Oleptro

Name: Oleptro

Oleptro Overview

Oleptro is a prescription medication used to treat depression. Oleptro belongs to a group of drugs called serotonin modulators, which affect the natural substance, serotonin, in the brain.

This medication comes as an extended release tablet and is taken once a day in the late evening, preferably at bedtime, on an empty stomach.

Oleptro tablets should be swallowed whole or broken in half along the score line. Do not chew or crush tablets.

Common side effects of Oleptro include drowsiness, dizziness, and dry mouth.  Do not drive or operate machinery until you know how Oleptro will affect you.

Uses of Oleptro

Oleptro is a prescription medication used to treat depression. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Oleptro Drug Class

Oleptro is part of the drug class:

  • Other antidepressants

Oleptro FDA Warning

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Oleptro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Oleptro tablets are not approved for use in pediatric patients.

How should I take trazodone?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

The trazodone immediate-release tablet should be taken after a meal or a snack.

Take Oleptro on an empty stomach at bedtime or late in the evening.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. You may break an Oleptro tablet in half along the score line if needed.

It may take up to 2 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Do not stop using trazodone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using trazodone.

Store at room temperature away from moisture, heat, and light.

Contraindications

Monoamine Oxidase Inhibitors (MAOIs)

The use of MAOI’s intended to treat psychiatric disorders with Oleptro or within 14 days of stopping treatment with Oleptro is contraindicated because of an increased risk of serotonin syndrome. The use of Oleptro within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. [see DOSAGE AND ADMINISTRATION (2.3) and WARNINGS AND PRECAUTIONS (5.9)].

Starting Oleptro in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see DOSAGE AND ADMINISTRATION (2.4) and WARNINGS AND PRECAUTIONS (5.2)].

Drug Interactions

Monoamine Oxidase Inhibitors (MAOIs)

[see Dosage and Administration (2.3 and 2.4), Contraindications (4.1), Warnings and Precautions (5.2 and 5.9)]

Serotonergic Drugs

[see Dosage and Administration (2.3 and 2.4), Contraindications (4.1), Warnings and Precautions (5.2 )]

Central Nervous System (CNS) Depressants

Trazodone may enhance the response to alcohol, barbiturates, and other CNS depressants.

Cytochrome P450 3A4 Inhibitors

In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with cytochrome P450 3A4 (CYP3A4) inhibitors. The effect of short-term administration of ritonavir (200 mg twice daily, 4 doses) on the pharmacokinetics of a single dose of trazodone (50 mg) has been studied in 10 healthy subjects. The Cmax of trazodone increased by 34%, the AUC increased 2.4-fold, the half-life increased by 2.2-fold, and the clearance decreased by 52%. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as itraconazole may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. If trazodone is used with a potent CYP3A4 inhibitor, the risk of cardiac arrhythmia may be increased [see Warnings and Precautions (5.5)] and a lower dose of trazodone should be considered.

Cytochrome P450 Inducers (e.g., carbamazepine)

Carbamazepine induces CYP3A4. Following co-administration of carbamazepine 400 mg per day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone and mchlorophenlypiperazine (an active metabolite) by 76% and 60% respectively, compared to precarbamazepine values. Patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs.

Digoxin and Phenytoin

Increased serum digoxin or phenytoin levels have been reported in patients receiving trazodone concurrently with either of these drugs. Monitor serum levels and adjust dosages as needed.

NSAIDs, Aspirin, or Other Drugs Affecting Coagulation or Bleeding

Due to a possible association between serotonin modulating drugs and gastrointestinal bleeding, patients should be monitored for and cautioned about the potential risk of bleeding associated with the concomitant use of trazodone and NSAIDs, aspirin, or other drugs that affect coagulation or bleeding [see Warnings and Precautions (5.8)].

Warfarin

There have been reports of altered (either increased or decreased) prothrombin times in taking both warfarin and trazodone.

Oleptro - Clinical Pharmacology

Mechanism of Action

The mechanism of trazodone’s antidepressant action is not fully understood, but is thought to be related to its potentiation of serotonergic activity in the CNS.

Pharmacodynamics

Preclinical studies have shown that trazodone selectively inhibits neuronal reuptake of serotonin and acts as an antagonist at 5-HT-2A/2C serotonin receptors.

Trazodone is not a monoamine oxidase inhibitor and, unlike amphetamine-type drugs, does not stimulate the central nervous system.

Trazodone antagonizes alpha 1-adrenergic receptors, a property which may be associated with postural hypotension.

