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ACCEL-DULOXETINE is a brand name for Duloxetine, supplied as a capsule (delayed release). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE .................................................................................................... 3 CONTRAINDICATIONS ..................................................................................................................... 5 WARNINGS AND…
Verbatim from this product's HC label. Tap a section to expand.
Dosage Considerations • ACCEL-DULOXETINE (duloxetine delayed-release capsules) is not indicated for use in children under 18 years of age (see WARNINGS AND PRECAUTIONS: General: Potential Association with Behavioural and Emotional Changes, Including Self-Harm).
• ACCEL-DULOXETINE may be administered with or without food; however, food may help reduce the incidence of initial nausea. Results from a well-controlled dose comparison study (N=647) have demonstrated that patients taking duloxetine delayed- release capsules 60 mg/day with food experienced similar rates of nausea as patients treated with duloxetine delayed-release capsules 30 mg/day with or without food.
• ACCEL-DULOXETINE should be swallowed whole and should not be chewed or crushed, nor should the contents be sprinkled on food or mixed with liquids. All of these might affect the enteric coating. • All patients who participated in the chronic low back pain clinical trials had a clinical diagnosis of CLBP with pain present on most days for at least 6 months and no signs of radiculopathy or spinal stenosis (see CLINICAL TRIALS).
Recommended Dose and Dose Adjustment Adults:
Major Depressive Disorder The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks. Therapeutic response is usually seen after 1-4 weeks of treatment.
There is no evidence that doses greater than 60 mg/day confer additional benefit (see CLINICAL TRIALS). Generalized Anxiety Disorder The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks (see Dosage for Elderly Patients).
Therapeutic response is usually seen after 1-4 weeks of treatment. While a 120 mg once daily dose was shown to be safe and effective, there is no evidence that doses greater than 60 mg/day confer additional benefit and the higher dose is less well tolerated.
Daily doses above 120 mg have not been evaluated for safety or efficacy and are not recommended (see CLINICAL TRIALS). Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks.
Adverse Drug Reaction Overview Major Depressive Disorder (MDD):
Duloxetine delayed-release capsules have been evaluated for safety in 2418 patients diagnosed with MDD who participated in multiple-dose pre-marketing trials, representing 1099 patient- years of exposure. Among these 2418 duloxetine delayed-release capsules-treated patients, 1139 patients participated in eight 8- or 9-week, placebo-controlled trials at doses ranging from 40 to 120 mg/day, while the remaining 1279 patients were followed for up to 1-year in an open-label safety study using flexible doses between 80 and 120 mg/day.
Two placebo- controlled studies with doses of 80 and 120 mg/day had 6-month maintenance extensions. Of these 2418 patients, 993 duloxetine delayed-release capsules-treated patients were exposed for at least 180 days and 445 duloxetine delayed-release capsules-treated patients were exposed for at least 1 year.
The long-term safety of duloxetine delayed-release capsules in MDD patients has also been evaluated in 533 patients in one long-term maintenance of effect study consisting of a 12-week, open-label, acute phase followed by a 26-week, double-blind continuation phase and in 514 patients in another long-term maintenance of effect study consisting of a 4 to 10 week, open-label, acute phase, a 24-week, open-label, continuation phase followed by a 52-week, double-blind, maintenance phase.
Generalized Anxiety Disorder (GAD):
Duloxetine delayed-release capsules have also been evaluated for safety in 1797 patients with GAD. Most patients in the acute placebo-controlled studies received duloxetine delayed-release capsules 60 mg QD or 120 mg QD as their final dose.
13 patient-years of exposure. Among these 1429 duloxetine delayed-release capsules-treated patients, 800 patients participated in three 12- to 13-week, placebo-controlled trials at doses ranging from 20 to 120 mg/day. An additional 449 patients were enrolled in an open-label safety study using 120 mg/day for a duration of 6 months (87 patients continued on to an open-label extension phase for an additional 24 weeks).
Hypersensitivity ACCEL-DULOXETINE (duloxetine delayed-release capsules) is contraindicated in patients with a known hypersensitivity to the drug or the other components of the product. Monoamine Oxidase Inhibitors (MAOIs) ACCEL-DULOXETINE should not be used concomitantly with a monoamine oxidase inhibitor (MAOI), including the antibiotic linezolid and the thiazine dye methylthioninium chloride (methylene blue) which are less well-known examples of MAOIs, or within at least 14 days of discontinuing treatment with an MAOI.
