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, 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 are at increased risk of seizures when using this medication.

Bupropion hydrochloride tablets should not be administered to individuals with a current or prior diagnosis of bulimia or anorexia nervosa due to the potential for increased risk of seizures.

The abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is contraindicated, as it may elevate the risk of seizures.

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

Known hypersensitivity to bupropion or any of its components contraindicates the use of this medication.

Warnings and Precautions

The use of bupropion hydrochloride tablets is associated with several important warnings and precautions that healthcare professionals must consider to ensure patient safety.

Suicidal Thoughts and Behaviors There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants, including bupropion. Healthcare providers should closely monitor these patients for any worsening of symptoms or emergence of suicidal thoughts and behaviors.

Neuropsychiatric Adverse Events Postmarketing reports have indicated that serious or clinically significant neuropsychiatric adverse events may occur during smoking cessation treatment with bupropion. These events can include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Patients attempting to quit smoking should be observed for these symptoms, and they must be instructed to discontinue bupropion and contact a healthcare provider if any of these adverse events arise.

Seizure Risk 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.

Hypertension Bupropion hydrochloride tablets can lead to increased blood pressure. It is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course.

Bipolar Disorder Screening Patients should be screened for bipolar disorder prior to treatment, and ongoing monitoring for symptoms of mania or hypomania is advised.

Psychosis and Other Reactions Patients should be instructed to contact a healthcare professional if they experience any neuropsychiatric reactions, including psychosis.

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

Monitoring Parameters Healthcare providers should monitor blood pressure before initiating treatment and periodically during the course of therapy to ensure patient safety.

Emergency Instructions Patients must be advised to discontinue bupropion and seek immediate medical attention if they experience any neuropsychiatric adverse events or seizures.

Side Effects

Patients may experience a range of adverse reactions while taking bupropion hydrochloride tablets. The most common adverse reactions 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, including bupropion. Patients should be closely monitored for the emergence or worsening of suicidal thoughts and behaviors. Additionally, neuropsychiatric adverse events may occur during smoking cessation, including changes in mood (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, anxiety, panic, and suicidal ideation, which may lead to suicide attempts or completed suicide.

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. Bupropion hydrochloride tablets may also increase blood pressure, necessitating 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.

Additional 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

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate a dose increase of the affected medication based on clinical response. However, the dosage should not exceed the maximum recommended limit.

Bupropion is known to inhibit CYP2D6, which can lead to increased plasma concentrations of various medications. This includes antidepressants like venlafaxine and nortriptyline, antipsychotics such as haloperidol, beta-blockers including metoprolol, and Type 1C antiarrhythmics like propafenone. Clinicians should monitor patients for potential adverse effects due to elevated levels of these drugs.

Additionally, bupropion may reduce plasma levels of digoxin; therefore, it is advisable to monitor digoxin concentrations in patients receiving both medications.

Caution is warranted when prescribing bupropion hydrochloride tablets to patients who are on medications that lower the seizure threshold, as this may increase the risk of seizures.

The concomitant use of bupropion hydrochloride tablets with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity, necessitating careful monitoring of patients.

There is also an increased risk of hypertensive reactions when bupropion hydrochloride tablets are used alongside monoamine oxidase inhibitors (MAOIs).

Lastly, it is important to note that bupropion hydrochloride tablets can cause false-positive results in urine drug screenings for amphetamines, which should be considered 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 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

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. The data collected from these trials did not reveal any 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 between elderly and younger patients, there remains a possibility of greater sensitivity to the medication in some older individuals.

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

Pregnancy

Pregnancy Category C. Data from epidemiological studies involving pregnant women exposed to bupropion during the first trimester indicate no overall increased risk of congenital malformations. It is important to note that all pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations and 15% to 20% for pregnancy loss. Reproductive developmental studies in rats and rabbits did not demonstrate clear teratogenic activity; however, in rabbits, there were slightly increased incidences of fetal malformations and skeletal variations at doses approximately equal to the maximum recommended human dose (MRHD) and higher. Additionally, decreased fetal weights were observed at doses twice the MRHD and greater.

Bupropion hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinicians should consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Human data from the international bupropion Pregnancy Registry, which included 675 first-trimester exposures, and a retrospective cohort study using the United Healthcare database with 1,213 first-trimester exposures, did not show an increased risk for malformations overall. Specifically, the observed rate of cardiovascular malformations in pregnancies with first-trimester exposure to bupropion was 1.3%, which aligns with the background rate of approximately 1%. Furthermore, no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester.

However, findings regarding the risk for left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD) following first-trimester bupropion exposure are inconsistent and do not allow for definitive conclusions. The United Healthcare database lacked sufficient power to evaluate the association with LVOTO, while the National Birth Defects Prevention Study (NBDPS) indicated an increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7). Conversely, the Slone Epidemiology case-control study did not find an increased risk for LVOTO. For VSD, the Slone Epidemiology Study reported an increased risk following first-trimester exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0), while the NBDPS and United Healthcare database studies did not find an association. The limitations of these studies, including small sample sizes and inconsistent findings, should be considered when interpreting the data.

