Dose Selection

The recommended starting dose of Oleptro is 150 mg once daily in adults. The dose may be increased by 75 mg/day every three days (i.e., start 225 mg on Day 4 of therapy). The maximum daily dose should not exceed 375 mg.

• Oleptro tablets should be taken orally at the same time every day, in the late evening preferably at bedtime, on an empty stomach.

• Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.

• Patients should be monitored for withdrawal symptoms when discontinuing treatment with trazodone hydrochloride. The dose should be gradually reduced whenever possible [see Warnings and Precautions (5.13)].

Maintenance Treatment

The efficacy of Oleptro for the maintenance treatment of MDD has not been evaluated. While there is no body of evidence available to answer the question of how long a patient treated with Oleptro should continue the drug, it is generally recommended that treatment be continued for several months after an initial response. Patients should be maintained on the lowest effective dose and be periodically reassessed to determine the continued need for maintenance treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Oleptro. Conversely, at least 14 days should be allowed after stopping Oleptro before starting an MAOI intended to treat psychiatric disorders [see CONTRAINDICATIONS (4.1)].

Use of Oleptro with Other MAOIs such as Linezolid or Methylene Blue

Do not start Oleptro in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see CONTRAINDICATIONS (4.1)].

In some cases, a patient already receiving Oleptro 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, Oleptro 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 Oleptro may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see WARNINGS AND PRECAUTIONS (5.2, 5.9)].

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 Oleptro is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see WARNINGS AND PRECAUTIONS (5.2)].

Important Administration Instructions

Oleptro tablets are scored to provide flexibility in dosing.

Oleptro can be swallowed whole or administered as a half tablet by breaking the tablet along the score line. Breaking the tablet in half does not affect the controlled-release properties of the tablet.

In order to maintain its controlled-release properties, Oleptro should not be chewed or crushed.