Bupropion hydrochloride

Description

Bupropion hydrochloride is an antidepressant belonging to the aminoketone class, distinguished by its chemical structure, which is unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, or other known antidepressant agents. Its chemical designation is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride, with a molecular weight of 276.21 g/mol and a molecular formula of C13H18ClNO•HCl.

The compound appears as a white to off-white crystalline powder that is highly soluble in water. It possesses a bitter taste and can induce a sensation of local anesthesia on the oral mucosa. Bupropion hydrochloride is formulated for oral administration in the form of film-coated tablets, available in two strengths: 75 mg (orange) and 100 mg (purple).

Each 75-mg tablet contains bupropion hydrochloride along with the following inactive ingredients: colloidal silicon dioxide, crospovidone, FD&C Yellow #6 Aluminum Lake, fumaric acid granular, hydroxypropyl cellulose, hypromellose, magnesium stearate, methylcellulose, polyethylene glycol, and titanium dioxide. The 100-mg tablet includes bupropion hydrochloride and the following inactive ingredients: colloidal silicon dioxide, crospovidone, D&C Red #7 Calcium Lake, fumaric acid granular, hydroxypropyl cellulose, hypromellose, magnesium stearate, methylcellulose, polyethylene glycol, and titanium dioxide.

Uses and Indications

Bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD).

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

The recommended starting dose is 200 mg per day, administered as 100 mg twice daily. To minimize the risk of seizures, the dose should be increased gradually. After an initial period of 3 days, the dose may be escalated to 300 mg per day, given as 100 mg three times daily, ensuring that there is an interval of at least 6 hours between doses. The usual target dose is 300 mg per day, maintained as 100 mg three times daily.

The maximum allowable dose is 450 mg per day, which can be administered as 150 mg three times daily. It is essential for healthcare professionals to periodically reassess the patient's dose and the necessity for ongoing maintenance treatment.

For patients with moderate to severe hepatic impairment, the recommended dose is 75 mg once daily. In cases of mild hepatic impairment, consideration should be given to reducing the dose and/or frequency of administration. Similarly, for patients with renal impairment, a reduction in dose and/or frequency may be warranted.

Contraindications

Use of bupropion hydrochloride tablets is contraindicated in the following situations:

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

Current or prior diagnoses of bulimia or anorexia nervosa are contraindicated due to the potential for exacerbating these conditions.

Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs may increase the risk of seizures; therefore, use is contraindicated in these circumstances.

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

Known hypersensitivity to bupropion or any of the other ingredients in bupropion hydrochloride tablets constitutes a contraindication to its use.

Warnings and Precautions

Patients undergoing treatment with bupropion should be closely monitored for a range of potential neuropsychiatric adverse events associated with smoking cessation. Postmarketing reports have indicated serious or clinically significant reactions, including mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and aggressive behaviors. Notably, there have been instances of suicidal ideation, suicide attempts, and completed suicides. It is imperative that healthcare providers observe patients for these symptoms and instruct them to discontinue bupropion and seek immediate medical attention if such adverse events arise.

The risk of seizures is dose-related; therefore, it is essential to initiate treatment at a lower dose and gradually increase it, ensuring that the maximum daily dose does not exceed 450 mg. Should a seizure occur, bupropion must be discontinued immediately.

Bupropion hydrochloride tablets have been associated with increased blood pressure. Healthcare professionals should monitor blood pressure prior to starting treatment and continue to do so periodically throughout the course of therapy. Additionally, patients should be screened for bipolar disorder prior to treatment, as bupropion may activate mania or hypomania in susceptible individuals. Continuous monitoring for these symptoms is recommended.

Patients should also be informed about the risk of angle-closure glaucoma, particularly in those with untreated anatomically narrow angles, as the use of antidepressants may exacerbate this condition.

A critical warning pertains to the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants. It is essential to monitor these populations for any worsening of symptoms or emergence of suicidal thoughts and behaviors.

In the event of neuropsychiatric adverse events, patients must be instructed to discontinue bupropion and contact a healthcare provider immediately. This includes any occurrences of psychosis or other neuropsychiatric reactions, which warrant prompt medical evaluation.

To ensure safe use of bupropion, regular monitoring of blood pressure is recommended before initiating treatment and at periodic intervals thereafter.

