1. Name of the medicinal product

Atomoxetine capsule USP 10mg Taj Pharma
Atomoxetine capsule USP 18mg Taj Pharma
Atomoxetine capsule USP 25mg Taj Pharma
Atomoxetine capsule USP 40mg Taj Pharma
Atomoxetine capsule USP 60mg Taj Pharma
Atomoxetine capsule USP 80mg Taj Pharma
Atomoxetine capsule USP 100mg Taj Pharma

  1. Qualitative and quantitative composition

a) Atomoxetine capsule USP 10mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 10mg
Excipients: Q.S.

b) Atomoxetine capsule USP 18mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 18mg
Excipients: Q.S.

c) Atomoxetine capsule USP 25mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 25mg
Excipients: Q.S.

d) Atomoxetine capsule USP 40mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 40mg
Excipients: Q.S.

e) Atomoxetine capsule USP 60mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 60mg
Excipients: Q.S.

f) Atomoxetine capsule USP 80mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 80mg
Excipients: Q.S.

g) Atomoxetine capsule USP 100mg Taj Pharma
Each hard gelatin capsule contains
Atomoxetine Hydrochloride USP
Equivalent to Atomoxetine 100mg
Excipients: Q.S.

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Hard Gelatin Capsule,

Atomoxetine 10mg/18mg/25mg/40mg/60mg/80mg/100mg Taj Pharma: White-blue capsule of size 4.

  1. Clinical particulars
  • Therapeutic indications

Atomoxetine Taj Pharma is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children of 6 years and older, in adolescents and in adults as part of a comprehensive treatment programme. Treatment must be initiated by a specialist in the treatment of ADHD, such as a paediatrician, child/adolescent psychiatrist, or psychiatrist. Diagnosis should be made according to current DSM criteria or the guidelines in ICD.

In adults, the presence of symptoms of ADHD that were pre-existing in childhood should be confirmed. Third-party corroboration is desirable and Atomoxetine Taj Pharma should not be initiated when the verification of childhood ADHD symptoms is uncertain. Diagnosis cannot be made solely on the presence of one or more symptoms of ADHD. Based on clinical judgment, patients should have ADHD of at least moderate severity as indicated by at least moderate functional impairment in 2 or more settings (for example, social, academic, and/or occupational functioning), affecting several aspects of an individual’s life.

Additional information for the safe use of this product

A comprehensive treatment programme typically includes psychological, educational, and social measures and is aimed at stabilising patients with a behavioural syndrome characterised by symptoms which may include chronic history of short attention span, distractibility, emotional lability, impulsivity, moderate to severe hyperactivity, minor neurological signs, and abnormal EEG. Learning may or may not be impaired.

Pharmacological treatment is not indicated in all patients with this syndrome and the decision to use the drug must be based on a very thorough assessment of the severity of the patient’s symptoms and impairment in relation to the patient’s age and the persistence of symptoms.

  • Posology and method of administration

Posology

Atomoxetine Taj Pharma can be administered as a single daily dose in the morning. Patients who do not achieve a satisfactory clinical response (tolerability [e.g. nausea or somnolence] or efficacy) when taking Atomoxetine Taj Pharma as a single daily dose might benefit from taking it as twice daily evenly divided doses in the morning and late afternoon or early evening.

Paediatric population

Dosing of paediatric population up to 70 kg body weight

Atomoxetine Taj Pharma should be initiated at a total daily dose of approximately 0.5mg/kg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is approximately 1.2mg/kg/day (depending on the patient’s weight and available dosage strengths of Atomoxetine Taj Pharma). No additional benefit has been demonstrated for doses higher than 1.2mg/kg/day. The safety of single doses over 1.8mg/kg/day and total daily doses above 1.8mg/kg have not been systematically evaluated. In some cases it might be appropriate to continue treatment into adulthood.

Dosing of paediatric population over 70 kg body weight

Atomoxetine Taj Pharma should be initiated at a total daily dose of 40mg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is 80mg. No additional benefit has been demonstrated for doses higher than 80mg (see section 5.1). The maximum recommended total daily dose is 100mg. The safety of single doses over 120mg and total daily doses above 150mg have not been systematically evaluated.

Adults

Atomoxetine Taj Pharma should be initiated at a total daily dose of 40mg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance daily dose is 80mg to 100mg. The maximum recommended total daily dose is 100mg. The safety of single doses over 120mg and total daily doses above 150mg have not been systematically evaluated.

Additional information for the safe use of this product

Pre-treatment screening

Prior to prescribing it is necessary to take an appropriate medical history and conduct a baseline evaluation of a patient’s cardiovascular status, including blood pressure and heart rate (see sections 4.3 and 4.4).

On-going monitoring

Cardiovascular status should be regularly monitored with blood pressure and pulse recorded after each adjustment of dose and then at least every 6 months. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed (see section 4.4).

Withdrawal of treatment

In the study programme no distinct withdrawal symptoms have been described. In cases of significant adverse effects, Atomoxetine Taj Pharma may be stopped abruptly; otherwise the drug may be tapered off over a suitable time period.

Treatment with Atomoxetine Taj Pharma need not be indefinite. Re-evaluation of the need for continued therapy beyond 1 year should be performed, particularly when the patient has reached a stable and satisfactory response.

Special populations

Hepatic insufficiency

For patients with moderate hepatic insufficiency (Child-Pugh class B), initial and target doses should be reduced to 50% of the usual dose. For patients with severe hepatic insufficiency (Child-Pugh class C), initial dose and target doses should be reduced to 25% of usual dose (see section 5.2).

Renal insufficiency

Subjects with end-stage renal disease had higher systemic exposure to Atomoxetine Taj Pharma than healthy subjects (about a 65% increase), but there was no difference when exposure was corrected formg/kg dose. Atomoxetine Taj Pharma can therefore be administered to ADHD patients with end-stage renal disease or lesser degrees of renal insufficiency using the usual dosing regimen. Atomoxetine Taj Pharma may exacerbate hypertension in patients with end-stage renal disease (see section 5.2).

Poor metabolisers

Approximately 7% of Caucasians have a genotype corresponding to a non-functional CYP2D6 enzyme (called CYP2D6 poor metabolisers). Patients with this genotype have a several-fold higher exposure to Atomoxetine Taj Pharma when compared to patients with a functional enzyme. Poor metabolisers are therefore at higher risk of adverse events (see sections 4.8 and 5.2). For patients with a known poor metaboliser genotype, a lower starting dose and slower up titration of the dose may be considered.

Elderly

The use of Atomoxetine Taj Pharma in patients over 65 years of age has not been systematically evaluated.

Paediatric population under 6 years of age

The safety and efficacy of Atomoxetine Taj Pharma in children under 6 years of age have not been established. Therefore, Atomoxetine Taj Pharma should not be used in children under 6 years of age (see section 4.4).

Method of administration

For oral use. Atomoxetine Taj Pharma can be administered with or without food.

  • Contraindications

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

Atomoxetine Taj Pharma should not be used in combination with monoamine oxidase inhibitors (MAOI). Atomoxetine Taj Pharma should not be used within a minimum of 2 weeks after discontinuing therapy with MAOI. Treatment with MAOI should not be initiated within 2 weeks after discontinuing Atomoxetine Taj Pharma.

Atomoxetine Taj Pharma should not be used in patients with narrow-angle glaucoma, as in clinical trials the use of Atomoxetine Taj Pharma was associated with an increased incidence of mydriasis.

Atomoxetine Taj Pharma should not be used in patients with severe cardiovascular or cerebrovascular disorders (see section 4.4 ‘Cardiovascular effects’). Severe cardiovascular disorders may include severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies (disorders caused by the dysfunction of ion channels). Severe cerebrovascular disorders may include cerebral aneurysm or stroke.

Atomoxetine Taj Pharma should not be used in patients with pheochromocytoma or a history of pheochromocytoma (see section 4.4 ‘Cardiovascular effects’).