Pharmacokinetics

Steady state AUC of Trazodone is equivalent after administration of Trazodone 100 mg immediate release (IR) three (3) times a day (mean ± SD AUCss = 33058 ± 8006 ng*h/mL) and Oleptro 300 mg once daily (mean ± SD AUCss = 29131 ± 9931 ng*h/mL) for one week. Steady State Cmax and Cmin of trazodone were not equivalent after administration of trazodone 100 mg IR 3 times a day (mean ± SD Cmax,ss = 3118 ± 758 ng/mL, Cmin,ss = 843 ± 274 ng/mL) and Oleptro 300 mg once daily (mean ± SD Cmax,ss = 1812 ± 621 ng/mL, Cmin,ss = 674 ± 355 ng/mL) for one week.

Absorption
Trazodone is well absorbed after oral administration, without selective localization in any tissue. Following single-dose administration of Oleptro 300 mg tablets under fasting conditions, a mean peak trazodone plasma concentration (Cmax) of 1188 ± 362 ng/mL was reported at a median Tmax of 9 hours post-dose. When Oleptro 300 mg tablets are taken shortly after ingestion of a high-fat meal, Cmax increases by about 86% compared to taking it under fasting conditions. However, AUC0-∞ and Tmax are not significantly affected by food.

Oleptro tablets are dose proportional following single-dose administration of doses ranging from 75 mg to 375 mg as intact or bisected tablets.

Metabolism
In vitro studies in human liver microsomes show that trazodone is metabolized, via oxidative cleavage, to an active metabolite, m-chlorophenylpiperazine (mCPP) by CYP3A4. Other metabolic pathways that may be involved in the metabolism of trazodone have not been well characterized. Trazodone is extensively metabolized; less than 1% of an oral dose is excreted unchanged in the urine.

Elimination
Elimination is predominantly renal, with 70 to 75% of an oral dose being recovered in the urine within the first 72 hours of ingestion. Following single-dose administration of Oleptro 300 mg tablets, a mean apparent terminal half-life of 10 hours was reported.

Protein Binding
Trazodone is 89 to 95% protein bound in vitro at concentrations attained with therapeutic doses in humans.

Medication Guide

Medication Guide

Oleptro™ (Oh-LEP-troe)

(trazodone hydrochloride)extended-release tablets

Read the Medication Guide that comes with Oleptro before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk to your healthcare provider or pharmacist if there is something you do not understand or you want to learn about Oleptro.

What is the most important information I should know about Oleptro?

Antidepressant medicines, depression or other serious mental illnesses, and suicidal thoughts or actions:

Talk to your healthcare provider about:

  • All risks and benefits of treatment with antidepressant medicines
  • All treatment choices for depression or other serious mental illnesses
  1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
  2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have or have a family history of bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
  3. How can I watch for and try to prevent suicidal thoughts and actions?
  • Pay close attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
  • Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings.
  • Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Call a healthcare provider right away if you have any of the following symptoms, especially if they are new, worse, or worry you:

  • Thoughts about suicide or dying
  • Attempts to commit suicide
  • New or worse depression
  • New or worse anxiety
  • Feeling very agitated or restless
  • Panic attacks
  • Trouble sleeping (insomnia)
  • New or worse irritability
  • Acting aggressive, being angry or violent
  • Acting on dangerous impulses
  • An extreme increase in activity and talking (mania)
  • Other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Talk to your healthcare provider about the side effects of your medicines.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you take. Keep a list of all medicines to show your healthcare provider. Do not start new medicines without first checking with your healthcare provider.

4. Oleptro is not approved for use in children. Talk to your healthcare provider for more information.

What is Oleptro?

Oleptro is a prescription medicine taken 1 time a day to treat major depressive disorder in adults.

Who should not take Oleptro?

  • If you take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
  • Do not take an MAOI within 2 weeks of stopping Oleptro unless directed to do so by your physician.

  • Do not start Oleptro if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.

What should I tell my healthcare provider before taking Oleptro?

Before you take Oleptro, tell your healthcare provider if you:

  • Have heart problems, including QT prolongation or a family history of it
  • Have ever had a heart attack
  • Have bipolar disorder
  • Have liver or kidney problems
  • Have other serious medical conditions
  • Are pregnant or plan to become pregnant. Oleptro may harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
  • Are breastfeeding or plan to breastfeed. It is not known if Oleptro passes into your breast milk. You and your healthcare provider should decide if you will take Oleptro or breastfeed.
  • Have taken a Monoamine Oxidase Inhibitor (MAOI) or if you have stopped taking an MAOI in the last 2 weeks.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using Oleptro with certain other medicines can affect each other causing serious side effects.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take Oleptro?

