Bupropion hydrochloride

Description

Bupropion Hydrochloride USP is an antidepressant belonging to the aminoketone class, which is chemically distinct from tricyclic, tetracyclic, selective serotonin reuptake inhibitors, and other known antidepressant agents. Its chemical designation is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight of bupropion hydrochloride is 276.2, and its molecular formula is C13H18ClNO•HCl.

The substance appears as a white, crystalline powder that is highly soluble in water. It has a bitter taste and can induce a sensation of local anesthesia on the oral mucosa. Bupropion Hydrochloride Extended-Release Tablets USP (XL) are formulated for oral administration and are available in strengths of 150 mg and 300 mg. These tablets are white to pale yellow in color and contain the labeled amount of bupropion hydrochloride along with inactive ingredients, which include cysteine hydrochloride, ethylcellulose, methacrylic acid copolymer dispersion, lecithin, magnesium stearate, polyvinyl alcohol, polyethylene glycol, povidone, silicon dioxide, talc, triethyl citrate, and titanium dioxide. The tablets are printed with black ink that consists of ammonium hydroxide, ferrosoferric oxide, propylene glycol, and shellac glaze.

Uses and Indications

Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major depressive disorder (MDD) in adults. Additionally, this medication is indicated for the prevention of seasonal affective disorder (SAD) in individuals at risk.

There are no teratogenic or nonteratogenic effects associated with the use of bupropion hydrochloride extended-release tablets (XL).

Dosage and Administration

Healthcare professionals are advised to initiate treatment with a gradual increase in dosage to minimize the risk of seizures. It is essential to periodically reassess the patient's dose and the necessity for maintenance treatment.

For the management of Major Depressive Disorder, the recommended starting dose is 150 mg administered once daily. The usual target dose is 300 mg once daily, with the option to increase the dose to 300 mg after 4 days if clinically indicated.

In the case of Seasonal Affective Disorder, treatment should commence in the autumn, prior to the onset of seasonal depressive symptoms. The starting dose is also 150 mg once daily, with a typical target dose of 300 mg once daily. After one week of treatment, the dose may be increased to 300 mg once daily, and it is recommended to continue treatment throughout the winter season.

For patients with hepatic impairment, those with moderate to severe conditions should receive 150 mg every other day. In patients with mild hepatic impairment, it is advisable to consider a reduction in the dose and/or frequency of administration.

In patients with renal impairment, a reduction in the dose and/or frequency of dosing should also be considered to ensure safety and efficacy.

Contraindications

Use of bupropion hydrochloride extended-release tablets (XL) is contraindicated in the following situations:

Patients with a seizure disorder are at increased risk of seizures when using this medication.

The use of bupropion is contraindicated in individuals with a current or prior diagnosis of bulimia or anorexia nervosa due to the potential for increased seizure risk.

Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is contraindicated, as it may elevate the risk of seizures.

Bupropion hydrochloride extended-release tablets (XL) should not be used in conjunction with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders, or within 14 days of discontinuing either treatment. Additionally, it should not be initiated in patients receiving linezolid or intravenous methylene blue.

Known hypersensitivity to bupropion or any of the components of bupropion hydrochloride extended-release tablets (XL) is a contraindication for use.

Warnings and Precautions

Serious neuropsychiatric adverse events have been reported in patients using bupropion hydrochloride extended-release tablets (XL) during smoking cessation. These events may include significant mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicide. Healthcare professionals should closely observe patients attempting to quit smoking with bupropion hydrochloride XL for the emergence of these symptoms. Patients should be instructed to discontinue the medication and contact their healthcare provider immediately if they experience any of these adverse events.

The risk of seizures is dose-related with bupropion hydrochloride XL. To minimize this risk, it is recommended to limit the daily dose to a maximum of 450 mg and to increase the dose gradually. If a seizure occurs, the medication should be discontinued.

Bupropion hydrochloride XL has the potential to increase blood pressure. Therefore, it is essential to monitor blood pressure prior to initiating treatment and periodically throughout the course of therapy.

Patients with a history of bipolar disorder should be screened prior to treatment, as bupropion may activate mania or hypomania. Continuous monitoring for these symptoms is advised. Additionally, patients should be instructed to report any occurrences of psychosis or other neuropsychiatric reactions to their healthcare professional.

There is a risk of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants, including bupropion hydrochloride XL.

General precautions should be taken into account, particularly the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants. Continuous monitoring for the emergence or worsening of suicidal thoughts and behaviors is critical.

Healthcare professionals should ensure that patients are aware of the need to seek emergency medical help if they experience any neuropsychiatric adverse events. Patients should also be advised to contact their healthcare provider if they experience psychosis or other neuropsychiatric reactions during treatment.

Regular monitoring of blood pressure is recommended before starting treatment and periodically during the course of therapy to ensure patient safety.