  • Special warnings and precautions for use

Suicide-related behaviour

Suicide-related behaviour (suicide attempts and suicidal ideation) has been reported in patients treated with Atomoxetine Taj Pharma. In double-blind clinical trials, suicide-related behaviours were uncommon, but more frequently observed among children and adolescents treated with Atomoxetine Taj Pharma compared to those treated with placebo, where there were no events. In adult double-blind clinical trials there was no difference in the frequency of suicide related behaviour between Atomoxetine Taj Pharma and placebo. Patients who are being treated for ADHD should be carefully monitored for the appearance or worsening of suicide-related behaviour.

Sudden death and pre-existing cardiac abnormalities

Sudden death has been reported in patients with structural cardiac abnormalities who were taking Atomoxetine Taj Pharma at usual doses. Although some serious structural cardiac abnormalities alone carry an increased risk of sudden death, Atomoxetine Taj Pharma should only be used with caution in patients with known serious structural cardiac abnormalities and in consultation with a cardiac specialist.

Cardiovascular effects

Atomoxetine Taj Pharma can affect heart rate and blood pressure. Most patients taking Atomoxetine Taj Pharma experience a modest increase in heart rate (mean < 10 bpm) and/or increase in blood pressure (mean < 5 mmHg) (see section 4.8).

However, combined data from controlled and uncontrolled ADHD clinical trials show that (approximately 8 – 12% of children and adolescents, and 6 – 10% of adults) experience more pronounced changes in heart rate (20 bpm or greater) and blood pressure (15 – 20 mmHg or greater). Analysis of these clinical trial data showed that approximately 15 – 26% of children and adolescents, and 27 – 32% of adults experiencing such changes in blood pressure and heart rate during Atomoxetine Taj Pharma treatment had sustained or progressive increases. Long-term sustained changes in blood pressure may potentially contribute to clinical consequences such as myocardial hypertrophy.

As a result of these findings, patients who are being considered for treatment with Atomoxetine Taj Pharma should have a careful history and physical exam to assess for the presence of cardiac disease, and should receive further specialist cardiac evaluation if initial findings suggest such history or disease.

It is recommended that heart rate and blood pressure be measured and recorded before treatment is started and, during treatment, after each adjustment of dose and then at least every 6 months to detect possible clinically important increases. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed.

Atomoxetine Taj Pharma should not be used in patients with severe cardiovascular or cerebrovascular disorders (see section 4.3 ‘Severe cardiovascular and cerebrovascular disorders’). Atomoxetine Taj Pharma should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure and heart rate, such as patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease.

Patients who develop symptoms such as palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease during Atomoxetine Taj Pharma treatment should undergo a prompt specialist cardiac evaluation.

In addition, Atomoxetine Taj Pharma should be used with caution in patients with congenital or acquired long QT or a family history of QT prolongation (see sections 4.5 and 4.8).

As orthostatic hypotension has also been reported, Atomoxetine Taj Pharma should be used with caution in any condition that may predispose patients to hypotension or conditions associated with abrupt heart rate or blood pressure changes.

Cerebrovascular effects

Patients with additional risk factors for cerebrovascular conditions (such as a history of cardiovascular disease, concomitant medications that elevate blood pressure) should be assessed at every visit for neurological signs and symptoms after initiating treatment with Atomoxetine Taj Pharma.

Hepatic effects

Very rarely, spontaneous reports of liver injury, manifested by elevated hepatic enzymes and bilirubin with jaundice, have been reported. Also very rarely, severe liver injury, including acute liver failure, has been reported. Atomoxetine Taj Pharma should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted.

Psychotic or manic symptoms

Treatment-emergent psychotic or manic symptoms, e.g. hallucinations, delusional thinking, mania or agitation in patients without a prior history of psychotic illness or mania can be caused by Atomoxetine Taj Pharma at usual doses. If such symptoms occur, consideration should be given to a possible causal role of Atomoxetine Taj Pharma, and discontinuation of treatment should be considered. The possibility that Atomoxetine Taj Pharma will cause the exacerbation of pre-existing psychotic or manic symptoms cannot be excluded.

Aggressive behaviour, hostility or emotional lability

Hostility (predominantly aggression, oppositional behaviour and anger) was more frequently observed in clinical trials among children, adolescents and adults treated with Atomoxetine Taj Pharma compared to those treated with placebo. Emotional lability was more frequently observed in clinical trials among children treated with Atomoxetine Taj Pharma compared to those treated with placebo. Patients should be closely monitored for the appearance or worsening of aggressive behaviour, hostility or emotional lability.

Possible allergic events

Although uncommon, allergic reactions, including anaphylactic reactions, rash, angioneurotic oedema, and urticaria, have been reported in patients taking Atomoxetine Taj Pharma.

Seizures

Seizures are a potential risk with Atomoxetine Taj Pharma. Atomoxetine Taj Pharma should be introduced with caution in patients with a history of seizure. Discontinuation of Atomoxetine Taj Pharma should be considered in any patient developing a seizure or if there is an increase in seizure frequency where no other cause is identified.

Growth and development

Growth and development should be monitored in children and adolescents during treatment with Atomoxetine Taj Pharma. Patients requiring long-term therapy should be monitored and consideration should be given to dose reduction or interrupting therapy in children and adolescents who are not growing or gaining weight satisfactorily.

Clinical data do not suggest a deleterious effect of Atomoxetine Taj Pharma on cognition or sexual maturation; however, the amount of available long-term data is limited. Therefore, patients requiring long-term therapy should be carefully monitored.

New-onset or worsening of comorbid depression, anxiety and tics

In a controlled study of paediatric patients with ADHD and comorbid chronic motor tics or Tourette’s disorder, Atomoxetine Taj Pharma-treated patients did not experience worsening of tics compared to placebo-treated patients. In a controlled study of adolescent patients with ADHD and comorbid major depressive disorder, Atomoxetine Taj Pharma-treated patients did not experience worsening of depression compared to placebo-treated patients. In two controlled studies (one in paediatric patients and one in adult patients) of patients with ADHD and comorbid anxiety disorders, Atomoxetine Taj Pharma-treated patients did not experience worsening of anxiety compared to placebo-treated patients.

There have been rare post-marketing reports of anxiety and depression or depressed mood and very rare reports of tics in patients taking Atomoxetine Taj Pharma (see section 4.8).

Patients who are being treated for ADHD with Atomoxetine Taj Pharma should be monitored for the appearance or worsening of anxiety symptoms, depressed mood and depression or tics.

Paediatric population under 6 years of age

Atomoxetine Taj Pharma should not be used in patients less than 6 years of age as efficacy and safety have not been established in this age group.

Other therapeutic use

Atomoxetine Taj Pharma is not indicated for the treatment of major depressive episodes and/or anxiety, as the results of clinical trials in adults in these conditions, where ADHD is not present, did not show an effect compared to placebo (see section 5.1).

  • Interaction with other medicinal products and other forms of interaction

Effects of other drugs on Atomoxetine Taj Pharma

MAOIs

Atomoxetine Taj Pharma should not be used with MAOIs (see section 4.3).

CYP2D6 inhibitors (SSRIs (e.g. fluoxetine, paroxetine), quinidine, terbinafine)

In patients receiving these drugs, Atomoxetine Taj Pharma exposure may be 6-to 8-fold increased and Css max 3 to 4 times higher, because it is metabolised by the CYP2D6 pathway. Slower titration and final lower dosage of Atomoxetine Taj Pharma may be necessary in patients who are already taking CYP2D6 inhibitor drugs. If a CYP2D6 inhibitor is prescribed or discontinued after titration to the appropriate Atomoxetine Taj Pharma dose has occurred, the clinical response and tolerability should be re-evaluated for that patient to determine if dose adjustment is needed.

Caution is advised when combining Atomoxetine Taj Pharma with potent inhibitors of cytochrome P450 enzymes other than CYP2D6 in patients who are poor CYP2D6 metabolisers as the risk of clinically relevant increases in Atomoxetine Taj Pharma exposure in vivo is unknown.

Salbutamol (or other β2 agonists)

Atomoxetine Taj Pharma should be administered with caution to patients treated with high dose nebulised or systemically administered salbutamol (or other β2 agonists) because cardiovascular effects can be potentiated.

