Bupropion hydrochloride

Description

Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. It is designated as (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight is 276.21 g/mol, and the molecular formula is C13H18ClNO•HCl. Bupropion hydrochloride appears as a white to off-white crystalline powder and is highly soluble in water. It has a bitter taste and produces a sensation of local anesthesia on the oral mucosa.

Bupropion hydrochloride is supplied for oral administration as 75-mg (orange) and 100-mg (purple) film-coated tablets. Each 75-mg tablet contains colloidal silicon dioxide, crospovidone, FD&C Yellow #6 Aluminum Lake, fumaric acid granular, hydroxypropyl cellulose, hypromellose, magnesium stearate, methylcellulose, polyethylene glycol, and titanium dioxide. Each 100-mg tablet contains 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 due to the increased risk of seizures associated with bupropion.

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 tablets should not be used within 14 days of discontinuing an MAOI, nor should an MAOI be initiated within 14 days of stopping bupropion hydrochloride tablets. Additionally, bupropion should not be started in patients receiving linezolid or intravenous methylene blue.

Patients with known hypersensitivity to bupropion or any other components of bupropion hydrochloride tablets should not use this medication.

Warnings and Precautions

Increased risk of suicidal thinking and behavior has been observed in children, adolescents, and young adults taking antidepressants. Healthcare professionals should closely monitor these populations for any worsening or emergence of suicidal thoughts and behaviors.

General Precautions

Neuropsychiatric adverse events may occur during smoking cessation. Postmarketing reports have indicated serious or clinically significant neuropsychiatric events, including mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, suicidal ideation, suicide attempts, and completed suicides have been reported. Patients attempting to quit smoking with bupropion should be observed for these symptoms. If any adverse events occur, patients must be instructed to discontinue bupropion and contact a healthcare provider immediately.

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

Bupropion hydrochloride tablets have the potential to increase blood pressure. Therefore, it is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course.

Patients should be screened for bipolar disorder, 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.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants.

Laboratory Tests

Blood pressure should be monitored before initiating treatment and periodically during the treatment to ensure patient safety.

Emergency Medical Help Instructions

Patients must be advised to seek immediate medical assistance if they experience psychosis or other neuropsychiatric reactions.

Discontinuation Instructions

Patients should discontinue bupropion and contact a healthcare provider if they experience any neuropsychiatric adverse events.

Side Effects

Patients may experience a range of adverse reactions while using 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.

A significant warning associated with bupropion is the increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults. Patients should be closely monitored for any worsening of mood or emergence of suicidal ideation during treatment.

Neuropsychiatric adverse events have been observed during smoking cessation, including changes in mood (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, anxiety, panic, and suicidal ideation. Instances of suicide attempts and completed suicides have also been reported.

The risk of seizures is dose-related, and it is recommended to gradually increase the dosage while limiting the daily dose to 450 mg. If a seizure occurs, discontinuation of the medication is advised. Additionally, bupropion hydrochloride tablets may elevate blood pressure; therefore, blood pressure should be monitored before and periodically 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 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 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 bupropion or an MAOI.

In cases of overdosage, 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 and 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 tablets with certain drug classes may lead to significant interactions that require careful consideration of dosage adjustments and monitoring.

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 necessary based on clinical response. However, the dosage should not exceed the maximum recommended limit.

CYP2D6 Substrates Bupropion is a known inhibitor of CYP2D6, which can lead to elevated plasma concentrations of drugs metabolized by this enzyme, including certain antidepressants, antipsychotics, beta-blockers, and Type 1C antiarrhythmics. A dose reduction of these medications should be considered when used concurrently with bupropion.

Digoxin Bupropion may decrease plasma levels of digoxin. It is advisable to monitor digoxin levels closely in patients receiving both medications to ensure therapeutic efficacy.

Drugs Lowering Seizure Threshold Caution is advised when prescribing bupropion hydrochloride tablets in conjunction with 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 result in central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is recommended.

Monoamine Oxidase Inhibitors (MAOIs) The use of bupropion alongside MAOIs can elevate the risk of hypertensive reactions. Close monitoring is warranted in patients receiving both treatments.

Drug-Laboratory Test Interactions Bupropion hydrochloride tablets may cause false-positive results in urine tests 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, 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 additional 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 assessed the safety and effectiveness of bupropion sustained-release tablets, with 275 participants aged 65 years and older and 47 participants aged 75 years and older. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, while clinical experience has not identified significant differences in responses between elderly and younger patients, it is important to acknowledge that some older individuals may exhibit greater sensitivity to the medication.

Elderly patients are more likely to experience decreased renal function, which may increase the risk of adverse reactions. Therefore, it is essential to consider renal function when selecting dosages for this population. Monitoring renal function in elderly patients may be beneficial to ensure appropriate dosing and minimize the risk of adverse effects.

Pregnancy

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions. Healthcare professionals should consider the lack of data when prescribing this medication to pregnant patients. It is advisable to weigh the potential benefits against any unknown risks to fetal outcomes. Women of childbearing potential should be counseled on the importance of effective contraception during treatment.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving 10 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, to bupropion and its active metabolites 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 tablets and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

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 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

In cases of bupropion overdose, significant clinical manifestations can occur, particularly with doses exceeding 30 grams. Seizures are a common complication, occurring in approximately one-third of reported overdose cases.

Clinical Symptoms Serious reactions associated with bupropion overdose may include hallucinations, loss of consciousness, and alterations in mental status. Additionally, patients may exhibit ECG changes, particularly conduction disturbances. Other symptoms reported in the context of overdose encompass sinus tachycardia, clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. It is important to note that fatalities have been documented, especially in instances involving large doses, where multiple uncontrolled seizures and cardiac failure were observed.

