Updated: 20 January 2010 Page 1 of 22 - Food and Drug Administration
This label may not be the latest approved by FDA.
For current labeling information, please visit
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Oleptro
safely and effectively. See full prescribing information for Oleptro.
OLEPTRO (trazodone hydrochloride) extended-release tablets
Initial U.S. Approval: 1981
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
See full prescribing information for complete boxed warning.
Increased risk of suicidal thinking and behavior in children,
adolescents and young adults taking antidepressants for major
depressive disorder (MDD) and other psychiatric disorders. Oleptro is
not approved for use in pediatric patients (5.1).
----------------------------INDICATIONS AND USAGE--------------------------Oleptro is indicated for the treatment of major depressive disorder (1).
? Efficacy was established in one 8-week trial of Oleptro as well as in trials
of trazodone immediate release formulation in patients with major
depressive disorder (14).
------------------------DOSAGE AND ADMINISTRATION---------------------? Starting dose: 150 mg once daily. May be increased by 75 mg per day
every three days. Maximum dose: 375 mg per day (2).
? Dosing at the same time every day in the late evening, preferably at
bedtime, on an empty stomach (2).
? Tablets should be swallowed whole or broken in half along the score line,
and should not be chewed or crushed (2).
? When discontinued, gradual dose reduction is recommended (2).
-----------------------DOSAGE FORMS AND STRENGTHS-------------------Bisectable tablets of 150 mg or 300 mg (3).
--------------------------------CONTRAINDICATIONS----------------------------None (4).
-------------------------WARNINGS AND PRECAUTIONS---------------------? Clinical Worsening/Suicide Risk: Monitor for clinical worsening and
suicidal thinking and behavior (5.1).
? Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions:
Have been reported with antidepressants. Discontinue Oleptro and initiate
supportive treatment (5.2).
? Activation of Mania/Hypomania: Screen for bipolar disorder and monitor
for mania/hypomania (5.3).
? QT Prolongation: Increases the QT interval. Avoid use with drugs that
also increase the QT interval and in patients with risk factors for prolonged
QT interval (5.4).
? Use in Patients with Heart Disease: Use with caution in patients with
cardiac disease (5.5).
Updated: 20 January 2010
? Orthostatic Hypotension and Syncope: Have occurred. Warn patients of
risk and symptoms of hypotension (5.6).
? Abnormal Bleeding: May increase the risk of bleeding. Use with NSAIDs,
aspirin, or other drugs that affect coagulation may compound this risk
(5.7).
? Interaction with MAOIs: Do not use concomitantly or within 14 days of
monoamine oxidase inhibitors (5.8).
? Priapism: Has occurred. Warn male patients of this risk and how/when to
seek medical attention (5.9).
? Hyponatremia: Can occur in association with SIADH (5.10).
? Potential for Cognitive and Motor Impairment: Has potential to impair
judgment, thinking, and motor skills. Advise patients to use caution when
operating machinery (5.11).
? Discontinuation Symptoms: May occur with abrupt discontinuation and
include anxiety and sleep disturbance. Upon discontinuation, taper Oleptro
and monitor for symptoms (5.12).
---------------------------------ADVERSE REACTIONS---------------------------Most common adverse reactions (incidence ¡Ý5% and twice that of placebo)
are: somnolence/sedation, dizziness, constipation, vision blurred (6).
To report SUSPECTED ADVERSE REACTIONS, contact Labopharm
at 1-877-345-6177 or FDA at 1-800-FDA-1088 or medwatch.
---------------------------------DRUG INTERACTIONS---------------------------? Monoamine Oxidase Inhibitors: Should not be used concomitantly with
Oleptro (5.8, 7).
? CNS Depressants: Trazodone may enhance effects of alcohol, barbiturates,
or other CNS depressants (7).
? CYP3A4 Inhibitors: May necessitate lower dose of Oleptro (7).
? CYP3A4 Inducers (e.g., carbamazepine): May necessitate higher dose of
Oleptro (7).
? Digoxin or Phenytoin: Monitor for increased serum levels (7).
? Warfarin: Monitor for increased or decreased prothrombin time (7).
? Serotonergic Medications: Serotonin syndrome has been reported (5.2, 7).
? NSAIDs, Aspirin or other Anticoagulants: Potential for increased risk of
bleeding (5.7, 7).
-------------------------USE IN SPECIFIC POPULATIONS---------------------? Pregnancy: Based on animal data, may cause fetal harm (8.1).
? Nursing Mothers: Use with caution (8.3).
? Pediatric Patients: Oleptro is not approved in pediatric patients (8.4).
? Renal or Hepatic Impairment: Use with caution (8.6, 8.7).
See 17 for PATIENT COUNSELING INFORMATION as well as
MEDICATION GUIDE.
Revised: 01/2010
Page 1 of 22
This label may not be the latest approved by FDA.