Based on the half-life of duloxetine, at least 5 days should be allowed after stopping ACCEL-DULOXETINE before starting an MAOI (see WARNINGS AND PRECAUTIONS: General: MAOIs). Hepatic Impairment ACCEL-DULOXETINE is contraindicated in patients with any liver disease resulting in hepatic impairment (see WARNINGS and PRECAUTIONS: General: Hepatic Impairment; and DOSAGE AND ADMINISTRATION: Dosage for Patients with Hepatic Impairment).
Uncontrolled Narrow-Angle Glaucoma In clinical trials, duloxetine delayed-release capsules were associated with an increased risk of mydriasis; therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma (see WARNINGS AND PRECAUTIONS: General: Ophthalmologic).
e. creatinine clearance <30 mL/min) or end-stage renal disease (see WARNINGS AND PRECAUTIONS: Renal Impairment). Thioridazine Concomitant use of ACCEL-DULOXETINE and thioridazine is contraindicated (see WARNINGS AND PRECAUTIONS: General: Thioridazine).
g. g. ciprofloxacin or enoxacin) (see DRUG INTERACTIONS). WARNINGS AND PRECAUTIONS General Potential Association with Behavioural and Emotional Changes, Including Self-Harm ______________________________________________________________________________ Accel-Duloxetine Product Monograph Page 6 of 87 Pediatrics: Placebo-Controlled Clinical Trial Data • Recent analyses of placebo-controlled clinical trial safety databases from selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants suggest that use of these drugs in patients under the age of 18 may be associated with behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo.
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Efficacy of duloxetine delayed-release capsules have been demonstrated within the first week. Some patients may benefit from dosages above the recommended 60 mg once daily up to a maximum dose of 120 mg per day. While a 120 mg/day dose was shown to be safe and ______________________________________________________________________________ Accel-Duloxetine Product Monograph Page 46 of 87 effective, there is no evidence that doses greater than 60 mg /day confer additional significant benefit, and the higher dose is less well tolerated (see ADVERSE EVENTS, Table 3).
Daily doses above 120 mg have not been evaluated for safety or efficacy and are not recommended (see CLINICAL TRIALS). Fibromyalgia The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks.
Some patients may respond within the first week. , 120 mg/day) confer additional benefit. Additionally, patients who do not respond to 60 mg/day may not respond to 120 mg/day (see CLINICAL TRIALS). Furthermore, doses higher than 60 mg/day are associated with more severe and frequent rate of adverse reactions (see ADVERSE REACTIONS).
Daily doses above 120 mg have not been evaluated for safety or efficacy and are not recommended (see CLINICAL TRIALS).
Chronic Low Back Pain:
The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks. Some patients may respond within the first week. There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions.
Daily doses above 120 mg have not been evaluated for safety or efficacy and are not recommended (see CLINICAL TRIALS). Chronic Pain Associated with Osteoarthritis of the Knee The recommended dose is 60 mg once daily. A lower starting dose of 30 mg may be considered for tolerability reasons in some patients, with a target dose of 60 mg/day within 1-2 weeks.
Some patients may respond within the first week. Some patients may benefit from dosages above the recommended 60 mg once daily up to a maximum dose of 120 mg per day, although the higher dose has been associated with a higher rate of adverse reactions.
Daily doses above 120 mg have not been evaluated for safety or efficacy and are not recommended (see CLINICAL TRIALS). Maintenance/Continuation/Extended Treatment Major Depressive Disorder It is generally agreed that acute episodes of major depression require several months or longer of sustained pharmacologic therapy beyond response to the acute episode.
There is insufficient evidence available to answer the question of how long a patient should continue to be treated with ACCEL-DULOXETINE. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.
Generalized Anxiety Disorder During long-term therapy, the dosage should be maintained at the lowest effective level and patients should be periodically re-assessed to determine the need to continue treatment (see CLINICAL TRIALS).
