Aplenzin Information
Aplenzin ()
Aplenzin ()
Aplenzin () Indications And Usage
Aplenzin () (bupropion hydrobromide extended-release tablets) is indicated for the treatment of major depressive disorder.
The efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled trials of inpatients and in one 6-week controlled trial of outpatients whose diagnoses corresponded most closely to the Major Depression category of the APA Diagnostic and Statistical Manual (DSM) [see ].
A major depressive episode (DSM-IV) implies the presence of 1) depressed mood or 2) loss of interest or pleasure; in addition, at least 5 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 bupropion in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial with the sustained-release formulation of bupropion [see ]. Nevertheless, the physician who elects to use Aplenzin () for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Aplenzin () Dosage Forms And Strengths
Aplenzin () Extended-Release Tablets, 174 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "174" in bottles of 30 tablets.
Aplenzin () Extended-Release Tablets, 348 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "348" in bottles of 30 tablets .
Aplenzin () Extended-Release Tablets, 522 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "522" in bottles of 30 tablets .
Aplenzin () Contraindications
Aplenzin () is contraindicated in patients with a seizure disorder.
Aplenzin () is contraindicated in patients treated with ZYBAN (bupropion hydrochloride) Sustained-Release Tablets; WELLBUTRIN (bupropion hydrochloride immediate-release formulation); WELLBUTRINSR (bupropion hydrochloride sustained-release formulation); WELLBUTRIN XL (bupropion hydrochloride extended-release formulation); or any other medications that contain bupropion because the incidence of seizure is dose dependent.
Aplenzin () is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in patients treated for bulimia with the immediate-release formulation of bupropion.
Aplenzin () is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).
The concurrent administration of Aplenzin () Tablets and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with Aplenzin () Tablets.
Aplenzin () is contraindicated in patients who have shown an allergic response to bupropion or the other ingredients that make up Aplenzin () Tablets.
Aplenzin () Warnings And Precautions
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 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) show that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 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 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.
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 [see and ].
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.
Aplenzin () is not approved for smoking cessation treatment, but bupropion under the name ZYBAN is approved for this use. Serious neuropsychiatric symptoms have been reported in patients taking bupropion for smoking cessation [see and ] Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these symptoms have occurred in patients taking bupropion who continued to smoke. When symptoms were reported, most were during bupropion treatment but some were following discontinuation of bupropion therapy.
These events have occurred in patients with and without pre-existing psychiatric disease; some have experienced worsening of their psychiatric illnesses. All patients being treated with bupropion as part of smoking cessation treatment should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness.
Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the pre-marketing studies of ZYBAN.
Advise patients and caregivers that the patient using bupropion for smoking cessation should stop taking bupropion and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many post-marketing cases, resolution of symptoms after discontinuation of ZYBAN was reported, and some persisted, therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.
The risks of using bupropion for smoking cessation should be weighed against the benefits of its use. ZYBAN has been demonstrated to increase the likelihood of abstinence from smoking for as long as six months compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial.
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 Aplenzin () is not approved for use in treating bipolar depression.
Bupropion is associated with a dose-related risk of seizures. The risk of seizures is also related to patient factors, clinical situations, and concomitant medications, which must be considered in selection of patients for therapy with Aplenzin () . Aplenzin () should be discontinued and not restarted in patients who experience a seizure while on treatment.
The seizure incidence with Aplenzin () has not been formally evaluated in clinical trials. Studies in mice suggest the potential for a significant reduction in the risk of seizure with bupropion HBr as compared to bupropion HCl. The seizure incidence is not expected to be worse than presented below for comparable doses of the immediate-release and sustained-release formulations of bupropion HCl.
Aplenzin () should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced frequency and/or dose is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 174 mg every other day in these patients.
Aplenzin () should be used with caution in patients with hepatic impairment (including mild to moderate hepatic cirrhosis) and reduced frequency and/or dose should be considered in patients with mild to moderate hepatic cirrhosis.
All patients with hepatic impairment should be closely monitored for possible adverse effects that could indicate high drug and metabolite levels.
Increased restlessness, agitation, anxiety, and insomnia, especially shortly after initiation of treatment, have been associated with treatment with bupropion.
Patients in placebo-controlled trials of major depressive disorder with WELLBUTRIN SR, the sustained-release formulation of bupropion hydrochloride, experienced agitation, anxiety, and insomnia as shown in Table 2.
