Duloxetine Dr 30 &Amp, 60 Teva 30mg. 60mg Capsule

DULOXETINE TEVA DR is indicated for the treatment of depression (as defined by DSM-IV criteria).

DULOXETINE TEVA DR is indicated for the treatment of diabetic peripheral neuropathic pain (DPNP).

Posology:

Depression: DULOXETINE TEVA DR should be initiated and maintained at a dose of 60 mg once daily without regard to meals. Although doses up to 120 mg per day have been used the efficacy of the 120 mg dose was not statistically significantly different from that of the 60 mg once daily dose and the adverse event rate was higher with the 120 mg dose.

Diabetic peripheral neuropathic pain: DULOXETINE TEVA DR should be administered at a dose of 60 mg once daily without regard to meals. Although doses up to 120 mg per day have been used the efficacy of the 120 mg dose was not statistically significantly different from that of the 60 mg once daily dose and the adverse event rate was higher with the 120 mg dose.

Special populations:

Renal impairment: Initial dose should be 30 mg once daily in patients with mild to moderate impairment of renal function (see section 4.3 and 5.2).

Hepatic impairment: Initial dose should be lower or less frequent in patients with mild to moderate impairment of hepatic function (see section 4.3 and 5.2).

Age: No dosage adjustment is recommended for elderly patients on the basis of age. Safety and efficacy have not been established in patients under the age of 18 years.

Method of administration: For oral use.

• Hypersensitivity to duloxetine or to any of the excipients listed in section 6.1
• Pregnancy and lactation.
• Severe impairment of hepatic function.
• Advanced renal impairment (creatinine clearance < 30 ml/min).
• Concomitant use of monoamine oxidase inhibitors (MAOIs) (see section 4.4).
• The initiation of treatment with DULOXETINE TEVA DR 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).

MAOIs (Monoamine Oxidase Inhibitors): DULOXETINE TEVA DR should not be used within at least 14 days of discontinuing treatment with a MAOI. Based on the half-life of DULOXETINE TEVA DR, at least 5 days should be allowed after stopping DULOXETINE TEVA DR, before starting a MAOI.

Mania and seizures: DULOXETINE TEVA DR 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, therefore, caution should be used when prescribing DULOXETINE TEVA DR to patients with increased intraocular pressure or those at risk of acute narrow-angle glaucoma.

Blood pressure and heart rate: DULOXETINE TEVA DR 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. Cases of hypertensive crisis have been reported with duloxetine, 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 TEVA DR 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 is used with medicines that may impair its metabolism (see section 4.5). For patients who experience a sustained increase in blood pressure while receiving DULOXETINE TEVA DR either dose reduction or gradual discontinuation should be considered (see section 4.8). In patients with uncontrolled hypertension DULOXETINE TEVA DR should not be initiated (see section 4.3).

Renal impairment: Increased plasma concentrations of duloxetine 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: Serotonin syndrome, a potentially life-threatening condition, may occur with duloxetine treatment, particularly with concomitant use of other serotonergic medicines (including SSRIs, SNRIs, tricyclic antidepressants or triptans), with medicines 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, inco-ordination) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). If concomitant treatment with DULOXETINE TEVA DR and other serotonergic medicines that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

St John's Wort: Adverse reactions may be more common during concomitant use of DULOXETINE TEVA DR and herbal preparations containing St John's Wort (Hypericum perforatum).

Suicide: The possibility of an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events) is inherent in depression, major depressive disorder and other psychiatric conditions and may persist 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. Close supervision of high-risk patients (with a history of suicide-related events or those exhibiting a significant degree of suicidal thoughts prior to commencement of treatment especially if they are under 25 years old) should accompany initial DULOXETINE TEVA DR therapy and following dose changes. Cases of suicidal ideation and suicidal behaviours have been reported during DULOXETINE TEVA DR therapy or early after treatment discontinuation. 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. Medical practitioners should encourage patients to report any distressing thoughts or feelings at any time.

Use in children and adolescents under 18 years of age: DULOXETINE TEVA DR 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. DULOXETINE TEVA DR may increase the risk of postpartum haemorrhage (see section 4.6). Caution is advised in patients taking anticoagulants and/or medicines 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 TEVA DR, 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.

