Venlafaxine Tablets USP 25mg Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT
a) Venlafaxine Tablets USP 25mg Taj Pharma

b) Venlafaxine Tablets USP 37.5mg Taj Pharma
c) Venlafaxine Tablets USP 50mg Taj Pharma
d) Venlafaxine Tablets USP 75mg Taj Pharma
e) Venlafaxine Tablets USP 100mg Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
a) Each tablet contains

Venlafaxine hydrochloride USP
equivalent to 25mg of venlafaxine
Colour:Sunset Yellow

b) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 37.5mg of venlafaxine
Colour:Sunset Yellow

c) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 50mg of venlafaxine
Colour:Sunset Yellow

d) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 75mg of venlafaxine
Colour:Sunset Yellow

e) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 100mg of venlafaxine
Colour:Sunset Yellow

For a full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM
Film coated tablets
Orange, 10 mm round biconvex, scored film-coated tablets.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications
Treatment of major depressive episodes.
For prevention of recurrence of major depressive episodes.

4.2  Posology and method of administration
Major depressive episodes
The recommended starting dose of immediate-release venlafaxine is 75mg/day in two or three divided doses taken with food. Patients not responding to the initial 75mg/day dose may benefit from dose increases up to a maximum dose of 375mg/day. Dosage increases can be made at intervals of 2 weeks or more. If clinically warranted due to symptom severity, dose increases can be made at more frequent intervals, but not less than 4 days.

Because of the risk of dose-related adverse effects, dose increments should be made only after a clinical evaluation (see section 4.4). The lowest effective dose should be maintained.

Patients should be treated for a sufficient period of time, usually several months or longer. Treatment should be reassessed regularly on a case-by-case basis. Longer-term treatment may also be appropriate for prevention of recurrence of major depressive episodes (MDE). In most of the cases, the recommended dose in prevention of recurrence of MDE is the same as the one used during the current episode.

Antidepressive medicinal products should continue for at least six months following remission.

Use in elderly patients
No specific dose adjustments of venlafaxine are considered necessary based on patient age alone.

However, caution should be exercised in treating the elderly (e.g., due to the possibility of renal impairment, the potential for changes in neurotransmitter sensitivity and affinity occurring with aging). The lowest effective dose should always be used, and patients should be carefully monitored when an increase in the dose is required.

Use in children and adolescents under the age of 18 years
Venlafaxine is not recommended for use in children and adolescents.

Controlled clinical studies in children and adolescents with major depressive disorder failed to demonstrate efficacy and do not support the use of venlafaxine in these patients (see sections 4.4 and 4.8).

The efficacy and safety of venlafaxine for other indications in children and adolescents under the age of 18 have not been established.

Use in patients with hepatic impairment
In patients with mild and moderate hepatic impairment, in general a 50% dose reduction should be considered. However, due to inter-individual variability in clearance, individualisation of dosage may be desirable.

There are limited data in patients with severe hepatic impairment. Caution is advised, and a dose reduction by more than 50% should be considered. The potential benefit should be weighed against the risk in the treatment of patients with severe hepatic impairment.

Use in patients with renal impairment
Although no change in dosage is necessary for patients with glomerular filtration rate (GFR) between 30-70ml/minute, caution is advised. For patients that require haemodialysis and in patients with severe renal impairment (GFR < 30ml/min), the dose should be reduced by 50%. Because of inter-individual variability in clearance in these patients, individualisation of dosage may be desirable.

Withdrawal symptoms seen on discontinuation of venlafaxine
Abrupt discontinuation should be avoided. When stopping treatment with venlafaxine, the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

For oral use.

It is recommended that venlafaxine immediate-release tablets be taken with food, at approximately the same time each day.

Patients treated with venlafaxine immediate-release tablets may be switched to venlafaxine prolonged-release capsules at the nearest equivalent daily dosage. For example, venlafaxine immediate-release tablets 37.5mg twice daily may be switched to venlafaxine prolonged-release capsules 75mg once daily. Individual dosage adjustments may be necessary.

 4.3 Contraindications
• Hypersensitivity to venlafaxine or to any of the excipients.

  • Concomitant treatment with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia.
  • Venlafaxine must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI.
  • Venlafaxine must be discontinued for at least 7 days before starting treatment with an irreversible MAOI (see sections 4.4 and 4.5).

 4.4 Special Warnings and precautions for use
• 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. Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

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 drugs 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 drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about 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.

  • Use in children and adolescents under 18 years of age.

Venlafaxine Tablets 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. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

  • Serotonin syndrome

As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with venlafaxine treatment, particularly with concomitant use of other agents, such as MAOinhibitors, that may affect the serotonergic neurotransmitter systems (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).

  • Narrow-angle glaucoma

Mydriasis may occur in association with venlafaxine. 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 commonly reported with venlafaxine. In some cases, severely elevated blood pressure requiring immediate treatment has been reported in postmarketing experience. All patients should be carefully screened for high blood pressure and preexisting hypertension should be controlled before initation 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 arrhythmia

Venlafaxine 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 postmarketing experience, fatal cardiac arrhythmias have been reported with the use of venlafaxine, especially in overdose. The balance of risks and benefits should be considered before prescribing venlafaxine to patients at high risk of serious cardiac arrhythmia.

