1. Name of the medicinal product

Duloxetine Delayed-Release Capsules USP 20mg Taj Pharma
Duloxetine Delayed-Release Capsules USP 30mg Taj Pharma
Duloxetine Delayed-Release Capsules USP 40mg Taj Pharma
Duloxetine Delayed-Release Capsules USP 60mg Taj Pharma

  1. Qualitative and quantitative composition

a) Duloxetine Delayed-Release Capsules USP 20mg Taj Pharma
Each delayed-release capsule contains:
Duloxetine Hydrochloride USP 22.4mg
Equivalent to 20mg
Excipients: Q.S.

b) Duloxetine Delayed-Release Capsules USP 30mg Taj Pharma
Each delayed-release capsule contains:
Duloxetine Hydrochloride USP 33.7mg
Equivalent to 30mg
Excipients: Q.S.

c) Duloxetine Delayed-Release Capsules USP 40mg Taj Pharma
Each delayed-release capsule contains:
Duloxetine Hydrochloride USP 44.9mg
Equivalent to 40mg
Excipients: Q.S.

d) Duloxetine Delayed-Release Capsules USP 60mg Taj Pharma
Each delayed-release capsule contains:
Duloxetine Hydrochloride USP 67.3mg
Equivalent to 60mg
Excipients: Q.S.

Excipient with known effect:

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Hard gastro-resistant or Delayed-Release capsules.

  1. Clinical particulars
  • Therapeutic indications

Treatment of major depressive disorder.
Treatment of diabetic peripheral neuropathic pain.
Treatment of generalised anxiety disorder.
Duloxetine Taj Pharma capsule is indicated in adults.

For further information see section 5.1.

  • Posology and method of administration

Posology

Major depressive disorder

The starting and recommended maintenance dose is 60 mg once daily with or without food. Dosages above 60 mg once daily, up to a maximum dose of 120 mg per day have been evaluated from a safety perspective in clinical trials. However, there is no clinical evidence suggesting that patients not responding to the initial recommended dose may benefit from dose up-titrations.

Therapeutic response is usually seen after 2-4 weeks of treatment.

After consolidation of the antidepressive response, it is recommended to continue treatment for several months, in order to avoid relapse. In patients responding to Duloxetine Taj Pharma, and with a history of repeated episodes of major depression, further long-term treatment at a dose of 60 to 120 mg/day could be considered.

Generalised anxiety disorder

The recommended starting dose in patients with generalised anxiety disorder is 30 mg once daily with or without food. In patients with insufficient response the dose should be increased to 60 mg, which is the usual maintenance dose in most patients.

In patients with co-morbid major depressive disorder, the starting and maintenance dose is 60 mg once daily (please see also dosing recommendation above).

Doses up to 120 mg per day have been shown to be efficacious and have been evaluated from a safety perspective in clinical trials. In patients with insufficient response to 60 mg, escalation up to 90 mg or 120 mg may therefore be considered. Dose escalation should be based upon clinical response and tolerability.

After consolidation of the response, it is recommended to continue treatment for several months, in order to avoid relapse.

Diabetic peripheral neuropathic pain

The starting and recommended maintenance dose is 60 mg daily with or without food. Dosages above 60 mg once daily, up to a maximum dose of 120 mg per day administered in evenly divided doses, have been evaluated from a safety perspective in clinical trials. The plasma concentration of Duloxetine Taj Pharma displays large inter-individual variability (see section 5.2). Hence, some patients that respond insufficiently to 60 mg may benefit from a higher dose.

Response to treatment should be evaluated after 2 months. In patients with inadequate initial response, additional response after this time is unlikely.

The therapeutic benefit should be reassessed regularly (at least every three months) (see section 5.1).

Special populations

Elderly

No dosage adjustment is recommended for elderly patients solely on the basis of age. However, as with any medicine, caution should be exercised when treating the elderly, especially with Duloxetine Taj Pharma capsules 120 mg per day for major depressive disorder, for which data are limited (see sections 4.4 and 5.2).

Hepatic impairment

Duloxetine Taj Pharma capsules must not be used in patients with liver disease resulting in hepatic impairment (see sections 4.3 and 5.2).

Renal impairment

No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/min). Duloxetine Taj Pharma capsules must not be used in patients with severe renal impairment (creatinine clearance <30 ml/min; see section 4.3).

Paediatric population

Duloxetine Taj Pharma should not be used in children and adolescents under the age of 18 years for the treatment of major depressive disorder because of safety and efficacy concerns (see sections 4.4, 4.8 and 5.1).

The safety and efficacy of Duloxetine Taj Pharma for the treatment of generalised anxiety disorder in paediatric patients aged 7-17 years have not been established. Current available data are described in sections 4.8, 5.1 and 5.2.

The safety and efficacy of Duloxetine Taj Pharma for the treatment of diabetic peripheral neuropathic pain has not been studied. No data are available.

Discontinuation of treatment

Abrupt discontinuation should be avoided. When stopping treatment with Duloxetine Taj Pharma capsules 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.

Method of administration

For oral use. Do not crush or chew. Swallow whole.

  • Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Concomitant use of Duloxetine Taj Pharma capsules with nonselective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated (see section 4.5).

Liver disease resulting in hepatic impairment (see section 5.2).

Duloxetine Taj Pharma capsules should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (i.e. potent CYP1A2 inhibitors) since the combination results in elevated plasma concentrations of Duloxetine Taj Pharma (see section 4.5).

Severe renal impairment (creatinine clearance <30 ml/min) (see section 4.4).

The initiation of treatment with Duloxetine Taj Pharma capsule is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).

  • Special warnings and precautions for use

Mania and seizures

Duloxetine Taj Pharma capsules should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/or seizures.

Mydriasis

Mydriasis has been reported in association with Duloxetine Taj Pharma; therefore, caution should be used when prescribing Duloxetine Taj Pharma to patients with increased intraocular pressure, or those at risk of acute narrow-angle glaucoma.

Blood pressure and heart rate

Duloxetine Taj Pharma has been associated with an increase in blood pressure and clinically significant hypertension in some patients. This may be due to the noradrenergic effect of Duloxetine Taj Pharma. Cases of hypertensive crisis have been reported with Duloxetine Taj Pharma, especially in patients with pre-existing hypertension. Therefore, in patients with known hypertension and/or other cardiac disease, blood pressure monitoring is recommended, especially during the first month of treatment. Duloxetine Taj Pharma should be used with caution in patients whose conditions could be compromised by an increased heart rate or by an increase in blood pressure. Caution should also be exercised when Duloxetine Taj Pharma is used with medicinal products that may impair its metabolism (see section 4.5). For patients who experience a sustained increase in blood pressure while receiving Duloxetine Taj Pharma either dose reduction or gradual discontinuation should be considered (see section 4.8). In patients with uncontrolled hypertension Duloxetine Taj Pharma should not be initiated (see section 4.3).

