Bupropion hydrochloride

Description

Bupropion hydrochloride extended-release tablets (XL) (bupropion hydrochloride) is an antidepressant of the aminoketone class. It is designated as (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight is 276.2, and the molecular formula is C13H18ClNO•HCl. Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa.

Bupropion hydrochloride extended-release tablets, USP (XL) are supplied for oral administration as 150 mg and 300 mg creamy-white to pale yellow round coated tablets. Each tablet contains the labeled amount of bupropion hydrochloride and the inactive ingredients: ethyl alcohol, ethylcellulose, glyceryl dibehenate, isopropyl alcohol, methacrylic acid and ethyl acrylate copolymer dispersion, polyethylene glycol, polyvinyl alcohol, povidone, silicon dioxide, and triethyl citrate. The tablets are printed with black ink, which contains ferrosoferric oxide, hypromellose, isopropyl alcohol, and propylene glycol.

Uses and Indications

Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major depressive disorder (MDD) in adults. Additionally, this medication is indicated for the prevention of seasonal affective disorder (SAD).

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

Dosage and Administration

Healthcare professionals are advised to initiate treatment with a gradual increase in dosage to minimize the risk of seizures. It is essential to periodically reassess the patient's dose and the necessity for maintenance therapy.

For the management of Major Depressive Disorder, the recommended starting dose is 150 mg administered once daily. After a period of 4 days, the dose may be increased to a usual target of 300 mg once daily.

In the case of Seasonal Affective Disorder, treatment should commence in the autumn, prior to the onset of seasonal depressive symptoms. The initial dose is also 150 mg once daily, with a potential increase to 300 mg once daily after one week. Treatment should be continued throughout the winter season.

For patients with hepatic impairment, those with moderate to severe conditions should receive a dose of 150 mg every other day. In patients with mild hepatic impairment, it is advisable to consider a reduction in either the dose or the frequency of administration.

In patients with renal impairment, a reduction in dose and/or frequency of dosing should also be considered to ensure safety and efficacy.

Contraindications

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

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

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

• Patients who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, as this may increase seizure risk.

• Concurrent use with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders is contraindicated. Bupropion hydrochloride extended-release tablets (XL) should not be used within 14 days of stopping an MAOI, nor should an MAOI be initiated within 14 days of stopping bupropion hydrochloride extended-release tablets (XL). Additionally, bupropion hydrochloride extended-release tablets (XL) should not be started in patients receiving linezolid or intravenous methylene blue.

• Known hypersensitivity to bupropion or any of the other ingredients in bupropion hydrochloride extended-release tablets (XL).

Warnings and Precautions

Serious neuropsychiatric adverse events have been reported in patients using bupropion hydrochloride extended-release tablets (XL) during smoking cessation. These events may include significant mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. It is imperative that healthcare professionals closely observe patients attempting to quit smoking with this medication for the emergence of these symptoms. Patients should be instructed to discontinue bupropion hydrochloride extended-release tablets (XL) and seek immediate medical advice if they experience any of these adverse events.

The risk of seizures associated with bupropion hydrochloride extended-release tablets (XL) is dose-dependent. To minimize this risk, it is recommended that the daily dose not exceed 450 mg and that any dose increases be made gradually. Should a seizure occur, the medication must be discontinued.

Bupropion hydrochloride extended-release tablets (XL) may elevate blood pressure; therefore, it is essential to monitor blood pressure prior to initiating treatment and periodically throughout the course of therapy.

Patients with a history of bipolar disorder should be screened prior to treatment, as bupropion can activate mania or hypomania. Continuous monitoring for these symptoms is advised.

In addition, patients should be informed about the potential for psychosis and other neuropsychiatric reactions. They must be instructed to contact a healthcare professional if such reactions occur.

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

There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants. Healthcare professionals should monitor these populations for any worsening or emergence of suicidal thoughts and behaviors.

To ensure safe use, it is critical to monitor blood pressure before starting treatment and at regular intervals thereafter. Patients should be advised to discontinue bupropion hydrochloride extended-release tablets (XL) and contact their healthcare provider if they experience any neuropsychiatric adverse events or if psychosis and other neuropsychiatric reactions occur.

Side Effects

Patients may experience a range of adverse reactions while using bupropion hydrochloride extended-release tablets (XL). These reactions can be categorized into common adverse reactions, serious warnings, and other important considerations.

Common adverse reactions reported include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitations, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash. These reactions were observed in clinical trials and may vary in frequency among patients.