Side Effects

Patients may experience a range of adverse reactions while taking bupropion hydrochloride tablets. The most common adverse reactions reported include agitation, dry mouth, constipation, headache or migraine, nausea or vomiting, dizziness, excessive sweating, tremor, insomnia, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmias, and auditory disturbances.

Serious adverse reactions warrant particular attention. There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants, necessitating careful monitoring for the emergence or worsening of these symptoms. Neuropsychiatric adverse events may occur 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 gradually increase the dose and limit the daily dose to 450 mg. If a seizure occurs, discontinuation of the medication is advised. Additionally, bupropion hydrochloride tablets can elevate blood pressure, requiring monitoring before and during treatment.

Patients with a history of bipolar disorder should be screened and monitored for activation of mania or hypomania. Instructing patients to contact a healthcare professional if they experience psychosis or other neuropsychiatric reactions is essential. Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants.

Other important considerations include the risk of seizures in patients with a seizure disorder, current or prior diagnoses of bulimia or anorexia nervosa, and the potential for serious reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion hydrochloride tablets should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) intended for psychiatric disorders or within 14 days of stopping treatment with either medication. Known hypersensitivity to bupropion or its ingredients is also a contraindication.

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, sinus tachycardia, and ECG changes such as conduction disturbances or arrhythmias. Severe reactions such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been noted, particularly in the context of multiple drug overdoses. Deaths associated with bupropion overdose have been documented, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Drug Interactions

Coadministration of bupropion with CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate an increase in bupropion dosage based on clinical response. However, the dosage should not exceed the maximum recommended limit.

Bupropion is a known inhibitor of CYP2D6, which can lead to increased plasma concentrations of various drugs metabolized by this enzyme. This includes certain 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). When these medications are used concurrently with bupropion, a dose reduction may be warranted.

Bupropion may also decrease plasma levels of digoxin; therefore, monitoring of digoxin levels is recommended when these drugs are used together.

Caution is advised when prescribing bupropion alongside drugs that lower the seizure threshold, as this combination may increase the risk of seizures.

Concomitant use of bupropion with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity.

The use of bupropion in conjunction with monoamine oxidase inhibitors (MAOIs) can elevate the risk of hypertensive reactions, necessitating careful monitoring.

Additionally, bupropion hydrochloride tablets may cause false-positive results in urine tests for amphetamines, which should be considered in the context of drug screening.

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 in the pediatric population have not been established. Healthcare professionals should refer to the Boxed Warning and Warnings and Precautions (5.1) for further information regarding the use of this medication in children and adolescents. Caution is advised when considering treatment options for pediatric patients.

Geriatric Use

Clinical trials involving approximately 6,000 subjects included 275 elderly patients aged 65 years and older, with 47 patients aged 75 years and older. The data indicate that there are no overall differences in safety or effectiveness between elderly patients and their younger counterparts. However, it is important to note that while clinical experience has not identified significant differences in responses, a greater sensitivity to treatment effects in some older individuals cannot be excluded.

Elderly patients are more likely to present with decreased renal function, which may increase the risk of adverse reactions. Therefore, careful consideration of renal function is essential when selecting dosages for this population. It may be prudent to monitor renal function in elderly patients to ensure appropriate dosing and minimize the risk of potential adverse effects.

Pregnancy

Pregnant patients should be advised to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy. The use of bupropion hydrochloride during pregnancy has not been well-studied, and the potential risks to fetal outcomes are not fully understood.

Additionally, bupropion hydrochloride is excreted in human milk in small amounts. Therefore, healthcare providers should consider the potential risks and benefits of treatment in breastfeeding women, as well as the implications for the nursing infant. Caution is recommended when prescribing this medication to women of childbearing potential.

Lactation

Bupropion hydrochloride is present in human milk in small amounts. Lactating mothers should be informed that this medication passes into breast milk, albeit in limited quantities. The effects of bupropion hydrochloride on breastfed infants have not been extensively studied; therefore, healthcare professionals should weigh the potential benefits of treatment against any potential risks to the nursing infant when considering the use of this medication in lactating mothers.

Renal Impairment

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

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, sinus tachycardia, and various ECG changes, such as conduction disturbances (including QRS prolongation) and arrhythmias. Additionally, symptoms such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have primarily been observed in cases involving multiple drug overdoses.

While most patients have recovered without lasting effects, there have been fatalities linked to bupropion overdoses, particularly in individuals who ingested large quantities of the drug. Reports indicate that these patients experienced multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death.

