Dyna Vortioxetine Tablet

VORTIOXETINE DYNA is indicated for the treatment of major depressive disorder and to reduce the risk of relapse.

Posology
The starting and recommended dose of VORTIOXETINE DYNA is 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily or reduced to a minimum of 5 mg daily. If a dose increase is required, this should be in periods of not less than one week of the treatment. A dose decrease may be considered for patients who do not tolerate higher doses. After the depressive symptoms resolve, treatment for at least 6 months is recommended for consolidation of the anti-depressive response.

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

Special populations
Elderly patients
The safety and efficacy of VORTIOXETINE DYNA have been established in elderly patients. However, caution should be exercised when treating the elderly. Treatment should be initiated with 5 mg daily and, depending on the individual patient response, the dose may be increased to 10 mg daily. Limited data are available with doses exceeding 10 mg daily.

Renal impairment
No dose adjustment is needed for patients with renal impairment or for patients with end-stage renal disease. However, caution should be exercised when treating patients with severe renal insufficiency (see section 5.2).

Hepatic impairment
No dose adjustment is needed for patients with mild or moderate hepatic impairment. VORTIOXETINE DYNA has not been studied in patients with severe hepatic impairment and caution should be exercised when prescribing to these patients (see section 5.2).

Cytochrome P450 inhibitors
Depending on individual patient response, a lower dose of VORTIOXETINE DYNA may be considered if strong CYP2D6 inhibitors (e.g. bupropion, quinidine, fluoxetine, paroxetine) are added to VORTIOXETINE DYNA treatment (see section 4.5).

Cytochrome P450 inducers
Depending on individual patient response, a dose adjustment of VORTIOXETINE DYNA may be considered if a broad cytochrome P450 inducer (e.g. rifampicin, carbamazepine, phenytoin) is added to VORTIOXETINE DYNA treatment (see section 4.5).

Paediatric population
The safety and efficacy of VORTIOXETINE DYNA in children and adolescents aged less than 18 years have not been established. No data are available.

Method of administration
The film-coated tablets are for oral use and can be taken with or without food. Missed dose: Doctors should advise patients who forget to take VORTIOXETINE DYNA to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• hypersensitivity to vortioxetine or to any of the ingredients of VORTIOXETINE DYNA listed in section 6.1
• concomitant use with monoamine oxidase inhibitors (MAOIs) selective MAO-A inhibitors (see section 4.5).

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 with VORTIOXETINE DYNA, 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 with VORTIOXETINE DYNA. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo, in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany treatment with VORTIOXETINE DYNA 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.

Seizures
Seizures are a potential risk with antidepressants, including VORTIOXETINE DYNA. Therefore, VORTIOXETINE DYNA should be introduced cautiously in patients who have a history of seizures or in patients with unstable epilepsy. Treatment with VORTIOXETINE DYNA should be discontinued in any patient who develops seizures or where there is an increase in seizure frequency.

Serotonin syndrome or neuroleptic malignant syndrome
Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS), potentially life-threatening conditions, may occur with VORTIOXETINE DYNA. The risk of SS or NMS is increased with concomitant use of serotonergic medicines (including triptans), with medicines which impair metabolism of serotonin (including MAOIs), antipsychotics and other dopamine antagonists. Patients should be monitored for the emergence of signs and symptoms of SS or NMS (see sections 4.3 and 4.4). Serotonin syndrome symptoms may include mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). If this occurs, treatment with VORTIOXETINE DYNA should be discontinued immediately and symptomatic treatment should be initiated.

Hyponatraemia
Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported with the use of antidepressants with serotonergic effect (SSRIs/SNRIs). Caution should be exercised in patients at risk, such as the elderly, cirrhotic patients or patients concomitantly treated with medications known to cause hyponatraemia. Discontinuation of VORTIOXETINE DYNA should be considered in patients with symptomatic hyponatraemia and appropriate medical intervention should be instituted.

Activation of hypomania or mania
VORTIOXETINE DYNA treatment should be used with caution in patients with a history of mania/hypomania and should be discontinued in any patient entering a manic phase.

Haemorrhage
Bleeding abnormalities, such as ecchymoses, purpura and other haemorrhagic events such as gastrointestinal or gynaecological bleeding may occur with VORTIOXETINE DYNA. Caution is advised in patients taking anticoagulants and/or medicinal products known to affect platelet function, e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin (see section 4.5), and in patients with known bleeding tendencies/disorders.