  • Convulsions

Convulsions may occur with venlafaxine therapy. As with all antidepressants, venlafaxine 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. 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

Medicinal products that inhibit serotonin uptake may lead to reduced platelet function. The risk of skin and mucous membrane bleeding, including gastrointestinal haemorrhage, may be increased in patients taking venlafaxine. As with other serotonin-reuptake inhibitors, venlafaxine should be used cautiously in patients predisposed to bleeding, including patients on anticoagulants and platelet inhibitors.

  • 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.

  • Co-administration with weight loss agents

The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established.

Co-administration of venlafaxine and weight loss agents is not recommended. Venlafaxine 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. As with other antidepressants, venlafaxine 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. This has been reported under initiation, dose changes and discontinuation of treatment.

As with other antidepressants, venlafaxine 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 commonly 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 very rare 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 prolonged (2-3 months or more). It is therefore advised that venlafaxine 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).

  • 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 may alter glycaemic control. Insulin and/or antidiabetic dosage may need to be adjusted.

  • Excipients of known effect

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The colouring sunset yellow FCF (E110) may cause allergic reactions.

 4.5 Interaction with other medicinal products and other forms of interaction
Monoamine Oxidase Inhibitors (MAOI)

Irreversible non-selective MAOIs
Venlafaxine must not be used in combination with irreversible non-selective MAOIs. Venlafaxine must not be initiated for at least 14 days after discontinuation of treatment with an irreversible non-selective MAOI. Venlafaxine 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-A inhibitor (moclobemide)
Due to the risk of serotonin syndrome, the combination of venlafaxine 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 treatment. It is recommended that venlafaxine 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 (see section 4.4).

Severe adverse reactions have been reported in patients who have recently been discontinued from an MAOI and started on venlafaxine, or have recently had venlafaxine 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
As with other serotonergic agents, serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system (including triptans, SSRIs, SNRIs, lithium, sibutramine, tramadol, or St. John’s Wort [Hypericum perforatum]), with medicinal agents which impair metabolism of serotonin (including MAOIs), or with serotonin precursors (such as tryptophan supplements).

If concomitant treatment of venlafaxine with 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 with serotonin precursors (such as tryptophan supplements) is not recommended (see section 4.4).

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

Ethanol
Venlafaxine has been shown not to increase the impairment of mental and motor skills caused by ethanol. However, as with all CNS-active substances, patients should be advised to avoid alcohol consumption.

Effect of other medicinal products on venlafaxine

Ketoconazole (CYP3A4 inhibitor)
A pharmacokinetic study with ketoconazole in CYP2D6 extensive (EM) and poor metabolisers (PM) resulted in higher AUC of venlafaxine (70% and 21% in CYP2D6 PM and EM subjects, respectively) and O-desmethylvenlafaxine (33% and 23% in CYP2D6 PM and EM subjects, respectively) following administration of ketoconazole. Concomitant use of CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, voriconazole, posaconazole, ketoconazole, nelfinavir, ritonavir, saquinavir, telithromycin) and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient’s therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Effect of venlafaxine on other medicinal products

Lithium
Serotonin syndrome may occur with the concomitant use of venlafaxine and lithium (see Serotonin syndrome).

Diazepam
Venlafaxine has no effects on the pharmacokinetics and pharmacodynamics of diazepam and its active metabolite, desmethyldiazepam. Diazepam does not appear to affect the pharmacokinetics of either venlafaxine or O-desmethylvenlafaxine. It is unknown whether a pharmacokinetic and/or pharmacodynamic interaction with other benzodiazepines exists.

Imipramine
Venlafaxine did not affect the pharmacokinetics of imipramine and 2-OH-imipramine. There was a dose-dependent increase of 2-OH-desipramine AUC by 2.5 to 4.5-fold when venlafaxine 75mg to 150mg daily was administered. Imipramine did not affect the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine. The clinical significance of this interaction is unknown. Caution should be exercised with co-administration of venlafaxine and imipramine.

Haloperidol
A pharmacokinetic study with haloperidol has shown a 42% decrease in total oral clearance, a 70% increase in AUC, an 88% increase in Cmax, but no change in half-life for haloperidol. This should be taken into account in patients treated with haloperidol and venlafaxine concomitantly. The clinical significance of this interaction is unknown.

Risperidone
Venlafaxine increased the risperidone AUC by 50%, but did not significantly alter the pharmacokinetic profile of the total active moiety (risperidone plus 9-hydroxyrisperidone). The clinical significance of this interaction is unknown.

Metoprolol
Concomitant administration of venlafaxine and metoprolol to healthy volunteers in a pharmacokinetic interaction study for both medicinal products resulted in an increase of plasma concentrations of metoprolol by approximately 30-40% without altering the plasma concentrations of its active metabolite, α-hydroxymetoprolol. The clinical relevance of this finding in hypertensive patients is unknown. Metoprolol did not alter the pharmacokinetic profile of venlafaxine or its active metabolite, O-desmethylvenlafaxine. Caution should be exercised with co-administration of venlafaxine and metoprolol.

Indinavir
A pharmacokinetic study with indinavir has shown a 28% decrease in AUC and a 36% decrease in Cmax for indinavir. Indinavir did not affect the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine. The clinical significance of this interaction is unknown.

