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, it is advised to increase the dose gradually. After an initial period of 3 days, the dose may be increased 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, administered in the same manner of 100 mg three times daily.

The maximum allowable dose is 450 mg per day, which should be given as 150 mg three times daily. It is important 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. Additionally, for patients with renal impairment, a reduction in dose and/or frequency may also 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.

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 precipitate seizures.

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 hydrochloride tablets 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, there have been reports of suicidal ideation, suicide attempts, and completed suicides. It is essential to observe patients attempting to quit smoking with bupropion for these symptoms. Patients should be instructed to discontinue bupropion and contact a healthcare provider if they experience any of these adverse events.

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 immediately.

Bupropion hydrochloride tablets have the potential to increase blood pressure. Therefore, it is crucial 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 should be advised to seek immediate medical assistance if they experience psychosis or other neuropsychiatric reactions.

Discontinuation Instructions

Patients attempting to quit smoking with bupropion should be closely observed for neuropsychiatric adverse events. They should be instructed to discontinue bupropion and contact a healthcare provider if they experience any such events. Additionally, bupropion should be discontinued if a seizure occurs.

Side Effects

Patients receiving bupropion hydrochloride tablets may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

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. These reactions were observed in clinical trials and may vary in frequency among patients.

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

Neuropsychiatric adverse events have been noted 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. Patients experiencing any of these symptoms should be advised to contact a healthcare professional immediately.

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, necessitating monitoring before and during treatment.

Activation of mania or hypomania has been reported, highlighting the importance of screening patients for bipolar disorder and monitoring for these symptoms. Angle-closure glaucoma has also been observed in patients with untreated anatomically narrow angles who are treated with antidepressants.

Other important considerations include the presence of a seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the 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 have been reported in approximately one-third of instances, along with other serious reactions such as hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (including QRS prolongation), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. 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 elevated 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 administered concurrently with bupropion.

When used alongside digoxin, bupropion may decrease plasma levels of digoxin. Therefore, it is advisable to monitor digoxin levels closely to ensure therapeutic efficacy.

Caution is warranted when prescribing bupropion in conjunction with drugs that lower the seizure threshold, as this combination may increase the risk of seizures.

The concomitant use of bupropion with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is recommended.

Additionally, the use of bupropion with monoamine oxidase inhibitors (MAOIs) can elevate the risk of hypertensive reactions. It is essential to avoid this combination or to implement appropriate monitoring.

Lastly, bupropion hydrochloride tablets may interfere with laboratory tests, leading to false-positive results for amphetamines in urine screenings. 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 further information regarding the use of this medication in children and adolescents. Caution is advised when considering treatment options for pediatric patients.

Geriatric Use

In clinical trials involving approximately 6,000 subjects treated with bupropion sustained-release tablets, 275 participants were aged 65 years and older, with 47 of these individuals aged 75 years and older. Overall, no significant differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, while clinical experience has not identified distinct 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 crucial to consider renal function when selecting dosages for this population. Monitoring renal function in elderly patients may be beneficial to ensure appropriate dosing and to mitigate potential risks associated with impaired renal function.

Pregnancy

There is no specific information available regarding the use of this drug during pregnancy. The prescribing information does not indicate whether the drug is contraindicated in pregnant patients, nor does it provide any data on potential risks to the fetus. Additionally, there are no recommendations for dosage modifications for individuals who are pregnant. Healthcare professionals should exercise caution and consider the lack of data when prescribing this medication to women of childbearing potential. Further research may be necessary to fully understand the implications of this drug in pregnant patients.

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.

Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside 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 not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information 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 for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

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

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

Fatalities linked to bupropion overdose have been observed, often occurring after multiple uncontrolled seizures. Other critical cardiovascular events such as bradycardia, cardiac failure, and cardiac arrest may precede these outcomes, underscoring the importance of prompt medical intervention.

Currently, there are no known antidotes for bupropion overdose. Therefore, supportive care and vigilant medical supervision are imperative for affected individuals. Healthcare professionals are advised to consult a Certified Poison Control Center for expert guidance in managing overdose cases. For assistance, they can contact 1-800-222-1222.

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 or female fertility were observed when rats were administered 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 given to females prior to mating and continued either through Day 13 of gestation or through lactation, while males received the treatment 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. There were no adverse effects noted 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, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal ideation and suicide during attempts to quit smoking while taking bupropion. New or exacerbated mental health issues, such as changes in behavior or thinking, aggression, hostility, agitation, depression, or suicidal thoughts or actions, have also been noted in 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.

Severe allergic reactions to bupropion hydrochloride tablets have been reported, with signs including rash, itching, hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, or difficulty breathing. The risk of seizures is known to increase with higher doses of bupropion hydrochloride tablets. Additionally, some patients have experienced significant increases in blood pressure while taking bupropion, particularly when used in conjunction with nicotine replacement therapy.

Periods of mania have been reported in some individuals taking bupropion hydrochloride tablets, characterized by symptoms such as markedly increased energy, severe insomnia, racing thoughts, reckless behavior, grandiose ideas, excessive happiness or irritability, and rapid speech. Unusual thoughts or behaviors, including delusions, hallucinations, paranoia, or confusion, have also been documented in patients receiving bupropion hydrochloride tablets.

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 stages of antidepressant treatment and when there are adjustments to the dosage.

Families and caregivers should monitor patients on a daily basis for the appearance of these symptoms, as changes can occur abruptly. Any severe, sudden, or previously unreported symptoms should be communicated to the patient’s prescriber or healthcare professional promptly.

Patients should be informed that some individuals may experience mood changes (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal thoughts and actions 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 cautioned that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can heighten 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 made aware that bupropion hydrochloride tablets contain the same active ingredient (bupropion hydrochloride) found in ZYBAN®, which is used for smoking cessation. Therefore, bupropion hydrochloride tablets should not be used in conjunction with ZYBAN® or any other medications containing bupropion.

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 hydrochloride tablets do not adversely affect their performance, patients should refrain from driving or operating complex, hazardous machinery.

Counseling should include a reminder for patients to 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. Patients should also inform their healthcare provider if they become pregnant or plan to become pregnant during treatment with bupropion hydrochloride tablets.

Storage instructions should be provided, advising patients to keep bupropion hydrochloride tablets at room temperature, between 68°F and 77°F (20°C to 25°C), and to keep the tablets dry and protected from light.

Patients should be instructed to take bupropion hydrochloride tablets in equally divided doses 3 or 4 times a day, ensuring that doses are 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. It is important to instruct patients that bupropion hydrochloride tablets should be swallowed whole and not crushed, divided, or chewed. Patients may take bupropion hydrochloride tablets 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

Patients receiving bupropion hydrochloride tablets for major depressive disorder (MDD) or other indications should be closely monitored by families and caregivers for signs of agitation, irritability, unusual behavioral changes, and suicidality. It is crucial for caregivers to report any concerning symptoms to healthcare providers immediately. Patients and their caregivers should be advised to discontinue bupropion and seek medical attention if they experience agitation, changes in mood or behavior, or suicidal thoughts. Additionally, any neuropsychiatric symptoms such as delusions, hallucinations, or confusion warrant prompt consultation with a healthcare professional.

Patients should also be instructed to stop taking bupropion and contact a healthcare provider if they develop any allergic reactions, including skin rash, hives, or respiratory difficulties. Postmarketing data indicate that serious neuropsychiatric events, including mood changes, psychosis, and suicidal ideation, have been reported in patients using bupropion for smoking cessation. Rare cases of severe skin reactions, such as erythema multiforme and Stevens-Johnson syndrome, as well as anaphylactic shock, have also been documented.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride as submitted by Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)