Co-administration with cytochrome P450 inhibitors
Co-administration of vortioxetine and bupropion resulted in a higher incidence of adverse reactions when bupropion was added to vortioxetine than when vortioxetine was added to bupropion. Depending on individual patient response, a lower dose of VORTIOXETINE DYNA may be considered if strong CYP2D6 inhibitors (e.g. bupropion, quinidine, fluoxetine, paroxetine) are added to VORTIOXETINE DYNA treatment (see sections 4.2 and 4.5).

Elderly
Data on the use of VORTIOXETINE DYNA in elderly patients with major depressive episodes are limited. Therefore, caution should be exercised when treating patients u2265 65 years of age with doses higher than 10 mg VORTIOXETINE DYNA once daily (see sections 4.2, 4.8 and 5.2).

Renal or hepatic impairment
Given that subjects with renal or hepatic impairment are vulnerable and given that the data on the use of VORTIOXETINE DYNA in these sub-populations are limited, caution should be exercised when treating these patients (see section 4.2 and 5.2).

VORTIOXETINE DYNA contains mannitol which may cause a mild laxative effect.

Paediatric population
VORTIOXETINE DYNA is not recommended for the treatment of depression in patients aged less than 18 years since the safety and efficacy of VORTIOXETINE DYNA have not been established in this age group. In clinical studies in children and adolescents treated with other antidepressants, suicide-related behaviour (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed than in those treated with placebo.

Vortioxetine, as contained in VORTIOXETINE DYNA, is extensively metabolised in the liver primarily through oxidation and subsequent glucuronic acid conjugation. In vitro, the cytochrome P450 isozymes CYP2D6, CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8 and CYP2B6 are involved in the metabolism of vortioxetine (see section 5.2).

Contraindicated combinations:
Monoamine Oxidase Inhibitors (MAOIs)
Due to the risk of serotonin syndrome, VORTIOXETINE DYNA is contraindicated in any combination with MAOIs. VORTIOXETINE DYNA must not be initiated for at least 14 days after discontinuation of treatment with an MAOI. VORTIOXETINE DYNA must be discontinued for at least 14 days before starting treatment with an MAOI (see section 4.3).

Reversible, selective MAO-A inhibitor (moclobemide): The combination of VORTIOXETINE DYNA with a reversible and selective MAO-A inhibitor, such as moclobemide, is contraindicated (see section 4.3). If the combination proves necessary, the added medicine should be given with minimum dosage and under close clinical monitoring for serotonin syndrome (see section 4.4).

Linezolid (MAOIs): The antibiotic linezolid is a weak MAOI and should not be given to patients treated with VORTIOXETINE DYNA (see section 4.3). Close monitoring for serotonin syndrome is necessary if used concomitantly (see section 4.4).

Potential for other medicines to affect VORTIOXETINE DYNA:
Serotonergic medicines
Co-administration of antidepressants and other medicines with serotonergic effect (e.g., pethidine, tramadol, sumatriptan and other triptans) may lead to serotonin syndrome (see section 4.4).

St. John's wort
Concomitant use of antidepressants with serotonergic effect and herbal remedies containing St. John's wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including serotonin syndrome (see section 4.4).

Irreversible, selective MAO-B inhibitor (selegiline, rasagiline)
Although a lower risk of serotonin syndrome is expected with selective MAO-B inhibitors than with MAO-A inhibitors, the combination of VORTIOXETINE DYNA with irreversible MAO-B inhibitors, such as selegiline or rasagiline should be administered with caution. Close monitoring for serotonin syndrome is necessary if used concomitantly (see section 4.4).

Medicines lowering the seizure threshold
Antidepressants with serotonergic effect including VORTIOXETINE DYNA can lower the seizure threshold. Caution is advised when concomitantly using VORTIOXETINE DYNA and other medicines capable of lowering the seizure threshold (e.g. antidepressants (tricyclics, SSRIs, SNRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol (see section 4.4).

ECT (electroconvulsive therapy)
There is no clinical experience with concurrent administration of VORTIOXETINE DYNA and ECT, therefore caution is advisable.

Pregnancy
VORTIOXETINE DYNAu2019s safety and efficacy in pregnant women has not been established. The following symptoms may occur in the new-born after maternal use of VORTIOXETINE DYNA in 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 a majority of instances, such complications begin immediately or soon (< 24 hours) after delivery. Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the new-born (PPHN). Although no studies have investigated the association of PPHN to VORTIOXETINE DYNA treatment, this potential risk cannot be ruled out taking into account the related mechanism of action (increase in serotonin concentrations).

