Bupropion hydrochloride

Description

Bupropion hydrochloride USP is an antidepressant belonging to the aminoketone class, distinct from tricyclic, tetracyclic, selective serotonin reuptake inhibitors, and other known antidepressant agents. Its chemical structure is closely related to diethylpropion and phenylethylamines, designated as (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight of bupropion hydrochloride is 276.2, with a molecular formula of C13H18ClNO•HCl.

The drug is presented as a white powder that is soluble in water, 0.1 N hydrochloric acid, and alcohol. 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 in two strengths: 150 mg and 300 mg. The 150 mg tablets are pink, round, biconvex coated, and imprinted with '188' in black ink on one side, while the 300 mg tablets are similarly shaped and colored, imprinted with '189' in black ink on one side.

Each tablet contains the labeled amount of bupropion hydrochloride along with inactive ingredients, including ethylcellulose, glyceryl behenate, hydrochloric acid, magnesium stearate, methacrylic acid and ethyl acrylate copolymer dispersion, methylene chloride, opacode® (which contains shellac glaze, ferrosoferric oxide, propylene glycol, and ammonium hydroxide), opadry® pink (comprising hypromellose, titanium dioxide, triacetin, talc, and iron oxide red), polyethylene glycol, povidone, silicon dioxide, and triethyl citrate. The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is excreted in the feces. The drug product complies with the requirements of USP Dissolution Test 14.

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).

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

Dosage and Administration

Dosing should be initiated at a low level and increased gradually to minimize the risk of seizures. Healthcare professionals are advised to periodically reassess the patient's dose and the necessity for ongoing 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. After an initial period of 4 days, the dose may be increased to 300 mg once daily 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 usual target dose of 300 mg once daily. After one week of treatment, the dose may be increased to 300 mg once daily. It is recommended to continue treatment 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, consideration should be given to reducing the dose and/or frequency of administration.

In patients with renal impairment, it is advisable to consider a reduction in the dose and/or frequency of dosing based on the severity of the impairment.

Contraindications

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

Patients with a seizure disorder due to the increased risk of seizures.

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

Patients who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, as this may also increase the risk of seizures.

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

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

Warnings and Precautions

Patients receiving bupropion hydrochloride should be closely monitored for the emergence of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults. There is an increased risk of suicidal thinking and behavior in these populations when taking antidepressants. Healthcare professionals are advised to observe patients for any worsening of symptoms and to take appropriate action if suicidal ideation or behavior is noted.

Neuropsychiatric Adverse Events During Smoking Cessation Postmarketing reports have indicated that serious neuropsychiatric adverse events may occur during smoking cessation attempts with bupropion hydrochloride. These events can include mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, and panic. Patients should be instructed to discontinue bupropion hydrochloride and seek immediate medical attention if they experience any of these symptoms.

Seizure Risk The risk of seizures is dose-related. To minimize this risk, it is recommended that the daily dose of bupropion hydrochloride not exceed 450 mg, and that the dose be increased gradually. If a seizure occurs, the medication should be discontinued immediately.

Hypertension Bupropion hydrochloride has the potential to elevate blood pressure. It is essential to monitor blood pressure prior to initiating treatment and periodically throughout the course of therapy to ensure patient safety.

Activation of Mania/Hypomania Patients with a history of bipolar disorder should be screened prior to treatment. Continuous monitoring for symptoms of mania or hypomania is necessary during treatment with bupropion hydrochloride.

Psychosis and Other Neuropsychiatric Reactions Patients should be advised to contact a healthcare professional if they experience any neuropsychiatric reactions, including psychosis. Prompt medical evaluation is crucial in these cases.

Angle-Closure Glaucoma There have been reports of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants. Caution should be exercised in these patients.

Laboratory Tests Blood pressure should be monitored before the initiation of treatment and periodically during the course of therapy to detect any significant changes.

Patients should be instructed to discontinue bupropion hydrochloride and contact a healthcare provider immediately if they experience any neuropsychiatric adverse events. This proactive approach is essential for ensuring patient safety and effective management of potential side effects.

Side Effects

Patients may experience a range of adverse reactions while using the medication. 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 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 changes in mood (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 gradually increase the dose. 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 extended-release tablets (XL) is contraindicated, as is the use of bupropion hydrochloride XL within 14 days of stopping an MAOI intended for psychiatric disorders.

In cases of overdosage, seizures were reported in approximately one third of all cases. 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 hydrochloride 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 combination of bupropion hydrochloride with MAOIs poses an increased risk of hypertensive reactions. Caution is warranted, and such combinations should generally be avoided.