Renal impairment

Increased plasma concentrations of Duloxetine Taj Pharma occur in patients with severe renal impairment on haemodialysis (creatinine clearance <30 ml/min). For patients with severe renal impairment, see section 4.3. See section 4.2 for information on patients with mild or moderate renal dysfunction.

Serotonin syndrome

As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with Duloxetine Taj Pharma treatment, particularly with concomitant use of other serotonergic agents (including SSRIs, SNRIs tricyclic antidepressants or triptans), with agents that impair metabolism of serotonin such as MAOIs, or with antipsychotics or other dopamine antagonists 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).

If concomitant treatment with Duloxetine Taj Pharma and other serotonergic agents 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.

St John’s wort

Adverse reactions may be more common during concomitant use of Duloxetine Taj Pharma capsules and herbal preparations containing St John’s wort (Hypericum perforatum).

Suicide

Major Depressive Disorder and Generalised Anxiety Disorder: 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 Duloxetine Taj Pharma capsule 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 thoughts prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicidal behaviour, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant medicinal products in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Cases of suicidal thoughts and suicidal behaviours have been reported during Duloxetine Taj Pharma therapy or early after treatment discontinuation (see section 4.8).

Close supervision of patients and in particular those at high risk should accompany medicinal product 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.

Diabetic Peripheral Neuropathic Pain: As with other medicinal products with similar pharmacological action (antidepressants), isolated cases of suicidal ideation and suicidal behaviours have been reported during Duloxetine Taj Pharma therapy or early after treatment discontinuation. Concerning risk factors for suicidality in depression, see above. Physicians should encourage patients to report any distressing thoughts or feelings at any time.

Use in children and adolescents under 18 years of age

Duloxetine Taj Pharma capsules should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempts 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 (see section 5.1). In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking (see section 4.8).

Haemorrhage

There have been reports of bleeding abnormalities, such as ecchymoses, purpura and gastrointestinal haemorrhage with selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs), including Duloxetine Taj Pharma. Caution is advised in patients taking anticoagulants and/or medicinal products known to affect platelet function (e.g. NSAIDs or acetylsalicylic acid (ASA)), and in patients with known bleeding tendencies.

Hyponatraemia

Hyponatraemia has been reported when administering Duloxetine Taj Pharma capsules, including cases with serum sodium lower than 110 mmol/l. Hyponatraemia may be due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH). The majority of cases of hyponatraemia were reported in the elderly, especially when coupled with a recent history of, or condition pre-disposing to, altered fluid balance. Caution is required in patients at increased risk for hyponatraemia, such as elderly, cirrhotic, or dehydrated patients or patients treated with diuretics.

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 abrupt treatment discontinuation occurred in approximately 45% of patients treated with Duloxetine Taj Pharma capsules and 23% of patients taking placebo. The risk of withdrawal symptoms seen with SSRI’s and SNRI’s may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. The most commonly reported reactions are listed in section 4.8. 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 Duloxetine Taj Pharma should be gradually tapered when discontinuing treatment over a period of no less than 2 weeks, according to the patient’s needs (see section 4.2).

Elderly

Data on the use of Duloxetine Taj Pharma capsule 120mg in elderly patients with major depressive disorder and generalized anxiety disorder are limited. Therefore, caution should be exercised when treating the elderly with the maximum dosage (see sections 4.2 and 5.2).

Akathisia/psychomotor restlessness

The use of Duloxetine Taj Pharma 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.

Medicinal products containing Duloxetine Taj Pharma

Duloxetine Taj Pharma is used under different trademarks in several indications (treatment of diabetic neuropathic pain, major depressive disorder, generalised anxiety disorder and stress urinary incontinence). The use of more than one of these products concomitantly should be avoided.

Hepatitis/increased liver enzymes

Cases of liver injury, including severe elevations of liver enzymes (>10 times upper limit of normal), hepatitis and jaundice have been reported with Duloxetine Taj Pharma (see section 4.8). Most of them occurred during the first months of treatment. The pattern of liver damage was predominantly hepatocellular. Duloxetine Taj Pharma should be used with caution in patients treated with other medicinal products associated with hepatic injury.

Sucrose

Duloxetine Taj Pharma capsules gastro-resistant capsules, hard contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs)/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 SSRIs/SNRI.

  • Interaction with other medicinal products and other forms of interaction

Monoamine oxidase inhibitors (MAOIs): Due to the risk of serotonin syndrome, Duloxetine Taj Pharma should not be used in combination with nonselective irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of Duloxetine Taj Pharma, at least 5 days should be allowed after stopping Duloxetine Taj Pharma capsules before starting an MAOI (see section 4.3).

The concomitant use of Duloxetine Taj Pharma with selective, reversible MAOIs, like moclobemide, is not recommended (see section 4.4). The antibiotic linezolid is a reversible non-selective MAOI and should not be given to patients treated with Duloxetine Taj Pharma (see section 4.4).

Inhibitors of CYP1A2: Because CYP1A2 is involved in Duloxetine Taj Pharma metabolism, concomitant use of Duloxetine Taj Pharma with potent inhibitors of CYP1A2 is likely to result in higher concentrations of Duloxetine Taj Pharma. Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of Duloxetine Taj Pharma by about 77% and increased AUCo-t 6-fold. Therefore Duloxetine Taj Pharma capsules should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3).

CNS medicinal products: The risk of using Duloxetine Taj Pharma in combination with other CNS-active medicinal products has not been systematically evaluated, except in the cases described in this section. Consequently, caution is advised when Duloxetine Taj Pharma capsule is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).

Serotoninergic agents: In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if Duloxetine Taj Pharma capsules is used concomitantly with serotonergic agents like SSRIs, SNRIs, tricyclics like clomipramine or amitriptyline, MAOIs like moclobemide or linezolid, St John’s wort (Hypericum perforatum) or triptans, tramadol, pethidine and tryptophan (see section 4.4).

Effect of Duloxetine Taj Pharma on other medicinal products

Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with Duloxetine Taj Pharma (60 mg twice daily).

Medicinal products metabolised by CYP2D6: Duloxetine Taj Pharma is a moderate inhibitor of CYP2D6. When Duloxetine Taj Pharma was administered at a dose of 60 mg twice daily with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. The co-administration of Duloxetine Taj Pharma (40 mg twice daily) increases steady state AUC of tolterodine (2 mg twice daily) by 71 %, but does not affect the pharmacokinetics of its active 5-hydroxyl metabolite and no dosage adjustment is recommended. Caution is advised if Duloxetine Taj Pharma capsule is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).

Oral contraceptives and other steroidal agents: Results of in vitro studies demonstrate that Duloxetine Taj Pharma does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not been performed.