Contradictory findings regarding this interaction were found. Systemically administered Salbutamol (600 μg i.v. over 2 hours) in combination with Atomoxetine Taj Pharma (60mg twice daily for 5 days) induced increases in heart rate and blood pressure. This effect was most marked after the initial co-administration of salbutamol and Atomoxetine Taj Pharma but returned towards baseline at the end of 8 hours. However, in a separate study the effects on blood pressure and heart rate of a standard inhaled dose of salbutamol (200 μg) were not increased by the short-term co-administration of Atomoxetine Taj Pharma (80mg once daily for 5 days) in a study of healthy Asian adults who were extensive Atomoxetine Taj Pharma metabolisers. Similarly, heart rate after multiple inhalations of salbutamol (800 μg) did not differ in the presence or absence of Atomoxetine Taj Pharma.

Attention should be paid to monitoring heart rate and blood pressure, and dose adjustments may be justified for either Atomoxetine Taj Pharma or salbutamol (or other β2 agonists) in the event of significant increases in heart rate and blood pressure during co-administration of these drugs.

There is the potential for an increased risk of QT-interval prolongation when Atomoxetine Taj Pharma is administered with other QT prolonging drugs (such as neuroleptics, class IA and III anti-arrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium, or cisapride), drugs that cause electrolyte imbalance (such as thiazide diuretics), and drugs that inhibit CYP2D6.

Seizures are a potential risk with Atomoxetine Taj Pharma. Caution is advised with concomitant use of medicinal drugs which are known to lower the seizure threshold (such as tricyclic antidepressants or SSRIs, neuroleptics, phenothiazines or butyrophenone, mefloquine, chloroquine, bupropion or tramadol) (see section 4.4.). In addition, caution is advised when stopping concomitant treatment with benzodiazepines due to potential withdrawal seizures.

Anti-hypertensive drugs

Atomoxetine Taj Pharma should be used cautiously with anti-hypertensive drugs. Because of a possible increase in blood pressure, Atomoxetine Taj Pharma may decrease the effectiveness of anti-hypertensive drugs/drugs used to treat hypertension. Attention should be paid to monitoring of blood pressure and review of treatment of Atomoxetine Taj Pharma or anti-hypertensive drugs may be justified in the case of significant changes of blood pressure.

Pressor agents or drugs that increase blood pressure

Because of possible increase in effects on blood pressure, Atomoxetine Taj Pharma should be used cautiously with pressor agents or medications that may increase blood pressure (such as salbutamol). Attention should be paid to monitoring of blood pressure, and review of treatment for either Atomoxetine Taj Pharma or pressor agents may be justified in the case of significant change in blood pressure.

Drugs that affect noradrenaline

Drugs that affect noradrenaline should be used cautiously when co-administered with Atomoxetine Taj Pharma because of the potential for additive or synergistic pharmacological effects. Examples include antidepressants, such as imipramine, venlafaxine, and mirtazapine, or the decongestants pseudoephedrine or phenylephrine.

Drugs that affect gastric pH

Drugs that elevate gastric pH (magnesium hydroxide/aluminium hydroxide, omeprazole) had no effect on Atomoxetine Taj Pharma bioavailability.

Drugs highly bound to plasma protein

In vitro drug-displacement studies were conducted with Atomoxetine Taj Pharma and other highly-bound drugs at therapeutic concentrations. Warfarin, acetylsalicylic acid, phenytoin, or diazepam did not affect the binding of Atomoxetine Taj Pharma to human albumin. Similarly, Atomoxetine Taj Pharma did not affect the binding of these compounds to human albumin.

  • Fertility, pregnancy and lactation

Pregnancy

Animal studies in general do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition, or postnatal development (see section 5.3). For Atomoxetine Taj Pharma clinical data on exposed pregnancies are limited. Such data are insufficient to indicate either an association or a lack of association between Atomoxetine Taj Pharma and adverse pregnancy and/or lactation outcomes.

Atomoxetine Taj Pharma should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.

Breast-feeding

Atomoxetine Taj Pharma and/or its metabolites were excreted in the milk of rats. It is not known if Atomoxetine Taj Pharma is excreted in human milk. Because of the lack of data, Atomoxetine Taj Pharma should be avoided during breast-feeding.

  • Effects on ability to drive and use machines

Data on the effects on the ability to drive and use machines are limited. Atomoxetine Taj Pharma has a minor influence on the ability to drive and use machines. Atomoxetine Taj Pharma has been associated with increased rates of fatigue, somnolence, and dizziness relative to placebo in paediatric and adult patients. Patients should be advised to use caution when driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected by Atomoxetine Taj Pharma.

  • Undesirable effects

Paediatric population

Summary of the safety profile

In paediatric placebo-controlled trials, headache, abdominal pain1 and decreased appetite are the adverse events most commonly associated with Atomoxetine Taj Pharma, and are reported by about 19%, 18% and 16% of patients, respectively, but seldom lead to drug discontinuation (discontinuation rates are 0.1% for headache, 0.2% for abdominal pain and 0.0% for decreased appetite). Abdominal pain and decreased appetite are usually transient.

Associated with decreased appetite, some patients experienced growth retardation early in therapy in terms of both weight and height gain. On average, after an initial decrease in weight and height gain, patients treated with Atomoxetine Taj Pharma recovered to mean weight and height as predicted by group baseline data over the long-term treatment.

Nausea, vomiting and somnolence2 can occur in about 10% to 11% of patients, particularly during the first month of therapy. However, these episodes were usually mild to moderate in severity and transient, and did not result in a significant number of discontinuations from therapy (discontinuation rates ≤ 0.5%).

In both paediatric and adult placebo-controlled trials, patients taking Atomoxetine Taj Pharma experienced increases in heart rate, systolic and diastolic blood pressure (see section 4.4).

Because of its effect on noradrenergic tone, orthostatic hypotension (0.2%) and syncope (0.8%) have been reported in patients taking Atomoxetine Taj Pharma. Atomoxetine Taj Pharma should be used with caution in any condition that may predispose patients to hypotension.

The following table of undesirable effects is based on adverse event reporting and laboratory investigations from clinical trials and post marketing spontaneous reports in children and adolescents.

Tabulated list of 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).

Table 1: Adverse reactions in paediatric population

System organ class Very common Common Uncommon Rare
Metabolism and nutrition disorders Appetite decreased Anorexia (loss of appetite)
Psychiatric disorders Irritability,

Mood swings,

Insomnia3,

Agitation*,

Anxiety,

Depression and depressed mood*,

Tics*

Suicide-related events,

Aggression,

Hostility,

Emotional lability*,

Psychosis (including hallucinations)*

Nervous system disorders Headache,

Somnolence2

Dizziness Syncope,

Tremor,

Migraine,

Paraesthesia*,

Hypoaesthesia*,

Seizure**

Eye disorders Mydriasis Vision blurred
Cardiac disorders Palpitations,

Sinus tachycardia,

QT-interval prolongation**

Vascular disorders Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders Dyspnoea (see section 4.4)
Gastro-intestinal disorders Abdominal pain1,

Vomiting,

Nausea

Constipation,

Dyspepsia

Hepatobiliary disorders Blood bilirubin increased* Abnormal/increased liver function tests,

Jaundice,

Hepatitis,

Liver injury,

Acute hepatic failure*

Skin and subcutaneous tissue disorders Dermatitis,

Pruritus,

Rash

Hyperhidrosis,

Allergic reactions

Renal and urinary disorders Urinary hesitation,

Urinary retention

Reproductive system and breast disorders Priapism,

Male genital pain

General disorders and administration site conditions Fatigue,

Lethargy,

Chest pain (see section 4.4)

Asthenia
Investigations Blood pressure increased4,

Heart rate increased4

Weight decreased

1 Also includes abdominal pain upper, stomach discomfort, abdominal discomfort and epigastric discomfort.

2 Also includes sedation.

3 Includes initial, middle and terminal (early morning wakening) insomnia.

4 Heart rate and blood pressure findings are based on measured vital signs.

* See section 4.4.