In clinical studies of major depressive disorder, these symptoms were sometimes of sufficient magnitude to require treatment with sedative/hypnotic drugs.
Symptoms in these studies were sufficiently severe to require discontinuation of treatment in 1% and 2.6% of patients treated with 300 and 400 mg/day, respectively, of bupropion hydrochloride sustained-release tablets and 0.8% of patients treated with placebo.
In placebo-controlled studies of major depressive disorder using WELLBUTRIN SR, the sustained-release formulation of bupropion hydrochloride, patients experienced weight gain or weight loss as shown in Table 3.
In studies conducted with the immediate-release formulation of bupropion hydrochloride, 35% of patients receiving tricyclic antidepressants gained weight, compared to 9% of patients treated with the immediate-release formulation of bupropion hydrochloride. If weight loss is a major presenting sign of a patient's depressive illness, the anorectic and/or weight-reducing potential of Aplenzin () Tablets should be considered.
Anaphylactoid/anaphylactic reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. In addition, there have been rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. A patient should stop taking Aplenzin () and consult a doctor if experiencing allergic or anaphylactoid/anaphylactic reactions (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment.
Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity have been reported in association with bupropion. These symptoms may resemble serum sickness.
In clinical practice, hypertension, in some cases severe, requiring acute treatment, has been reported in patients receiving bupropion alone and in combination with nicotine replacement therapy. These reactions have been observed in both patients with and without evidence of preexisting hypertension.
Data from a comparative study of the sustained-release formulation of bupropion hydrochloride (ZYBAN Sustained-Release Tablets), nicotine transdermal system (NTS), the combination of sustained-release bupropion hydrochloride plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients treated with the combination of sustained-release bupropion hydrochloride and NTS. In this study, 6.1% of patients treated with the combination of sustained-release bupropion hydrochloride and NTS had treatment-emergent hypertension compared to 2.5%, 1.6%, and 3.1% of patients treated with sustained-release bupropion hydrochloride, NTS, and placebo, respectively. The majority of these patients had evidence of preexisting hypertension. Three patients (1.2%) treated with the combination of ZYBAN and NTS and 1 patient (0.4%) treated with NTS had study medication discontinued due to hypertension compared to none of the patients treated with ZYBAN or placebo. Monitoring of blood pressure is recommended in patients who receive the combination of bupropion and nicotine replacement.
There is no clinical experience establishing the safety of Aplenzin () Tablets in patients with a recent history of myocardial infarction or unstable heart disease. Therefore, care should be exercised if it is used in these groups.
Bupropion was well tolerated in depressed patients who had previously developed orthostatic hypotension while receiving tricyclic antidepressants, and was also generally well tolerated in a group of 36 depressed inpatients with stable congestive heart failure (CHF). However, bupropion was associated with a rise in supine blood pressure in the study of patients with CHF, resulting in discontinuation of treatment in 2 patients for exacerbation of baseline hypertension.
Aplenzin () Adverse Reactions
The following risks are discussed in greater detail in other sections of the labeling:
Adverse reactions from Table 5 occurring in at least 5% of patients treated with the sustained-release formulation of bupropion hydrochloride and at a rate at least twice the placebo rate are listed below for the 300- and 400-mg/day dose groups.
Aplenzin () is bioequivalent to WELLBUTRIN XL, which has been demonstrated to have similar bioavailability both to the immediate-release formulation of bupropion and to the sustained-release formulation of bupropion. The information included under this subsection and under the subsections 6.2 and 6.3 is based primarily on data from controlled clinical trials with WELLBUTRIN SR Tablets, the sustained-release formulation of bupropion hydrochloride.
In placebo-controlled clinical trials, 9% and 11% of patients treated with 300 and 400 mg/day, respectively, of the sustained-release formulation of bupropion hydrochloride and 4% of patients treated with placebo discontinued treatment due to adverse reactions. The specific adverse reactions in these trials that led to discontinuation in at least 1% of patients treated with either 300 mg/day or 400 mg/day of WELLBUTRIN SR, the sustained-release formulation of bupropion hydrochloride, and at a rate at least twice the placebo rate are listed in Table 4.
In clinical trials with the immediate-release formulation of bupropion, 10% of patients and volunteers discontinued due to an adverse reaction. Reactions resulting in discontinuation, in addition to those listed above for the sustained-release formulation of bupropion hydrochloride, include vomiting, seizures, and sleep disturbances.