Anticoagulants and antiplatelet agents: Caution should be exercised when Duloxetine Taj Pharma is combined with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction. Furthermore, increases in INR values have been reported when Duloxetine Taj Pharma was co-administered to patients treated with warfarin. However, concomitant administration of Duloxetine Taj Pharma with warfarin under steady state conditions, in healthy volunteers, as part of a clinical pharmacology study, did not result in a clinically significant change in INR from baseline or in the pharmacokinetics of R- or S-warfarin.

Effects of other medicinal products on Duloxetine Taj Pharma

Antacids and H2 antagonists: Co-administration of Duloxetine Taj Pharma with aluminium- and magnesium-containing antacids or Duloxetine Taj Pharma with famotidine had no significant effect on the rate or extent of Duloxetine Taj Pharma absorption after administration of a 40 mg oral dose.

Inducers of CYP1A2: Population pharmacokinetic analyses have shown that smokers have almost 50% lower plasma concentrations of Duloxetine Taj Pharma compared with non-smokers.

  • Fertility, pregnancy and lactation

Fertility

Duloxetine Taj Pharma had no effect on male fertility, and effects in females were only evident at doses that caused maternal toxicity.

Pregnancy

There are no adequate data on the use of Duloxetine Taj Pharma in pregnant women. Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of Duloxetine Taj Pharma lower than the maximum clinical exposure (see section 5.3).

The potential risk for humans is unknown.

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 the association of PPHN to SNRI treatment, this potential risk cannot be ruled out with Duloxetine Taj Pharma taking into account the related mechanism of action (inhibition of the re-uptake of serotonin).

As with other serotonergic medicinal products, discontinuation symptoms may occur in the neonate after maternal Duloxetine Taj Pharma use near term. Discontinuation symptoms seen with Duloxetine Taj Pharma may include hypotonia, tremor, jitteriness, feeding difficulty, respiratory distress and seizures. The majority of cases have occurred either at birth or within a few days of birth.

Duloxetine Taj Pharma capsules should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus. Women should be advised to notify their physician if they become pregnant, or intend to become pregnant, during therapy.

Breast feeding

Duloxetine Taj Pharma is very weakly excreted into human milk based on a study of 6 lactating patients, who did not breast feed their children. The estimated daily infant dose on a mg/kg basis is approximately 0.14% of the maternal dose (see section 5.2). As the safety of Duloxetine Taj Pharma in infants is not known, the use of Duloxetine Taj Pharma capsules while breast-feeding is not recommended.

  • Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Duloxetine Taj Pharma capsules may be associated with sedation and dizziness. Patients should be instructed that if they experience sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.

  • Undesirable effects
  1. Summary of the safety profile

The most commonly reported adverse reactions in patients treated with Duloxetine Taj Pharma capsules were nausea, headache, dry mouth, somnolence, and dizziness. However, the majority of common adverse reactions were mild to moderate, they usually started early in therapy, and most tended to subside even as therapy was continued.

  1. Tabulated summary of adverse reactions

Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials.

Table 1: Adverse reactions

Frequency estimate: 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), very rare (<1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Very commonCommonUncommonRareVery Rare
Infections and infestations
Laryngitis
Immune system disorders
Anaphylactic reaction

Hypersensitivity disorder

Endocrine disorders
Hypothyroidism
Metabolism and nutrition disorders
Decreased AppetiteHyperglycaemia (reported especially in diabetic patients)Dehydration

Hyponatraemia

SIADH 6

Psychiatric disorders
Insomnia

Agitation

Libido decreased

Anxiety

Orgasm abnormal

Abnormal dreams

Suicidal ideation 5,7

Sleep disorder

Bruxism

Disorientation

Apathy

Suicidal behaviour 5,7

Mania

Hallucinations

Aggression and anger 4

Nervous system disorders
Headache

Somnolence

Dizziness

Lethargy

Tremor

Paraesthesia

Myoclonus

Akathisia 7

Nervousness

Disturbance in attention

Dysgeusia

Dyskinesia

Restless legs syndrome

Poor quality sleep

Serotonin syndrome 6

Convulsion 1

Psychomotor restlessness 6

Extra-pyramidal symptoms 6

Eye disorders
Blurred visionMydriasis

Visual impairment

Glaucoma
Ear and labyrinth disorders
Tinnitus 1Vertigo

Ear pain

Cardiac disorders
PalpitationsTachycardia

Supra-ventricular arrhythmia, mainly atrial fibrillation

Vascular disorders
Blood pressure increase 3

Flushing

Syncope 2

Hypertension 3,7

Orthostatic hypotension 2

Peripheral coldness

Hypertensive crisis 3,6
Respiratory, thoracic and mediastinal disorders
YawningThroat tightness

Epistaxis

Interstitial lung disease10

Eosinophilic pneumonia6

Gastrointestinal disorders
Nausea

Dry mouth

Constipation Diarrhoea

Abdominal pain

Vomiting

Dyspepsia

Flatulence

Gastrointestinal haemorrhage 7

Gastroenteritis

Eructation

Gastritis

Dysphagia

Stomatitis

Haematochezia

Breath odour

Microscopic colitis 9

Hepato-biliary disorders
Hepatitis 3

Elevated liver enzymes (ALT, AST, alkaline phosphatase)

Acute liver injury

Hepatic failure 6

Jaundice 6

Skin and subcutaneous tissue disorders
Sweating increased

Rash

Night sweats Urticaria

Dermatitis contact

Cold sweat

Photosensitivity reactions

Increased tendency to bruise

Stevens-Johnson Syndrome 6

Angio-neurotic oedema 6

Cutaneous vasculitis
Musculoskeletal and connective tissue disorders
Musculo-skeletal pain

Muscle spasm

Muscle tightness

Muscle twitching

Trismus
Renal and urinary disorders
Dysuria

Pollakiuria

Urinary retention

Urinary hesitation

Nocturia

Polyuria

Urine flow decreased

Urine odour abnormal
Reproductive system and breast disorders
Erectile dysfunction

Ejaculation disorder

Ejaculation delayed

Gynaecological haemorrhage

Menstrual disorder

Sexual dysfunction

Testicular pain

Menopausal symptoms

Galactorrhoea

Hyperprolactinaemia

General disorders and administration site conditions
Falls 8

Fatigue

Chest pain 7

Feeling abnormal

Feeling cold

Thirst

Chills

Malaise

Feeling hot

Gait disturbance

Investigations
Weight decreaseWeight increase

Blood creatine phosphokinase increased

Blood potassium increased

Blood cholesterol increased

1 Cases of convulsion and cases of tinnitus have also been reported after treatment discontinuation.

2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of treatment.

3 See section 4.4.

4 Cases of aggression and anger have been reported particularly early in treatment or after treatment discontinuation.

5 Cases of suicidal ideation and suicidal behaviours have been reported during Duloxetine Taj Pharma therapy or early after treatment discontinuation (see section 4.4).