** See sections 4.4 and 4.5.

CYP2D6 poor metabolisers (PM)

The following adverse events occurred in at least 2% of CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared with CYP2D6 extensive metaboliser (EM) patients: appetite decreased (24.1% of PMs, 17.0% of EMs); insomnia combined (including insomnia, middle insomnia and initial insomnia, 14.9% of PMs, 9.7% of EMs); depression combined (including depression, major depression, depressive symptom, depressed mood and dysphoria, 6.5% of PMs and 4.1% of EMs), weight decreased (7.3% of PMs, 4.4% of EMs), constipation 6.8% of PMs, 4.3% of EMs); tremor (4.5% of PMs, 0.9% of EMs); sedation (3.9% of PMs, 2.1% of EMs); excoriation (3.9% of PMs, 1.7% of EMs); enuresis (3.0% of PMs, 1.2% of EMs); conjunctivitis (2.5% of PMs, 1.2% of EMs); syncope (2.5% of PMs, 0.7% of EMs); early morning awakening (2.3% of PMs, 0.8% of EMs); mydriasis (2.0% of PMs, 0.6% of EMs). The following event did not meet the above criteria but is noteworthy: generalised anxiety disorder (0.8% of PMs and 0.1% of EMs). In addition, in trials lasting up to 10 weeks, weight loss was more pronounced in PM patients (mean of 0.6 kg in EM and 1.1kg in PM).

Adults

Summary of the safety profile

In adult ADHD clinical trials, the following system organ classes had the highest frequency of adverse events during treatment with Atomoxetine Taj Pharma: gastrointestinal, nervous system and psychiatric disorders. The most common adverse events (≥ 5%) reported were appetite decreased (14.9%), insomnia (11.3%) headache (16.3%), dry mouth (18.4%) and nausea (26.7%). The majority of these events were mild or moderate in severity and the events most frequently reported as severe were nausea, insomnia, fatigue and headache. A complaint of urinary retention or urinary hesitancy in adults should be considered potentially related to Atomoxetine Taj Pharma.

The following table of undesirable effects is based on adverse event reporting and laboratory investigations from clinical trials and post marketing spontaneous reports in adults.

Tabulated list of 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).

Table 2: Adverse reactions in adults

System organ class Very common Common Uncommon Rare
Metabolism and nutrition disorders Appetite decreased
Psychiatric disorders Insomnia2 Agitation*

Libido decreased,

Sleep disorder,

Depression and depressed mood*,

Anxiety

Suicide-related events*,

Aggression,

Hostility and emotional lability*,

Restlessness

Tics*

Psychosis (including hallucinations)*
Nervous system disorders Headache Dizziness,

Dysgeusia,

Paraesthesia,

Somnolence (including sedation),

Tremor

Syncope,

Migraine,

Hypoaesthesia*

Seizure**
Eye disorders Vision blurred
Cardiac disorders Palpitations,

Tachycardia

QT-interval prolongation**
Vascular disorders Flushing,

Hot flush

Peripheral coldness Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders Dyspnoea (see section 4.4)
Gastro-intestinal disorders Dry mouth,

Nausea

Abdominal pain1,

Constipation,

Dyspepsia,

Flatulence

Vomiting

Hepatobiliary disorders Abnormal/increased liver function tests,

Jaundice,

Hepatitis,

Liver injury,

Acute hepatic failure,

Blood bilirubin increased*

Skin and subcutaneous tissue disorders Dermatitis,

Hyperhydrosis,

Rash

Allergic reactions4,

Pruritus,

Urticaria

Musculo-skeletal and connective tissue disorders Muscle spasms
Renal and urinary disorders Dysuria,

Pollakuria

Urinary hesitation,

Urinary retention

Micturation urgency
Reproductive system and breast disorders Dysmenorrhoea,

Ejaculation disorder,

Erectile dysfunction,

Prostatitis,

Male genital pain

Ejaculation failure,

Menstruation irregular,

Orgasm abnormal

Priapism
General disorders and administration site conditions Asthenia,

Fatigue,

Lethargy,

Chills,

Feeling jittery,

Irritability,

Thirst

Feeling cold,

Chest pain (see section 4.4)

Investigations Blood pressure increased3,

Heart rate increased3

Weight decreased

1 Also includes abdominal pain upper, stomach discomfort, abdominal discomfort and epigastric discomfort.

2 Also includes initial insomnia, middle insomnia and terminal (early morning wakening) insomnia.

3 Heart rate and blood pressure findings are based on measured vital signs.

4 Includes anaphylactic reactions and angioneurotic oedema.

* See section 4.4.

** See sections 4.4 and 4.5.

CYP2D6 poor metabolisers (PM)

The following adverse events occurred in at least 2% of CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared with CYP2D6 extensive metaboliser (EM) patients: vision blurred (3.9% of PMs, 1.3% of EMs), dry mouth (34.5% of PMs, 17.4% of EMs), constipation (11.3% of PMs, 6.7% of EMs), feeling jittery (4.9% of PMs, 1.9% of EMs), decreased appetite (23.2% of PMs, 14.7% of EMs), tremor (5.4% of PMs, 1.2% of EMs), insomnia (19.2% of PMs, 11.3% of EMs), sleep disorder (6.9% of PMs, 3.4% of EMs), middle insomnia (5.4% of PMs, 2.7% of EMs), terminal insomnia (3 % of PMs, 0.9% of EMs), urinary retention (5.9% of PMs, 1.2% of EMs), erectile dysfunction (20.9% of PMs, 8.9% of EMs), ejaculation disorder (6.1% of PMs, 2.2% of EMs), hyperhidrosis (14.8% of PMs, 6.8% of EMs), peripheral coldness (3% of PMs, 0.5% of EMs).

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

Signs and symptoms

During post-marketing, there have been reports of non-fatal acute and chronic overdoses of Atomoxetine Taj Pharma alone. The most commonly reported symptoms accompanying acute and chronic overdoses were gastrointestinal symptoms, somnolence, dizziness, tremor and abnormal behaviour. Hyperactivity and agitation have also been reported. Signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g. tachycardia, blood pressure increased, mydriasis, dry mouth) were also observed and reports of pruritus and rash have been received. Most events were mild to moderate. In some cases of overdose involving Atomoxetine Taj Pharma, seizures have been reported and very rarely QT prolongation. There have also been reports of fatal, acute overdoses involving a mixed ingestion of Atomoxetine Taj Pharma and at least one other drug.

There is limited clinical trial experience with Atomoxetine Taj Pharma overdose.

Management

An airway should be established. Activated charcoal may be useful in limiting absorption if the patient presents within 1 hour of ingestion. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures. The patient should be observed for a minimum of 6 hours. Because Atomoxetine Taj Pharma is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose.

  1. Pharmacological properties
    • Pharmacodynamic properties

Pharmacotherapeutic group: Psychoanaleptics, centrally acting sympathomimetics.

Mechanism of action and pharmacodynamic effects

Atomoxetine Taj Pharma is a highly selective and potent inhibitor of the pre-synaptic noradrenaline transporter, its presumed mechanism of action, without directly affecting the serotonin or dopamine transporters. Atomoxetine Taj Pharma has minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors. Atomoxetine Taj Pharma has two major oxidative metabolites: 4-hydroxyAtomoxetine Taj Pharma and N-desmethylAtomoxetine Taj Pharma. 4-hydroxyAtomoxetine Taj Pharma is equipotent to Atomoxetine Taj Pharma as an inhibitor of the noradrenaline transporter but, unlike Atomoxetine Taj Pharma, this metabolite also exerts some inhibitory activity at the serotonin transporter. However, any effect on this transporter is likely to be minimal, as the majority of 4-hydroxyAtomoxetine Taj Pharma is further metabolised such that it circulates in plasma at much lower concentrations (1% of Atomoxetine Taj Pharma concentration in extensive metabolisers and 0.1% of Atomoxetine Taj Pharma concentration in poor metabolisers). N-desmethylAtomoxetine Taj Pharma has substantially less pharmacological activity compared with Atomoxetine Taj Pharma. It circulates in plasma at lower concentrations in extensive metabolisers and at comparable concentrations to the parent drug in poor metabolisers at steady-state.

