Bupropion hydrochloride

Description

Bupropion hydrochloride extended-release tablets (XL) are an antidepressant belonging to the aminoketone class, distinct from tricyclic, tetracyclic, selective serotonin reuptake inhibitors, and other known antidepressants. The chemical designation is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride, with a molecular weight of 276.2 and a molecular formula of C₁₃H₁₈ClNO·HCl.

The active pharmaceutical ingredient is presented as a white, crystalline powder that is highly soluble in water, exhibiting a bitter taste and a local anesthetic effect on the oral mucosa. Bupropion hydrochloride extended-release tablets are formulated for oral administration in strengths of 150 mg and 300 mg, appearing as white to off-white tablets. Each tablet contains the specified amount of bupropion hydrochloride, USP, along with inactive ingredients including povidone, tartaric acid, glyceryl distearate, magnesium stearate, hydroxypropyl cellulose, ethylcellulose, methacrylic acid copolymer dispersion, and colloidal silicon dioxide.

The tablets are marked with black ink, which consists of shellac glaze (modified) in SD-45, isopropyl alcohol, black iron oxide (non-irradiated), n-butyl alcohol, propylene glycol, and ammonium hydroxide. The extended-release tablet's insoluble shell may remain intact during gastrointestinal transit and is excreted in feces. The formulation meets the requirements of USP Dissolution Test #4.

Uses and Indications

This drug is indicated for the treatment of major depressive disorder (MDD) in adults. Additionally, it is indicated for the prevention of seasonal affective disorder (SAD).

There are no teratogenic effects associated with this drug, and no nonteratogenic effects have been reported.

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 therapy.

For the management of Major Depressive Disorder, the recommended starting dose is 150 mg administered once daily. After a period of 4 days, the dose may be increased to a usual target of 300 mg once daily.

In the case of Seasonal Affective Disorder, treatment should commence in the autumn, prior to the onset of seasonal depressive symptoms. The initial dose is also 150 mg once daily, with a potential increase to 300 mg once daily after one week. Treatment should be continued throughout the winter season.

For patients with hepatic impairment, those with moderate to severe conditions should receive a dose of 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, due to an increased risk of seizures.

• Individuals with a current or prior diagnosis of bulimia or anorexia nervosa, as these conditions may heighten the risk of seizures.

• Patients who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, as this may also increase seizure risk.

• Concurrent use with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders is contraindicated. Bupropion hydrochloride should not be used within 14 days of discontinuing an MAOI, nor should it 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).

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, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, there have been reports of suicidal ideation, suicide attempts, and completed suicides. It is imperative that healthcare professionals 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 seek immediate medical attention if they experience any of these adverse events.

The risk of seizures associated with bupropion hydrochloride is dose-related. To minimize this risk, it is recommended that the daily dose not exceed 450 mg and that the dose be increased gradually. Should a seizure occur, the medication must be discontinued immediately.

Bupropion hydrochloride has the potential to elevate 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.

Psychosis and other neuropsychiatric reactions may occur; patients should be instructed to contact a healthcare professional if they experience such reactions. Additionally, there is a risk of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants.

There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants, including bupropion. It is crucial to monitor these populations for any worsening of symptoms or the emergence of suicidal thoughts and behaviors.

To ensure safe use, healthcare professionals should conduct regular blood pressure assessments before and during treatment. Patients should be advised to seek emergency medical help if they experience any neuropsychiatric reactions and to discontinue bupropion hydrochloride XL and contact their healthcare provider if they encounter any neuropsychiatric adverse events.

Side Effects

Patients may experience a range of adverse reactions while using this medication, categorized by seriousness and frequency.

Common adverse reactions, occurring in at least 5% of patients and at a rate greater than twice that 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 particular attention. A WARNING regarding suicidal thoughts and behaviors is indicated, as there is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Patients should be closely monitored for any worsening or emergence of suicidal thoughts and behaviors.

Neuropsychiatric adverse events have been reported during smoking cessation, 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 hydrochloride may increase blood pressure, necessitating monitoring before and during treatment.

Activation of mania or hypomania has been observed, highlighting the importance of screening patients for bipolar disorder and monitoring for these symptoms. Patients should be instructed 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 potential for serious reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. The use of monoamine oxidase inhibitors (MAOIs) in conjunction with bupropion hydrochloride or within 14 days of stopping treatment is contraindicated.

In cases of overdose, seizures were reported in approximately one third of all instances. 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

Coadministration of bupropion hydrochloride with certain drug classes may necessitate careful monitoring and potential dosage adjustments due to significant interactions.

