Venlafaxine XR Adco 37.5 mg. 75 mg. 150 mg. 225 mg XR capsules

Venlafaxine XR Adco is indicated for the treatment of depression, including depression with associated anxiety. Venlafaxine XR Adco is indicated for the prevention of relapses of an episode of depression in patients responding to an initial six to eight weeks of treatment. In patients responding to six months of relapse prevention, Venlafaxine XR Adco may be used to prevent recurrence. Safety and efficacy beyond one year have not been demonstrated. When Venlafaxine XR Adco is used for long-term it should periodically be re-evaluated for the usefulness of the product in the individual patient. Venlafaxine XR Adco is indicated for the treatment of generalised anxiety disorder and for the treatment of Social Anxiety Disorder. The effectiveness of Venlafaxine XR Adco in the treatment of Social Anxiety Disorder for more than 12 weeks has not been demonstrated.

The usual recommended dose for Venlafaxine XR Adco is 75 mg, given once daily. If after several weeks further clinical improvement is required, the dose may be increased to 150 mg, given once daily. If needed, the dose can be further increased up to 225 mg given once daily. Dose increments should be made at intervals of approximately 2 weeks or more, but not less than 4 days. The dose for depressed patients may be further increased, if needed, up to 375 mg, given once daily.

Venlafaxine XR Adco should be administered once daily, at approximately the same time either in the morning or in the evening. The extended-release formulation contains spheroids, which release the medicine slowly into the digestive tract. The insoluble portion of these spheroids are eliminated and may be seen in stools.

Depressed patients, who are currently being treated at a therapeutic dose with immediate release formulation may be switched to Venlafaxine XR Adco at the nearest equivalent dose (mg/day). Individual dosage adjustments may however be necessary.

Patients with renal impairment should receive lower doses of Venlafaxine XR Adco. The total daily dose of Venlafaxine XR Adco should be reduced by 25 to 50 % for patients with renal impairment with a glomerular filtration rate (GFR) of 10 to 70 mL/min. The total daily dose of Venlafaxine XR Adco should be reduced by 50 % in haemodialysis patients. Because of individual variability in clearance in these patients, individualisation of dosage may be desirable.

Patients with hepatic impairment should have their total daily dose of Venlafaxine XR Adco reduced by 50 % in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment have not been studied; therefore, caution should be used if considering treating these patients with Venlafaxine XR Adco and a further reduction should be considered. Since there is a variability in clearance between hepatically impaired patients, individualisation of dosing, including further dose reductions (> 50 %), may be desirable in some patients.

Not for use in children under 18 years (see section 4.3).

No specific dosage adjustments of Venlafaxine XR Adco are recommended based on patient age.

The need for long-term therapy with Venlafaxine XR Adco must be periodically reassessed. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Dose tapering is recommended whenever possible when discontinuing Venlafaxine XR Adco therapy (see sections 4.4 & 4.8). Tapering over at least a two-week period is recommended if Venlafaxine XR Adco has been used for more than 6 weeks. In clinical trials with venlafaxine extended-release capsules, tapering was achieved by reducing the daily dose by 75 mg at one week intervals. The period required for tapering may depend on the dose, duration of therapy and the individual patient. Patients should be advised to consult their doctor before abruptly discontinuing Venlafaxine XR Adco (see section 4.4 & 4.8).

It is recommended that Venlafaxine XR Adco be taken with food. Each capsule should be swallowed whole with fluid. Do not divide, crush, chew or place capsule in water.

Venlafaxine XR Adco is contraindicated in:

• Patients with a known hypersensitivity to venlafaxine or to any of the ingredients listed in section 6.1.
• Patients concomitantly taking monoamine oxidase inhibitors (MAOIu2019s).
• Venlafaxine XR Adco must not be initiated for at least 14 days after discontinuation of treatment with a MAOI. Venlafaxine XR Adco must be discontinued for at least 7 days before starting treatment with any MAOI (see section 4.5). Severe adverse reactions have been reported when Venlafaxine XR Adco therapy is initiated soon after discontinuation of a MAOI and when a MAOI is initiated soon after discontinuation of Venlafaxine XR Adco. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures and death (see section 4.5).
• Children under 18 years (see section 4.4).
• Pregnancy and lactation (see section 4.6).