 4.6 Fertility, pregnancy and lactation

Pregnancy
There are no adequate data from the use of venlafaxine in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk.
As with other serotonin reuptake inhibitors (SSRIs/SNRIs), discontinuation symptoms may occur in the newborns if venlafaxine is used until or shortly before birth. Some newborns exposed to venlafaxine late in the third trimester have developed complications requiring tube-feeding, respiratory support or prolonged hospitalisation. Such complications can arise immediately upon delivery.
The following symptoms may be observed in neonates if the mother has used an SSRI/SNRI late in pregnancy: irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping.

These symptoms may be due to either serotonergic effects or exposure symptoms. In the majority of cases, these complications are observed immediately or within 24 hours after partus.

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 newborn (PPHN). Although no studies have investigated an association of PPHN to SNRI treatment, this potential risk cannot be ruled out with venlafaxine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin).

Lactation
Venlafaxine and its active metabolite, O-desmethylvenlafaxine, are excreted in breast milk. There have been post-marketing reports of breast-fed infants who experienced crying, irritability, and abnormal sleep patterns. Symptoms consistent with venlafaxine drug discontinuation have also been reported after stopping breast-feeding. A risk to the suckling child cannot be excluded. Therefore, a decision to continue/discontinue breast-feeding or to continue/discontinue therapy with venlafaxine should be made, taking into account the benefit of breast-feeding to the child and the benefit of venlafaxine therapy to the woman.

4.7 Effects on ability to drive and use machines
Any psychoactive medicinal product may impair judgment, thinking, and motor skills. Therefore, any patient receiving venlafaxine should be cautioned about their ability to drive or operate hazardous machinery.

4.8 Undesirable Effects
The most commonly (>1/10) reported adverse reactions in clinical studies were nausea, dry mouth, headache and sweating (including night sweats).

Adverse reactions are listed below by system organ class and frequency.

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be estimated from the available data).

Body System Very Common Common Uncommon Rare Not Known
Haematological / Lymphatic Ecchymosis,

Gastrointestinal haemorrhage

Mucous membrane bleeding,

Prolonged bleeding time,

Thrombocytopaenia,

Blood dyscrasias, (including agranulocytosis, aplastic anaemia, neutropaenia and pancytopaenia)

Metabolic/ Nutritional Serum cholesterol increased,

Weight loss

Weight gain Abnormal liver function tests,

Hyponatraemia,

Hepatitis,

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH),

Prolactin increased

Nervous Dry mouth (10.0%),

Headache (30.3%)*

Abnormal dreams,

Decreased libido,

Dizziness,

Increased muscle tonus (hypertonia),

Insomnia,

Nervousness,

Paresthesia,

Sedation,

Tremor,

Confusion,

Depersonalisation

Apathy,

Hallucinations,

Myoclonus,

Agitation,

Impaired coordination and balance

Akathisia/ Psychomotor restlessness,

Convulsion,

Manic reaction

Neuroleptic Malignant Syndrome (NMS),

Serotonergic syndrome,

Delirium,

Extrapyramidal reactions (including dystonia and dyskinaesia),

Tardive dyskinaesia,

Suicidal ideation and behaviours**

Vertigo,

Aggression***

Special Senses Abnormality of accommodation,

Mydriasis,

Visual disturbance

Altered taste sensation,

Tinnitus

Angle-closure glaucoma
Cardiovascular Hypertension,

Vasodilatation (mostly hot flashes/flushes),

Palpitations

Postural hypotension,

Syncope,

Tachycardia

Hypotension,

QT prolongation,

Ventricular fibrillation,

Ventricular tachycardia (including torsade de pointes)

Respiratory Yawning Pulmonary eosinophilia
Digestive Nausea (20.0%) Appetite decreased (anorexia),

Constipation,

Vomiting

Bruxism,

Diarrhoea

Pancreatitis
Skin Sweating (including night sweats) [12.2%] Rash,

Alopecia

Erythema multiforme,

Toxic epidermal necrolysis,

Stevens-Johnson syndrome,

Pruritus,

Urticaria

Musculoskeletal Rhabdomyolysis
Urogenital Abnormal ejaculation/orgasm (males),

Anorgasmia,

Erectile dysfunction (impotence),

Urination impaired (mostly hesitancy),

Menstrual disorders associated with increased bleeding or increased irregular bleeding (e.g., menorrhagia, metrorrhagia),

Pollakiuria

Abnormal orgasm (females),

Urinary retention

Urinary incontinence Urogenital
Body as a Whole Asthenia (fatigue),

Chills

Angioedema,

Photosensitivity reaction

Anaphylaxis

 

*In pooled clinical trials, the incidence of headache was 30.3% with venlafaxine versus 31.3% with placebo.

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

*** See section 4.4.

Discontinuation of venlafaxine (particularly when abrupt) commonly leads to withdrawal symptoms.

Dizziness, sensory disturbances (including paraethesia), 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 prolonged. It is therefore advised that when venlafaxine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

Paediatric patients
In general, the adverse reaction profile of venlafaxine (in placebo-controlled clinical trials) in children and adolescents (ages 6 to 17) was similar to that seen for adults. As with adults, decreased appetite, weight loss, increased blood pressure, and increased serum cholesterol were observed (see section 4.4).

In paediatric clinical trials the adverse reaction suicidal ideation was observed. There were also increased reports of hostility and, especially in major depressive disorder, self-harm.

Particularly, the following adverse reactions were observed in paediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose
In postmarketing experience, overdose with venlafaxine was reported predominantly in combination with alcohol and/or other medicinal products. 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), ventricular tachycardia, bradycardia, hypotension, vertigo, and death.