Atomoxetine Taj Pharma is not a psychostimulant and is not an amphetamine derivative. In a randomised, double-blind, placebo-controlled, abuse-potential study in adults comparing effects of Atomoxetine Taj Pharma and placebo, Atomoxetine Taj Pharma was not associated with a pattern of response that suggested stimulant or euphoriant properties.

Clinical efficacy and safety

Paediatric population

Atomoxetine Taj Pharma has been studied in trials in over 5,000 children and adolescents with ADHD. The acute efficacy of Atomoxetine Taj Pharma in the treatment of ADHD was initially established in six randomised, double-blind, placebo-controlled trials of six to nine weeks duration. Signs and symptoms of ADHD were evaluated by a comparison of mean change from baseline to endpoint for Atomoxetine Taj Pharma-treated and placebo-treated patients. In each of the six trials, Atomoxetine Taj Pharma was statistically significantly superior to placebo in reducing ADHD signs and symptoms.

Additionally, the efficacy of Atomoxetine Taj Pharma in maintaining symptom response was demonstrated in a 1 year, placebo-controlled trial with over 400 children and adolescents, primarily conducted in Europe (approximately 3 months of open-label acute treatment followed by 9 months of double-blind, placebo-controlled maintenance treatment). The proportion of patients relapsing after 1 year was 18.7% and 31.4% (Atomoxetine Taj Pharma and placebo, respectively). After 1 year of Atomoxetine Taj Pharma treatment, patients who continued Atomoxetine Taj Pharma for 6 additional months were less likely to relapse or to experience partial symptom return compared with patients who discontinued active treatment and switched to placebo (2% versus 12%, respectively). For children and adolescents, periodic assessment of the value of ongoing treatment during long-term treatment should be performed.

Atomoxetine Taj Pharma was effective as a single daily dose and as a divided dose administered in the morning and late afternoon/early evening. Atomoxetine Taj Pharma administered once daily demonstrated statistically significantly greater reduction in severity of ADHD symptoms compared with placebo, as judged by teachers and parents.

Active comparator studies

In a randomised, double-blind, parallel group, 6-week paediatric study to test the non-inferiority of Atomoxetine Taj Pharma to a standard extended-release methylphenidate comparator, the comparator was shown to be associated with superior response rates compared to Atomoxetine Taj Pharma. The percentage of patients classified as responders was 23.5% (placebo), 44.6% (Atomoxetine Taj Pharma) and 56.4% (methylphenidate). Both Atomoxetine Taj Pharma and the comparator were statistically superior to placebo and methylphenidate was statistically superior to Atomoxetine Taj Pharma (p = 0.016). However, this study excluded patients who were stimulant nonresponders.

Adult population

Atomoxetine Taj Pharma has been studied in trials in over 4800 adults who met DSM-IV diagnostic criteria for ADHD. The acute efficacy of Atomoxetine Taj Pharma in the treatment of adults was established in six randomised, double-blind, placebo-controlled trials of ten to sixteen weeks’ duration. Signs and symptoms of ADHD were evaluated by a comparison of mean change from baseline to endpoint for Atomoxetine Taj Pharma treated and placebo treated patients. In each of the six trials, Atomoxetine Taj Pharma was statistically significantly superior to placebo in reducing ADHD signs and symptoms (table 3). Atomoxetine Taj Pharma-treated patients had statistically significantly greater improvements in clinical global impression of severity (CGI-S) at endpoint compared to placebo-treated patients in all of the 6 acute studies, and statistically significantly greater improvements in ADHD-related functioning in all 3 of the acute studies in which this was assessed (table 3). Long-term efficacy was confirmed in 2 six-month placebo controlled studies, but not demonstrated in a third (table 3).

Table 3: Mean changes in efficacy measures for placebo-controlled studies

Changes from baseline in patients with at least one post-baseline value (LOCF)
CAARS-Inv:SV or AISRSa CGI-S AAQoL
Study Treatment N Mean change p-value Mean change p-value Mean change p-value
Acute studies
LYAA ATX

PBO

133

134

-9.5

-6.0

0.006 -0.8

-0.4

0.011
LYAO ATX

PBO

124

124

-10.5

-6.7

0.002 -0.9

-0.5

0.002
LYBY ATX

PBO

72

75

-13.6

-8.3

0.007 -1.0

-0.7

0.048
LYDQ ATX

PBO

171

158

-8.7

-5.6

<0.001 -0.8

-0.6

0.022 14.9

11.1

0.030
LYDZ ATX

PBO

192

198

-10.7

-7.2

<0.001 -1.1

-0.7

<0.001 15.8

11.0

<0.005
LYEE ATX

PBO

191

195

-14.3

-8.8

<0.001 -1.3

-0.8

<0.001 12.83

8.20

<0.001
Long-term studies
LYBV ATX

PBO

185

109

-11.6

-11.5

0.412 -1.0

-0.9

0.173 13.90

11.18

0.045
LYCU ATX

PBO

214

216

-13.2

-10.2

0.005 -1.2

-0.9

0.001 13.14

8.62

0.004
LYCW ATX

PBO

113

120

-14.3

-8.3

<0.001 -1.2

-0.7

<0.001

Abbreviations: AAQoL = Adult ADHD Quality of Life Total Score; AISRS = Adult ADHD Investigator Symptom Rating Scale Total Score; ATX = Atomoxetine Taj Pharma; CAARS-Inv:SV = Conners Adult ADHD Rating Scale, Investigator Rated, screening version Total ADHD Symptom Score; CGI-S = Clinical Global Impression of Severity; LOCF = last observation carried forward; PBO = placebo.

a ADHD symptom scales; results shown for Study LYBY are for AISRS; results for all others are for CAARS-Inv:SV.

In sensitivity analyses using a baseline-observation-carried-forward method for patients with no post-baseline measure (i.e. all patients treated), results were consistent with results shown in table 3.

In analyses of clinically meaningful response in all 6 acute and both successful long-term studies, using a variety of a priori and post hoc definitions, Atomoxetine Taj Pharma-treated patients consistently had statistically significantly higher rates of response than placebo-treated patients (table 4).

Table 4: Number (n) and percent of patients meeting criteria for response in pooled placebo-controlled studies

Response defined by improvement of at least 1 point on CGI-S Response defined by 40% improvement on CAARS-Inv:SV at endpoint
Group Treatment N n (%) p-value N n (%) p-value
Pooled acute studiesa
ATX

PBO

640

652

401 (62.7%)

283 (43.4%)

<0.001 841

851

347 (41.3%)

215 (25.3%)

<0.001
Pooled long-term studiesa
ATX

PBO

758

611

482 (63.6%)

301 (49.3%)

<0.001 663

557

292 (44.0%)

175 (31.4%)

<0.001

a Includes all studies in Table 3 except: Acute CGI-S response analysis excludes 2 studies in patients with comorbid disorders (LYBY, LYDQ); Acute CAARS response analysis excludes 1 study in which the CAARS was not administered (LYBY).

In two of the acute studies, patients with ADHD and comorbid alcoholism or social anxiety disorder were studied and in both studies ADHD symptoms were improved. In the study with comorbid alcohol abuse, there were no differences between Atomoxetine Taj Pharma and placebo with respect to alcohol use behaviours. In the study with co-morbid anxiety, the comorbid condition of anxiety did not deteriorate with Atomoxetine Taj Pharma treatment.

The efficacy of Atomoxetine Taj Pharma in maintaining symptom response was demonstrated in a study where after an initial active treatment period of 24 weeks, patients who met criteria for clinically meaningful response (as defined by improvement on both CAARS-Inv:SV and CGI-S scores) were randomized to receive Atomoxetine Taj Pharma or placebo for an additional 6 months of double-blind treatment. Higher proportions of Atomoxetine Taj Pharma-treated patients than placebo-treated patients met criteria for maintaining clinically meaningful response at the end of 6 months (64.3% vs. 50.0%; p= 0.001). Atomoxetine Taj Pharma-treated patients demonstrated statistically significantly better maintenance of functioning than placebo-treated patients as shown by lesser mean change on the Adult ADHD Quality of Life (AAQoL) total score at the 3-month interval (p= 0.003) and at the 6-month interval (p= 0.002).