Table 5 enumerates treatment-emergent adverse reactions that occurred among patients treated with 300 and 400 mg/day of the sustained-release formulation of bupropion hydrochloride and with placebo in controlled trials. Reactions that occurred in either the 300- or 400-mg/day group at an incidence of 1% or more and were more frequent than in the placebo group are included. Reported adverse reactions were classified using a COSTART-based Dictionary.
Accurate estimates of the incidence of adverse reactions associated with the use of any drug are difficult to obtain. Estimates are influenced by drug dose, detection technique, setting, physician judgments, etc. The figures cited cannot be used to predict precisely the incidence of untoward reactions in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. These incidence figures also cannot be compared with those obtained from other clinical studies involving related drug products as each group of drug trials is conducted under a different set of conditions.
Finally, it is important to emphasize that the tabulation does not reflect the relative severity and/or clinical importance of the reactions. A better perspective on the serious adverse reactions associated with the use of bupropion is provided in
Additional reactions to those listed in Table 5 that occurred at an incidence of at least 1% in controlled clinical trials of the immediate-release formulation of bupropion hydrochloride (300 to 600 mg/day) and that were numerically more frequent than placebo were: cardiac arrhythmias (5% vs 4%), hypertension (4% vs 2%), hypotension (3% vs 2%), tachycardia (11% vs 9%), appetite increase (4% vs 2%), dyspepsia (3% vs 2%), menstrual complaints (5% vs 1%), akathisia (2% vs 1%), impaired sleep quality (4% vs 2%), sensory disturbance (4% vs 3%), confusion (8% vs 5%), decreased libido (3% vs 2%), hostility (6% vs 4%), auditory disturbance (5% vs 3%), and gustatory disturbance (3% vs 1%).
In addition to the adverse events noted above, the following events have been reported in clinical trials and postmarketing experience with the sustained-release formulation of bupropion hydrochloride in depressed patients and in nondepressed smokers, as well as in clinical trials and postmarketing clinical experience with the immediate-release formulation of bupropion hydrochloride.
Adverse events for which frequencies are provided below occurred in clinical trials with the sustained-release formulation of bupropion hydrochloride. The frequencies represent the proportion of patients who experienced a treatment-emergent adverse event on at least one occasion in placebo-controlled studies for depression (n = 987) or smoking cessation (n = 1,013), or patients who experienced an adverse event requiring discontinuation of treatment in an open-label surveillance study with the sustained-release formulation of bupropion hydrochloride (n = 3,100). All treatment-emergent adverse events are included except those listed in Tables 2 through 5, those events listed in other safety-related sections, those adverse events subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, those events not reasonably associated with the use of the drug, and those events that were not serious and occurred in fewer than 2 patients. Events of major clinical importance are described in
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions of frequency: Frequent adverse events are defined as those occurring in at least 1/100 patients. Infrequent adverse events are those occurring in 1/100 to 1/1,000 patients, while rare events are those occurring in less than 1/1,000 patients.
Adverse events for which frequencies are not provided occurred in clinical trials or postmarketing experience with bupropion. Only those adverse events not previously listed for sustained-release bupropion are included. The extent to which these events may be associated with Aplenzin () is unknown.
Aplenzin () Drug Interactions
Few systemic data have been collected on the metabolism of bupropion following concomitant administration with other drugs or, alternatively, the effect of concomitant administration of bupropion on the metabolism of other drugs.
Because bupropion is extensively metabolized, the coadministration of other drugs may affect its clinical activity. studies indicate that bupropion is primarily metabolized to hydroxybupropion by the CYP2B6 isoenzyme. Therefore, the potential exists for a drug interaction between Aplenzin () and drugs that are substrates or inhibitors/inducers of the CYP2B6 isoenzyme (e.g., orphenadrine, thiotepa, cyclophosphamide, ticlopidine, and clopidogrel). In addition, studies suggest that paroxetine, sertraline, norfluoxetine, and fluvoxamine as well as nelfinavir, ritonavir, and efavirenz inhibit the hydroxylation of bupropion. No clinical studies have been performed to evaluate this finding. The threohydrobupropion metabolite of bupropion does not appear to be produced by the cytochrome P450 isoenzymes. The effects of concomitant administration of cimetidine on the pharmacokinetics of bupropion and its active metabolites were studied in 24 healthy young male volunteers. Following oral administration of two 150 mg tablets of the sustained-release formulation of bupropion hydrochloride with and without 800 mg of cimetidine, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and C, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.