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 should be written for the smallest quantity of the medicinal product 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. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. 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 are known.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other antidepressants –
The mechanism of venlafaxine’s antidepressant action in humans is believed to be associated with its potentiation of neurotransmitter activity in the central nervous system. Preclinical studies have shown that venlafaxine and its major metabolite, O-desmethylvenlafaxine (ODV), are inhibitors of serotonin and noradrenaline reuptake. Venlafaxine also weakly inhibits dopamine uptake. Venlafaxine and its active metabolite reduce β-adrenergic responsiveness after both acute (single dose) and chronic administration. Venlafaxine and ODV are very similar with respect to their overall action on neurotransmitter reuptake and receptor binding.

Venlafaxine has virtually no affinity for rat brain muscarinic, cholinergic, H1-histaminergic or α1-adrenergic receptors in vitro. Pharmacological activity at these receptors may be related to various side effects seen with other antidepressant medicinal products, such as anticholinergic, sedative and cardiovascular side effects.

Venlafaxine does not possess monoamine oxidase (MAO) inhibitory activity.

In vitro studies revealed that venlafaxine has virtually no affinity for opiate or benzodiazepine sensitive receptors.

Major depressive episodes
The efficacy of venlafaxine immediate-release as a treatment for major depressive episodes was demonstrated in five randomised, double-blind, placebo-controlled, short-term trials ranging from 4 to 6 weeks duration, for doses up to 375mg/day. The efficacy of venlafaxine prolonged-release as a treatment for major depressive episodes was established in two placebo-controlled, short-term studies for 8 and 12 weeks duration, which included a dose range of 75 to 225mg/day.

In one longer-term study, adult outpatients who had responded during an 8-week open trial on venlafaxine prolonged-release (75, 150, or 225mg) were randomised to continuation of their same venlafaxine prolonged-release dose or to placebo, for up to 26 weeks of observation for relapse.

In a second longer-term study, the efficacy of venlafaxine in prevention of recurrent depressive episodes for a 12-month period was established in a placebo-controlled double-blind clinical trial in adult outpatients with recurrent major depressive episodes who had responded to venlafaxine treatment (100 to 200mg/day, on a b.i.d. schedule) on the last episode of depression.

5.2 Pharmacokinetic properties
Venlafaxine is extensively metabolised, primarily to the active metabolite, O-desmethylvenlafaxine (ODV). Mean ± SD plasma half-lives of venlafaxine and ODV are 5±2 hours and 11±2 hours, respectively. Steady-state concentrations of venlafaxine and ODV are attained within 3 days of oral multiple-dose therapy. Venlafaxine and ODV exhibit linear kinetics over the dose range of 75mg to 450mg/day.

Absorption
At least 92% of venlafaxine is absorbed following single oral doses of immediate-release venlafaxine.

Absolute bioavailability is 40% to 45% due to presystemic metabolism. After immediate-release venlafaxine administration, the peak plasma concentrations of venlafaxine and ODV occur in 2 and 3 hours, respectively. Following the administration of venlafaxine prolonged-release capsules, peak plasma concentrations of venlafaxine and ODV are attained within 5.5 hours and 9 hours, respectively. When equal daily doses of venlafaxine are administered as either an immediate-release tablet or prolonged-release capsule, the prolonged-release capsule provides a slower rate of absorption, but the same extent of absorption compared with the immediate-release tablet. Food does not affect the bioavailability of venlafaxine and ODV.

Distribution
Venlafaxine and ODV are minimally bound at therapeutic concentrations to human plasma proteins (27% and 30%, respectively). The volume of distribution for venlafaxine at steady-state is 4.4±1.6 L/kg following intravenous administration.

Metabolism
Venlafaxine undergoes extensive hepatic metabolism. In vitro and in vivo studies indicate that venlafaxine is biotransformed to its major active metabolite, ODV, by CYP2D6. In vitro and in vivo studies indicate that venlafaxine is metabolised to a minor, less active metabolite, N-desmethylvenlafaxine, by CYP3A4. In vitro and in vivo studies indicate that venlafaxine is a weak inhibitor of CYP2D6. Venlafaxine did not inhibit CYP1A2, CYP2C9, or CYP3A4.

Elimination
Venlafaxine and its metabolites are excreted primarily through the kidneys. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%).

Mean ± SD plasma steady-state clearances of venlafaxine and ODV are 1.3±0.6L/h/kg and 0.4±0.2L/h/kg, respectively.

Special populations
Age and gender
Subject age and gender do not significantly affect the pharmacokinetics of venlafaxine and ODV.

CYP2D6 extensive/poor metabolisers
Plasma concentrations of venlafaxine are higher in CYP2D6 poor metabolisers than extensive metabolisers. Because the total exposure (AUC) of venlafaxine and ODV is similar in poor and extensive metabolisers, there is no need for different venlafaxine dosing regimens for these two groups.

Patients with hepatic impairment
In Child-Pugh A (mildly hepatically impaired) and Child-Pugh B (moderately hepatically impaired) subjects, venlafaxine and ODV half-lives were prolonged compared to normal subjects. The oral clearance of both venlafaxine and ODV was reduced. A large degree of intersubject variability was noted. There are limited data in patients with severe hepatic impairment (see section 4.2).