Management and Supportive Care There are currently no known antidotes for bupropion; therefore, the management of overdose relies heavily on supportive care and close medical supervision. In the event of an overdose, it is critical to ensure an adequate airway, oxygenation, and ventilation. Continuous monitoring of cardiac rhythm and vital signs is essential to manage potential complications effectively.

Healthcare professionals are advised to consult a Certified Poison Control Center for further guidance in overdose situations. Assistance can be obtained by calling 1-800-222-1222. Prompt and appropriate intervention is vital to mitigate the risks associated with bupropion overdose.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice with bupropion administered at doses up to 300 mg/kg/day and 150 mg/kg/day, respectively. These doses correspond to approximately 6 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, which is approximately 2 to 6 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, 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.

Regarding reproductive toxicity, no adverse effects on male and female fertility were observed when rats received oral doses of bupropion up to 300 mg/kg/day, which is approximately 6 times the MRHD on a mg/m² basis. This treatment was administered to females prior to mating and continued either through Day 13 of gestation or through lactation, while males were treated for 60 days prior to and during mating. However, doses of 200 mg/kg/day or greater, approximately 4 times the MRHD on a mg/m² basis, resulted in transient ataxia or behavioral changes in adult female rats. Importantly, there were no adverse effects on fertility, reproduction, or the growth and development of male or female offspring.

Postmarketing Experience

Some patients have reported experiencing changes in mood, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Suicidal ideation and suicide attempts have also been noted in individuals attempting to quit smoking while taking bupropion.

Additionally, new or exacerbated mental health issues, such as changes in behavior or thinking, aggression, hostility, agitation, depression, or suicidal thoughts or actions, have been documented in some individuals using bupropion for smoking cessation. These symptoms were more frequently observed in patients with a prior history of mental health disorders compared to those without such a history.

Patients experiencing a seizure while on bupropion hydrochloride tablets are advised to discontinue use and contact their healthcare provider immediately. Reports have also indicated that some individuals may develop severe hypertension while taking bupropion hydrochloride tablets.

Furthermore, episodes of mania have been reported, characterized by symptoms such as significantly increased energy, severe insomnia, racing thoughts, reckless behavior, grandiose ideas, excessive happiness or irritability, and increased talkativeness. Unusual thoughts or behaviors, including delusions, hallucinations, paranoia, or confusion, have also been observed in some patients.

Severe allergic reactions to bupropion hydrochloride tablets have been reported, with symptoms including rash, itching, hives, fever, swollen lymph nodes, painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, or difficulty breathing.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Medication Guide) thoroughly. It is important for 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 (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior, as well as worsening depression and suicidal ideation, particularly during the initial phase of antidepressant treatment and when there are adjustments to the dosage.

Families and caregivers should monitor patients on a daily basis for any abrupt changes in behavior, as these can occur suddenly. Any severe or unexpected symptoms should be reported to the patient’s prescriber or healthcare professional promptly.

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, panic, and suicidal thoughts when attempting to quit smoking while taking bupropion. If patients experience any of these symptoms, they should discontinue bupropion and contact a healthcare professional immediately.

Education on hypersensitivity symptoms is essential, and patients should discontinue bupropion hydrochloride tablets if they experience a severe allergic reaction. Additionally, patients must be instructed to stop taking bupropion hydrochloride tablets and not to restart them if they experience a seizure during treatment.

Patients should be made aware that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures, and they should minimize or avoid alcohol consumption. It is also important to inform patients that bupropion hydrochloride tablets may cause mild pupillary dilation, which could lead to an episode of angle-closure glaucoma in susceptible individuals.

Patients should be educated that bupropion hydrochloride tablets contain the same active ingredient as ZYBAN®, which is used for smoking cessation, and that they should not be used in combination with ZYBAN® or any other medications containing bupropion. Furthermore, patients should be advised that any CNS-active drug, including bupropion hydrochloride tablets, may impair their ability to perform tasks that require judgment or motor and cognitive skills. Until they are certain that bupropion does not adversely affect their performance, patients should refrain from driving or operating complex machinery.

Patients should notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter medications, as bupropion hydrochloride tablets may interact with other drugs. Additionally, patients should inform their healthcare provider if they become pregnant or plan to become pregnant during treatment with bupropion hydrochloride tablets.

Storage instructions for bupropion hydrochloride tablets include keeping them at room temperature, between 68°F and 77°F (20°C to 25°C), and ensuring they remain dry and protected from light. Patients should take bupropion hydrochloride tablets in equally divided doses 3 or 4 times a day, with doses separated by at least 6 hours to minimize the risk of seizure. If a dose is missed, patients should not take an extra tablet to compensate but should take the next tablet at the regular time due to the dose-related risk of seizure.

Patients should be instructed to swallow bupropion hydrochloride tablets whole and not to crush, divide, or chew them. These tablets can be taken with or without food.

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) as defined by USP Controlled Room Temperature guidelines. It is essential to protect the product from moisture to maintain its quality and efficacy.

Additional Clinical Information

The maximum recommended dose of bupropion hydrochloride tablets is 450 mg per day, administered as 150 mg three times daily, with a gradual titration rate to minimize the risk of seizure. Clinicians should counsel patients and caregivers to discontinue the medication and seek immediate medical attention if they observe any atypical changes in behavior, mood, or thinking, including suicidal ideation or behavior. Patients should also be advised to report any neuropsychiatric symptoms such as delusions, hallucinations, or confusion, as well as any signs of allergic reactions, including skin rash or difficulty breathing.

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, rare cases of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock have been reported.

FDA Insert (PDF)

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

View full prescribing information (PDF)