Suicide/suicidal thoughts or clinical worsening

Patients with major depressive disorder, both adults and children, may experience worsening of their depression and or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. A casual role, however, for antidepressant medicine in inducing such behaviour has not been established. Patients being treated with Venlafaxine XR Adco should, nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy or at any time of dose changes, either increases or decreases.

Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorders should be observed when treating patients with other psychiatric and non-psychiatric disorders.

The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness, impulsivity, akathisia, hypomania and mania). Although a causal link between the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing Venlafaxine XR Adco, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patientu2019s presenting symptoms. If the decision is made to discontinue treatment, Venlafaxine XR Adco should be tapered (see section 4.2).

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. A meta-analysis of placebo-controlled clinical trials of antidepressant medicines 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 medicine therapy, especially in early treatment and following dose changes. Patients (and caregivers of patients) should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restless), hypomania, mania, other unusual changes in behaviour, worsening of depression, and suicidal ideation, especially when initiating therapy or during any change in dose or dosage regimen. The risk of suicide attempt must be considered especially in depressed patients, and the smallest quantity of medicine, consistent with good patient management, should be provided to reduce the risk of overdose. Risk assessment for suicide should be performed regularly.

Paediatric population

Venlafaxine XR Adco should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo.

Serotonin syndrome

Serotonin syndrome, a potentially life-threatening condition may occur with Venlafaxine XR Adco treatment, particularly with concomitant use of other medicines that may affect the serotonergic neurotransmitter system (including triptans, SSRIs, SNRIs, amphetamines, lithium, sibutramine, St. John's Wort [ Hypericum perforatum ], fentanyl and its analogues, tramadol, dextromethorphan, tapentadol, pethidine, methadone and pentazocine), with medicines that impair metabolism of serotonin (such as MAOIs e.g. methylene blue), with serotonin precursors (such as tryptophan supplements) or with antipsychotics or other dopamine antagonists (see sections 4.3 and 4.5).

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). Serotonin syndrome in its most severe form, can resemble Neuroleptic Malignant Syndrome (NMS), which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs and mental status changes.

If concomitant treatment with Venlafaxine XR Adco and other medicines that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Venlafaxine XR Adco with serotonin precursors (such as tryptophan supplements) is not recommended.

Narrow-angle glaucoma

Mydriasis may occur in association with Venlafaxine XR Adco. It is recommended that patients with raised intraocular pressure or patients at risk for acute narrow-angle glaucoma (angle-closure glaucoma) be closely monitored.

Blood pressure

Dose-related increases in blood pressure have been frequently reported with venlafaxine. In some cases, severely elevated blood pressure requiring immediate treatment has been reported in post marketing experience. All patients should be carefully screened for high blood pressure and pre-existing hypertension should be controlled before initiation of treatment. Blood pressure should be reviewed periodically, after initiation of treatment and after dose increases.

Caution should be exercised in patients whose underlying conditions might be compromised by increases in blood pressure, e.g., those with impaired cardiac function.

Heart rate

Increases in heart rate can occur, particularly with higher doses. Caution should be exercised in patients whose underlying conditions might be compromised by increases in heart rate.

Cardiac disease and risk of dysrhythmia

Venlafaxine XR Adco has not been evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Therefore, it should be used with caution in these patients. In post marketing experience, cases of QTc prolongation, Torsade de Pointes (TdP), ventricular tachycardia, and fatal cardiac dysrhythmias have been reported with the use of venlafaxine, especially in overdose or in patients with other risk factors for QTc prolongation/TdP. The balance of risks and benefits should be considered before prescribing Venlafaxine XR Adco to patients at high risk of serious cardiac dysrhythmias or QTc prolongation (see section 5.1).

Convulsions

Convulsions may occur with Venlafaxine XR Adco therapy. Venlafaxine XR Adco should be introduced with caution in patients with a history of convulsions and concerned patients should be closely monitored. Treatment should be discontinued in any patient who develops seizures.