Breastfeeding
The safety of VORTIOXETINE DYNA in breastfeeding women has not been established. Available data in animals have shown excretion of vortioxetine/vortioxetine metabolites in milk. It is expected that VORTIOXETINE DYNA will be excreted into human milk (see section 5.3). A risk to the breastfeeding child cannot be excluded.

Fertility
Fertility studies in male and female rats showed no effect of vortioxetine, as in VORTIOXETINE DYNA, on fertility, sperm quality or mating performance (see section 5.3). Human case reports with medicines 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.

VORTIOXETINE DYNA has no or negligible influence on the ability to drive and use machines. However, as adverse reactions such as dizziness have been reported, patients should exercise caution when driving or operating hazardous machinery, especially when starting treatment with VORTIOXETINE DYNA or when changing the dose.

a) Summary of the safety profile
The most common adverse reaction was nausea. Adverse reactions were usually mild or moderate and occurred within the first two weeks of treatment. The reactions were usually transient and did not generally lead to cessation of therapy.

b) Tabulated summary of adverse reactions
System Organ Class
Frequency
Side effects
Infections and infestations
Frequent
Nasopharyngitis, influenza
Immune system disorders
Frequency unknown
Anaphylactic reaction, angioedema
Metabolism and nutrition disorders
Frequent
Frequency unknown
Decreased appetite
Hyponatraemia
Psychiatric disorders
Frequent
Less frequent
Insomnia, abnormal dreams
Bruxism
Nervous system disorders
Frequent
Frequency unknown
Headache, dizziness, somnolence, sedation
Serotonin syndrome
Vascular disorders
Less frequent
Frequency unknown
Flushing
Haemorrhage (including contusion, ecchymosis, epistaxis, gastrointestinal or vaginal bleeding)
Gastrointestinal disorders
Frequent
Nausea, diarrhoea, dry mouth, constipation, vomiting, dyspepsia, flatulence, abdominal discomfort
Skin and subcutaneous tissue disorders
Frequent
Less frequent
Frequency unknown
Hyperhidrosis, pruritus generalised
Night sweats
Urticaria, rash
Musculoskeletal, connective tissue and bone disorders
Frequent
Frequency unknown
Back pain, arthralgia
Bone fractures
Reproductive system and breast disorders
Frequency unknown
Sexual dysfunction
General disorders and administrative site conditions
Frequent
Fatigue
Injury, poisoning and procedural complication
Frequent
Accidental overdose

c) Description of selected adverse reactions
Nausea
Nausea was usually mild or moderate and occurred within the first two weeks of treatment. The reactions were usually transient and did not generally lead to cessation of therapy. Gastrointestinal adverse reactions, such as nausea, occurred more frequently in women than men.

d) Other special populations
Elderly patients
For doses u226510 mg VORTIOXETINE DYNA once daily, the withdrawal rate from the studies was higher in patients aged u2265 65 years. For doses of 20 mg VORTIOXETINE DYNA once daily, the incidences of nausea and constipation were higher in patients aged u2265 65 years (than in patients aged < 65 years (see section 4.4).

Sexual Dysfunction
VORTIOXETINE DYNA may cause sexual dysfunction especially at the 20 mg dose. The following manifestations, i.e. difficulties with satisfaction of orgasm and ease of sexual arousal, were the most prevalent. (see section 5.1).

Class effect
Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving a medicine from related pharmacological classes of antidepressants (SSRIs and TCAs). The mechanism behind this risk is unknown, and it is not known to what extent this risk is also relevant for VORTIOXETINE DYNA.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the online service for adverse drug reaction reporting by following the link: https://www.sahpra.org.za/Publications/Index/8 An email can be sent directly to the company, [email protected] to ensure safety of the product.

There is limited experience with VORTIOXETINE DYNA overdose. In clinical studies, no patient ingested more than 75 mg vortioxetine, as in VORTIOXETINE DYNA on a single occasion. The clinical studies included subjects who were administered 40 to 75 mg and ingestion of VORTIOXETINE DYNA in this dose range may cause an aggravation of the following signs and symptoms: Nausea, postural dizziness, diarrhoea, abdominal discomfort, generalised pruritus, somnolence and flushing.

Management of overdose: Management of overdose should consist of treating clinical symptoms and relevant monitoring. Medical follow-up in a specialised environment is recommended.