Monoamine Oxidase Inhibitors (MAOIs): Due to the risk of serotonin syndrome, DULOXETINE TEVA DR should not be used in combination with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) or within at least 14 days of discontinuing treatment with a MAOI. Based on the half-life of duloxetine, at least 5 days should be allowed after stopping DULOXETINE TEVA DR before starting a MAOI (see section 4.3). The concomitant use of DULOXETINE TEVA DR 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 TEVA DR (see section 4.4).

Inhibitors of CYP1A2: Because CYP1A2 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine. Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of duloxetine by about 77 % and increased AUC o-t 6-fold. Therefore, DULOXETINE TEVA DR should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine. Caution is advised if administering DULOXETINE TEVA DR with inhibitors of CYP1A2 (e.g. quinolone antibiotics) and a lower DULOXETINE TEVA DR dose should be used.

Inhibitors of CYP2D6: Because CYP2D6 is involved in duloxetine metabolism, concomitant use of DULOXETINE TEVA DR with inhibitors of CYP2D6 may result in higher concentrations of DULOXETINE TEVA DR. Paroxetine (20 mg once daily) decreased the apparent plasma clearance of duloxetine by about 37 %. Caution is advised if administering DULOXETINE TEVA DR with inhibitors of CYP2D6 (e.g. SSRIs).

CNS medicines: The risk of using duloxetine in combination with other CNS-active medicines has not been systematically evaluated, except in the cases described in this section. Consequently, caution is advised when DULOXETINE TEVA DR is taken in combination with other centrally-acting medicines or substances, including alcohol and sedative medicines (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbitone, sedative antihistamines).

Serotonergic medicines: In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic medicines. Caution is advisable if DULOXETINE TEVA DR is used concomitantly with serotonergic medicines like SSRIs such as paroxetine, SNRIs, tricyclic antidepressants 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 on other medicines: Medicines metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily). DULOXETINE TEVA DR is therefore unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

Medicines metabolised by CYP2D6: Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine 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 (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 TEVA DR is co-administered with medicines 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 medicines: Results of in vitro studies demonstrate that duloxetine does not induce the catalytic activity of CYP3A. Specific in vivo medicine interaction studies have not been performed.

Anticoagulants and antiplatelet medicines: Caution should be exercised when DULOXETINE TEVA DR is combined with oral anticoagulants or antiplatelet medicines due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction. Furthermore, increases in INR values have been reported when duloxetine was co-administered to patients treated with warfarin. However, concomitant administration of duloxetine 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 medicines on duloxetine: Antacids and H2 antagonists: Co-administration of duloxetine with aluminium- and magnesium-containing antacids, or duloxetine with famotidine, had no significant effect on the rate or extent of duloxetine 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 compared with non-smokers.

Medicines highly bound to plasma protein: Duloxetine is highly bound to plasma proteins (> 90 %). Therefore, administration of DULOXETINE TEVA DR to a patient taking another medicine that is highly protein bound may cause an increase in free concentrations of either medicine.

Women of childbearing potential / Contraception in males and females: Women should be advised to notify their medical practitioner if they become pregnant, or intend to become pregnant, during therapy.

Pregnancy: Safety in pregnant women has not been established, therefore DULOXETINE TEVA DR should not be taken during pregnancy. Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure (see section 5.3). There was no evidence of teratogenicity in animal studies (see section 4.3).

Breastfeeding: The safety of duloxetine has not been established and not recommended during lactation. DULOXETINE TEVA DR and/or its metabolites are excreted into the milk of lactating rats (see section 4.3).

Fertility: In animal studies, duloxetine had no effect on male fertility, and effects in females were only evident at doses that caused maternal toxicity.

DULOXETINE TEVA DR may be associated with undesirable effects such as sedation and dizziness. Therefore patients should be cautioned that if they experience sedation or dizziness they should avoid driving or operating machinery while taking DULOXETINE TEVA DR.

a. Summary of the safety profile: The most commonly reported adverse reactions in patients treated with DULOXETINE TEVA DR 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.

b. Tabulated summary of adverse reactions: TABLE 1 GIVES THE ADVERSE REACTIONS OBSERVED FROM SPONTANEOUS REPORTING AND IN PLACEBO-CONTROLLED CLINICAL TRIALS.