Hyponatraemia

Cases of hyponatraemia and/or the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion may occur with Venlafaxine XR Adco. This has most frequently been reported in volume-depleted or dehydrated patients. Elderly patients, patients taking diuretics, and patients who are otherwise volume-depleted may be at greater risk for this event.

Abnormal bleeding

Medicines that inhibit serotonin uptake may lead to reduced platelet function. Bleeding events related to SSRI and SNRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to gastrointestinal and life-threatening haemorrhages. The risk of haemorrhage may be increased in patients taking Venlafaxine XR Adco. As with other serotonin-reuptake inhibitors, Venlafaxine XR Adco should be used cautiously in patients predisposed to bleeding, including patients on anticoagulants and platelet inhibitors.

Postpartum haemorrhage

SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections 4.6 & 4.8).

Serum cholesterol

Clinically relevant increases in serum cholesterol were recorded in 5,3 % of venlafaxine treated patients and 0,0 % of placebo-treated patients treated for at least 3 months in placebo-controlled clinical trials. Measurement of serum cholesterol levels should be considered during long-term treatment.

Allergic phenomenon

Patients should be advised to notify their doctor if they develop a rash, hives, or a related allergic phenomenon.

Co-administration with weight loss medicines

The safety and efficacy of Venlafaxine XR Adco therapy in combination with weight loss medicines, including phentermine, have not been established. Co-administration of Venlafaxine XR Adco and weight loss medicines is not recommended. Venlafaxine XR Adco is not indicated for weight loss alone or in combination with other products.

Mania/hypomania

Mania/hypomania may occur in a small proportion of patients with mood disorders who have received antidepressants, including Venlafaxine XR Adco. Venlafaxine XR Adco should be used cautiously in patients with a history or family history of bipolar disorder.

Aggression

Aggression may occur in a small number of patients who have received antidepressants, including Venlafaxine XR Adco. This has been reported under initiation, dose changes and discontinuation of treatment. Venlafaxine XR Adco should be used cautiously in patients with a history of aggression.

Discontinuation of treatment

Withdrawal symptoms, when treatment is discontinued, are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials, adverse events seen on treatment discontinuation (tapering and post-tapering) occurred in approximately 31 % of patients treated with venlafaxine and 17 % of patients taking placebo. The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most frequently reported reactions. Generally, these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been less frequent reports of such symptoms in patients who have inadvertently missed a dose. Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be extended (2 to 3 months or more). It is therefore advised that Venlafaxine XR Adco should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see section 4.2).

Sexual dysfunction

Serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SNRIs.

Akathisia/psychomotor restlessness

The use of venlafaxine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Dry mouth

Dry mouth is reported in 10 % of patients treated with venlafaxine. This may increase the risk of caries, and patients should be advised upon the importance of dental hygiene.

Diabetes

In patients with diabetes, treatment with an SSRI or Venlafaxine XR Adco may alter glycaemic control. Insulin and/or oral antidiabetic dosage may need to be adjusted.

Medicine-Laboratory test interactions

False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of Venlafaxine XR Adco therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.

Colourants

Venlafaxine XR 150 Adco contains Allura Red AC (E129) and Sunset Yellow FCF (E110), which may cause allergic reactions. Venlafaxine XR 225 Adco contains Carmoisine (E122), which may cause allergic reactions.

Monoamine Oxidase Inhibitors (MAOI)

Irreversible non-selective MAOIs Venlafaxine XR Adco must not be used in combination with irreversible non-selective MAOIs. Venlafaxine XR Adco must not be initiated for at least 14 days after discontinuation of treatment with an irreversible non-selective MAOI. Venlafaxine XR Adco must be discontinued for at least 7 days before starting treatment with an irreversible non-selective MAOI (see sections 4.3 and 4.4).

Reversible, selective MAO-inhibitor (moclobemide) Due to the risk of serotonin syndrome, the combination of Venlafaxine XR Adco with a reversible and selective MAOI, such as moclobemide, is not recommended. Following treatment with a reversible MAO-inhibitor, a shorter withdrawal period than 14 days may be used before initiation of Venlafaxine XR Adco treatment. It is recommended that Venlafaxine XR Adco should be discontinued for at least 7 days before starting treatment with a reversible MAOI (see section 4.4).

