Budeprion Sr

Budeprion Sr

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Questions & Answers

Side Effects & Adverse Reactions

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 short-term 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 18-24) with major depressive disorder (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 4400 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 1000 patients treated) are provided in Table 1.

Table 1
Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated
Increases Compared to Placebo
< 18 14 additional cases
18 to 24 5 additional cases
Decreases Compared to Placebo
25 to 64 1 fewer case
≥ 65 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, andunusual changes in behavior, especially during the initial few months of a courseof 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 immediatelyto health care providers. Such monitoring should include daily observation by familiesand caregivers. Prescriptions for BUDEPRION SR® should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder:A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that BUDEPRION SR® is not approved for use in treating bipolar depression.

Patients should be made aware that BUDEPRION SR® contains the same active ingredient found in ZYBAN®, used as an aid to smoking cessation treatment, andthat BUDEPRION SR® should not be used in combination with ZYBAN®, or any othermedications that contain bupropion, such as WELLBUTRIN® (bupropion hydrochloride tablets), the immediate-release formulation or WELLBUTRIN XL® [bupropion hydrochloride extended-release tablets (XL)], the extended-release formulation.

Seizures: Bupropion is associated with a dose-related risk of seizures. The risk of seizures is also related to patient factors, clinical situations, and concomitantmedications, which must be considered in selection of patients for therapy withBUDEPRION SR®.

BUDEPRION SR® should be discontinued and not restarted in patients who experiencea seizure while on treatment.

• Dose: At doses of BUDEPRION SR® up to a dose of 300 mg/day, the incidenceof seizure is approximately 0.1% (1/1000) and increases to approximately 0.4%(4/1000) at the maximum recommended dose of 400 mg/day.Data for the immediate-release formulation of bupropion revealed a seizure incidenceof approximately 0.4% (i.e., 13 of 3200 patients followed prospectively) inpatients treated at doses in a range of 300 to 450 mg/day. The 450 mg/day upperlimit of this dose range is close to the currently recommended maximum dose of400 mg/day for BUDEPRION SR®. This seizure incidence (0.4%) may exceed thatof other marketed antidepressants and BUDEPRION SR® up to 300 mg/day by asmuch as 4-fold. This relative risk is only an approximate estimate because nodirect comparative studies have been conducted.

Additional data accumulated for the immediate-release formulation of bupropionsuggested that the estimated seizure incidence increases almost tenfold between 450and 600 mg/day, which is twice the usual adult dose and one and one-half the maximumrecommended daily dose (400 mg) of BUDEPRION SR®. This disproportionateincrease in seizure incidence with dose incrementation calls for caution in dosing.

Data for BUDEPRION SR® revealed a seizure incidence of approximately 0.1%(i.e., 3 of 3100 patients followed prospectively) in patients treated at doses ina range of 100 to 300 mg/day. It is not possible to know if the lower seizure incidenceobserved in this study involving the sustained-release formulation ofbupropion resulted from the different formulation or the lower dose used.However, as noted above, the immediate-release and sustained-release formulationsare bioequivalent with regard to both rate and extent of absorption duringsteady state (the most pertinent condition to estimating seizure incidence),since most observed seizures occur under steady-state conditions.

• Patient factors: Predisposing factors that may increase the risk of seizure withbupropion use include history of head trauma or prior seizure, central nervoussystem (CNS) tumor, the presence of severe hepatic cirrhosis and concomitantmedications that lower seizure threshold.

• Clinical situations: Circumstances associated with an increased seizure riskinclude, among others, excessive use of alcohol or sedatives (including benzodiazepines);addiction to opiates, cocaine, or stimulants; use of over-the-counterstimulants and anorectics; and diabetes treated with oral hypoglycemics or insulin.

• Concomitant medications: Many medications (e.g., antipsychotics, antidepressants,theophylline, systemic steroids) are known to lower seizure threshold.

Recommendations for Reducing the Risk of Seizure: Retrospective analysis of clinical experience gained during the development of bupropion suggests that therisk of seizure may be minimized if

• The total daily dose of BUDEPRION SR® does not exceed 400 mg.

• The daily dose is administered twice daily, and

• The rate of incrementation of dose is gradual.

• No single dose should exceed 200 mg to avoid high peak concentrations of bupropion and/or its metabolites.

BUDEPRION SR® should be administered with extreme caution to patients with ahistory of seizure, cranial trauma, or other predisposition(s) toward seizure, orpatients treated with other agents (e.g. antipsychotics, other antidepressants,theophylline, systemic steroids, etc.) that lower seizure threshold.

Hepatic Impairment: BUDEPRION SR® should be used with extreme caution in patientswith severe hepatic cirrhosis. In these patients a reduced frequency and/or dose isrequired, as peak bupropion levels, as well as AUC, levels are substantially increasedand accumulation is likely to occur in such patients to a greater extent than usual. Thedose should not exceed 100 mg every day or 150 mg every other day in these patients(see CLINICAL PHARMACOLOGY, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).

Potential for Hepatotoxicity:In rats receiving large doses of bupropion chronically, there was an increase in incidence of hepatic hyperplastic nodules and hepatocellular hypertrophy. In dogs receiving large doses of bupropion chronically, various histologic changes were seen in the liver, and laboratory tests suggesting mild hepatocellular injury were noted.

Legal Issues

There is currently no legal information available for this drug.

FDA Safety Alerts

There are currently no FDA safety alerts available for this drug.

Manufacturer Warnings

There is currently no manufacturer warning information available for this drug.

FDA Labeling Changes

There are currently no FDA labeling changes available for this drug.

Uses

BUDEPRION SR® is indicated for the treatment of major depressive disorder. The efficacy of bupropion in the treatment of major depressive episode was established in two 4-week controlled trials of depressed inpatients and in one 6-week controlled trial of depressed outpatients whose diagnoses corresponded most closely to the Major Depression category of the APA Diagnostic and Statistical Manual (DSM) (see CLINICAL PHARMACOLOGY).

A major depressive episode (DSM-IV) implies the presence of 1) depressed mood or 2) loss of interest or pleasure; in addition, at least five of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

The efficacy of BUDEPRION SR® in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo controlled trial (see CLINICAL PHARMACOLOGY). Nevertheless, the physician who elects to use BUDEPRION SR® for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

History

There is currently no drug history available for this drug.

Other Information

BUDEPRION SR® (bupropion hydrochloride), an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. The molecular weight is 276.2. The molecular formula is C13H18CINO•HCI. Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. The structural formula is:

Chemical Structure

BUDEPRION SR® is supplied for oral administration as 100 mg and 150 mg, film-coated, extended-release tablets. Each tablet contains the labeled amount of bupropion hydrochloride and the inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, magnesium stearate, and microcrystalline cellulose. The 100 mg tablet also contains FD&C red # 40, FD&C yellow # 5, hypromellose, iron oxide yellow, macrogol, polydextrose, titanium dioxide and triacetin. The 150 mg tablet also contains hypromellose, iron oxide yellow, macrogol, polydextrose, titanium dioxide and triacetin.

This product meets USP Drug Release Test #3.

Budeprion Sr Manufacturers


  • Cardinal Health
    Budeprion Sr (Bupropion Hydrochloride) Tablet, Extended Release [Cardinal Health]
  • Bryant Ranch Prepack
    Budeprion Sr (Bupropion Hydrochloride) Tablet, Extended Release [Bryant Ranch Prepack]
  • Teva Pharmaceuticals Usa Inc
    Budeprion Sr (Bupropion Hydrochloride) Tablet, Extended Release [Teva Pharmaceuticals Usa Inc]

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