In the event of a bupropion overdose, it is imperative to consult a Certified Poison Control Center for current guidance and recommendations. Contact information for certified poison control centers can be found in the Physician’s Desk Reference (PDR), or by calling 1-800-222-1222 or visiting www.poison.org.

There are no known antidotes for bupropion. Management of an overdose should focus on supportive care, which includes close medical supervision and monitoring. It is essential to consider the possibility of a multiple drug overdose. Healthcare professionals should ensure the maintenance of an adequate airway, oxygenation, and ventilation, while also monitoring cardiac rhythm and vital signs. Induction of emesis is not recommended in cases of bupropion overdose.

Nonclinical Toxicology

Lifetime carcinogenicity studies conducted in rats and mice evaluated the effects of bupropion at doses up to 300 mg per kg per day in rats and 150 mg per kg per day in mice. These doses correspond to approximately 7 and 2 times the maximum recommended human dose (MRHD) on a mg per 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 per kg per day, which is approximately 2 to 7 times the MRHD on a mg per m² basis; lower doses were not assessed. 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.

Bupropion demonstrated a positive response in the Ames bacterial mutagenicity assay, with a mutation rate 2 to 3 times higher than the control in 2 of 5 strains tested. Additionally, an increase in chromosomal aberrations was noted in 1 of 3 in vivo rat bone marrow cytogenetic studies.

A fertility study in rats administered doses up to 300 mg per kg per day indicated no evidence of impaired fertility.

Postmarketing Experience

Some patients have reported experiencing changes in mood, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and homicidal ideation. Additional symptoms noted include aggression, hostility, agitation, anxiety, and panic. Instances of suicidal ideation and suicide have also been documented in patients attempting to quit smoking while taking bupropion. It is advised that patients discontinue bupropion and consult a healthcare professional if they encounter any of these symptoms.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, specifically the Medication Guide, which contains essential information regarding the use of bupropion hydrochloride tablets. It is important to inform patients, their families, and caregivers about the benefits and risks associated with this treatment and to counsel them on its appropriate use.

Patients should be instructed to read the Medication Guide thoroughly and to seek assistance in understanding its contents. They should be encouraged to discuss any questions or concerns they may have regarding the information provided.

Healthcare providers should alert patients to the importance of monitoring for specific symptoms while taking bupropion hydrochloride tablets. 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 changes in behavior, 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 are made. Families and caregivers should be advised to observe for these symptoms on a daily basis, as changes can occur abruptly. Any severe or sudden onset of these symptoms should be reported to the patient’s prescriber or healthcare professional, as they may indicate 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, psychosis, hallucinations, paranoia, delusions, aggression, and suicidal ideation when attempting to quit smoking while on bupropion. If such symptoms arise, patients should discontinue bupropion and contact a healthcare professional immediately.

Education on hypersensitivity symptoms is crucial, and patients should be instructed to discontinue bupropion hydrochloride tablets if they experience a severe allergic reaction. Additionally, patients must be advised to stop taking bupropion if they experience a seizure during treatment, as well as to avoid excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics, which can increase the risk of seizures.

Patients should minimize or avoid alcohol consumption while on bupropion. They should also be made aware that bupropion hydrochloride tablets may cause mild pupillary dilation, which could lead to angle-closure glaucoma in susceptible individuals. Patients may wish to undergo an examination to determine their susceptibility and consider a prophylactic procedure if necessary.

It is important to inform patients that bupropion hydrochloride tablets contain the same active ingredient as ZYBAN, which is used for smoking cessation, and that these should not be used in combination with ZYBAN or any other medications containing bupropion.

Patients should be counseled that bupropion hydrochloride tablets may impair their ability to perform tasks requiring judgment, motor, and cognitive skills. Until they are confident that the medication does not adversely affect their performance, patients should refrain from driving or operating complex machinery.

Finally, healthcare providers should encourage patients to notify them if they are taking or plan to take any prescription or over-the-counter medications, as bupropion hydrochloride tablets may interact with other drugs, affecting their metabolism.

Storage and Handling

The product is supplied in a tight, light-resistant container to ensure its integrity. It should be stored at a temperature range of 20ºC to 25ºC (68ºF to 77ºF), with permissible excursions between 15ºC and 30ºC (59ºF to 86ºF). It is essential to protect the product from moisture to maintain its quality and efficacy.

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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)