For current labeling information, please visit
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1
Clinical Worsening and Suicide Risk
5.2
Serotonin Syndrome or Neuroleptic Malignant Syndrome
(NMS)-like Reactions
5.3
Screening Patients for Bipolar Disorder and Monitoring for
Mania/Hypomania
5.4
QT Prolongation and Risk of Sudden Death
5.5
Use in Patients with Heart Disease
5.6
Orthostatic Hypotension and Syncope
5.7
Abnormal Bleeding
5.8
Interaction with MAOIs
5.9
Priapism
5.10
Hyponatremia
5.11
Potential for Cognitive and Motor Impairment
5.12
Discontinuation Symptoms
6 ADVERSE REACTIONS
6.1
Clinical Studies Experience
6.2
Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.3
Nursing Mothers
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Renal Impairment
8.7
Hepatic Impairment
9 DRUG ABUSE AND DEPENDENCE
9.1
Controlled Substance
9.2
Abuse
10 OVERDOSAGE
10.1
Human Experience
10.2
Management of Overdose
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
12.2
Pharmacodynamics
12.3
Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Information for Patients
17.2 Medication Guide
* Sections or subsections omitted from the Full Prescribing Information are
not listed.
Updated: 20 January 2010
Page 2 of 22
This label may not be the latest approved by FDA.
For current labeling information, please visit
FULL PRESCRIBING INFORMATION
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 is not
approved for use in pediatric patients [see Warnings and Precautions (5.1) and Patient Counseling
Information (17.1)].
1
INDICATIONS AND USAGE
Oleptro? is indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of
Oleptro has been established in a trial of outpatients with MDD as well as in trials with the immediate
release formulation of trazodone [see Clinical Studies (14)].
2
DOSAGE AND ADMINISTRATION
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 (5.12)].
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.
Important Administration Instructions
Updated: 20 January 2010
Page 3 of 22
This label may not be the latest approved by FDA.
For current labeling information, please visit
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.
3
DOSAGE FORMS AND STRENGTHS
Oleptro tablets are available in the following strengths:
?
?
4
Oleptro bisectable tablets containing 150 mg of trazodone hydrochloride (yellowish-beige, capsuleshaped tablet, coated and scored on both sides with DDS 080 printed on one side)
Oleptro bisectable tablets containing 300 mg of trazodone hydrochloride (beige-orange, capsuleshaped tablet, coated and scored on both sides with DDS 081 printed on one side)
CONTRAINDICATIONS
None.
5
5.1
WARNINGS AND PRECAUTIONS
Clinical Worsening and Suicide Risk
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of
their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes
in behavior, whether or not they are taking antidepressant medications, and this risk may persist until
significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders
and these disorders themselves are the strongest predictors of suicide. There has been a long standing
concern, however, that antidepressants may have a role in inducing worsening of depression and the
emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of shortterm placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase
the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18
¨C 24) with MDD and other psychiatric disorders. 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
with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive
compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9
antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with
MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2
months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of
suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs
studied. There were differences in absolute risk of suicidality across the different indications, with the
highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within
age strata and across indications. These risk differences (drug-placebo difference in the number of cases
of suicidality per 1,000 patients treated) are provided in Table 1.
Age Range
Updated: 20 January 2010
Table 1
Drug-Placebo Difference in Number of Cases of
Page 4 of 22
This label may not be the latest approved by FDA.
For current labeling information, please visit
< 18
18 ¨C 24
25 ¨C 64
¡Ý 65
Suicidality per 1,000 Patients Treated
Increases Compared to Placebo
14 additional cases
5 additional cases
Decreases Compared to Placebo
1 fewer case
6 fewer cases
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number
was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months.
However, there is substantial evidence from placebo-controlled maintenance trials in adults with
depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored
appropriately and observed closely for clinical worsening, suicidality, and unusual changes in
behavior, especially during the initial few months of a course of drug therapy, or at times of dose
changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness,
impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and
pediatric patients being treated with antidepressants for major depressive disorder as well as for other
indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such
symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been
established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the
medication, in patients whose depression is persistently worse, or who are experiencing emergent
suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if
these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive
disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need
to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the
other symptoms described above, as well as the emergence of suicidality, and to report such
symptoms immediately to health care providers. Such monitoring should include daily observation
by families and caregivers. Prescriptions for Oleptro should be written for the smallest quantity of
tablets consistent with good patient management, in order to reduce the risk of overdose.
5.2
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions
The development of a potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome
(NMS)-like reactions have been reported with antidepressants alone and may occur with trazodone
treatment, but particularly with concomitant use of other serotoninergic drugs (including SSRIs, SNRIs
and triptans) and with drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors
[MAOIs]), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may
include mental status changes (e.g., agitation, hallucinations, and coma), autonomic instability (e.g.,
tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia,
incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). Serotonin
syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes
Updated: 20 January 2010
Page 5 of 22
................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related download
- behavioral benefits of trazodone are sustained for the long term in
- safety data sheet trazodone hydrochloride tablets strength chewy
- trazodone hydrochloride tablets usp medication guide
- trazodone hydrochloride label food and drug administration
- reference id 4119349 food and drug administration
- benzodiazepines for the treatment of sleep disorders
- trazodone extended release for major depressive disorder
- updated 20 january 2010 page 1 of 22 food and drug administration
- trazodone a new antiepileptic drug for dravet syndrome
- medications to treat opioid withdrawal symptoms oregon pain guidance
Related searches
- male femininity page 1 the new age
- american journal of food and nutrition
- food and drug recalls 2019
- difference between 22 long and 22 wmr
- schedule 1 line 22 1040
- january 22 holidays and observances
- 1 of 2 page numbering
- drug administration calculator
- end of chapter 22 questions and answers
- food and drug administration agency
- fda food and drug regulations
- food and drug administration fda