1 Dosing Considerations • Switching to or from Monoamine Oxidase Inhibitor (MAOI) Antidepressants At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with APO-LEVOMILNACIPRAN.
Conversely, at least 14 days should be allowed after stopping APO-LEVOMILNACIPRAN before starting an MAOI antidepressant. 4 Drug-Drug Interactions. • Use of APO-LEVOMILNACIPRAN with Other Drugs that Inhibit Monoamine Oxidase such as Linezolid or Methylene Blue Do not start APO-LEVOMILNACIPRAN in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin toxicity.
In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered. 4 Drug-Drug Interactions and 7 WARNINGS AND PRECAUTIONS, Serotonin toxicity / serotonin syndrome.
In some cases, a patient already receiving APO-LEVOMILNACIPRAN 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 treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, APO- LEVOMILNACIPRAN 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. Therapy with APO- APO-LEVOMILNACIPRAN (levomilnacipran extended release capsules) Page 6 of 53 LEVOMILNACIPRAN may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.
The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with APO-LEVOMILNACIPRAN is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use.
See 7 WARNINGS AND PRECAUTIONS, Serotonin toxicity / serotonin syndrome. 2 Recommended Dose and Dosage Adjustment Initiating Treatment Adults: The recommended dose range for APO-LEVOMILNACIPRAN is 40 mg to 120 mg once daily. APO-LEVOMILNACIPRAN should be initiated at 20 mg once daily for 2 days and then increased to 40 mg once daily.
In clinical studies, added benefit was not consistently demonstrated for doses greater than 40 mg/day. If the physician, based on clinical judgment, decides a dose increase above 40 mg/day is warranted for an individual patient, the dose may be increased in increments of 40 mg.
The maximum recommended dose should not exceed 120 mg/day. Maintenance/Continuation/Extended Treatment It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy.
Long-term efficacy of levomilnacipran extended release capsules for up to 26 weeks, following response during 20 weeks of acute, open-label treatment, was established in a placebo-controlled trial. Physicians choosing to use APO-LEVOMILNACIPRAN should periodically reassess patients to determine the need for continued treatment.
Dosing in Special Populations and Conditions Hepatic Impairment:
No dose adjustment is required in patients with mild, moderate or severe hepatic impairment. 3 Pharmacokinetics.
Renal Impairment:
Based on a population pharmacokinetic analysis, no dose adjustment is necessary in patients with mild renal impairment (creatinine clearance of 60 to 89 mL/min). For patients with moderate renal impairment (creatinine clearance of 30 to 59 mL/min), the dose should not exceed 80 mg/day.
For patients with more severe renal impairment (creatinine clearance of 15 to 29 mL/min) the dose should not exceed 40 mg/day. 3 Pharmacokinetics. APO-LEVOMILNACIPRAN is not recommended for patients with end stage renal disease.
Geriatric Patients (> 65 years of age):
No dose adjustment is required in geriatric patients on the basis of age. 3 Pharmacokinetics. APO-LEVOMILNACIPRAN (levomilnacipran extended release capsules) Page 7 of 53 In a multiple-dose clinical pharmacokinetic study, elderly subjects (> 65 years) had a slightly higher exposure (Cmax by 24% and AUC by 26%) of levomilnacipran than younger subjects (18 to 45 years).
Because levomilnacipran is predominately excreted by the kidney, renal clearance of levomilnacipran should be considered when determining the dose.
Pediatrics (< 18 years of age):
Health Canada has not authorized an indication for pediatric use. 3 Pediatrics.
Sex:
No dose adjustment is required based on sex. 3 Pharmacokinetics. Discontinuing Treatment Discontinuation symptoms have been reported with discontinuation of serotonergic drugs such as levomilnacipran extended release capsules. Gradual dose reduction is recommended, instead of abrupt discontinuation, whenever possible.
Monitor patients for these symptoms when discontinuing APO-LEVOMILNACIPRAN. If intolerable symptoms occur following a dose decrease or upon discontinuation of treatment, consider resuming the previously prescribed dose and decreasing the dose at a more gradual rate.
See 7 WARNINGS AND PRECAUTIONS, Discontinuation Symptoms. 4 Administration APO-LEVOMILNACIPRAN should be taken at approximately the same time each day. APO- LEVOMILNACIPRAN should be swallowed whole. Do not open, chew or crush the capsule.
APO-LEVOMILNACIPRAN can be taken with or without food. 5 Drug-Food Interactions. 5 Missed Dose In the event that a dose is missed, the patient should take the missed dose as soon as […]