6 Estimated frequency of post-marketing surveillance reported adverse reactions; not observed in placebo-controlled clinical trials.

7 Not statistically significantly different from placebo.

8 Falls were more common in the elderly (65 years old)

9 Estimated frequency based on all clinical trial data.

10Estimated frequency based on placebo-controlled clinical trials

  1. Description of selected adverse reactions

Discontinuation of Duloxetine Taj Pharma (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia or electric shock-like sensations, particularly in the head), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, agitation or anxiety, nausea and/or vomiting, tremor, headache, myalgia, irritability, diarrhoea, hyperhydrosis and vertigo are the most commonly reported reactions.

Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when Duloxetine Taj Pharma treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

In the 12 week acute phase of three clinical trials of Duloxetine Taj Pharma in patients with diabetic neuropathic pain, small but statistically significant increases in fasting blood glucose were observed in Duloxetine Taj Pharma-treated patients. HbA1c was stable in both Duloxetine Taj Pharma-treated and placebo-treated patients. In the extension phase of these studies, which lasted up to 52 weeks, there was an increase in HbA1c in both the Duloxetine Taj Pharma and routine care groups, but the mean increase was 0.3% greater in the Duloxetine Taj Pharma-treated group. There was also a small increase in fasting blood glucose and in total cholesterol in Duloxetine Taj Pharma-treated patients while those laboratory tests showed a slight decrease in the routine care group.

The heart rate-corrected QT interval in Duloxetine Taj Pharma-treated patients did not differ from that seen in placebo-treated patients. No clinically significant differences were observed for QT, PR, QRS, or QTcB measurements between Duloxetine Taj Pharma-treated and placebo-treated patients.

  1. Paediatric population

A total of 509 paediatric patients aged 7 to 17 years with major depressive disorder and 241 patients aged 7 to 17 years with generalized anxiety disorder were treated with Duloxetine Taj Pharma in clinical trials. In general, the adverse reaction profile of Duloxetine Taj Pharma in children and adolescents was similar to that seen for adults.

A total of 467 paediatric patients initially randomized to Duloxetine Taj Pharma in clinical trials experienced a 0.1 kg mean decrease in weight at 10-weeks compared with a 0.9 kg mean increase in 353 placebo-treated patients. Subsequently, over the four- to six-month extension period, patients on average trended toward recovery to their expected baseline weight percentile based on population data from age- and gender-matched peers.

In studies of up to 9 months an overall mean decrease of 1% in height percentile (decrease of 2% in children (7-11 years) and increase of 0.3% in adolescents (12-17 years)) was observed in Duloxetine Taj Pharma-treated paediatric patients (see section 4.4).

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.

  • Overdose

Cases of overdoses, alone or in combination with other medicinal products, with Duloxetine Taj Pharma doses of 5400 mg were reported. Some fatalities have occurred, primarily with mixed overdoses, but also with Duloxetine Taj Pharma alone at a dose of approximately 1000 mg. Signs and symptoms of overdose (Duloxetine Taj Pharma alone or in combination with other medicinal products) included somnolence, coma, serotonin syndrome, seizures, vomiting and tachycardia.

No specific antidote is known for Duloxetine Taj Pharma but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. A free airway should be established. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption. Duloxetine Taj Pharma has a large volume of distribution and forced diuresis, haemoperfusion, and exchange perfusion are unlikely to be beneficial.

  1. Pharmacological properties
    • Pharmacodynamic properties

Pharmacotherapeutic group: Other antidepressants.

Mechanism of action

Duloxetine Taj Pharma is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors. Duloxetine Taj Pharma dose-dependently increases extracellular levels of serotonin and noradrenaline in various brain areas of animals.

Pharmacodynamic effects

Duloxetine Taj Pharma normalised pain thresholds in several preclinical models of neuropathic and inflammatory pain and attenuated pain behaviour in a model of persistent pain. The pain inhibitory action of Duloxetine Taj Pharma is believed to be a result of potentiation of descending inhibitory pain pathways within the central nervous system.

Clinical efficacy and safety

Major Depressive Disorder: Duloxetine Taj Pharma capsules was studied in a clinical programme involving 3,158 patients (1,285 patient-years of exposure) meeting DSM-IV criteria for major depression. The efficacy of Duloxetine Taj Pharma capsules at the recommended dose of 60 mg once a day was demonstrated in three out of three randomised, double-blind, placebo-controlled, fixed dose acute studies in adult outpatients with major depressive disorder. Overall, Duloxetine Taj Pharma capsule’s efficacy has been demonstrated at daily doses between 60 and 120 mg in a total of five out of seven randomised, double-blind, placebo-controlled, fixed dose acute studies in adult outpatients with major depressive disorder.

Duloxetine Taj Pharma capsules demonstrated statistical superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAM-D) total score (including both the emotional and somatic symptoms of depression). Response and remission rates were also statistically significantly higher with Duloxetine Taj Pharma capsules compared with placebo. Only a small proportion of patients included in pivotal clinical trials had severe depression (baseline HAM-D>25).

In a relapse prevention study, patients responding to 12-weeks of acute treatment with open-label Duloxetine Taj Pharma capsule 60 mg once daily were randomised to either Duloxetine Taj Pharma capsule 60 mg once daily or placebo for a further 6-months. Duloxetine Taj Pharma capsule 60 mg once daily demonstrated a statistically significant superiority compared to placebo (p=0.004) on the primary outcome measure, the prevention of depressive relapse, as measured by time to relapse. The incidence of relapse during the 6-months double-blind follow-up period was 17% and 29% for Duloxetine Taj Pharma and placebo, respectively.

During 52 weeks of placebo-controlled double blind treatment, Duloxetine Taj Pharma-treated patients with recurrent MDD had a significantly longer symptom free period (p<0.001) compared with patients randomised to placebo. All patients had previously responded to Duloxetine Taj Pharma during open-label Duloxetine Taj Pharma treatment (28 to 34 weeks) at a dose of 60 to 120 mg/day. During the 52-week placebo-controlled double blind treatment phase 14.4% of the Duloxetine Taj Pharma-treated patients and 33.1% of the placebo-treated patients experience a return of their depressive symptoms (p<0.001).

The effect of Duloxetine Taj Pharma capsule 60 mg once a day in elderly depressed patients (≥65 years) was specifically examined in a study that showed a statistically significant difference in the reduction of the HAMD17 score for Duloxetine Taj Pharma-treated patients compared to placebo. Tolerability of Duloxetine Taj Pharma capsule 60 mg once daily in elderly patients was comparable to that seen in the younger adults. However, data on elderly patients exposed to the maximum dose (120mg per day) are limited and thus, caution is recommended when treating this population.