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

Neuropsychiatric adverse events have been noted during smoking cessation treatment, including changes in mood (such as depression and mania), psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. Patients experiencing these symptoms should seek immediate medical attention.

There is a dose-related risk of seizures associated with bupropion. To minimize this risk, it is recommended to limit the daily dose to 450 mg and to increase the dose gradually. If a seizure occurs, discontinuation of the medication is advised.

Bupropion hydrochloride XL may also lead to increased blood pressure; therefore, blood pressure should be monitored before and periodically during treatment. Additionally, patients with a history of bipolar disorder should be screened and monitored for activation of mania or hypomania.

Psychosis and other neuropsychiatric reactions have been reported, and patients are advised to contact a healthcare professional if such reactions occur. Angle-closure glaucoma has 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 risks associated with abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion 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. Additionally, patients with known hypersensitivity to bupropion or any of its ingredients should avoid this medication.

Drug Interactions

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate an increase in the dosage of bupropion. However, it is important to ensure that the dosage does not exceed the maximum recommended limit.

Bupropion acts as an inhibitor of CYP2D6, which can lead to elevated concentrations of certain 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 associated with these increased drug levels.

Caution is warranted when prescribing bupropion hydrochloride extended-release tablets (XL) alongside medications that may lower the seizure threshold. The risk of central nervous system (CNS) toxicity is heightened when bupropion XL is used in conjunction with dopaminergic drugs, including levodopa and amantadine.

Additionally, the concomitant use of bupropion hydrochloride extended-release tablets (XL) and monoamine oxidase inhibitors (MAOIs) can increase the risk of hypertensive reactions.

It is also noteworthy that bupropion hydrochloride extended-release tablets (XL) 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 for bupropion hydrochloride extended-release tablets (XL). When considering the use of this medication in children or adolescents, healthcare professionals should carefully balance the potential risks with the clinical need for treatment.

Geriatric Use

Clinical trials involving bupropion hydrochloride sustained-release tablets included approximately 6,000 patients, of whom 275 were aged 65 years and older, and 47 were aged 75 years and older. Additionally, several hundred patients aged 65 years and older participated in clinical trials utilizing the immediate-release formulation of bupropion hydrochloride for depression.

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

Bupropion is extensively metabolized in the liver to active metabolites, which are subsequently metabolized and excreted by the kidneys. Given that elderly patients are more likely to have decreased renal function, careful consideration of renal function is essential in dose selection for this population. Monitoring renal function may be beneficial to mitigate the risk of adverse reactions, which may be heightened in patients with impaired renal function.

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at National Pregnancy Registry for AntidepressantsNational Pregnancy Registry for Antidepressants.

Data from epidemiological studies involving pregnant women exposed to bupropion during the first trimester have not identified an increased risk of congenital malformations overall. However, there are risks to the mother associated with untreated depression. In a prospective, longitudinal study, women with a history of major depressive disorder who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression compared to those who continued treatment. Therefore, healthcare providers should consider the risks of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Animal studies have shown that when bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. Conversely, in pregnant rabbits, non-dose-related increases in the incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater, with decreased fetal weights noted at doses twice the MRHD and higher. No maternal toxicity was evident at doses of 50 mg/kg/day or less in these studies.

The estimated background risk for major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 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 overall increased risk for malformations. However, the registry suggested a possible increase in cardiac malformations, although no increased risk for cardiovascular malformations overall has been observed. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester was 1.3%, which is similar to the background rate of approximately 1%.

Study findings regarding bupropion exposure during the first trimester and the risk of left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD) are inconsistent and do not allow for definitive conclusions regarding possible associations. In a pre- and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day from embryonic implantation through lactation had no effect on pup growth or development.

In summary, while data suggest that bupropion does not significantly increase the risk of congenital malformations overall, careful consideration of the risks associated with untreated depression is essential when managing treatment in pregnant patients.

Lactation

Bupropion is excreted in breast milk. In a pre- and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 3 times the maximum recommended human dose on a mg/m² basis) from embryonic implantation through lactation had no effect on pup growth or development.

The effects of bupropion on breastfed infants have not been established. Therefore, healthcare professionals should weigh the potential benefits of bupropion therapy against the risks to the nursing infant when considering its use in lactating mothers.