______________________________________________________________________________ Accel-Duloxetine Product Monograph Page 47 of 87 Fibromyalgia, Chronic Low Back Pain, Chronic Pain Associated with Osteoarthritis of the Knee, and Neuropathic Pain Associated with Diabetic […]
Another 57 patients, originally treated with placebo, were exposed to duloxetine delayed-release capsules for up to 12 months at 60 mg twice daily in an extension phase. Among these 1429 patients, 881 had ≥6 months of exposure to duloxetine delayed- release capsules, and 515 had greater than 12 months of exposure.
Fibromyalgia:
Duloxetine delayed-release capsules have also been evaluated for safety in 1236 patients with fibromyalgia. 49 patient-years) as a maximum dose. 99 patient-years exposure to duloxetine). 3%) received duloxetine delayed-release capsules 60 mg QD.
2%) received duloxetine 120 mg QD at some point during the acute phase.
Chronic Pain Associated with Osteoarthritis (OA) of the Knee:
Duloxetine delayed-release capsules have been evaluated for safety in 503 duloxetine-treated patients with OA of the knee in two 13-week, placebo-controlled trials and one 10-week placebo-controlled “add-on” trial with NSAIDs (see CLINICAL TRIALS).
Clinical Trial Adverse Drug Reactions The data in the following tables and text cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials.
Similarly, the cited frequencies cannot be compared with data obtained from other clinical investigations involving different treatments, uses, or investigators. The cited data provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence in the population studied.
Adverse Events Reported as Reasons for Discontinuation of Treatment Placebo-Controlled MDD Trials: Approximately 10% of the 1139 patients who received duloxetine delayed-release capsules in acute placebo-controlled trials discontinued treatment due to an adverse event, compared with 4% of the 777 patients receiving placebo.
, discontinuation occurring in at least 1% of the duloxetine delayed-release capsules-treated patients and at a rate of at least twice that of placebo). 3% of the 665 patients receiving placebo. 5%) were the common adverse events reported as reasons for discontinuation and considered to be drug-related (as defined under MDD Trials, above).
Placebo-Controlled Trials for Neuropathic Pain Associated with DPN:
Approximately 12% of the 800 patients who received […]
• The small denominators in the clinical trials database, as well as the variability in placebo rates, preclude reliable conclusions on the relative safety profiles among these drugs.
Adults and Pediatrics:
Additional data • There are clinical trial and post-marketing reports with SSRIs and other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, and depersonalization.
In some cases, the events occurred within several weeks of starting treatment. Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioural changes.
An FDA meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients ages 18 to 24 years with psychiatric disorder showed an increased risk of suicidal behaviour with antidepressants compared to placebo.
Akathisia/Psychomotor Restlessness The use of SSRI’s and other newer antidepressants, including duloxetine, has been very rarely associated with the development of akathisia, which is characterized by a subjectively unpleasant or distressing restlessness and a need to move, often accompanied by an inability to sit or stand.
This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental. Discontinuation Symptoms Patients currently taking SSRIs or newer antidepressants should NOT be discontinued abruptly, due to risk of discontinuation symptoms.
At the time that a medical decision is made to discontinue an SSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abrupt cessation is recommended (see WARNINGS AND PRECAUTIONS: Dependence: Discontinuation of Treatment; ADVERSE REACTIONS: Adverse Events Following Discontinuation of Treatment; and DOSAGE AND ADMINISTRATION: Discontinuation of Treatment).
Monoamine Oxidase Inhibitors (MAOIs):
In patients receiving a serotonin reuptake inhibitor in combination with a MAOI, there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes ______________________________________________________________________________ Accel-Duloxetine Product Monograph Page 7 of 87 that include extreme agitation progressing to delirium and coma.
These reactions have also been reported in patients who have recently discontinued serotonin reuptake inhibitors and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. The effects of combined use of duloxetine delayed-release capsules (duloxetine hydrochloride) and MAOIs have not been evaluated in humans or animals.
Therefore, because ACCEL-DULOXETINE is an inhibitor of both serotonin and norepinephrine reuptake, it is recommended that ACCEL-DULOXETINE not be used in combination with a MAOI, including the antibiotic linezolid and methylene blue, a surgical dye, 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 ACCEL-DULOXETINE before starting a MAOI (see CONTRAINDICATIONS: MAOIs; and DRUG INTERACTIONS). […]