Tramadol
• Sumatriptan
• Mefloquine
• Bupropion
• Quinidine
• Fluoxetine
• Paroxetine
• Pethidine
• Rifampicin
• Carbamazepine
• Phenytoin

• Hepatic function
• Serum sodium

Suicide/suicidal thoughts or clinical worsening

• Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs
• As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs
• It is general clinical experience that the risk of suicide may increase in the early stages of recovery
• Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment
• Close supervision of patients and in particular those at high risk should accompany treatment especially in early treatment and following dose changes
• Patients (and caregivers of patients) should be alerted to the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present

The mechanism of action of vortioxetine is thought to be related to its direct modulation of serotonergic receptor activity and inhibition of the serotonin (5-HT) transporter. Non-clinical data indicate that vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter, leading to modulation of neurotransmission in several systems, including predominantly the serotonin but probably also the norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems within the forebrain . 

This multimodal activity is considered responsible for the antidepressant and anxiolytic-like effects and the improvement of cognitive function, learning and memory observed with vortioxetine in animal studies. However, the precise contribution of the individual targets to the observed pharmacodynamic profile remains unclear and caution should be applied when extrapolating animal data directly to man.

Tablet 5mg

• Brintellix (H.Lundbeck) orginator
• Vortioxetine 5mg Lundbeck (H.Lundbeck)

Tablet 10mg

• Brintellix (H.Lundbeck) orginator
• Vortioxetine 10mg Lundbeck (H.Lundbeck)

Tablet 20mg

• Brintellix (H.Lundbeck) orginator
• Vortioxetine 20mg Lundbeck (H.Lundbeck)