Patients with renal impairment
In dialysis patients, venlafaxine elimination half-life was prolonged by about 180% and clearance reduced by about 57% compared to normal subjects, while ODV elimination half-life was prolonged by about 142% and clearance reduced by about 56%. Dosage adjustment is necessary in patients with severe renal impairment and in patients that require haemodialysis (see section 4.2).

5.3 Preclinical safety data
Studies with venlafaxine in rats and mice revealed no evidence of carcinogenesis. Venlafaxine was not mutagenic in a wide range of in vitro and in vivo tests.

Animal studies regarding reproductive toxicity have found in rats a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation. The cause of these deaths is unknown. These effects occurred at 30mg/kg/day, 4 times the human daily dose of 375mg of venlafaxine (on an mg/kg basis). The no-effect dose for these findings was 1.3 times the human dose. The potential risk for humans is unknown.

Reduced fertility was observed in a study in which both male and female rats were exposed to ODV.

This exposure was approximately 1 to 2 times that of a human venlafaxine dose of 375mg/day. The human relevance of this finding is unknown.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Tablet Core:
Lactose monohydrate
Microcrystalline cellulose
Croscarmellose sodium
Povidone K30
Magnesium stearate

Tablet Coating:
Opadry 03B23319 Orange containing;
Hypromellose 6 cP
Titanium dioxide (E171)
Macrogol / PEG 400
Sunset yellow FCF lake (E110)

6.2 Incompatibilities
Not applicable.

6.3  Shelf life
48 months

6.4 Special precautions for storage
No special precautions for storage

6.5 Nature and contents of container
Al/PVC Blister
HDPE Container with LDPE screw Cap
14, 28, 30, 42, 56 tablets
* Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling
No special requirements

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Venlafaxine Tablets USP 25mg Taj Pharma

Package leaflet: Information for the patient

a) Venlafaxine Tablets USP 25mg Taj Pharma
b) Venlafaxine Tablets USP 37.5mg Taj Pharma
c) Venlafaxine Tablets USP 50mg Taj Pharma
d) Venlafaxine Tablets USP 75mg Taj Pharma
e) Venlafaxine Tablets USP 100mg Taj Pharma

IMPORTANT THINGS YOU SHOULD KNOW ABOUT Venlafaxine
Please read all of this leaflet before you start to take your medicine as it contains important information about Venlafaxine.
Venlafaxine is used to treat depression and social anxiety disorder (also known as social phobia).
Venlafaxine is not for use in children and adolescents – see in section 2 ‘Children and adolescents’.
If you have any concerns about how you feel, or about this medication, it is important that you talk to your doctor – even if you feel anxious or worried about doing so.You may find it helpful to tell a friend or relative that you are depressed or suffering from an anxiety disorder, and that you have been prescribed this medication; it might be useful to show them this leaflet.
Venlafaxine may not start to work immediately. Some people taking antidepressants may feel worse before feeling better. Your doctor may ask to see you again in a couple of weeks after you start treatment and then regularly until you start to feel well again. Tell your doctor if you do not start to feel better.
Some people who are depressed may think of harming or killing themselves. If this happens you should see your doctor or go to a hospital straight away – see in section 2 ‘Thoughts of suicide and worsening of your depression or anxiety disorder’.
If you take too many tablets it is important to seek immediate medical attention, even if you feel well, because of the risk of serious side effects.
Do not stop taking Venlafaxine or change your dose without the advice of your doctor even if you feel better. If you stop taking Venlafaxine abruptly you may get withdrawal reactions – see in section 3 ‘If you stop taking Venlafaxine’.
If you have heart problems such as fast or irregular heart rate or high blood pressure you should talk to your doctor before taking Venlafaxine – see in section 2 ‘Before you take Venlafaxine’.
Taking certain other medicines with Venlafaxine may cause problems. You should tell your doctor if you are taking any other medicines – see in section 2 ‘What you need to know before you take Venlafaxine’.
See your doctor without delay if you feel restless and feel like you can’t keep still, feel ‘high’ or very over-excited, have jerky muscle movements which you can’t control. See section 4 ‘Possible side effects’ for other important information.
If you are pregnant, or intend to become pregnant, or breast-feeding, you should talk to your doctor – see in section 2 ‘Pregnancy and breast-feeding’.
More information on all of these points is provided in the rest of this leaflet.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
 – If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).

What is in this leaflet
1. What Venlafaxine is and what it is used for
2. What you need to know before you take Venlafaxine
3. How to take Venlafaxine
4. Possible side effects
5. How to store Venlafaxine
6. Contents of the pack and other information

1. WHAT VENLAFAXINE IS AND WHAT IT IS USED FOR
The name of your medicine is Venlafaxine 37.5 mg Tablets or Venlafaxine 75 mg Tablets (referred to as Venlafaxine throughout this leaflet).

Venlafaxine contains the active substance venlafaxine.

Venlafaxine is an antidepressant that belongs to a group of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs). This group of medicines is used to treat depression and other conditions such as anxiety. It is thought that people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the brain. It is not fully understood how antidepressants work, but they may help by increasing the levels of serotonin and noradrenaline in the brain.