CYP2B6 Inducers When bupropion is administered alongside CYP2B6 inducers such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, an increase in bupropion dosage may be required to maintain clinical efficacy. However, any dosage increase should not exceed the maximum recommended dose.

CYP2D6 Substrates Bupropion is a known inhibitor of CYP2D6 and may elevate the plasma concentrations of drugs metabolized by this enzyme. This includes various antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). A dose reduction of these concomitant medications should be considered to mitigate the risk of adverse effects.

Drugs That Lower Seizure Threshold Bupropion hydrochloride should be used with caution in patients taking other medications that lower the seizure threshold, as this may increase the risk of seizures.

Dopaminergic Drugs Concomitant use of bupropion with dopaminergic agents such as levodopa and amantadine may lead to central nervous system (CNS) toxicity. Close monitoring for signs of CNS effects is advised.

Monoamine Oxidase Inhibitors (MAOIs) The use of bupropion in conjunction with MAOIs can heighten the risk of hypertensive reactions. Caution is warranted, and monitoring for hypertensive symptoms is recommended.

Drug-Laboratory Test Interactions Bupropion hydrochloride may cause false-positive results in urine drug screenings for amphetamines. This potential interaction should be communicated to healthcare providers conducting such tests.

Packaging & NDC

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

Pediatric Use

Safety and effectiveness in the pediatric population have not been established for bupropion hydrochloride extended-release tablets (XL). When considering the use of this medication in children or adolescents, healthcare professionals should carefully balance the potential risks with the clinical need. For further details, refer to the Boxed Warning and Warnings and Precautions (5.1).

Geriatric Use

Clinical trials involving approximately 6,000 patients assessed the safety and efficacy of bupropion hydrochloride sustained-release tablets, with 275 participants aged 65 years and older and 47 participants aged 75 years and older. Overall, no significant differences in safety or effectiveness were observed between elderly patients and their younger counterparts. However, it is important to note that while clinical experience has not identified distinct differences in responses between these age groups, a greater sensitivity to the medication in some older individuals cannot be excluded.

Elderly patients may be at an increased risk of adverse reactions, particularly those with impaired renal function. Given that geriatric patients are more likely to experience decreased renal function, careful consideration of this factor is essential when selecting dosages. It is advisable to monitor renal function in elderly patients to ensure appropriate dosing and to mitigate potential risks associated with renal impairment.

Pregnancy

Pregnant patients should be advised to notify their healthcare provider if they become pregnant or intend to become pregnant while undergoing treatment with bupropion hydrochloride extended-release tablets (XL). It is important for these patients to discuss the potential risks to the fetus associated with the use of bupropion hydrochloride XL during pregnancy.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women who have been exposed to bupropion hydrochloride XL. Healthcare providers should encourage patients to participate in this registry to contribute to the understanding of the effects of this medication during pregnancy.

If a patient becomes pregnant during treatment with bupropion hydrochloride XL, it is essential to consult with their healthcare provider regarding the continuation of therapy and to consider registering with the National Pregnancy Registry for Antidepressants. Patients can register by calling 1-844-405-6185.

Lactation

Bupropion hydrochloride passes into breast milk. Lactating mothers should consult their healthcare provider to discuss the most appropriate feeding method for their infant while undergoing treatment with bupropion hydrochloride extended-release tablets (XL). It is advisable for patients who are breastfeeding or intend to breastfeed during treatment with bupropion hydrochloride extended-release tablets (XL) to seek guidance from their healthcare provider.

Renal Impairment

There is no information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution and consider the lack of specific guidance when prescribing to patients with reduced kidney function.

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 were reported. Other serious adverse reactions associated with bupropion overdose include hallucinations, loss of consciousness, alterations in mental status, sinus tachycardia, and various ECG changes such as conduction disturbances or arrhythmias. Additional symptoms may encompass clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure, particularly in scenarios involving multiple drug overdoses.

While the majority of patients have recovered without lasting effects, there have been fatalities linked to bupropion overdoses, especially in cases where large doses were ingested. Reports indicate that patients who succumbed to overdose experienced multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death.

In the event of a suspected overdose, it is imperative to consult a Certified Poison Control Center for current guidance and recommendations. Healthcare professionals can reach the Poison Control Center at 1-800-222-1222 or visit www.poison.org for further information.

There are no known antidotes for bupropion; therefore, management of an overdose should focus on supportive care. This includes close medical supervision and monitoring of the patient. It is also essential to consider the possibility of a multiple drug overdose when assessing the situation.