Reversible, non-selective MAOI (linezolid) The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with Venlafaxine XR Adco (see section 4.4).

Severe adverse reactions have been reported in patients who have recently been discontinued from an MAOI and started on Venlafaxine XR Adco or have recently had Venlafaxine XR Adco therapy discontinued prior to initiation of an MAOI. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, and hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death.

Serotonin syndrome

Serotonin syndrome, a potentially life-threatening condition, may occur with Venlafaxine XR Adco treatment, particularly with concomitant use of other medicines that may affect the serotonergic neurotransmitter system (including triptans, SSRIs, SNRIs, amphetamines, lithium, sibutramine, St. John's Wort [ Hypericum perforatum ], fentanyl and its analogues, tramadol, dextromethorphan, tapentadol, pethidine, methadone and pentazocine), with medicines that impair metabolism of serotonin (such as MAOIs e.g. methylene blue), with serotonin precursors (such as tryptophan supplements) or with antipsychotics or other dopamine antagonists (see sections 4.3 and 4.4).

If concomitant treatment with Venlafaxine XR Adco and an SSRI, an SNRI or a serotonin receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Venlafaxine XR Adco with serotonin precursors (such as tryptophan supplements) is not recommended (see section 4.4).

CNS-active medicines

The risk of using Venlafaxine XR Adco in combination with other CNS-active medicines has not been systematically evaluated. Consequently, caution is advised when Venlafaxine XR Adco is taken in combination with other CNS-active medicines.

Ethanol

Venlafaxine has been shown not to increase the impairment of mental and motor skills caused by ethanol. However, Venlafaxine XR Adco is a CNS-active medicine and patients should be advised to avoid alcohol consumption.

Medicines that prolong the QT interval

The risk of QTc prolongation and/or ventricular dysrhythmias (e.g., TdP) is increased with concomitant use of other medicines which prolong the QTc interval. Co-administration of such medicines should be avoided (see section 4.4).

Relevant classes include:

• class Ia and III anti-dysrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)
• some antipsychotics (e.g. thioridazine)
• some macrolides (e.g. erythromycin)
• some antihistamines
• some quinolone antibiotics (e.g. moxifloxacin)

The above list is not exhaustive and other individual medicines known to significantly increase QT interval should be avoided.

Venlafaxine XR Adco must not be administered to pregnant or lactating women. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRIs/SNRIs exposure within the month prior to birth (see sections 4.4 & 4.8).

Women of childbearing potential / Contraception in males and females Patients should be advised to notify their doctor if they become pregnant or intend to become pregnant during treatment with Venlafaxine XR Adco.

Pregnancy Venlafaxine XR Adco must not be administered to pregnant women. Safety during human pregnancy and lactation has not been established (see section 4.3). Some neonates exposed to venlafaxine late in the third trimester have developed complications requiring tube-feeding; respirator; support or extended hospitalisation. Such complications can arise immediately upon delivery.

Breastfeeding Venlafaxine and its active metabolite, O-desmethylvenlafaxine, are excreted in human milk. Therefore, mothers on treatment with Venlafaxine XR Adco should not breastfeed (see section 4.3).

Venlafaxine XR Adco causes dizziness and sedation; it may therefore impair judgment, thinking, and motor skills. Patients receiving Venlafaxine XR Adco should therefore be cautioned about their ability to drive or operate hazardous machinery.

Summary of the safety profile The most frequent observed adverse reactions reported in clinical studies were nausea, dry mouth, headache and sweating (including night sweats). The occurrence of many frequently observed adverse events is dose related.

Tabulated list of adverse reactions

System Organ Class Frequency Side Effect

Blood and lymphatic system disorders Frequency unknown Agranulocytosis*, aplastic anaemia*, pancytopaenia*, neutropaenia*, thrombocytopaenia*

Immune system disorders Frequency unknown Anaphylactic reaction*

Endocrine disorders Frequency unknown Inappropriate antidiuretic hormone secretion*, increased blood prolactin*

Metabolism and nutrition disorders Frequent Decreased appetite Frequency unknown Hyponatraemia*, increased appetite*