In a series of studies in healthy volunteers, ritonavir (100 mg twice daily or 600 mg twice daily) or ritonavir 100 mg plus lopinavir 400 mg (KALETRA®) twice daily reduced exposure of bupropion and its major metabolites in a dose dependent manner by approximately 20% to 80%. Similarly, efavirenz 600 mg once daily for 2 weeks reduced the exposure of bupropion by approximately 55%. This effect of retonavir, KALETRA, and efavirenz is thought to be due the induction of bupropion metabolism. Patients receiving any of these drugs with bupropion may need increased doses of bupropion, but the maximum recommended dose of bupropion should not be exceeded [see ].
While not systematically studied, certain drugs may induce the metabolism of bupropion (e.g., carbamazepine, phenobarbital, phenytoin).
Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 healthy volunteers.
Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in humans. In one study, following chronic administration of bupropion hydrochloride, 100 mg 3 times daily to 8 healthy male volunteers for 14 days, there was no evidence of induction of its own metabolism. Nevertheless, there may be the potential for clinically important alterations of blood levels of coadministered drugs.
Aplenzin () Use In Specific Populations
Of the approximately 6,000 patients who participated in clinical trials with bupropion hydrochloride sustained-release tablets (depression and smoking cessation studies), 275 were ≥65 years old and 47 were ≥75 years old. In addition, several hundred patients 65 and over participated in clinical trials using the immediate-release formulation of bupropion hydrochloride (depression studies). No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that of younger subjects; however, another pharmacokinetic study, single and multiple dose, has suggested that the elderly are at increased risk for accumulation of bupropion and its metabolites [see ].
Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of toxic reaction to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [].
Aplenzin () should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced frequency and/or dose is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 174 mg every other day in these patients.
Aplenzin () should be used with caution in patients with hepatic impairment (including mild to moderate hepatic cirrhosis) and reduced frequency and/or dose should be considered in patients with mild to moderate hepatic cirrhosis.
All patients with hepatic impairment should be closely monitored for possible adverse effects that could indicate high drug and metabolite levels [see and .
Aplenzin () Overdosage
Overdoses of up to 30 g or more of bupropion have been reported. Seizure was reported in approximately one third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.
Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.
Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. EEG monitoring is also recommended for the first 48 hours post-ingestion. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients.
Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the management of bupropion overdoses. No specific antidotes for bupropion are known.
Due to the dose-related risk of seizures with Aplenzin () , hospitalization following suspected overdose should be considered. Based on studies in animals, it is recommended that seizures be treated with intravenous benzodiazepine administration and other supportive measures, as appropriate.
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the (PDR).
Aplenzin () Description
Aplenzin () (bupropion hydrobromide), 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 (±)-2-(tert-butylamino)-3'-chloropropiophenone hydrobromide. The molecular weight is 320.6. The molecular formula is CHClNO•HBr. Bupropion hydrobromide powder is white or almost white, crystalline, and soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. The structural formula is:
Aplenzin () Tablets are supplied for oral administration as 174 mg, 348 mg, and 522 mg white to off white extended-release tablets. Each tablet contains the labeled amount of bupropion hydrobromide and the inactive ingredients: ethylcellulose, glyceryl behenate, polyvinyl alcohol, polyethylene glycol, povidone, and dibutyl sebacate. Carnauba wax is included in the 174 mg and 348 mg strengths. The tablets are printed with edible black ink.
The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is eliminated in the feces.
Aplenzin () Clinical Pharmacology
Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied.
Following chronic dosing of Aplenzin () 348 mg Tablets, the mean peak steady-state plasma concentration and area under the curve of bupropion were 134.3 (± 38.2) ng/mL and 1409 (± 346) ng∙hr/mL, respectively. Steady-state plasma concentrations of bupropion were reached within 8 days. The elimination half-life (±SD) of bupropion after a single dose is 21.3 (± 6.7) hours.
In a study comparing 10-day dosing with Aplenzin () Tablets 348 mg once daily and WELLBUTRIN XL Tablets 300 mg once daily, following a 3-day titration with once daily WELLBUTRIN XL Tablets 150 mg, Aplenzin () peak plasma concentration and area under the curve for bupropion and the 3 metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) were equivalent to WELLBUTRIN XL Tablets 300 mg, with the average being 8 to14% lower.
In a single dose study, two Aplenzin () Tablets 174 mg once daily and one Aplenzin () Tablet 348 mg once daily were evaluated. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.