  • Take Oleptro exactly as your healthcare provider tells you.
  • Oleptro should be taken 1 time a day.
  • Oleptro should be taken at the same time each day in the late evening, if possible at bedtime, on an empty stomach.
  • Do not stop taking Oleptro without talking to your healthcare provider.
  • Oleptro should be swallowed whole or broken in half along the score line. Do not chew or crush Oleptro. Tell your healthcare provider if you cannot swallow Oleptro either whole or as a half tablet.

What should I avoid while taking Oleptro?

  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how Oleptro affects you. Oleptro can slow your thinking and motor skills.
  • Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking Oleptro until you talk with your healthcare provider. Oleptro may make your sleepiness or dizziness worse if you take it with alcohol or other medicines that cause sleepiness or dizziness.

What are the possible side effects of Oleptro?

Oleptro can cause serious side effects or death. See “What is the most important information I should know about Oleptro?”

Serious side effects include:

  • Serotonin syndrome. Symptoms of serotonin syndrome include: agitation, hallucinations, problems with coordination, fast heartbeat, tight muscles, trouble walking, nausea, vomiting, diarrhea.
  • Visual problems
    • eye pain
    • changes in vision
    • swelling or redness in or around the eye
      Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.
  • Feeling high or in a very good mood, then becoming irritable, or having too much energy, feeling like you have to keep talking or do not sleep (Mania).
  • Irregular or fast heartbeat or faint (QT prolongation).
  • Low blood pressure. You feel dizzy or faint when you change positions (go from sitting to standing).
  • Unusual bruising or bleeding.
  • Erection lasting for more than 6 hours (Priapism).
  • Low sodium in your blood (Hyponatremia). Symptoms of hyponatremia include: headache, feeling weak, feeling confused, trouble concentrating, memory problems and feeling unsteady when you walk.

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Oleptro include:

  • Sleepiness
  • Dizziness
  • Constipation
  • Blurry vision

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Oleptro. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Oleptro?

  • Store Oleptro between 59°F to 86°F (15°C to 30°C)
  • Keep in tight container
  • Keep out of the light

Keep Oleptro and all medicines out of the reach of children.

General information about Oleptro.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Oleptro for a condition for which it was not prescribed. Do not give Oleptro to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Oleptro. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Oleptro that is written for health professionals.

For more information, go to www.Oleptro.com or call 1-877-345-6177.

What are the ingredients in Oleptro?

Active ingredient: trazodone hydrochloride

Inactive ingredients: hydroxypropyl distarch phosphate (Contramid®), hypromellose, sodium stearyl fumarate, colloidal silicon dioxide, iron oxide yellow, iron oxide red, talc, polyethylene glycol 3350, titanium dioxide, polyvinyl alcohol, black ink (food grade).

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Angelini Pharma Inc.

Gaithersburg, MD 20877

© 2014, Angelini Pharma Inc.

All rights reserved.

U.S. Patent Nos. 6,607,748, 7,829,120 and 8,133,893

Oleptro™ is a trademark of Angelini Pharma Inc.

Contramid® is a registered trademark of Paladin Labs Inc.

[June 2014]

What is trazodone?

Oleptro (trazodone) is an antidepressant medicine. It affects chemicals in the brain that may be unbalanced in people with depression.

Oleptro is used to treat major depressive disorder (MDD).

Oleptro may also be used for purposes not listed in this medication guide.

For the Consumer

Applies to trazodone: oral tablet, oral tablet extended release

Along with its needed effects, trazodone (the active ingredient contained in Oleptro) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking trazodone:

More common
  • Blurred vision
  • confusion
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • lightheadedness
  • sweating
  • unusual tiredness or weakness
Less common
  • Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • confusion about identity, place, and time
  • decreased concentration
  • fainting
  • general feeling of discomfort or illness
  • headache
  • lack of coordination
  • muscle tremors
  • nervousness
  • pounding in the ears
  • shortness of breath
  • slow or fast heartbeat
  • swelling
Rare
  • Skin rash
  • unusual excitement

Some side effects of trazodone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Dry mouth (usually mild)
  • muscle or bone pain
  • trouble sleeping
  • trouble with remembering
  • unpleasant taste
Less common
  • Constipation
  • continuing ringing or buzzing or other unexplained noise in the ears
  • diarrhea
  • hearing loss
  • muscle aches or pains
  • weight loss

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