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 in this study. The potential for these lesions to serve as precursors to liver neoplasms remains unresolved. Conversely, the mouse study did not reveal similar liver lesions, nor was there an increase in malignant tumors in the liver or other organs in either species.

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

A fertility study conducted in rats at doses up to 300 mg/kg/day indicated no evidence of impaired fertility. No information is available regarding teratogenic effects or animal pharmacology and toxicology.

Postmarketing Experience

Some patients have reported experiencing changes in mood, including depression and mania, during treatment with bupropion. Additional psychiatric events noted include psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. There have also been reports of suicidal ideation and suicide attempts in individuals attempting to quit smoking while on bupropion therapy. These events were reported voluntarily or identified through surveillance programs.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, specifically the Medication Guide, to understand the benefits and risks associated with bupropion hydrochloride extended-release tablets (XL). It is essential to counsel patients, their families, and caregivers on the appropriate use of this medication.

Providers should instruct patients and their support systems to read the Medication Guide thoroughly and assist them in comprehending its contents. Patients should be encouraged to discuss the information within the Medication Guide and to ask any questions they may have.

Healthcare providers must inform patients about the importance of monitoring for specific symptoms while taking bupropion hydrochloride extended-release tablets (XL). Patients, along with their families and caregivers, should be vigilant for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, and other unusual behavioral changes, as well as worsening depression and suicidal ideation. These symptoms are particularly critical to observe during the initial stages of treatment and when dosage adjustments occur. Families and caregivers should be advised to monitor for these symptoms daily, as changes can be abrupt, and any severe or sudden onset symptoms should be reported to the prescriber.

Patients should be informed that such symptoms may indicate an increased risk for suicidal thoughts and behaviors, necessitating close monitoring and potential medication adjustments. Additionally, it is important to communicate that some individuals may experience mood changes, psychosis, hallucinations, paranoia, delusions, aggression, and suicidal ideation when attempting to quit smoking while on bupropion.

Patients must be instructed to discontinue bupropion hydrochloride extended-release tablets (XL) and contact a healthcare professional if they experience any concerning symptoms. They should also be educated about the signs of hypersensitivity and advised to stop the medication if a severe allergic reaction occurs. Furthermore, patients should discontinue the medication and not restart it if they experience a seizure during treatment.

Providers should caution patients that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures, and patients should minimize or avoid alcohol consumption. It is also important to inform patients that bupropion hydrochloride extended-release tablets (XL) may cause mild pupillary dilation, which could lead to angle-closure glaucoma in susceptible individuals. Patients may wish to undergo an examination to assess their susceptibility and consider a prophylactic procedure if necessary.

Patients should be made aware that bupropion hydrochloride extended-release tablets (XL) contain the same active ingredient as ZYBAN, which is used for smoking cessation, and should not be used in conjunction with ZYBAN or any other bupropion-containing medications.

Additionally, healthcare providers should advise patients that bupropion hydrochloride extended-release tablets (XL) may impair their ability to perform tasks requiring judgment, motor, and cognitive skills. Until patients are confident that the medication does not adversely affect their performance, they should refrain from driving or operating complex machinery.

Finally, patients should be counseled to notify their healthcare provider of any prescription or over-the-counter medications they are taking or plan to take, as interactions may affect the metabolism of bupropion hydrochloride extended-release tablets (XL) and other drugs.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a controlled room temperature of 25°C (77°F). Temporary excursions are permissible within the range of 15°C to 30°C (59°F to 86°F), in accordance with USP guidelines for controlled room temperature. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients and their caregivers should be advised to discontinue bupropion hydrochloride and seek immediate medical attention if they experience agitation, depressed mood, or any atypical changes in behavior or thinking, including suicidal ideation or behavior. Families and caregivers of patients receiving antidepressants for major depressive disorder or other indications should closely monitor for signs of agitation, irritability, and unusual behavioral changes, reporting any concerning symptoms to healthcare providers promptly. Daily observation is recommended.

Postmarketing experience has revealed serious neuropsychiatric adverse events in patients using bupropion for smoking cessation, including mood changes, psychosis, and suicidal thoughts or actions. Additionally, anaphylactoid and anaphylactic reactions have been reported, presenting with symptoms such as pruritus, urticaria, and dyspnea, necessitating medical intervention. Rare cases of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock have also been documented in association with bupropion.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride (xl) as submitted by Chartwell RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)