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 individuals 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 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 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 the context of 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 close medical supervision are essential for managing affected patients. Healthcare professionals are advised to consult a Certified Poison Control Center for specific guidance in cases of overdose. The Poison Control Center can be reached at 1-800-222-1222 or through their website at www.poison.org.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice with bupropion hydrochloride at doses of up to 300 mg/kg/day and 150 mg/kg/day, respectively. These doses correspond to approximately 7 and 2 times the maximum recommended human dose (MRHD) on a mg/m² basis. In the rat study, an increase in nodular proliferative lesions of the liver was observed at doses ranging from 100 to 300 mg/kg/day, which is approximately 2 to 7 times the MRHD on a mg/m² basis; lower doses were not evaluated. The potential for these lesions to serve as precursors to liver neoplasms remains unresolved. Conversely, 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 2 of 5 strains in one Ames bacterial mutagenicity assay, indicating a mutation rate that was 2 to 3 times higher than the control. However, it yielded negative results in another assay. Additionally, an increase in chromosomal aberrations was noted in 1 of 3 in vivo rat bone marrow cytogenetic studies.

A fertility study conducted in rats at doses up to 300 mg/kg/day indicated no evidence of impaired fertility.

Postmarketing Experience

Postmarketing experience has revealed that some patients have reported changes in mood, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Instances of suicidal ideation and suicide have also been noted, particularly in individuals attempting to quit smoking while using 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 observed. These symptoms may arise upon initiation of bupropion therapy, develop after several weeks of treatment, or occur following discontinuation of the medication.

Patients experiencing a seizure while taking bupropion hydrochloride extended-release tablets (XL) are advised to discontinue use immediately and contact their healthcare provider. Re-administration of bupropion hydrochloride extended-release tablets (XL) is contraindicated in such cases.

Reports indicate that some individuals may develop high blood pressure, which can be severe, while on bupropion hydrochloride extended-release tablets (XL). The risk of elevated blood pressure may increase when combined with nicotine replacement therapies, such as nicotine patches.

Additionally, some patients have experienced episodes of mania while taking bupropion hydrochloride extended-release tablets (XL), characterized by significantly increased energy, severe insomnia, racing thoughts, reckless behavior, unusually grand ideas, and heightened happiness or irritability.

Unusual thoughts or behaviors have also been reported, including delusions, hallucinations, paranoia, and confusion.

Severe allergic reactions to bupropion hydrochloride extended-release tablets (XL) have been documented. Patients should discontinue the medication and seek immediate medical attention if they experience symptoms such as 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, as these may indicate a serious allergic reaction.

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 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 hydrochloride extended-release tablets (XL) and contact a healthcare professional immediately.

Education on hypersensitivity symptoms is essential, and patients should discontinue bupropion hydrochloride extended-release tablets (XL) if they experience a severe allergic reaction. Additionally, patients must be instructed to stop taking bupropion hydrochloride extended-release tablets (XL) and not to restart 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 increase the risk of seizures, and they should minimize or avoid alcohol consumption. It is also important to inform patients that bupropion hydrochloride extended-release tablets (XL) may cause mild pupillary dilation, which can lead to angle-closure glaucoma in susceptible individuals.

Patients should be made aware that bupropion hydrochloride extended-release tablets (XL) contain the same active ingredient (bupropion) as ZYBAN, which is used for smoking cessation, and that these medications should not be used together or with any other products containing bupropion hydrochloride.

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

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

Patients must be instructed to swallow bupropion hydrochloride extended-release tablets (XL) whole, without crushing, dividing, or chewing them, to ensure the proper release rate. If a dose is missed, patients should not take an extra tablet to compensate but should take the next tablet at the regular scheduled time due to the dose-related risk of seizure. Bupropion hydrochloride extended-release tablets (XL) should be taken in the morning and may be consumed with or without food.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with the United States Pharmacopeia (USP) standards and features a child-resistant closure. It should be stored at a temperature of 25°C (77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as outlined by USP Controlled Room Temperature guidelines.

Additional Clinical Information

Patients and caregivers should be advised to discontinue bupropion hydrochloride extended-release tablets (XL) and seek immediate medical attention if they observe any signs of agitation, depressed mood, or atypical changes in behavior or thinking, including suicidal ideation or behavior. Families and caregivers of patients receiving antidepressants for major depressive disorder or other indications should be vigilant in monitoring for the emergence of agitation, irritability, and other concerning symptoms, reporting any such changes to healthcare providers promptly. It is recommended that prescriptions for bupropion XL be limited to the smallest quantity necessary to minimize the risk of overdose.

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, anaphylactoid and anaphylactic reactions have been reported, presenting with symptoms such as pruritus, urticaria, and dyspnea, necessitating medical intervention. Rare cases of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock have also been documented, along with reports of delayed hypersensitivity symptoms like arthralgia and fever with rash.

FDA Insert (PDF)

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

View full prescribing information (PDF)