Psychiatric disorders Frequent Insomnia, abnormal dreams, nervousness, decreased libido, anorgasmia Less frequent Mania, hypomania, hallucination, derealisation, apathy, abnormal orgasm, apathy Frequency unknown Suicidal ideation and suicidal behaviours a , aggression b , confusional state*, depersonalisation*, agitation*, bruxism*

Nervous system disorders Frequent Dizziness, sedation, tremor, paraesthesia, dysgeusia Less frequent Syncope, myoclonus, convulsion Frequency unknown Headache* c , akathisia*, balance disorder*, abnormal coordination*, dyskinaesia*, serotonin syndrome*, neuroleptic malignant syndrome (NMS)*, dystonia*, tardive dyskinaesia*

Eye disorders Frequent Visual impairment, mydriasis, accommodation disorder, including blurred vision Frequency unknown Angle-closure glaucoma*

Ear and labyrinth disorders Frequency unknown Vertigo, tinnitus*

Cardiac disorders Less frequent Ventricular fibrillation Frequency unknown Tachycardia, palpitations*, Torsade de Pointes*, ventricular tachycardia*, electrocardiogram QT extended*

Vascular disorders Frequent Hypertension, hot flushes Less frequent Orthostatic hypotension Frequency unknown Hypotension*

Respiratory, thoracic and mediastinal disorders Frequent Yawning Frequency unknown Dyspnoea*, interstitial lung disease*, pulmonary eosinophilia*, pharyngitis*, rhinitis*

Gastrointestinal disorders Frequent Nausea, dry mouth, constipation, vomiting Frequency unknown Gastrointestinal haemorrhage*, pancreatitis*, diarrhoea*, anorexia*, dyspepsia*, eructation*, flatulence*

Hepato-biliary disorders Frequency unknown Abnormal liver function test*, hepatitis*

Skin and subcutaneous tissue disorders Frequent Rash Less frequent Ecchymosis, photosensitivity reaction Frequency unknown Hyperhidrosis* (including night sweats), pruritus*, urticaria*, alopecia*, angioedema*, Stevens-Johnson syndrome*, toxic epidermal necrolysis*, erythema multiforme*

Musculoskeletal, connective tissue and bone disorders Frequent Hypertonia Frequency unknown Rhabdomyolysis*, myalgia*

Renal and urinary disorders Frequent Urinary hesitation, urinary retention Frequency unknown Urinary incontinence*, pollakiuria*

Reproductive system and breast disorders Frequent Erectile dysfunction, ejaculation disorder Frequency unknown Menorrhagia*, metrorrhagia*, postpartum haemorrhage c ;

General disorders and administration site conditions Frequent Fatigue, asthenia, pain Frequency unknown Mucosal haemorrhage*, chills*

Investigations Frequent Decreased weight, increased weight, increased blood cholesterol Frequency unknown Extended bleeding time*

* ADR identified post-marketing

a Cases of suicidal ideation and suicidal behaviours have been reported during venlafaxine therapy or early after treatment discontinuation (see section 4.4).

b See section 4.4

c This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections 4.4 & 4.6).

Description of selected adverse events

Discontinuation of treatment Discontinuation of Venlafaxine XR Adco (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, vertigo, headache and flu syndrome are the most commonly reported reactions. Generally, these events are mild to moderate and are self-limiting; however, in some patients, they may be severe and/or extended. It is therefore advised that when Venlafaxine XR Adco treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

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 u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

In post marketing experience, overdose with venlafaxine was reported predominantly in combination with alcohol and/or other medicines. The most commonly reported events in overdose include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, convulsion, and vomiting. Other reported events include electrocardiographic changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation (see section 5.1), ventricular tachycardia, bradycardia, hypotension, vertigo, and deaths.

Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine treated patients have a higher burden of suicide risk factors than SSRI patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristics of venlafaxine treated patients, is not clear. Prescriptions for Venlafaxine XR Adco should be written for the smallest quantity of the medicine consistent with good patient management in order to reduce the risk of overdose.

Recommended treatment General supportive and symptomatic measures are recommended; cardiac rhythm and vital signs must be monitored. When there is a risk of aspiration, induction of emesis is not recommended. Administration of activated charcoal may also limit absorption of the active substance. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for Venlafaxine XR Adco are known.