Infections and infestations: Less frequent Laryngitis

Immune system disorders: Less frequent Anaphylactic reaction, hypersensitivity disorder, angioedema

Endocrine disorders: Less frequent Hypothyroidsim

Metabolism and nutrition disorders: Frequent Decreased appetite Less frequent Hyperglycaemia (reported especially in diabetic patients), dehydration, hyponatraemia, SIADH

Psychiatric disorders: Frequent Insomnia, agitation, decreased libido, anxiety, abnormal orgasm, abnormal dreams Less frequent Suicidal ideation, sleep disorder, bruxism, disorientation, apathy, suicidal behaviour, mania, hallucinations, aggression and anger

Nervous system disorders: Frequent Headache, somnolence, dizziness, lethargy, tremor, paraesthesia Less frequent Myoclonus, akathisia, nervousness, disturbance in attention, dysgeusia, dyskinesia, restless legs syndrome, poor quality sleep, serotonin syndrome

Convulsion, psychomotor restlessness, extra-pyramidal symptoms

Eye disorders: Frequent Blurred vision Less frequent Mydriasis, visual impairment, glaucoma

Ear and labyrinth disorders: Frequent Tinnitus Less frequent Vertigo, ear pain

Cardiac disorders: Frequent Palpitations Less frequent Tachycardia, supraventricular, dysrhythmia, mainly atrial fibrillation

Vascular disorders: Frequent Blood pressure increase, flushing Less frequent Syncope, hypertension, orthostatic hypotension, peripheral coldness, hypertensive crisis

Respiratory, thoracic and mediastinal disorders: Frequent Yawning Less frequent Throat tightness, epistaxis, interstitial lung disease

Gastrointestinal disorders: Frequent Nausea, dry mouth, constipation, diarrhoea, abdominal pain, vomiting, dyspepsia, flatulence Less frequent Gastrointestinal haemorrhage, gastroenteritis, eructation, gastritis, dysphagia, stomatitis, haematochezia, breath odour, microscopic colitis

Hepato-biliary disorders: Less frequent Hepatitis, elevated liver enzymes (ALT, AST, alkaline phosphatase), acute liver injury, hepatic failure, jaundice

Skin and subcutaneous tissue disorders: Frequent Sweating increased, rash Less frequent Night sweats, urticaria, contact dermatitis, cold sweat, photosensitivity reactions, increased tendency to bruise, Stevens-Johnson Syndrome, cutaneous vasculitis

Musculoskeletal and connective tissue disorders: Frequent Musculoskeletal pain, muscle spasm Less frequent Muscle tightness, muscle twitching, trismus

Renal and urinary disorders: Frequent Dysuria, pollakiuria Less frequent Urinary retention, urinary hesitation, nocturia, polyuria, urine flow decreased, urine odour abnormal

Reproductive system and breast disorders: Frequent Erectile dysfunction, ejaculation disorder, ejaculation delayed Less frequent Gynaecological haemorrhage, menstrual disorder, sexual dysfunction, testicular pain, menopausal symptoms, galactorrhoea, hyperprolactinaemia, postpartum haemorrhage

General disorders and administration site conditions: Frequent Falls, fatigue Less frequent Chest pain, feeling abnormal, feeling cold, thirst, chills, malaise, feeling hot, gait disturbance

Investigations: Frequent Decreased weight Less frequent Weight increase, increased blood creatine phosphokinase, increased blood potassium, increased blood cholesterol

Signs and symptoms: There is limited clinical experience with DULOXETINE TEVA DR overdose in humans. In pre-marketing clinical trials, no cases of fatal overdose of duloxetine have been reported. Four non-fatal acute ingestions of DULOXETINE TEVA DR (300 to 1 400 mg), alone or in combination with other medicines have been reported. The predicted signs would be related to the central nervous and gastrointestinal systems (e.g. tremors, clonic convulsions, ataxia, emesis and decreased appetite).

Management of overdose: No specific antidote is known for DULOXETINE TEVA DR, 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. Activated charcoal may be useful in limiting absorption. Duloxetine has a large volume of distribution and forced diuresis, haemoperfusion, and exchange perfusion are unlikely to be beneficial.