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The following serious adverse reactions are described elsewhere in the labeling:
- Clinical Worsening and Suicide Risk [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Serotonin Syndrome or NMS-like Reactions [see WARNINGS AND PRECAUTIONS]
- QT Prolongation and Risk of Sudden Death [see WARNINGS AND PRECAUTIONS]
- Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
- Abnormal bleeding events [see WARNINGS AND PRECAUTIONS]
- Priapism [see WARNINGS AND PRECAUTIONS]
- Hyponatremia [see WARNINGS AND PRECAUTIONS]
- Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
- Discontinuation symptoms [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions (reported in ≥ 5% and at twice the rate of placebo) are: somnolence/sedation, dizziness, constipation, vision blurred.
Table 2 presents the summary of adverse events (AEs) leading to discontinuation of Oleptro treatment with an incidence of at least 1% and at least twice that for placebo.
Table 2: AEs with
discontinuation as action taken ( ≥ 1% incidence and incidence 2x placebo)
N = 202
|Confusional state||2 (1.0%)|
|Coordination abnormal||2 (1.0%)|
|Balance disorder / Gait disturbance||2 (1.0%)|
Clinical Studies Experience
The data described below reflects exposure in a clinical trial of 406 patients, including 204 exposed to placebo and 202 exposed to Oleptro. Patients were between 18-80 years of age and 69.3% and 67.5% of patients had at least one previous episode of depression in the last 24 months in the placebo and active-treated group, respectively. In individual patients, doses were flexible and ranged from 150 to 375 mg per day. The mean daily dose during the 6-week treatment period was 310 mg. The tablets were administered orally and were given once a day for a total duration of 8 weeks, including the titration period.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Table 3 presents the summary of all treatment emergent AEs that occurred at an incidence of ≥ 5% in the Oleptro group, whether considered by the clinical investigator to be related to the study drug or not.
Table 3: Most Common
Treatment Emergent Adverse Events ( ≥ 5% of Patients on Active Treatment)
N = 204
N = 202
|Somnolence/Sedation||39 (19%)||93 (46%)|
|Headache||55 (27%)||67 (33%)|
|Dry mouth||26 (13%)||51 (25%)|
|Dizziness||25 (12%)||50 (25%)|
|Nausea||26 (13%)||42 (21%)|
|Fatigue||17 (8%)||30 (15%)|
|Diarrhea||23 (11%)||19 (9%)|
|Constipation||4 (2%)||16 (8%)|
|Back pain||7 (3%)||11 (5%)|
|Vision blurred||0 (0%)||11 (5%)|
Adverse events related to sexual dysfunction (regardless of causality) were reported by 4.9% and 1.5% of patients treated with Oleptro and placebo, respectively. In the Oleptro group, ejaculation disorders occurred in 1.5% of patients, decreased libido occurred in 1.5% of patients, and erectile dysfunction and abnormal orgasm < 1% of patients.
Vital Signs and Weight
There were no notable changes in vital signs (blood pressure, respiratory rate, pulse) or weight in either treatment group.
Following is a list of treatment-emergent adverse reactions with an incidence of ≥ 1% to < 5% (i.e., less common) in patients treated with Oleptro. This listing is not intended to include reactions (i) already listed in previous tables or elsewhere in the labeling (ii) for which the association with treatment is remote, (iii) which were so general as to be uninformative, and (iv) which were not considered to have significant clinical implications. Reactions are classified by body-system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; Infrequent adverse reactions are those occurring in less than 1/100 patients.
General Disorders and Administration Site Conditions— Frequent: edema; Infrequent: gait disturbance
Immune System Disorders— Infrequent: hypersensitivity
Psychiatric Disorders— Frequent: agitation, confusional state, disorientation
Respiratory, Thoracic and Mediastinal Disorders— Frequent: dyspnea
Vascular Disorders— Infrequent: flushing
Spontaneous reports regarding trazodone hydrochloride received from postmarketing experience include the following: abnormal dreams, agitation, alopecia, anxiety, aphasia, apnea, ataxia, breast enlargement or engorgement, cardiospasm, cerebrovascular accident, chills, cholestasis, clitorism, congestive heart failure, diplopia, edema, extrapyramidal symptoms, grand mal seizures, hallucinations, hemolytic anemia, hirsutism, hyperbilirubinemia, increased amylase, increased salivation, insomnia, leukocytosis, leukonychia, jaundice, lactation, liver enzyme alterations, methemoglobinemia, nausea/vomiting (most frequently), paresthesia, paranoid reaction, priapism [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION], pruritus, psoriasis, psychosis, rash, stupor, inappropriate ADH syndrome, tardive dyskinesia, unexplained death, urinary incontinence, urinary retention, urticaria, vasodilation, vertigo, and weakness.
Cardiovascular system effects which have been reported include the following: conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and QT prolongation. In postmarketing surveillance, prolonged QT interval, Torsades de Pointes, and ventricular tachycardia have been reported with the immediate-release form of trazodone at doses of 100 mg per day or less [see WARNINGS AND PRECAUTIONS].
Read the Oleptro (trazodone hydrochloride extended-release tablets) Side Effects Center for a complete guide to possible side effects
Monoamine Oxidase Inhibitors (MAOIs)
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] 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].
There have been reports of altered (either increased or decreased) prothrombin times in taking both warfarin and trazodone.
Drug Abuse And Dependence
Oleptro is not a controlled substance.
Although trazodone hydrochloride has not been systematically studied in preclinical or clinical studies for its potential for abuse, no indication of drug-seeking behavior was seen in the clinical studies with Oleptro. However, it is difficult to predict the extent to which a CNS-active drug will be misused, diverted, and abused. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of trazodone hydrochloride (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).
Read the Oleptro Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/1/2014
Additional Oleptro Information
Report Problems to the Food and Drug Administration
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