Generalised Anxiety Disorder: Duloxetine Taj Pharma capsules demonstrated statistically significant superiority over placebo in five out of five studies including four randomised, double-blind, placebo-controlled acute studies and a relapse prevention study in adult patients with generalised anxiety disorder.

Duloxetine Taj Pharma capsules demonstrated statistically significant superiority over placebo as measured by improvement in the Hamilton Anxiety Scale (HAM-A) total score and by the Sheehan Disability Scale (SDS) global functional impairment score. Response and remission rates were also higher with Duloxetine Taj Pharma capsules compared to placebo. Duloxetine Taj Pharma capsules showed comparable efficacy results to venlafaxine in terms of improvements on the HAM-A total score.

In a relapse prevention study, patients responding to 6 months of acute treatment with open-label Duloxetine Taj Pharma capsules were randomised to either Duloxetine Taj Pharma capsules or placebo for a further 6-months. Duloxetine Taj Pharma capsules 60 mg to 120 mg once daily demonstrated statistically significant superiority compared to placebo (p<0.001) on the prevention of relapse, as measured by time to relapse. The incidence of relapse during the 6-months double-blind follow-up period was 14% for Duloxetine Taj Pharma capsules and 42% for placebo.

The efficacy of Duloxetine Taj Pharma capsule 30-120 mg (flexible dosing) once a day in elderly patients (>65 years) with generalised anxiety disorder was evaluated in a study that demonstrated statistically significant improvement in the HAM-A total score for Duloxetine Taj Pharma treated patients compared to placebo treated patients. The efficacy and safety of Duloxetine Taj Pharma capsule 30-120 mg once daily in elderly patients with generalised anxiety disorder was similar to that seen in studies of younger adult patients. However, data on elderly patients exposed to the maximum dose (120 mg per day) are limited and, thus, caution is recommended when using this dose with the elderly population.

Diabetic Peripheral Neuropathic Pain: The efficacy of Duloxetine Taj Pharma capsules as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months. Patients meeting diagnostic criteria for major depressive disorder were excluded from these trials. The primary outcome measure was the weekly mean of 24-hour average pain, which was collected in a daily diary by patients on an 11-point Likert scale.

In both studies, Duloxetine Taj Pharma capsule 60 mg once daily and 60 mg twice daily significantly reduced pain compared with placebo. The effect in some patients was apparent in the first week of treatment. The difference in mean improvement between the two active treatment arms was not significant. At least 30% reported pain reduction was recorded in approximately 65% of Duloxetine Taj Pharma treated patients versus 40% for placebo. The corresponding figures for at least 50% pain reduction were 50% and 26% respectively. Clinical response rates (50% or greater improvement in pain) were analysed according to whether or not the patient experienced somnolence during treatment. For patients not experiencing somnolence, clinical response was observed in 47% of patients receiving Duloxetine Taj Pharma and 27% of patients on placebo. Clinical response rates in patients experiencing somnolence were 60% on Duloxetine Taj Pharma and 30% on placebo. Patients not demonstrating a pain reduction of 30% within 60 days of treatment were unlikely to reach this level during further treatment.

In an open label long-term uncontrolled study, the pain reduction in patients responding to 8-weeks of acute treatment of Duloxetine Taj Pharma capsule 60 mg once daily was maintained for a further 6-months as measured by change on the Brief Pain Inventory (BPI) 24-hour average pain item.

Paediatric population

Duloxetine Taj Pharma has not been studied in patients under the age of 7.

Two randomized, double-blind, parallel clinical trials were performed in 800 paediatric patients aged 7 to 17 years with major depressive disorder (see section 4.2). These two studies included a 10 week placebo and active (fluoxetine) controlled acute phase followed by six months period of active controlled extension treatment. Neither Duloxetine Taj Pharma (30-120 mg) nor the active control arm (fluoxetine 20-40 mg) statistically separated from placebo on change from baseline to endpoint in the Children´s Depression Rating Scale-Revised (CDRS-R) total score. Discontinuation due to adverse events was higher in patients taking Duloxetine Taj Pharma compared with those treated with fluoxetine, mostly due to nausea. During the 10-week acute treatment period, suicidal behaviours were reported (Duloxetine Taj Pharma 0/333 [0%], fluoxetine 2/225 [0.9%], placebo 1/220 [0.5%]). Over the entire 36-week course of the study, 6 out of 333 patients initially randomized to Duloxetine Taj Pharma and 3 out of 225 patients initially randomized to fluoxetine experienced suicidal behaviour (exposure adjusted incidence 0.039 events per patient year for Duloxetine Taj Pharma and 0.026 for fluoxetine). In addition, one patient who transitioned from placebo to Duloxetine Taj Pharma experienced a suicidal behaviour while taking Duloxetine Taj Pharma.

A randomised, double-blind, placebo-controlled study was performed in 272 patients aged 7-17 years with generalised anxiety disorder. The study included a 10 week placebo-controlled acute phase, followed by an 18 week extension treatment period. A flexible dose regimen was used in this study, to allow for slow dose escalation from 30 mg once daily to higher doses (maximum 120 mg once daily). Treatment with Duloxetine Taj Pharma showed a statistically significantly greater improvement in GAD symptoms, as measured by PARS severity score for GAD (mean difference between Duloxetine Taj Pharma and placebo of 2.7 points [95% CI 1.3-4.0]), after 10 weeks of treatment. The maintenance of the effect has not been evaluated. There was no statistically significant difference in discontinuation due to adverse events between Duloxetine Taj Pharma and placebo groups during the 10 week acute treatment phase. Two patients who transitioned from placebo to Duloxetine Taj Pharma after the acute phase experienced suicidal behaviours while taking Duloxetine Taj Pharma during the extension phase. A conclusion on the overall benefit/risk in this age group has not been established (see also sections 4.2 and 4.8).

The European Medicines Agency has waived the obligation to submit the results of studies with Duloxetine Taj Pharma in all subsets of the paediatric population in the treatment of major depressive disorder, diabetic neuropathic pain and generalised anxiety disorder. See section 4.2 for information on paediatric use.

  • Pharmacokinetic properties

Duloxetine Taj Pharma is administered as a single enantiomer. Duloxetine Taj Pharma is extensively metabolised by oxidative enzymes (CYP1A2 and the polymorphic CYP2D6), followed by conjugation. The pharmacokinetics of Duloxetine Taj Pharma demonstrate large intersubject variability (generally 50-60%), partly due to gender, age, smoking status and CYP2D6 metaboliser status.

Absorption: Duloxetine Taj Pharma is well absorbed after oral administration with a Cmax occurring 6 hours post dose. The absolute oral bioavailability of Duloxetine Taj Pharma ranged from 32% to 80% (mean of 50%). Food delays the time to reach the peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (approximately 11 %). These changes do not have any clinical significance.