QT/QTc study

A thorough QT/QTc study, conducted in healthy adult CYP2D6 poor metaboliser (PM) subjects dosed up to 60mg of Atomoxetine Taj Pharma BID, demonstrated that at maximum expected concentrations the effect of Atomoxetine Taj Pharma on QTc-interval was not significantly different from placebo. There was a slight increase in QTc-interval with increased Atomoxetine Taj Pharma concentration.

  • Pharmacokinetic properties

The pharmacokinetics of Atomoxetine Taj Pharma in children and adolescents are similar to those in adults. The pharmacokinetics of Atomoxetine Taj Pharma has not been evaluated in children under 6 years of age.

Absorption

Atomoxetine Taj Pharma is rapidly and almost completely absorbed after oral administration, reaching mean maximal observed plasma concentration (Cmax) approximately 1 to 2 hours after dosing. The absolute bioavailability of Atomoxetine Taj Pharma following oral administration ranged from 63% to 94%, depending upon inter-individual differences in the modest first-pass metabolism. Atomoxetine Taj Pharma can be administered with or without food.

Distribution

Atomoxetine Taj Pharma is widely distributed and is extensively (98%) bound to plasma proteins, primarily albumin.

Biotransformation

Atomoxetine Taj Pharma undergoes biotransformation primarily through the cytochrome P450 2D6 (CYP2D6) enzymatic pathway. Individuals with reduced activity of this pathway (poor metabolisers) represent about 7% of the Caucasian population and have higher plasma concentrations of Atomoxetine Taj Pharma compared with people with normal activity (extensive metabolisers). For poor metabolisers, AUC of Atomoxetine Taj Pharma is approximately 10-fold greater and Css max is about 5-fold greater than extensive metabolisers. The major oxidative metabolite formed is 4-hydroxyAtomoxetine Taj Pharma that is rapidly glucuronidated. 4-hydroxyAtomoxetine Taj Pharma is equipotent to Atomoxetine Taj Pharma but circulates in plasma at much lower concentrations. Although 4-hydroxyAtomoxetine Taj Pharma is primarily formed by CYP2D6, in individuals that lack CYP2D6 activity, 4-hydroxyAtomoxetine Taj Pharma can be formed by several other cytochrome P450 enzymes, but at a slower rate. Atomoxetine Taj Pharma does not inhibit or induce CYP2D6 at therapeutic doses.

Cytochrome P450 enzymes

Atomoxetine Taj Pharma did not cause clinically significant inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6, and CYP2C9.

Elimination

The mean elimination half-life of Atomoxetine Taj Pharma after oral administration is 3.6 hours in extensive metabolisers and 21 hours in poor metabolisers. Atomoxetine Taj Pharma is excreted primarily as 4-hydroxyAtomoxetine Taj Pharma-O-glucuronide, mainly in the urine.

Linearity/non-linearity

Pharmacokinetics of Atomoxetine Taj Pharma is linear over the range of doses studied in both extensive and poor metabolisers.

Special populations

Hepatic impairment results in a reduced Atomoxetine Taj Pharma clearance, increased Atomoxetine Taj Pharma exposure (AUC increased 2-fold in moderate impairment and 4-fold in severe impairment), and a prolonged half-life of parent drug compared to healthy controls with the same CYP2D6 extensive metaboliser genotype. In patients with moderate to severe hepatic impairment (Child-Pugh class B and C) initial and target doses should be adjusted (see section 4.2).

Atomoxetine Taj Pharma mean plasma concentrations for end-stage renal disease (ESRD) subjects were generally higher than the mean for healthy control subjects shown by Cmax (7% difference) and AUC0 – ∞ (about 65% difference) increases. After adjustment for body weight, the differences between the two groups are minimised. Pharmacokinetics of Atomoxetine Taj Pharma and its metabolites in individuals with ESRD suggest that no dose adjustment would be necessary (see section 4.2).

  • Preclinical safety data

Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, or reproduction and development. Due to the dose limitation imposed by the clinical (or exaggerated pharmacological) response of the animals to the drug combined with metabolic differences among species, maximum tolerated doses in animals used in non-clinical studies produced Atomoxetine Taj Pharma exposures similar to or slightly above those that are achieved in CYP2D6 poor metabolising patients at the maximum recommended daily dose.

A study was conducted in young rats to evaluate the effects of Atomoxetine Taj Pharma on growth and neurobehavioural and sexual development. Slight delays in onset of vaginal patency (all doses) and preputial separation (≥ 10mg/kg/day), and slight decreases in epididymal weight and sperm number (≥ 10mg/kg/day) were seen; however, there were no effects on fertility or reproductive performance. The significance of these findings to humans is unknown.

Pregnant rabbits were treated with up to 100mg/kg/day of Atomoxetine Taj Pharma by gavage throughout the period of organogenesis. At this dose, in 1 of 3 studies, decrease in live foetuses, increase in early resorption, slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. These findings were observed at doses that caused slight maternal toxicity. The incidence of these findings is within historical control values. The no-effect dose for these findings was 30mg/kg/day. Exposure (AUC) to unbound Atomoxetine Taj Pharma in rabbits, at 100mg/kg/day, was approximately 3.3-times (CYP2D6 extensive metabolisers) and 0.4-times (CYP2D6 poor metabolisers) those in humans at the maximum daily dose of 1.4mg/kg/day. The findings in one of three rabbit studies were equivocal and the relevance to man is unknown.

  1. Pharmaceutical particulars
  • List of excipients

Pregelatinized maize starch,

Magnesium stearate.

Atomoxetine Taj Pharma strength Body Cap
25mg Titanium dioxide,

Gelatin

Titanium dioxide,

Indigotine-FD&C Blue 2,

Gelatin

10A1 Black ink ((Shellac glaze 45% (20% esterified) in ethanol, Iron oxide black, Propylene glycol, Ammonium hydroxide 28%.

  • Incompatibilities

Not applicable.

  • Shelf life

2 years.

  • Special precautions for storage

Store in the original package in order to protect from moisture.

  • Nature and contents of container

Pack Size:

PVC/Aclar/PVC – Al blisters, paper folding box.

Each pack contains 7, 14, 28, 30, 56, 84, 60, 90, capsules.

Each carton contains 100, 120, 240, 360 and 500 hard gelatin capsules

Not all pack sizes may be marketed.

  • Special precautions for disposal and other handling

The capsules are not intended to be opened. Atomoxetine Taj Pharma is an ocular irritant. In the event of capsules content coming in contact with the eye, the affected eye should be flushed immediately with water, and medical advice obtained. Hands and any potentially contaminated surfaces should be washed as soon as possible. Any unused medicinal product or waste material should be disposed of in accordance with local 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

Atomoxetine capsule USP 80mg Taj Pharma

Package leaflet: Information for the patient

Atomoxetine Taj Pharma

Read all of this leaflet carefully before you (or a child in your care) starts 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 or for your child 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).

In the next sections, the word You means You or a child in your care.

What is in this leaflet:

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

1. WHAT Atomoxetine Taj Pharma IS AND WHAT IT IS USED FOR

What it is used for

Atomoxetine Taj Pharma hard capsules contain Atomoxetine Taj Pharma and are used to treat attention-deficit and hyperactivity disorder (ADHD). It is used in children over six years of age, in young people and in adults. It is used only as a part of the total treatment of the disease which also requires treatments which do not involve medicines, such as counselling and behavioural therapy.

It is not for use as a treatment for ADHD in children under 6 years of age as it is not known if the drug works or is safe in these people.

In adults, Atomoxetine Taj Pharma is used to treat ADHD when the symptoms are very troublesome and affect your work or social life and when you have had symptoms of the disease as a child.

How it works

Atomoxetine Taj Pharma increases the amount of noradrenaline in the brain. This is a chemical that is produced naturally, and increases attention and decreases impulsiveness and hyperactivity in patients with ADHD. This medicine has been prescribed to help control the symptoms of ADHD. This medicine is not a stimulant and is therefore not addictive.

It may take a few weeks after you start the medicine for your symptoms to fully improve.

