) DESVENLAFAXINE (Desvenlafaxine Extended-Release Tablets) Page 6 of 64 • DESVENLAFAXINE is not indicated for use in children under the age of 18. 1 Pregnant Women). • Due to the potential for life-threatening serotonin toxicity: − Concurrent use with MAOIs is contraindicated.
− Washout periods are necessary if switching between desvenlafaxine and MAOIs. − Use with other serotonergic agents is not recommended (see 7 WARNINGS AND PRECAUTIONS, Neurologic, Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions).
− Dose tapering is recommended when switching between antidepressants, including venlafaxine. • Dosing: − Reduced doses may be needed for the elderly, and those with renal impairment. − All dose changes should be gradual, including discontinuation.
− Monitor for discontinuation symptoms when decreasing or stopping treatment. • Periodically reassess the need for ongoing therapy. • Monitor for agitation, suicidal tendencies. Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages, especially when initiating therapy or during any change in dose or dosage regimen.
This includes monitoring for agitation-type emotional and behavioural changes. See 7 WARNINGS AND PRECAUTIONS, Psychiatric, Potential Association with Behavioural and Emotional Changes, Including Self-Harm. 2 Recommended Dose and Dosage Adjustment • Initial Treatment The recommended starting dose of DESVENLAFAXINE (desvenlafaxine (as base) extended- release tablets) is 50 mg once daily, with or without food.
In clinical studies, no additional benefit was demonstrated at doses greater than 50 mg/day. If the physician, based on clinical judgment, decides a dose increase above 50 mg/day is warranted for an individual patient, the maximum recommended dose should not exceed 100 mg/day.
In clinical studies, doses of 50 to 400 mg/day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg/day, and adverse events and discontinuations were more frequent at higher doses.
Patients should be periodically reassessed to determine the need for continued treatment. DESVENLAFAXINE (Desvenlafaxine Extended-Release Tablets) Page 7 of 64 • Maintenance/Continuation/Extended Treatment 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.
Long-term efficacy of desvenlafaxine (50 mg daily) for up to 26 weeks, following response during 20 weeks of acute, open-label treatment, was established in a placebo-controlled trial. Patients should be periodically reassessed to determine the need for maintenance treatment.
9 Discontinuation). • Switching Patients from Other Antidepressants to DESVENLAFAXINE Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine. Tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms (see 2 CONTRAINDICATIONS).
• Switching Patients to or from a Monoamine Oxidase Inhibitor At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with DESVENLAFAXINE. In addition, based on the half-life of desvenlafaxine, at least 7 days should be allowed after stopping desvenlafaxine before starting an MAOI.
• Use of Reversible MAOIs, such as Linezolid or Methylene Blue Do not start DESVENLAFAXINE in a patient who is being treated with a reversible MAOI such as linezolid or in whom intravenous methylene blue has been administered because there is increased risk of serotonin syndrome (see 2 CONTRAINDICATIONS).
In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered. In some cases, a patient already receiving DESVENLAFAXINE therapy may require urgent treatment with linezolid or intravenous methylene blue.
If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue are judged to outweigh the risks of serotonin syndrome in a particular patient, DESVENLAFAXINE should be stopped promptly, and linezolid or intravenous methylene blue can be administered.
The patient should be monitored for symptoms of serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first (see 7 WARNINGS AND PRECAUTIONS). Therapy with DESVENLAFAXINE may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.
DESVENLAFAXINE (Desvenlafaxine Extended-Release Tablets) Page 8 of 64 Special Populations • Severe renal impairment and end-stage renal disease The recommended dose in patients with severe renal impairment (24-hr CrCl < 30 mL/min) or end-stage renal disease (ESRD) is 50 mg every other day.
Because of individual variability in clearance in these patients, individualization of dosage may be desirable. 3 Pharmacokinetics, Renal Insufficiency). 3 Pharmacokinetics, Hepatic Insufficiency). • Geriatrics (≥ 65 years of age) No dosage adjustment is required solely on the basis of age; however, possible reduced renal clearance of desvenlafaxine should be considered when […]