Venlafaxine is a treatment for adults with depression. Treating depression properly is important to help you get better. If it is not treated, your condition may not go away and may become more serious and more difficult to treat.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE VENLAFAXINE
Do not take Venlafaxine

  • If you are allergic to venlafaxine or any of the other ingredients of Venlafaxine (section 6 contains a full list).
  • If you are also taking, or have taken within the last 14 days, any medicines known as irreversible monoamine oxidase inhibitors (MAOIs), used to treat depression or Parkinson’s disease. Taking an irreversible MAOI together with Venlafaxine, can cause serious or even life-threatening side effects. Also, you must wait at least 7 days after you stop taking Venlafaxine before you take any MAOI (see also the section entitled “Other medicines and Venlafaxine” and the information in that section about “Serotonin syndrome”).

Warnings and precautions
If any of the following apply to you, please tell your doctor before taking Venlafaxine:

  • If you use other medicines that, if taken concomitantly with Venlafaxine, could increase the risk of developing serotonin syndrome (see the section “Other medicines and Venlafaxine”).
  • If you have eye problems, such as certain kinds of glaucoma (increased pressure in the eye).
  • If you have a history of high blood pressure.
  • If you have a history of heart problems.
  • If you have been told you have an abnormal heart rhythm.
  • If you have a history of fits (seizures).
  • If you have a history of low sodium levels in your blood (hyponatraemia).
  • If you have a tendency to develop bruises or a tendency to bleed easily (history of bleeding disorders), or if you are taking other medicines that may increase the risk of bleeding e.g., warfarin (use to prevent blood clots).
  • If your cholesterol levels get higher.
  • If you have a history of, or if someone in your family has had, mania or bipolar disorder (feeling overexcited or euphoric).
  • If you have a history of aggressive behaviour. Venlafaxine may cause a sensation of restlessness or an inability to sit or stand still during the first few weeks of treatment. You should tell your doctor if this happens to you.

Thoughts of suicide and worsening of your depression or anxiety
If you are depressed and/or anxious, you can sometimes have thoughts of harming or killing yourself. These may be increased when you first start taking antidepressants, since these medicines all take time to work, usually about two weeks, but sometimes longer.

You may be more likely to think like this:

  • If you have previously had thoughts about killing yourself or harming yourself.
  • If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in young adults (less than 25 years old) with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that you are depressed or anxious, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Dry mouth
Dry mouth is reported in 10% of patients treated with venlafaxine. This may increase the risk of tooth decay (caries). Therefore, you should take special care in your dental hygiene.

Diabetes
Your blood glucose levels may be altered due to Venlafaxine. Therefore, the dosage of your diabetes medicines may need to be adjusted.

Children and adolescents
Venlafaxine should normally not be used for children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side effects, such as suicide attempt, suicidal thoughts and hostility (predominantly aggression, oppositional behaviour and anger) when they take this class of medicines. Despite this, your doctor may prescribe Venlafaxine for patients under 18 because he/she decides that this is in their best interests. If your doctor has prescribed Venlafaxine for a patient under 18, and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen when patients under 18 are taking Venlafaxine. Also, the long-term safety effects concerning growth, maturation and cognitive and behavioural development of Venlafaxine in this age group has not yet been demonstrated.

Other medicines and Venlafaxine
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Do not start or stop taking any medicines, including those bought without a prescription, natural and herbal remedies, before checking with your doctor or pharmacist.

Your doctor should decide whether you can take Venlafaxine with other medicines, such as:

  • Monoamine oxidase inhibitors which are used to treat depression or Parkinson’s disease must not be taken with Venlafaxine.Tell your doctor if you have taken these medicines within the last 14 days. (MAOIs: see the section “What you need to know before you take Venlafaxine”).
  • Products associated with serotonin syndrome:
    Serotonin syndrome:
    A potentially life-threatening condition or Neuroleptic Malignant Syndrome (NMS)-like reactions (see the section “Possible Side Effects”), may occur with venlafaxine treatment, particularly when taken with other medicines.
    Examples of these medicines include:
  • Triptans (used for migraine)
  • Other medicines to treat depression, for instance SNRI, SSRIs, tricyclics, or medicines containing lithium
  • Medicines containing amphetamines (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
  • Medicines containing linezolid, an antibiotic (used to treat infections)
  • Medicines containing moclobemide, a reversible MAOI (used to treat depression)
  • Medicines containing sibutramine (used for weight loss)
  • Medicines containing tramadol (a pain-killer), fentanyl, tapentadol, pethidine, or pentazocine (used to treat severe pain)
  • Medicines containing dextromethorphan (used to treat coughing)
  • Medicines containing methadone (used to treat opioid drug addiction or severe pain)
  • Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
  • Products containing St. John’s Wort (also called Hypericum perforatum, a natural or herbal remedy used to treat mild depression)
  • Products containing tryptophan (used for problems such as sleep and depression)
  • Antipsychotics (used to treat a disease with symptoms such as hearing, seeing or sensing things which are not there, mistaken beliefs, unusual suspiciousness, unclear reasoning and becoming withdrawn)

Signs and symptoms of serotonin syndrome may include a combination of the following: restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, fast heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Tell your doctor immediately, or go to the casualty department at your nearest hospital if you think serotonin syndrome is happening to you.

You must tell your doctor if you are taking medicines that can affect your heart rhythm.