Side Effects

Patients may experience a range of adverse reactions while using bupropion hydrochloride extended-release tablets (XL). The following sections outline common and serious adverse reactions, as well as important warnings and considerations.

Common adverse reactions, occurring in 5% or more of patients and at least twice the rate of placebo, include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitations, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash.

Serious adverse reactions warrant careful monitoring. There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants, necessitating vigilance for the emergence or worsening of these symptoms. Neuropsychiatric adverse events during smoking cessation have been reported, including mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides.

The risk of seizures is dose-related; therefore, it is recommended to limit the daily dose to 450 mg and to increase the dose gradually. If a seizure occurs, discontinuation of the medication is advised. Additionally, bupropion can elevate blood pressure, so monitoring is essential before and during treatment.

Patients with a history of bipolar disorder should be screened and monitored for activation of mania or hypomania. Instruct patients to contact a healthcare professional if they experience psychosis or other neuropsychiatric reactions.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants. Other important considerations include a history of seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the risks associated with abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Bupropion should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) intended for psychiatric disorders, or within 14 days of stopping treatment with either bupropion or an MAOI. Known hypersensitivity to bupropion or its ingredients is also a contraindication.

In cases of overdose, seizures were reported in approximately one-third of patients. Other serious reactions associated with bupropion overdose include hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (such as conduction disturbances or arrhythmias), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. Deaths have been reported in patients who ingested large doses of bupropion, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Drug Interactions

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate an increase in the dosage of bupropion. However, it is important to ensure that the dosage does not exceed the maximum recommended limit.

Bupropion acts as an inhibitor of CYP2D6, which can lead to elevated concentrations of certain medications, including antidepressants (e.g., venlafaxine, nortriptyline), antipsychotics (e.g., haloperidol), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone). A dose reduction of these concomitant medications should be considered to mitigate the risk of adverse effects.

Caution is warranted when prescribing bupropion hydrochloride extended-release tablets (XL) alongside drugs that may lower the seizure threshold, as this combination could increase the risk of seizures.

The concurrent use of bupropion hydrochloride extended-release tablets (XL) with dopaminergic agents, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity. Therefore, careful monitoring is advised.

Additionally, there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (XL) are administered in conjunction with monoamine oxidase inhibitors (MAOIs).

It is also noteworthy that bupropion hydrochloride extended-release tablets (XL) can lead to false-positive results in urine drug screenings for amphetamines, which should be taken into account during testing.

Packaging & NDC

The table below lists all NDC Code configurations of Bupropion Hydrochloride, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of bupropion hydrochloride extended-release tablets (XL) in the pediatric population have not been established. When considering the use of this medication in children or adolescents, healthcare professionals should carefully balance the potential risks against the clinical need for treatment.

Geriatric Use

Clinical trials involving bupropion hydrochloride sustained-release tablets included approximately 6,000 patients, of whom 275 were aged 65 years and older, and 47 were aged 75 years and older. Additionally, several hundred patients aged 65 and older participated in clinical trials utilizing the immediate-release formulation of bupropion hydrochloride for depression.

No overall differences in safety or effectiveness were observed between elderly patients and younger subjects in these studies. However, while clinical experience has not identified significant differences in responses between these age groups, it is important to note that greater sensitivity in some older individuals cannot be ruled out.

Bupropion is extensively metabolized in the liver to active metabolites, which are subsequently metabolized and excreted by the kidneys. Given that elderly patients are more likely to have decreased renal function, the risk of adverse reactions may be heightened in this population. Therefore, it is advisable to consider renal function when selecting doses for geriatric patients, and monitoring of renal function may be beneficial to ensure safety and efficacy in this demographic.

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at National Pregnancy Registry for AntidepressantsNational Pregnancy Registry for Antidepressants.

Data from epidemiological studies involving pregnant women exposed to bupropion during the first trimester have not identified an increased risk of congenital malformations overall. However, there are risks to the mother associated with untreated depression. In a prospective, longitudinal study, women with a history of major depressive disorder who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression compared to those who continued treatment. Therefore, healthcare providers should consider the risks of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Animal studies have shown that when bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. Conversely, when given to pregnant rabbits during organogenesis, non-dose-related increases in the incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater, with decreased fetal weights noted at doses twice the MRHD and higher.

The estimated background risk for major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data from the international bupropion Pregnancy Registry, which included 675 first trimester exposures, and a retrospective cohort study using the United Healthcare database with 1,213 first trimester exposures did not show an overall increased risk for malformations. However, the Registry suggested a possible increase in cardiac malformations, although no increased risk for cardiovascular malformations overall has been observed. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester was 1.3%, which is similar to the background rate of approximately 1%.