Drug-Laboratory Test Interactions Bupropion hydrochloride may interfere with urine drug screening tests, potentially resulting in false-positive results for amphetamines. This should be taken into account when interpreting test results.

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 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 with the clinical need. For further details, refer to the Boxed Warning and Warnings and Precautions (5.1).

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 years and older participated in trials utilizing the immediate-release formulation of bupropion hydrochloride.

No overall differences in safety or effectiveness were observed between geriatric patients and younger subjects. However, while clinical experience has not identified significant differences in responses between these groups, it is important to note that greater sensitivity to the drug may be present in some elderly individuals.

Elderly patients are at an increased risk of adverse reactions, particularly those with impaired renal function. Given that this population is more likely to experience decreased renal function, careful consideration should be given to this factor when selecting dosages. Monitoring of renal function may be beneficial in this demographic to ensure safety and efficacy.

Pregnancy

Pregnant patients should be aware that there are no specific safety concerns or dosage modifications related to the use of this medication during pregnancy as detailed in the prescribing information. Additionally, there are no special precautions indicated for the use of this medication in pregnant individuals. Healthcare professionals should consider the absence of explicit pregnancy-related data when advising women of childbearing potential regarding the use of this medication. As always, the benefits and risks should be carefully weighed in the context of individual patient circumstances.

Lactation

Bupropion hydrochloride is excreted in breast milk. Lactating mothers should consult their healthcare provider to discuss the most appropriate feeding options for their infant while undergoing treatment with bupropion hydrochloride extended-release tablets (XL). It is important for healthcare providers to be informed if the mother is breastfeeding or intends to breastfeed during the course of treatment with this medication.

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 is no information available regarding dosage adjustments, special monitoring requirements, or precautions 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.

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, fatalities have been associated with bupropion overdoses, particularly in those who ingested large quantities. 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 assistance.

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

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice, administering bupropion hydrochloride at doses 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.

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, an increase in chromosomal aberrations was reported 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.

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 occurring in the context of smoking cessation efforts 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 ensure they are well-informed about their treatment. It is important to instruct patients, their families, and caregivers to be vigilant for the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, and other unusual changes in behavior, as well as worsening depression and suicidal ideation. These symptoms are particularly critical to monitor during the initial stages of antidepressant treatment and when there are adjustments to the dosage.

Families and caregivers should be encouraged to observe the patient on a daily basis for any abrupt changes in behavior, as these may indicate a need for immediate communication with the prescriber or healthcare professional, especially if the symptoms are severe or were not part of the patient's initial presentation. Such symptoms may be associated with an increased risk for suicidal thoughts and behaviors, necessitating close monitoring and potential medication adjustments.

Patients should be informed that some individuals may experience mood changes, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, particularly when attempting to quit smoking while taking bupropion. They should be instructed to discontinue bupropion hydrochloride extended-release tablets (XL) and contact a healthcare professional if they experience any of these symptoms.

Education on hypersensitivity is essential; patients should be made aware of the symptoms of severe allergic reactions and instructed to discontinue bupropion hydrochloride extended-release tablets (XL) if such reactions occur. Additionally, patients must be advised to stop taking bupropion hydrochloride extended-release tablets (XL) and not to restart if they experience a seizure during treatment.

Healthcare providers should counsel patients regarding the risks associated with excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics, as these can increase the risk of seizures. Patients should be encouraged to minimize or avoid alcohol consumption.

Patients should also be informed that bupropion hydrochloride extended-release tablets (XL) can cause mild pupillary dilation, which may lead to an episode of angle-closure glaucoma in susceptible individuals. It is important to educate patients that bupropion hydrochloride extended-release tablets (XL) contain the same active ingredient (bupropion) found in ZYBAN, which is used for smoking cessation, and that these should not be used in combination with ZYBAN or any other medications containing bupropion hydrochloride.

Furthermore, patients should be advised that bupropion hydrochloride extended-release tablets (XL), being a CNS-active drug, may impair their ability to perform tasks that require judgment or motor and cognitive skills. Until they are certain that the medication does not adversely affect their performance, patients should refrain from driving or operating complex, hazardous machinery.

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

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. It is essential to protect the product from light to maintain its integrity and efficacy.

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 be vigilant in monitoring for signs of agitation, irritability, and unusual behavioral changes, as well as the emergence of suicidality, and report any concerning symptoms to healthcare providers. Daily observation by families and caregivers is recommended.

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

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride as submitted by Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)