Examples of these medicines include:

  • Antiarrhythmics such as quinidine, amiodarone, sotalol or dofetilide (used to treat abnormal heart rhythm)
  • Antipsychotics such as thioridazine (See also Serotonin syndrome above)
  • Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections)
  • Antihistamines (used to treat allergy)

The following medicines may also interact with Venlafaxine and should be used with caution. It is especially important to mention to your doctor or pharmacist if you are taking medicines containing:

  • Atazanavir, clarithromycin, indinavir, itraconazole, voriconazole, posaconazole, ketoconazole, nelfinavir, ritonavir, saquinavir and telithromycin
  • Haloperidol or risperidone (to treat psychiatric conditions)
  • Metoprolol (a beta blocker to treat high blood pressure and heart problems)
  • Oral contraceptives

Taking Venlafaxine with food and drink
Venlafaxine should be taken with food (see section 3 “How to take Venlafaxine”).
You should avoid alcohol while you are taking Venlafaxine.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should use Venlafaxine only after discussing the potential benefits and the potential risks to your unborn child with your doctor.

Make sure your midwife and/or doctor know you are on Venlafaxine. When taken during pregnancy, similar drugs (SSRIs) may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born. If this happens to your baby you should contact your midwife and/or doctor immediately.

If you are taking Venlafaxine during pregnancy, other symptoms your baby might have when it is born is not feeding properly, in addition to having trouble breathing. If your baby has these symptoms when it is born and you are concerned, contact your doctor and/or midwife who will be able to advise you. Venlafaxine passes into breast milk. There is a risk of an effect on the baby. Therefore, you should discuss the matter with your doctor, and he/she will decide whether you should stop breast-feeding or stop the therapy with Venlafaxine.

Driving and operating machinery
Venlafaxine can cause impaired judgement, thinking, and movement and coordination as well as problems with vision. If you are affected by any of these you should not drive, operate machinery or take part in any activities where such effects could put you or others at risk.

Important information about some of the ingredients of Venlafaxine
This product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. HOW TO TAKE VENLAFAXINE
Always take Venlafaxine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The usual recommended starting dose is 75 mg per day in divided doses. The dose can be raised by your doctor gradually and, if needed, even up to a maximum dose of 375 mg daily for depression.

Take Venlafaxine at approximately the same time each day, in the morning and in the evening.

Venlafaxine should be taken with food.

If you have liver or kidney problems, talk to your doctor, since your dose of Venlafaxine may need to be different.

The 37.5mg tablets and 75mg tablets come in special “calendar” packs which help you remember to take your tablets when you should.

The following instructions will help you:

1. Remove a card.
2. Go to the correct day of the week.
3. Take the tablet from the card or part of the card, marked “AM”, in the morning.
4. Your next tablet should be taken in the evening from the card or part of the card, marked “PM”.
5. Continue taking a tablet every morning and evening.
6. When you have finished a card, move on to the next one.

Do not stop taking Venlafaxine without talking to your doctor (see the section “If you stop taking Venlafaxine”).

If you take more Venlafaxine than you should
Call your doctor or pharmacist immediately if you take more than the amount of Venlafaxine prescribed by your doctor.

The symptoms of a possible overdose may include a rapid heart beat, changes in level of alertness (ranging from sleepiness to coma), blurred vision, seizures or fits, and vomiting.

If you forget to take Venlafaxine
If you miss a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take only a single dose as usual. Do not take more than the daily amount of Venlafaxine that has been prescribed for you in one day.

If you stop taking Venlafaxine
Do not stop taking your treatment or reduce the dose without the advice of your doctor even if you feel better. If your doctor thinks that you no longer need Venlafaxine, he/she may ask you to reduce your dose slowly before stopping treatment altogether. Side effects are known to occur when people stop using Venlafaxine, especially when Venlafaxine is stopped suddenly or the dose is reduced too quickly. Some patients may experience symptoms such as tiredness, dizziness, light-headedness, headache, sleeplessness, nightmares, dry mouth, loss of appetite, nausea, diarrhoea, nervousness, agitation, confusion, ringing in the ears, tingling or rarely electric shock sensations, weakness, sweating, seizures, or flu-like symptoms.

Your doctor will advise you on how you should gradually discontinue Venlafaxine treatment. If you experience any of these or other symptoms that are troublesome, ask your doctor for further advice. If you have any further questions on the use of this product, ask your doctor or pharmacist.

 4. POSSIBLE SIDE EFFECTS
Like all medicines, Venlafaxine can cause side effects, although not everybody gets them.

If any of the following happen, do not take more Venlafaxine. Tell your doctor immediately, or go to the casualty department at your nearest hospital:

Uncommon (may affect up to 1 in 100 people)

  • Swelling of the face, mouth, tongue, throat, hands, or feet and/or a raised itchy rash (hives), trouble swallowing or breathing

Rare (may affect up to 1 in 1,000 people)

  • Chest tightness, wheezing, trouble swallowing or breathing
  • Severe skin rash, itching, or hives (elevated patches of red or pale skin that often itch)
  • Signs and symptoms of serotonin syndrome which may include restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting. In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, fast heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).
  • Signs of infection, such as high temperature, chills, shivering, headaches, sweating, flu-like symptoms. This may be the result of a blood disorder which leads to an increased risk of infection.
  • Severe rash, which may lead to severe blistering and peeling of the skin.
  • Unexplained muscle pain, tenderness or weakness. This may be a sign of rhabdomyolysis.