Distribution: Duloxetine Taj Pharma is approximately 96% bound to human plasma proteins. Duloxetine Taj Pharma binds to both albumin and alpha-l acid glycoprotein. Protein binding is not affected by renal or hepatic impairment.

Biotransformation: Duloxetine Taj Pharma is extensively metabolised and the metabolites are excreted principally in urine. Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites glucuronide conjugate of 4-hydroxy Duloxetine Taj Pharma and sulphate conjugate of 5-hydroxy 6-methoxy Duloxetine Taj Pharma. Based upon in vitro studies, the circulating metabolites of Duloxetine Taj Pharma are considered pharmacologically inactive. The pharmacokinetics of Duloxetine Taj Pharma in patients who are poor metabolisers with respect to CYP2D6 has not been specifically investigated. Limited data suggest that the plasma levels of Duloxetine Taj Pharma are higher in these patients.

Elimination: The elimination half-life of Duloxetine Taj Pharma ranges from 8 to 17 hours (mean of 12 hours). After an intravenous dose the plasma clearance of Duloxetine Taj Pharma ranges from 22 l/hr to 46 l/hr (mean of 36 l/hr). After an oral dose the apparent plasma clearance of Duloxetine Taj Pharma ranges from 33 to 261 l/hr (mean 101 l/hr).

Special populations

Gender: Pharmacokinetic differences have been identified between males and females (apparent plasma clearance is approximately 50% lower in females). Based upon the overlap in the range of clearance, gender-based pharmacokinetic differences do not justify the recommendation for using a lower dose for female patients.

Age: Pharmacokinetic differences have been identified between younger and elderly females (≥65 years) (AUC increases by about 25% and half-life is about 25% longer in the elderly), although the magnitude of these changes is not sufficient to justify adjustments to the dose. As a general recommendation, caution should be exercised when treating the elderly (see sections 4.2 and 4.4).

Renal impairment: End stage renal disease (ESRD) patients receiving dialysis had 2-fold higher Duloxetine Taj Pharma Cmax and AUC values compared with healthy subjects. Pharmacokinetic data on Duloxetine Taj Pharma is limited in patients with mild or moderate renal impairment.

Hepatic impairment: Moderate liver disease (Child Pugh Class B) affected the pharmacokinetics of Duloxetine Taj Pharma. Compared with healthy subjects, the apparent plasma clearance of Duloxetine Taj Pharma was 79% lower, the apparent terminal half-life was 2.3 times longer, and the AUC was 3.7 times higher in patients with moderate liver disease. The pharmacokinetics of Duloxetine Taj Pharma and its metabolites have not been studied in patients with mild or severe hepatic insufficiency.

Breast-feeding mothers: The disposition of Duloxetine Taj Pharma was studied in 6 lactating women who were at least 12-weeks postpartum. Duloxetine Taj Pharma is detected in breast milk, and steady-state concentrations in breast milk are about one-fourth those in plasma. The amount of Duloxetine Taj Pharma in breast milk is approximately 7 µg/day while on 40 mg twice daily dosing. Lactation did not influence Duloxetine Taj Pharma pharmacokinetics.

Paediatric population: Pharmacokinetics of Duloxetine Taj Pharma in paediatric patients aged 7 to 17 years with major depressive disorder following oral administration of 20 to 120 mg once daily dosing regimen was characterized using population modelling analyses based on data from 3 studies. The model-predicted Duloxetine Taj Pharma steady state plasma concentrations in paediatric patients were mostly within the concentration range observed in adult patients.

  • Preclinical safety data

Duloxetine Taj Pharma was not genotoxic in a standard battery of tests and was not carcinogenic in rats. Multinucleated cells were seen in the liver in the absence of other histopathological changes in the rat carcinogenicity study. The underlying mechanism and the clinical relevance are unknown. Female mice receiving Duloxetine Taj Pharma for 2 years had an increased incidence of hepatocellular adenomas and carcinomas at the high dose only (144 mg/kg/day), but these were considered to be secondary to hepatic microsomal enzyme induction. The relevance of this mouse data to humans is unknown. Female rats receiving Duloxetine Taj Pharma (45 mg/kg/day) before and during mating and early pregnancy had a decrease in maternal food consumption and body weight, oestrous cycle disruption, decreased live birth indices and progeny survival, and progeny growth retardation at systemic exposure levels estimated to be at the most at maximum clinical exposure (AUC). In an embryotoxicity study in the rabbit, a higher incidence of cardiovascular and skeletal malformations was observed at systemic exposure levels below the maximum clinical exposure (AUC). No malformations were observed in another study testing a higher dose of a different salt of Duloxetine Taj Pharma. In prenatal/postnatal toxicity studies in the rat, Duloxetine Taj Pharma induced adverse behavioural effects in the offspring at exposures below maximum clinical exposure (AUC).

Studies in juvenile rats reveal transient effects on neurobehaviour, as well as significantly decreased body weight and food consumption; hepatic enzyme induction; and hepatocellular vacuolation at 45 mg/kg/day. The general toxicity profile of Duloxetine Taj Pharma in juvenile rats was similar to that in adult rats. The no-adverse effect level was determined to be 20 mg/kg/day.

  1. Pharmaceutical particulars
    • List of excipients

Capsule content:

Sugar spheres (containing maize starch and sucrose)

Hypromellose 2910

Crospovidone (type B)

Talc

Sucrose

Carboxy methyl ethyl cellulose

Povidone

Titanium dioxide

Macrogol

Polysorbate 80

Capsule shell:

Gelatin

Titanium dioxide

Sodium laurilsulphate

Indigo carmine

Edible ink:

Shellac

Propylene glycol

Yellow iron oxide

  • Incompatibilities

Not applicable.

  • Shelf life

3 years.

  • Special precautions for storage

This medicine does not require any special storage conditions.

  • Nature and contents of container

Aluminium-Aluminium blister.

Duloxetine Taj Pharma capsule is available in:

Blister packs of 7, 10, 14, 28, 28×1, 30, 90, 98, 98×1, 100 and 500 capsules.

Not all pack sizes may be marketed.

  • Special precautions for disposal and other handling

No special requirements.

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

Duloxetine Delayed-Release Capsules USP 40mg Taj Pharma

Duloxetine Taj Pharma

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 of the side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

  1. What Duloxetine Taj Pharma is and what it is used for
  2. What you need to know before you take Duloxetine Taj Pharma
  3. How to take Duloxetine Taj Pharma
  4. Possible side effects
  5. How to store Duloxetine Taj Pharma
  6. Contents of the pack and other information
  7. What Duloxetine Taj Pharma is and what it is used for

Duloxetine Taj Pharma contains the active substance Duloxetine Taj Pharma. Duloxetine Taj Pharma increases the levels of serotonin and noradrenaline in the nervous system.