Findings regarding bupropion exposure during the first trimester and the risk for left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD) are inconsistent and do not allow for definitive conclusions regarding possible associations. In studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively. While no evidence of fetal malformations was found in rats, pregnant rabbits exhibited non-dose-related increases in fetal malformations and skeletal variations at the lowest dose tested and greater, with decreased fetal weights observed at doses of 50 mg/kg/day and higher. No maternal toxicity was evident at doses of 50 mg/kg/day or less. Additionally, in a pre- and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day from embryonic implantation through lactation had no effect on pup growth or development.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure, assuming a daily consumption of 150 mL/kg, was found to be 2% of the maternal weight-adjusted dose.

There are no data available regarding the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports have not identified a clear association of adverse reactions in breastfed infants. However, it is important to note that postmarketing reports have described seizures in breastfed infants, although the relationship between bupropion exposure and these seizures remains unclear.

The developmental and health benefits of breastfeeding should be weighed against the mother’s clinical need for bupropion hydrochloride extended-release tablets (XL) and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Overdoses of bupropion have been documented, with instances involving doses of 30 grams or more. In approximately one third of these cases, seizures have been reported, highlighting the potential neurological risks associated with excessive intake.

Serious adverse reactions stemming from bupropion overdose may include hallucinations, loss of consciousness, alterations in mental status, and respiratory failure. These symptoms are particularly concerning in scenarios involving multiple drug overdoses, where the risk of severe complications is heightened.

Fatalities linked to bupropion overdose have been observed, often occurring after multiple uncontrolled seizures, bradycardia, and subsequent cardiac arrest. This underscores the critical nature of prompt recognition and management of overdose situations.

Currently, there are no known antidotes for bupropion. Therefore, the primary approach to managing an overdose involves supportive care and vigilant medical supervision. Healthcare professionals are advised to consult a Certified Poison Control Center for specific guidance in overdose cases. The Poison Control Center can be reached at 1-800-222-1222 or through their website at www.poison.org.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice using bupropion hydrochloride at doses of up to 300 mg/kg/day and 150 mg/kg/day, respectively. These doses correspond to approximately 7 and 2 times the maximum recommended human dose (MRHD) on a mg/m² basis. In the rat study, an increase in nodular proliferative lesions of the liver was observed at doses ranging from 100 to 300 mg/kg/day of bupropion hydrochloride, which is approximately 2 to 7 times the MRHD on a mg/m² basis; lower doses were not evaluated. The potential for these lesions to serve as precursors to liver neoplasms remains unresolved. Conversely, similar liver lesions were not detected in the mouse study, and no increase in malignant tumors of the liver or other organs was noted in either species.

In terms of mutagenicity, bupropion demonstrated a positive response in 2 of 5 strains in one Ames bacterial mutagenicity assay, resulting in a mutation rate that was 2 to 3 times higher than the control. However, it yielded negative results in another assay. Additionally, bupropion was associated with an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies.

No evidence of impaired fertility was observed in a fertility study conducted in rats at doses up to 300 mg/kg/day. There is no information available regarding teratogenic effects.

Postmarketing Experience

Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports include changes in mood, such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, instances of suicidal ideation, suicide attempts, and completed suicides have been documented.

Neuropsychiatric adverse events have occurred in both patients with and without pre-existing psychiatric conditions, with some individuals experiencing a worsening of their psychiatric illnesses. It is recommended that patients be observed for the occurrence of these neuropsychiatric adverse events. Patients and caregivers should be advised to discontinue bupropion hydrochloride extended-release tablets (XL) and contact a healthcare provider immediately if symptoms such as agitation, depressed mood, or atypical changes in behavior or thinking arise, or if suicidal ideation or behavior develops.

In many postmarketing cases, resolution of symptoms following the discontinuation of bupropion has been reported. However, in some instances, symptoms have persisted, indicating the need for ongoing monitoring and supportive care until resolution occurs.

Patient Counseling

Healthcare providers should inform patients that the use of antidepressants has been associated with an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults during short-term trials. It is important to note that these trials did not indicate an increased risk in individuals aged 65 and older.

Providers should emphasize the necessity of close monitoring for all patients initiating antidepressant therapy, regardless of age. This includes vigilance for any worsening of symptoms or the emergence of suicidal thoughts and behaviors. Families and caregivers should be advised to maintain open communication with the prescriber and to observe the patient closely, particularly during the initial months of treatment or when there are changes in dosage.

Patients receiving antidepressants for any indication should be monitored for clinical worsening, suicidality, and any unusual changes in behavior. Healthcare providers should stress the importance of daily observation by families and caregivers, who should be alerted to watch for signs of agitation, irritability, and other concerning symptoms. It is crucial that any such symptoms, especially those indicating suicidality, are reported to healthcare providers immediately.

Additionally, when prescribing bupropion hydrochloride extended-release tablets (XL), providers should write prescriptions for the smallest quantity necessary to ensure effective patient management, thereby minimizing the risk of overdose.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and features a child-resistant closure. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP Controlled Room Temperature guidelines. Additionally, it is crucial to keep the product out of reach of children to ensure safety.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride as submitted by Slate Run Pharmaceuticals, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)