Additionally, a multiple dose study compared 14-day dosing with Aplenzin () Tablets 522 mg once daily to dosing with three Aplenzin () Tablets 174 mg once daily, following a 3-day titration with one Aplenzin () Tablet 174 mg once daily, and a succeeding 5-day titration with two Aplenzin () tablets 174 mg once daily. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.
These findings demonstrate that Aplenzin () Tablets 174 mg, 348 mg and 522 mg are dose proportional. A 348 mg dose can be achieved by administering either one Aplenzin () Tablet 348 mg or two Aplenzin () Tablets 174 mg. A 522 mg dose can be achieved by administering either one Aplenzin () Tablet 522 mg, three Aplenzin () Tablets 174 mg, or one Aplenzin () Tablet 174 mg plus one Aplenzin () Tablet 348 mg.
Aplenzin () Clinical Studies
The efficacy of bupropion as a treatment for major depressive disorder was established with the immediate-release formulation of bupropion hydrochloride in two 4-week, placebo-controlled trials in adult inpatients and in one 6-week, placebo-controlled trial in adult outpatients. In the first study, patients were titrated in a bupropion hydrochloride dose range of 300 to 600 mg/day of the immediate-release formulation on a 3 times daily schedule; 78% of patients received maximum doses of 450 mg/day or less. This trial demonstrated the effectiveness of bupropion on the Hamilton Depression Rating Scale (HDRS) total score, the depressed mood item (item 1) from that scale, and the Clinical Global Impressions (CGI) severity score. A second study included 2 fixed doses of the immediate-release formulation of bupropion hydrochloride (300 and 450 mg/day) and placebo. This trial demonstrated the effectiveness of bupropion, but only at the 450-mg/day dose of the immediate-release formulation; the results were positive for the HDRS total score and the CGI severity score, but not for HDRS item 1. In the third study, outpatients received 300 mg/day of the immediate-release formulation of bupropion hydrochloride. This study demonstrated the effectiveness of bupropion on the HDRS total score, HDRS item 1, the Montgomery-Asberg Depression Rating Scale, the CGI severity score, and the CGI improvement score.
In a longer-term study, outpatients meeting DSM-IV criteria for major depressive disorder, recurrent type, who had responded during an 8-week open trial on bupropion hydrochloride (150 mg twice daily of the sustained-release formulation), were randomized to continuation of their same dose of bupropion or placebo, for up to 44 weeks of observation for relapse. Response during the open phase was defined as CGI Improvement score of 1 (very much improved) or 2 (much improved) for each of the final 3 weeks. Relapse during the double-blind phase was defined as the investigator's judgment that drug treatment was needed for worsening depressive symptoms. Patients receiving continued bupropion treatment experienced significantly lower relapse rates over the subsequent 44 weeks compared to those receiving placebo.
Although there are no independent trials demonstrating the antidepressant effectiveness of Aplenzin () or WELLBUTRIN XL, studies have demonstrated similar bioavailability of WELLBUTRIN XL to both the immediate-release formulation and to the sustained-release formulation of bupropion under steady-state conditions, i.e., WELLBUTRIN XL 300 mg once daily was shown to have bioavailability that was similar to that of 100 mg 3 times daily of the immediate-release formulation of bupropion and to that of 150 mg 2 times daily of the sustained-release formulation of bupropion, with regard to both peak plasma concentration and extent of absorption, for parent drug and metabolites. Further, it has been demonstrated that Aplenzin () is bioequivalent to WELLBUTRIN XL.
Aplenzin () How Supplied/storage And Handling
Aplenzin () Extended-Release Tablets, 174 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "174" in bottles of 30 tablets (NDC 0024-5810-30).
Aplenzin () Extended-Release Tablets, 348 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "348" in bottles of 30 tablets (NDC 0024-5811-30).
Aplenzin () Extended-Release Tablets, 522 mg of bupropion hydrobromide, are white to off white, round tablets printed with "BR" over "522" in bottles of 30 tablets (NDC 0024-5812-30).
Aplenzin () Patient Counseling Information
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Aplenzin () and should counsel them in its appropriate use.
A patient Medication Guide [see below about "Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions," "Quit Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior,"and other important information about using Aplenzin () is available for Aplenzin () . The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Aplenzin () .
Aplenzin ()
Aplenzin ()
Aplenzin ()
Aplenzin ()