Duloxetine Taj Pharma is a medicine to be taken by mouth to treat Stress Urinary Incontinence (SUI) in women.

Stress Urinary Incontinence is a medical condition in which patients have accidental loss or leakage of urine during physical exertion or activities such as laughing, coughing, sneezing, lifting or exercise.

Duloxetine Taj Pharma is believed to work by increasing the strength of the muscle that holds back urine when you laugh, sneeze or perform physical activities.

The efficacy of Duloxetine Taj Pharma is reinforced when combined with a training program called Pelvic Floor Muscle Training (PFMT).

  1. What you need to know before you take Duloxetine Taj Pharma

DO NOT take Duloxetine Taj Pharma if you:

  • are allergic to Duloxetine Taj Pharma or any of the other ingredients of this medicine (listed in section 6)
  • have liver disease
  • have severe kidney disease
  • are taking or have taken within the last 14 days, another medicine known as a monoamine oxidase inhibitor (MAOI) (see ‘Other medicines and Duloxetine Taj Pharma’)
  • are taking fluvoxamine which is usually used to treat depression, ciprofloxacin or enoxacin which are used to treat some infections

Talk to your doctor if you have high blood pressure or heart disease.

Your doctor will tell you if you should be taking Duloxetine Taj Pharma .

Warnings and Precautions

The following are reasons why Duloxetine Taj Pharma may not be suitable for you. Talk to your doctor before you take Duloxetine Taj Pharma if you:

  • are taking medicines to treat depression (see ‘Other medicines and Duloxetine Taj Pharma’)
  • are taking St. John’s Wort, a herbal treatment (Hypericum perforatum)
  • have kidney disease
  • have had seizures (fits)
  • have had mania
  • suffer from bipolar disorder
  • have eye problems, such as certain kinds of glaucoma (increased pressure in the eye)
  • have a history of bleeding disorders (tendency to develop bruises)
  • are at risk of low sodium levels (for example if you are taking diuretics, especially if you are elderly)
  • are currently being treated with another medicine which may cause liver damage
  • are taking other medicines containing Duloxetine Taj Pharma (see ‘Other medicines and Duloxetine Taj Pharma’)

Duloxetine Taj Pharma may cause a sensation of restlessness or an inability to sit or stand still. You should tell your doctor if this happens to you.

Medicines like Duloxetine Taj Pharma (so called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have continued after stopping treatment.

Thoughts of suicide and worsening of depression or anxiety disorder

Although Duloxetine Taj Pharma is not indicated for the treatment of depression, its active ingredient (Duloxetine Taj Pharma) is used as an antidepressant medicine. If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting 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 or harming yourself
  • are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years 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 have an anxiety disorder, 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.

Children and adolescents under 18 years of age

Duloxetine Taj Pharma should 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. Also, the long-term safety effects concerning growth, maturation, and cognitive and behavioural development of Duloxetine Taj Pharma in this age group have not yet been demonstrated.

Other medicines and Duloxetine Taj Pharma

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

The main ingredient of this medicine, Duloxetine Taj Pharma, is used in other medicines for other conditions:

  • diabetic neuropathic pain, depression, anxiety and urinary incontinence

Using more than one of these medicines at the same time should be avoided. Check with your doctor if you are already taking other medicines containing Duloxetine Taj Pharma.

Your doctor should decide whether you can take Duloxetine Taj Pharma with other medicines. Do not start or stop taking any medicines, including those bought without a prescription and herbal remedies, before checking with your doctor.

You should also tell your doctor if you are taking any of the following:

Monoamine oxidase inhibitors (MAOIs): You should not take Duloxetine Taj Pharma if you are taking or have recently taken (within the last 14 days) another antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking a MAOI together with many prescription medicines, including Duloxetine Taj Pharma, can cause serious or even life-threatening side effects. You must wait at least 14 days after you have stopped taking an MAOI before you can take Duloxetine Taj Pharma. Also, you need to wait at least 5 days after you stop taking Duloxetine Taj Pharma before you take a MAOI.

Medicines that cause sleepiness: These include medicines prescribed by your doctor including benzodiazepines, strong painkillers, antipsychotics, phenobarbital and antihistamines.

Medicines that increase the level of serotonin: Triptans, tramadol, tryptophan, SSRIs (such as paroxetine and fluoxetine), SNRIs (such as venlafaxine), tricyclic antidepressants (such as clomipramine, amitriptyline), pethidine, St John’s Wort and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of side effects; if you get any unusual symptoms taking any of these medicines together with Duloxetine Taj Pharma, you should see your doctor.

Oral anticoagulants or antiplatelet agents: Medicines which thin the blood or prevent the blood from clotting. These medicines might increase the risk of bleeding.

Duloxetine Taj Pharma with food, drink and alcohol

Duloxetine Taj Pharma may be taken with or without food. You should take extra care if you drink alcohol while taking Duloxetine Taj Pharma.

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.

  • Tell your doctor if you become pregnant, or you are trying to become pregnant, while you are taking Duloxetine Taj Pharma. You should use Duloxetine Taj Pharma only after discussing the potential benefits and any potential risks to your unborn child with your doctor.
    Make sure your midwife and/or doctor knows you are on Duloxetine Taj Pharma.
    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 take Duloxetine Taj Pharma near the end of your pregnancy, your baby might have some symptoms when it is born. These usually begin at birth or within a few days of your baby being born. These symptoms may include floppy muscles, trembling, jitteriness, not feeding properly, trouble with breathing and fits. If your baby has any of these symptoms when it is born, or you are concerned about your baby’s health, contact your doctor or midwife who will be able to advise you.
  • Tell your doctor if you are breast-feeding. The use of Duloxetine Taj Pharma while breast-feeding is not recommended. You should ask your doctor or pharmacist for advice.

Driving and using machines

Duloxetine Taj Pharma may make you feel sleepy or dizzy. Do not drive or use any tools or machines until you know how Duloxetine Taj Pharma affects you.

Duloxetine Taj Pharma contains sucrose

Duloxetine Taj Pharma contains sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

  1. How to take Duloxetine Taj Pharma

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Duloxetine Taj Pharma is for oral use. You should swallow your capsule whole with a drink of water. Do not crush or chew.

The recommended dose of Duloxetine Taj Pharma is 40mg twice a day (in the morning and late afternoon/evening). Your doctor may decide to start your treatment with 20mg twice a day for two weeks before increasing the dose to 40mg twice a day.

To help you remember to take Duloxetine Taj Pharma, you may find it easier to take it at the same times every day.

Do not stop taking Duloxetine Taj Pharma, or change your dose, without talking to your doctor. Treating your disorder 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 difficult to treat.

If you take more Duloxetine Taj Pharma than you should

Call your doctor or pharmacist immediately if you take more than the amount of Duloxetine Taj Pharma prescribed by your doctor. Symptoms of overdose include sleepiness, coma, serotonin syndrome (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), fits, vomiting and fast heart rate.