Animal studies have shown that bupropion was administered orally during the period of organogenesis in rats and rabbits at doses up to 450 mg/kg/day and 150 mg/kg/day, respectively, which are approximately 11 and 7 times the MRHD on a mg/m² basis. No clear evidence of teratogenic activity was found in either species; however, increased incidences of fetal malformations and skeletal variations were noted in rabbits at the lowest tested dose (25 mg/kg/day, approximately equal to the MRHD on a mg/m² basis) and higher. Decreased fetal weights were observed at doses of 50 mg/kg and greater. In rats administered bupropion at doses up to 300 mg/kg/day (approximately 7 times the MRHD on a mg/m² basis) prior to mating and throughout pregnancy and lactation, no apparent adverse effects on offspring development were observed.

Lactation

There are no specific warnings or considerations regarding nursing mothers or lactation mentioned in the provided text. Therefore, the use of this medication in lactating mothers does not present any known risks or concerns based on the available information. Healthcare professionals should continue to monitor the health of breastfed infants as part of standard care.

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

In cases of bupropion overdose, significant clinical manifestations can occur, necessitating immediate medical intervention. Reports indicate that overdoses of 30 grams or more have been documented, with seizures occurring in approximately one-third of these instances.

Potential Symptoms Serious adverse reactions associated with bupropion overdose may include hallucinations, loss of consciousness, sinus tachycardia, and various ECG changes, particularly conduction disturbances. In severe cases, fatalities have been reported, especially among patients who have ingested large doses, leading to multiple uncontrolled seizures and cardiac failure.

Management Procedures There are currently no known antidotes for bupropion; therefore, supportive care and close medical supervision are critical in managing overdose cases. Healthcare professionals should ensure that the patient has an adequate airway, oxygenation, and ventilation. Continuous monitoring of cardiac rhythm and vital signs is essential.

Induction of emesis is not recommended in the event of a bupropion overdose. Instead, it is advisable to consult a Certified Poison Control Center for further guidance and management strategies tailored to the specific situation.

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 and 150 mg per kg per day, respectively. 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, 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.

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. These symptoms have been observed in some individuals upon initiation of bupropion therapy, while others developed them after several weeks of treatment or following discontinuation of the medication.

The incidence of seizures has been reported to increase with higher doses of bupropion hydrochloride tablets. Additionally, some patients have experienced significant elevations in blood pressure while on this medication.

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, grandiosity, excessive happiness or irritability, and rapid speech.

Unusual thoughts or behaviors, including delusions, hallucinations, paranoia, or confusion, have been observed in some patients during treatment with bupropion hydrochloride tablets.

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, specifically the Medication Guide, which provides essential information regarding the use of bupropion hydrochloride tablets. It is important for healthcare providers to inform patients, their families, and caregivers about the benefits and risks associated with this treatment and to counsel them on its appropriate use.

Healthcare providers should instruct patients, their families, and caregivers to read the Medication Guide thoroughly and assist them in understanding its contents. Patients should be encouraged to discuss any questions or concerns they may have regarding the information presented in the Medication Guide.

Patients should be made aware of specific symptoms to monitor while taking bupropion hydrochloride tablets. They should be instructed to alert their prescriber if they experience anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or any unusual changes in behavior, as well as worsening depression or suicidal ideation, particularly during the initial stages of treatment or when doses are adjusted. Families and caregivers should be advised to observe for these symptoms on a daily basis, as changes may occur abruptly, and any severe or sudden symptoms should be reported to the healthcare professional.

Patients should be informed that some individuals may experience mood changes, psychosis, hallucinations, paranoia, delusions, aggression, and suicidal thoughts when attempting to quit smoking while on bupropion. They should be instructed to discontinue the medication and contact a healthcare professional if they experience such symptoms.

Education on hypersensitivity is crucial; patients should be informed about the signs of severe allergic reactions and instructed to discontinue bupropion hydrochloride tablets if such reactions occur. Additionally, patients should be advised to stop taking the medication and not to restart it if they experience a seizure during treatment. They should be cautioned that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures and should minimize or avoid alcohol consumption.

Patients should be made aware that bupropion hydrochloride tablets can cause mild pupillary dilation, which may lead to angle-closure glaucoma in susceptible individuals. It is also important to inform patients that bupropion hydrochloride is the same active ingredient found in ZYBAN, which is used for smoking cessation, and that bupropion hydrochloride tablets should not be used in combination with ZYBAN or any other medications containing bupropion.

Healthcare providers should counsel patients that bupropion hydrochloride tablets may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Until patients are certain that the medication does not adversely affect their performance, they 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 therapy, as bupropion hydrochloride is present in human milk in small amounts.

Patients should be instructed to store bupropion hydrochloride tablets at room temperature, between 59°F and 86°F (15°C to 30°C), keeping them dry and protected from light. They should take the 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. Finally, patients should be instructed to swallow bupropion hydrochloride tablets whole, without crushing, dividing, or chewing them, and they can take the medication with or without food.

Storage and Handling

The product is supplied in a tight, light-resistant container to ensure optimal stability and efficacy. 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 integrity.

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 AvPAK. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)