Frequency not known (cannot be estimated from the available data)

  • suicidal ideation and suicidal behaviours; cases of suicidal ideation and suicidal behaviours have been reported during venlafaxine therapy or early after treatment discontinuation (see section 2, What you need to know before you take Venlafaxine)

Other side effects that you should tell your doctor about include (The frequency of these side effects are included in the list “Other side effects that may occur” below):

  • Coughing, wheezing, shortness of breath which may be accompanied by a high temperature
  • Black (tarry) stools or blood in stools
  • Itchiness, yellow skin or eyes, or dark urine, which may be symptoms of inflammation of the liver (hepatitis)
  • Heart problems, such as fast or irregular heart rate, increased blood pressure
  • Eye problems, such as blurred vision, dilated pupils
  • Nerve problems, such as dizziness, pins and needles, movement disorder (muscle spasms or stiffness), seizures or fits
  • Psychiatric problems, such as hyperactivity and euphoria (feeling unusually overexcited)
  • Withdrawal effects (see the section “How to take Venlafaxine, if you stop taking Venlafaxine”)
  • Prolonged bleeding – if you cut or injure yourself, it may take slightly longer than usual for bleeding to stop.

Other side effects that may occur

Very common: may affect more than 1 in 10 people

  • dizziness; headache, drowsiness
  • insomnia
  • nausea; dry mouth; constipation
  • sweating (including night sweats)

Common: may affect up to 1 in 10 people

  • appetite decreased
  • confusion; feeling separated (or detached) from yourself; lack of orgasm; decreased libido; agitation; nervousness; abnormal dreams
  • tremor; a sensation of restlessness or an inability to sit or stand still; pins and needles; altered taste sensation; increased muscle tonus
  • visual disturbance including blurred vision; dilated pupils; inability of the eye to automatically change focus from distant to near objects
  • ringing in the ears (tinnitus)
  • fast heartbeat; palpitations
  • increase in blood pressure; flushing
  • shortness of breath; yawning
  • vomiting; diarrhoea
  • mild rash; itching
  • increased frequency in urination; inability to pass urine; difficulties passing urine
  • menstrual irregularities such as increased bleeding or increased irregular bleeding; abnormal ejaculation/orgasm (males); erectile dysfunction (impotence)
  • weakness (asthenia); fatigue; chills
  • weight gain; weight loss
  • increased cholesterol

Uncommon: may affect up to 1 in 100 people

  • over activity, racing thoughts and decreased need for sleep (mania)
  • hallucinations; feeling separated (or detached) from reality; abnormal orgasm ; lack of feeling or emotion; feeling over-excited; grinding of the teeth
  • fainting; involuntary movements of the muscles; impaired coordination and balance;
  • feeling dizzy (particularly when standing up too quickly); decrease in blood pressure
  • vomiting blood, black tarry stools (faeces) or blood in stools; which can be a sign of internal bleeding
  • sensitivity to sunlight; bruising; abnormal hair loss
  • inability to control urination
  • stiffness, spasms and involuntary movements of the muscles
  • slight changes in blood levels of liver enzymes

Rare: may affect up to 1 in 1,000 people

  • seizures or fits
  • coughing, wheezing and shortness of breath which may be accompanied by a high temperature
  • disorientation and confusion often accompanied by hallucination (delirium)
  • excessive water intake (known as SIADH)
  • decrease in blood sodium levels
  • severe eye pain and decreased or blurred vision
  • abnormal, rapid or irregular heartbeat, which could lead to fainting
  • severe abdominal or back pains (which could indicate a serious problem in the gut, liver or pancreas)
  • itchiness, yellow skin or eyes, dark urine, or flu-like symptoms, which are symptoms of inflammation of the liver (hepatitis)

Very rare (may affect up to 1 in 10,000 people)

  • prolonged bleeding, which may be a sign of reduced number of platelets in your blood, leading to an increased risk of bruising or bleeding
  • abnormal breast milk production
  • unexpected bleeding, e.g. bleeding gums, blood in the urine or in vomit, or the appearance of unexpected bruises or broken blood vessels (broken veins)

Frequency not known (cannot be estimated from the available data)

  • aggression
  • vertigo (sensation of dizziness or spinning)

Venlafaxine sometimes causes unwanted effects that you may not be aware of, such as increases in blood pressure or abnormal heart beat; slight changes in blood levels or liver enzymes, sodium or cholesterol. More rarely, Venlafaxine may reduce the function of platelets in your blood, leading to an increased risk of bruising or bleeding. Therefore, your doctor may wish to do blood tests occasionally, particularly if you have been taking Venlafaxine for a long time.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5.HOW TO STORE VENLAFAXINE
Keep out of the reach and sight of children.
Do not use Venlafaxine after the expiry date, which is stated on the packaging.
This medicinal product does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. CONTENTS OF THE PACK AND FURTHER INFORMATION

What Venlafaxine contain
The active substance is venlafaxine.
a) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 25mg of venlafaxine
Colour:Sunset Yellow 

b) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 37.5mg of venlafaxine
Colour:Sunset Yellow

c) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 50mg of venlafaxine
Colour:Sunset Yellow

d) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 75mg of venlafaxine
Colour:Sunset Yellow

e) Each tablet contains
Venlafaxine hydrochloride USP
equivalent to 100mg of venlafaxine
Colour:Sunset Yellow

Other ingredients in these tablets are: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate, ferric oxide yellow, ferric oxide red  and ferric oxide black.

What Venlafaxine look like and contents of the pack
Venlafaxine tablets are mottled-beige, round tablets.
Venlafaxine tablets come in calendar packs of 28 and 56 tablets.
Not all pack sizes may be marketed.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

 

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.