Antidepressants
Duloxetine HCL 67,3 mg E.Q Dulextine 60 mg
30Capsules
CA-09
429/2011
11/9/2011
Mechanism Of Action | (Duloxetine hydrochloride) is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) for oral administration.It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance and stop the movement of pain signals in the brain. |
INDICATIONS | Major Depressive Disorder - Duloxetine is indicated for the treatment of major depressive disorder (MDD). A major depressive episode implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation. Diabetic Peripheral Neuropathic Pain - Duloxetine is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy. Generalized Anxiety Disorder - Duloxetine is indicated for the treatment of generalized anxiety disorder (GAD). Generalized anxiety disorder is defined as excessive anxiety and worry, present more days than not, for at least 6 months. The excessive anxiety and worry must be difficult to control and must cause significant distress or impairment in normal functioning. It must be associated with at least 3 of the following 6 symptoms: restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension, and/or sleep disturbance. |
CONTRAINDICATIONS | Duloxetine is contraindicated in patients with a known hypersensitivity to Duloxetine or any of the inactive ingredients .Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated .Duloxetine use may be associated with an increased risk of mydriasis; therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma. |
Side EFFECTS | Nausea, dry mouth, constipation, loss of appetite, fatigue, drowsiness, dizziness, increased sweating, blurred vision, rash, or itching may occur. Some unlikely but serious side effects may occur: unusual or severe mental/mood changes (e.g., anxiety, mania), weight loss, change in sexual desire and ability, uncontrolled movements (tremor), difficulty urinating. Some highly unlikely but very serious side effects may occur: chest pain, stomach pain, black stools, vomit that looks like coffee grounds, easy bruising/bleeding, unusual bleeding, seizures. |
WARNINGS | All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, aggressiveness, akathisia, and mania, have been reported in adult and pediatric patients being treated with antidepressants. There is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients are experiencing such symptoms. If the decision has been made to discontinue treatment, medication should be tapered, because abrupt discontinuation can be associated with certain symptoms Screening Patients for Bipolar Disorder — A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a manic episode in patients at risk for bipolar disorder. Therefore, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Duloxetine is not approved for use in treating bipolar depression. Serotonin Syndrome — The development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including Duloxetine treatment, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of Duloxetine with serotonin precursors (such as tryptophan) is not recommended. Hepatotoxicity —Because it is possible that Duloxetine and alcohol may interact to cause liver injury or that Duloxetine may aggravate pre-existing liver disease, Duloxetine should ordinarily not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease. Orthostatic Hypotension and Syncope — Orthostatic hypotension and syncope have been reported with therapeutic doses of Duloxetine. The risk of blood pressure decreases may be greater in patients taking concomitant medications that induce orthostatic hypotension (such as antihypertensives) or are potent CYP1A2 inhibitors and in patients taking Duloxetine at doses above 60 mg daily. Consideration should be given to discontinuing Duloxetine in patients who experience symptomatic orthostatic hypotension and/or syncope during Duloxetine therapy. Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment. Activation of Mania/Hypomania —Activation of mania/hypomania has been reported in a small proportion of patients with mood disorders who were treated with other marketed drugs effective in the treatment of major depressive disorder. As with these other agents, Duloxetine should be used cautiously in patients with a history of mania. Duloxetine should be prescribed with care in patients with a history of a seizure disorder. Hyponatremia — Cases of hyponatremia have been reported and appeared to be reversible when Duloxetine was discontinued RenallyAnd HepaticallyImpaired Patients — Duloxetine is not recommended for patients with end-stage renal disease (requiring dialysis) or in severe renal impairment (estimated creatinine clearance < 30 mL/min).It is also recommended that Duloxetine not be administered to patients with any hepatic insufficiency. |
DRUG INTERACTIONS | Inhibitors of CYP1A2 — Concomitant use of Duloxetine with fluvoxamine, an inhibitor of CYP1A2, results in approximately a 6-fold increase in AUC and about a 2.5-fold increase in Cmax of Duloxetine. Some quinolone antibiotics would be expected to have similar effects and these combinations should be avoided. Inhibitors of CYP2D6 — Because CYP2D6 is involved in Duloxetine metabolism, concomitant use of Duloxetine with potent inhibitors of CYP2D6 may result in higher concentrations of Duloxetine. These inhibitors include paroxetine, fluoxetine, and quinidine. Drugs Metabolized by CYP2D6 —Co-administration of Duloxetine with other drugs that are extensively metabolized by the isozyme CYP2D6 and which have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants, such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution. Plasma TCA concentrations may need to be monitored and the dose of the TCA may need to be reduced if a TCA is co-administered with Duloxetine. Because of the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, Duloxetine and thioridazine should not be co-administered. Serotonergic Drugs — Based on the mechanism of action of SNRIs and SSRIs, including Duloxetine and the potential for serotonin syndrome, caution is advised when Duloxetine is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's Wort. The concomitant use of Duloxetine with other SSRIs, SNRIs or tryptophan is not recommended. Potential for Interaction with Drugs that Affect Gastric Acidity — Duloxetine has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, Duloxetine , unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using Duloxetine in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of Duloxetine. MAO Inhibitors:Avoid taking drugs called MAO inhibitors with or within 2 weeks of starting Duloxetine or at least 5 days after stopping it. Aspirin and NSAID drugs: Aspirin is similar to NSAID drugs, and can increase the risk of bleeding in combination with this medication. Discuss the risks and benefits with your doctor. |
Pregnancy And lactations | Pregnancy — Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Breast Feeding—Nursing while on Duloxetine is not recommended. |
Dosage And Administration | Initial Treatment Major Depressive Disorder - Duloxetine should be administered at a total dose of 40 mg/day (given as 20 mg BID) to 60 mg/day (given either once a day or as 30 mg BID) without regard to meals. Diabetic Peripheral Neuropathic Pain - Duloxetine should be administered at a total dose of 60 mg/day given once a day, without regard to meals. For patients for whom tolerability is a concern, a lower starting dose may be considered. Since diabetes is frequently complicated by renal disease, a lower starting dose and gradual increase in dose should be considered for patients with renal impairment. Generalized Anxiety Disorder - For most patients, the recommended starting dose for Duloxetine is 60 mg administered once daily without regard to meals. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. If a decision is made to increase the dose beyond 60 mg once daily, dose increases should be in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated. Maintenance/Continuation/Extended Treatment Major Depressive Disorder - Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment. Diabetic Peripheral Neuropathic Pain - As the progression of diabetic peripheral neuropathy is highly variable and management of pain is empirical, the effectiveness of Duloxetine must be assessed individually. Generalized Anxiety Disorder - Generalized anxiety disorder is generally recognized as a chronic condition. The physician who elects to use Duloxetine for extended periods should periodically evaluate the long-term usefulness of the drug for the individual patient. Dosage for Elderly Patients —As with any drug, caution should be exercised in treating the elderly. Discontinuing Duloxetine —A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. |
OVERDOSE | : Signs and symptoms of overdose (mostly with mixed drugs) included serotonin syndrome, somnolence, vomiting, and seizures. There is no specific antidote to Doluxetine, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. An adequate airway, oxygenation, and ventilation should be assured, and cardiac rhythm and vital signs should be monitored. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption of Duloxetine from the gastrointestinal tract. |
Storage Conditions | Store below 30°C in a dry place Keep out of reach of children |