About ADHD

Children and young people with ADHD find it hard to sit still and hard to concentrate. It is not their fault that they cannot do these things. Many children and young people struggle to do these things. However, with ADHD this can cause problems with everyday life. Children and young people with ADHD may have difficulty learning and doing homework. They find it hard to behave well at home, at school or in other places. ADHD does not affect the intelligence of a child or young person.

Adults with ADHD find it difficult to do all the things that children find difficult however this may mean they have problems with work, relationships, low self-esteem and education.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE Atomoxetine Taj Pharma

Do not take Atomoxetine Taj Pharma

  • if you are allergic to Atomoxetine Taj Pharma or any of the other ingredients of this medicine (listed in section 6).
  • if you took a medicine known as a monoamine oxidase inhibitor (MAOI), for example phenelzine, in the last two weeks. An MAOI is sometimes used for depression and other mental-health problems; taking Atomoxetine Taj Pharma with an MAOI could cause serious side effects or be life-threatening. (You also need to wait at least 14 days after you stop taking Atomoxetine Taj Pharma before you take an MAOI).
  • if you have an eye disease called narrow-angle glaucoma (increased pressure in your eye).
  • if you have serious problems with your heart which may be affected by an increase in heart rate and/or blood pressure, as this may be an effect of Atomoxetine Taj Pharma.
  • if you have serious problems with the blood vessels in your brain – such as a stroke, swelling and weakening of part of a blood vessel (aneurysm) or narrow or blocked blood vessels.
  • if you have a tumour of your adrenal gland (pheochromocytoma).

Do not take Atomoxetine Taj Pharma if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before you take Atomoxetine Taj Pharma. This is because Atomoxetine Taj Pharma can make these problems worse.

Warnings and precautions

Both adult and children should be aware of the following warnings and precautions. Talk to your doctor or pharmacist before taking Atomoxetine Taj Pharma if you have:

  • thoughts about killing yourself or trying to kill yourself.
  • problems with your heart (including heart defects) or an increased heartbeat. Atomoxetine Taj Pharma can increase your heart rate (pulse). Sudden death has been reported in patients with heart defects.
  • high blood pressure. Atomoxetine Taj Pharma can increase blood pressure.
  • low blood pressure. Atomoxetine Taj Pharma can cause dizziness or fainting in people with low blood pressure.
  • problems with sudden changes in your blood pressure or your heart rate.
  • cardiovascular disease or past medical history of stroke.
  • liver problems. You may need a lower dose.
  • psychotic symptoms including hallucinations (hearing voices or seeing things which are not there), believing things that are not true or being suspicious.
  • mania (feeling elated or over-excited, which causes unusual behaviour) and agitation.
  • aggressive feelings.
  • unfriendly and angry (hostility) feelings.
  • a history of epilepsy or have had seizures for any other reason. Atomoxetine Taj Pharma might lead to an increase in seizure frequency.
  • different moods than usual (mood swings) or feel very unhappy.
  • hard-to-control, repeated twitching of any parts of the body or you repeat sounds and words.

Tell your doctor or pharmacist if any of the above applies to you before starting treatment. This is because Atomoxetine Taj Pharma can make these problems worse. Your doctor will want to monitor how the medicine affects you.

Checks that your doctor will make before you start to take Atomoxetine Taj Pharma

These checks are to decide if Atomoxetine Taj Pharma is the correct medicine for you.

Your doctor will measure your:

  • blood pressure and your heart rate (pulse) before and during the time you take Atomoxetine Taj Pharma.
  • height and weight if you are a child or teenager during the time you take Atomoxetine Taj Pharma.

Your doctor will talk to you about:

  • any other medicines you are taking.
  • whether there is any family history of sudden unexplained death.
  • any other medical problems (such as heart problems) you or your family may have.

It is important that you provide as much information as you can. This will help your doctor decide if Atomoxetine Taj Pharma is the correct medicine for you. Your doctor may decide that other medical tests are needed before you start taking this medicine.

Other medicines and Atomoxetine Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes non-prescription medicines.

Your doctor will decide if you can take Atomoxetine Taj Pharma with your other medicines and in some cases your doctor may need to adjust your dose or increase your dose much more slowly.

Do not take Atomoxetine Taj Pharma with medicines called MAOIs (monoamine oxidase inhibitors) used for depression (see section 2 “Do not take Atomoxetine Taj Pharma”).

If you are taking other medicines, Atomoxetine Taj Pharma may affect how well they work or may cause side effects. If you are taking any of the following medicines, check with your doctor or pharmacist before taking Atomoxetine Taj Pharma:

  • Medicines that increase blood pressure or are used to control blood pressure.
  • Medicines such as antidepressants, for example imipramine, venlafaxine, mirtazapine, fluoxetine and paroxetine.
  • Some cough and cold remedies which contain medicines that can affect blood pressure. It is important to check with your pharmacist when you get any of these products.
  • Some medicines used to treat mental-health conditions.
  • Medicines that are known to increase the risk of seizures.
  • Some medicines that cause Atomoxetine Taj Pharma to stay in the body for longer than normal (such as quinidine and terbinafine).
  • Salbutamol (a medicine to treat asthma) which when taken by mouth or injected may make you feel as if your heart is racing, but this will not make your asthma worse.

The medicines below may lead to an increased risk of an abnormal rhythm of the heart when taken with Atomoxetine Taj Pharma:

  • medicines used to control the rhythm of the heart,
  • medicines which change the concentration of salts in the blood,
  • medicines for malaria prevention and treatment,
  • some antibiotic medicines (such as erythromycin and moxifloxacin)

If you are not sure about whether any medicines you are taking are included in the list above, ask your doctor or pharmacist before taking Atomoxetine Taj Pharma.

Pregnancy, breast-feeding and fertility

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.

It is not known if this medicine can affect an unborn baby or pass into breast milk.

This medicine should not be used during pregnancy, unless your doctor has advised you to do so.

You should either avoid taking this medicine if you are breast-feeding or discontinue breast-feeding.

Driving and using machines

You may feel tired, sleepy or dizzy after taking Atomoxetine Taj Pharma.

You should be careful if you are driving a car or operating machinery until you know how Atomoxetine Taj Pharma affects you. If you feel tired, sleepy or dizzy you should not drive or operate machinery.

Important information about the content of the capsules

Do not open Atomoxetine Taj Pharma capsules because the contents of the capsule can irritate the eye. If the contents of the capsules come into contact with the eye, the affected eye should be flushed immediately with water and medical advice obtained. Hands and any other part of the body that may have come into contact with the capsule contents should also be washed as soon as possible.

  1. HOW TO TAKE Atomoxetine 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.

Atomoxetine Taj Pharma is usually taken one or two times a day (morning and late afternoon or early evening).

Children should not take this medicine without help from an adult.

If you are taking Atomoxetine Taj Pharma once a day and experience sleepiness or feel sick, your doctor may change your treatment schedule to twice a day.

The capsules should be swallowed whole, either with or without food.

The capsules should not be opened and the contents inside the capsules should not be removed and taken in any other way. Taking the medicine at the same time each day may help you remember to take it.

How much to take

If you are a child or teenager (6 years or older)

Your doctor will tell you how much Atomoxetine Taj Pharma you should take and will calculate this according to your body weight. The doctor will normally start you on a lower dose before increasing the amount of Atomoxetine Taj Pharma you need to take, according to your body weight.

  • Body weight up to 70 kg: a starting total daily dose of 0.5mg per kg of body weight for a minimum of 7 days. Your doctor may then decide to increase this to the usual maintenance dose of about 1.2mg per kg of body weight daily.
  • Body weight over 70 kg: a starting total daily dose of 40mg for a minimum of 7 days. Your doctor may then decide to increase this to the usual maintenance dose of 80mg daily. The maximum daily dose your doctor will prescribe is 100mg.

Adults

Atomoxetine Taj Pharma should be started at a total daily dose of 40mg for a minimum of 7 days. Your doctor may then decide to increase this to the usual maintenance dose of 80mg -100mg daily. The maximum daily dose your doctor will prescribe is 100mg.

If you have problems with your liver your doctor may prescribe a lower dose.