If you forget to take Duloxetine Taj Pharma

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 a double dose to make up for a forgotten dose. Do not take more than the daily amount of Duloxetine Taj Pharma that has been prescribed for you in one day.

If you stop taking Duloxetine Taj Pharma

DO NOT stop taking your capsules without the advice of your doctor even if you feel better. If your doctor thinks that you no longer need Duloxetine Taj Pharma he or she will ask you to reduce your dose over 2 weeks.

Some patients, who suddenly stop taking Duloxetine Taj Pharma after more than 1 week of therapy, have had symptoms such as:

  • dizziness, tingling feelings like pins and needles or electric shock-like feelings (particularly in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, sleepiness, feeling restless or agitated, feeling anxious, feeling sick (nausea) or being sick (vomiting), shaking (tremor), headaches, muscle pain, feeling irritable, diarrhoea, excessive sweating or vertigo.

These symptoms are usually not serious and disappear within a few days, but if you have symptoms that are troublesome you should ask your doctor for advice.

If you have further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are normally mild to moderate and often disappear after a short time.

Very common side effects (may affect more than 1 in 10 people)

  • feeling sick (nausea), dry mouth, constipation
  • fatigue

Common side effects (may affect up to 1 in 10 people)

  • lack of appetite
  • trouble sleeping, feeling agitated, decreased sex drive, anxiety, difficulty sleeping
  • headache, dizziness, feeling sluggish, feeling sleepy, tremor, numbness, including numbness, pricking or tingling of the skin
  • blurred eyesight
  • feeling of dizziness or ‘spinning’ (vertigo)
  • increased blood pressure, flushing
  • diarrhoea, stomach pain, being sick (vomiting), heartburn or indigestion
  • increased sweating
  • weakness, shivering

Uncommon side effects (may affect up to 1 in 100 people )

  • throat inflammation that causes a hoarse voice
  • allergic reactions
  • decreased thyroid gland activity which can cause tiredness or weight gain
  • dehydration
  • grinding or clenching the teeth, feeling disorientated, lack of motivation, difficulty or failure to experience orgasm, unusual dreams
  • feeling nervous, difficulty concentrating, changes in sense of taste, poor sleep quality
  • large pupils (the dark centre of the eye), problems with eyesight, eyes feel dry
  • tinnitus (hearing sound in the ear when there is no external sound), ear pain
  • feeling the heart pumping in the chest, fast and/or irregular heartbeat
  • fainting
  • increased yawning
  • vomiting blood, or black tarry stools (faeces), gastroenteritis, inflammation of the mouth, burping, difficulty swallowing, breaking wind, bad breath
  • inflammation of the liver that may cause abdominal pain and yellowing of the skin or whites of the eyes
  • (itchy) rash, night sweats, hives, cold sweats, increased tendency to bruise
  • muscle pain, muscle tightness, muscle spasm, contraction of the jaw muscle
  • difficulty to start urinating, painful urination, needing to pass urine during the night, frequent urination, abnormal urine odour
  • abnormal vaginal bleeding, menopausal symptoms
  • chest pain, feeling cold, thirst, feeling hot
  • weight loss, weight gain
  • Duloxetine Taj Pharma may cause effects that you may not be aware of, such as increases in liver enzymes or blood levels of potassium, creatine phosphokinase, sugar or cholesterol

Rare side effects (may affect up to 1 in 1000 people)

  • serious allergic reaction which causes difficulty in breathing or dizziness with swollen tongue or lips
  • low levels of sodium in the blood (mostly in elderly people; the symptoms may include feeling dizzy, weak, confused, sleepy or very tired, or feeling or being sick, more serious symptoms are fainting, fits or falls), syndrome of inappropriate secretion of anti-diuretic hormone (SIADH)
  • suicidal behaviour, suicidal thoughts, mania (over activity, racing thoughts and decreased need for sleep), hallucinations, aggression and anger
  • ‘Serotonin syndrome’ (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), fits, sudden involuntary jerks or twitches of the muscles, sensation of restlessness or an inability to sit or stand still, difficulty controlling movement e.g. lack of coordination or involuntary movements of the muscles, restless legs syndrome
  • increased pressure in the eye (glaucoma)
  • dizziness, lightheadedness or fainting on standing up, cold fingers and/or toes
  • throat tightness, nose bleeds
  • passing bright red blood in your stools, inflammation of the large intestine (leading to diarrhoea)
  • liver failure, yellowing of the skin or whites of the eyes (jaundice)
  • Stevens-Johnson syndrome (serious illness with blistering of the skin, mouth, eyes and genitals), serious allergic reaction which causes swelling of the face or throat (angioedema), sensitivity to sunlight
  • muscle twitching
  • difficulty or inability to pass urine, needing to pass more urine than normal, having a decreased urine flow
  • abnormal periods, including heavy, painful, irregular or prolonged periods, unusually light or missed periods, abnormal production of breast milk
  • falls (mostly in elderly people), abnormal gait
  • coughing, wheezing and shortness of breath which may be accompanied by a high temperature

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

  • inflammation of the blood vessels in the skin (cutaneous vasculitis)

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.

  1. How to store Duloxetine Taj Pharma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

  1. Contents of the pack and other information

What Duloxetine Taj Pharma contains

The active substance is Duloxetine Taj Pharma.

Each capsule contains 20mg/30mg/40mg/60mg of Duloxetine Taj Pharma (as hydrochloride).

The other ingredients are:

Capsule content: sugar spheres (containing maize starch and sucrose), hypromellose 2910 (E464), crospovidone (type B), talc, sucrose, carboxymethyl ethyl cellulose, povidone, titanium dioxide, Macrogol, Polysorbate 80 (See end of section 2 for further information on sucrose).

Capsule shell (for 20mg strength): gelatin, titanium dioxide, sodium lauryl sulfate, iron oxide yellow, indigo carmine.

Capsule shell (for 40mg strength): gelatin, titanium dioxide, sodium lauryl sulfate, indigo carmine iron oxide yellow, iron oxide red.

Edible black ink (for 20 and 40mg strengths): shellac, propylene glycol, black iron oxide, potassium hydroxide.

What Duloxetine Taj Pharma looks like and contents of the pack

Duloxetine Taj Pharma is a gastro-resistant capsule, hard. Each capsule of Duloxetine Taj Pharma contains pellets of Duloxetine Taj Pharma hydrochloride with a covering to protect them from stomach acid.

Duloxetine Taj Pharma is available in 20mg/30mg/40mg/60mg of Duloxetine Taj Pharma strengths.

Duloxetine Taj Pharma is available in packs of 7, 10, 14, 20, 28, 30, 50, 56, 84, 98, 100 and 500 capsules.

Not all pack sizes may be marketed.

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