If you take more Atomoxetine Taj Pharma than you should

If you take more than the prescribed dose, contact your doctor or the nearest hospital casualty department immediately and tell them how many capsules you have taken. The most commonly reported symptoms accompanying overdoses are gastrointestinal symptoms, sleepiness, dizziness, tremor and abnormal behaviour.

If you forget to take Atomoxetine Taj Pharma

If you miss a dose, you should take it as soon as possible, but you should not take more than your total daily dose in any 24-hour period. Do not take a double dose to make up for a forgotten dose.

If you stop taking Atomoxetine Taj Pharma

If you stop taking Atomoxetine Taj Pharma there are usually no side effects, but your ADHD symptoms may return. You should talk to your doctor first before you stop treatment.

Things your doctor will do when you are on treatment

Your doctor will do some tests:

  • before you start – to make sure that Atomoxetine Taj Pharma is safe and will be of benefit
  • after you start – they will be done at least every 6 months, but possibly more often

They will also be done when the dose is changed. These tests will include:

  • measuring height and weight in children and young people
  • measuring blood pressure and heart rate
  • checking whether you have any problems or if side effects have got worse while taking Atomoxetine Taj Pharma

Long-term treatment

Atomoxtine does not need to be taken forever. If you take Atomoxetine Taj Pharma for more than a year, your doctor will review your treatment, to see if the medicine is still needed.

If you have any 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.

Although some people get side effects, most people find that Atomoxetine Taj Pharma helps them. Your doctor will talk to you about these side effects.

Some side effects could be serious. If you have any of the side effects below, see a doctor straight away.

Uncommon (may affect up to 1 in 100 people):

  • feeling or having a very fast heartbeat, abnormal rhythms of the heart
  • thinking about or feeling like killing yourself
  • feeling aggressive
  • feeling unfriendly and angry (hostility)
  • mood swings or mood changes
  • serious allergic reaction with symptoms of swelling of the face and throat, difficulty breathing, hives (small raised, itchy patches of skin)
  • seizures
  • psychotic symptoms including hallucinations (hearing voices or seeing things which are not there), believing things that are not true or being suspicious

Children and young adults aged under 18 have an increased risk of side effects such as:

  • thinking about or feeling like killing yourself (may affect up to 1 in 100 people)
  • mood swings or mood changes (may affect up to 1 in 10 people)

Adults have a reduced risk (may affect up to 1 in 1000 people) of side effects such as:

  • seizures
  • psychotic symptoms including hallucinations (hearing voices or seeing things which are not there), believing things that are not true or being suspicious

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

  • liver injury

You should stop taking Atomoxetine Taj Pharma and call your doctor immediately if you have any of the following:

  • dark urine
  • yellow skin or yellow eyes
  • tummy pain which is sore when you press it (tenderness) on the right side just below your ribs
  • a feeling of sickness (nausea) that is unexplained
  • tiredness
  • itching
  • feeling that you are coming down with the flu.

Other side effects reported include the following. If they get serious, tell your doctor or pharmacist.

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

CHILDREN and YOUNG PEOPLE over 6 years

  • headache
  • pain in the stomach
  • decreased appetite (not feeling hungry)
  • feeling sick
  • being sick
  • sleepiness
  • increased blood pressure
  • increased heart rate (pulse)

These effects may disappear after a while in most patients.

ADULTS

  • feeling sick
  • dry mouth
  • headache
  • decreased appetite (not feeling hungry)
  • problems getting to sleep, staying asleep and waking early
  • increased blood pressure
  • increased heart rate (pulse)

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

CHILDREN and YOUNG PEOPLE over 6 years

  • being irritable or agitated
  • problems sleeping including waking early
  • depression
  • feeling sad or hopeless
  • feeling anxious
  • tics
  • large pupils (the dark centre of the eye)
  • dizziness
  • constipation
  • loss of appetite
  • upset stomach, indigestion
  • swollen, reddened and itchy skin
  • rash
  • feeling lazy (lethargy)
  • chest pain
  • tiredness
  • weight loss

ADULTS

  • feeling agitated
  • decreased interest in sex
  • sleep disturbance
  • depression
  • feeling sad or hopeless
  • feeling anxious
  • dizziness
  • an abnormal taste or change in taste that will not go away
  • tremor
  • tingling or numbness in the hands or feet
  • sleepiness, drowsy, feeling tired
  • constipation
  • stomach ache
  • indigestion
  • wind (flatulence)
  • being sick
  • hot flush or flushing
  • feeling or having a very fast heartbeat
  • swollen, reddened and itchy skin
  • increased sweating
  • rash
  • problems going to the toilet such as not be able to urinate, frequent or hesitant urinating, pain on urinating
  • inflammation of the prostate gland (prostatitis)
  • groin pain in men
  • failure to obtain an erection
  • retarded orgasm
  • difficulty maintaining an erection
  • menstrual cramps
  • lack of strength or energy
  • tiredness
  • feeling lazy (lethargy)
  • chills
  • feeling irritable, jittery
  • feeling thirsty
  • weight loss

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

CHILDREN and YOUNG PEOPLE over 6 years

  • fainting
  • tremor
  • migraine
  • blurred vision
  • abnormal skin sensations such as burning, prickling, itching or tingling
  • tingling or numbness in the hands or feet
  • seizure (fits)
  • feeling or having a very fast heartbeat (QT prolongation)
  • shortness of breath
  • increased sweating
  • itchy skin
  • lack of strength or energy

ADULTS

  • restlessness
  • tics
  • fainting
  • migraine
  • blurred vision
  • heart rhythm abnormal (QT prolongation)
  • feeling cold in fingers and toes
  • chest pain
  • shortness of breath
  • raised red itchy rashes (hives)
  • muscle spasms
  • an urge to urinate
  • abnormal or absence of orgasm
  • irregular menstruation
  • ejaculation failure

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

CHILDREN and YOUNG PEOPLE over 6 years

  • poor blood circulation which makes toes and fingers numb and pale (Raynaud’s disease)
  • problems going to the toilet such as frequent or hesitant urinating, pain on urinating
  • prolonged and painful erections
  • groin pain in males

ADULTS

  • poor blood circulation which makes toes and fingers numb and pale (Raynaud’s disease)
  • prolonged and painful erections

Effects on growth

Some children experience reduced growth (weight and height) when they start taking Atomoxetine Taj Pharma. However, with long-term treatment, children recover to the weight and height for their age range. Your doctor will watch your child’s height and weight over time. If your child is not growing or gaining weight as expected, your doctor may change your child’s dose or decide to stop Atomoxetine Taj Pharma temporarily.

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 ATOMOXETINE TAJ PHARMA

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

Store in the original package in order to protect from moisture.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Do not use this medicine if you notice any visible signs of deterioration.

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 protect the environment.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Atomoxetine Taj Pharma contains

  • The active substance is Atomoxetine Taj Pharma hydrochloride. Each hard capsule contains Atomoxetine Taj Pharma hydrochloride equivalent to 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or 100mg of Atomoxetine Taj Pharma.
  • The other ingredients are pregelatinized Maize Starch, Magnesium Stearate, Titanium Dioxide, Gelatin, 10A1 Black Ink (Shellac Glaze 45% (20% Esterified) In Ethanol, Iron Oxide Black, Propylene Glycol, Ammonium Hydroxide 28%).

What Atomoxetine Taj Pharma looks like and contents of the pack

Atomoxetine capsule USP 10mg Taj Pharma
Atomoxetine capsule USP 18mg Taj Pharma
Atomoxetine capsule USP 25mg Taj Pharma
Atomoxetine capsule USP 40mg Taj Pharma
Atomoxetine capsule USP 60mg Taj Pharma
Atomoxetine capsule USP 80mg Taj Pharma
Atomoxetine capsule USP 100mg Taj Pharma

Each strength of Atomoxetine White capsule of size 4 containing white to off-white powder.

Pack Size:

The capsules are packed in PVC/Aclar/PVC – Al blisters and enclosed in a paper folding box.

Each pack contains 7, 14, 28, 30, 56, 84, 60, 90, capsules.

Each carton contains 100, 120, 240, 360 and 500 hard gelatin capsules

Not all pack sizes may be marketed.