Bupropion hydrochloride

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

The dosage of the medication should be increased gradually to minimize the risk of seizures. Healthcare professionals are advised to periodically reassess the patient's dose and the necessity for maintenance treatment.

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 be initiated in the autumn, prior to the onset of seasonal depressive symptoms. The starting dose is also 150 mg once daily, with a usual target dose of 300 mg once daily. After one week of treatment, the dose may be increased to 300 mg once daily, and it is recommended to continue treatment 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 the dose and/or frequency of dosing.

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

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.

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 lead to seizure risk.

Concurrent use with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders is contraindicated, as well as within 14 days of discontinuing such treatment. Additionally, bupropion hydrochloride extended-release tablets (XL) should not be initiated in patients receiving linezolid or intravenous methylene blue due to potential interactions.

Known hypersensitivity to bupropion or any of the components of bupropion hydrochloride extended-release tablets (XL) is also a contraindication.

Warnings and Precautions

The use of bupropion hydrochloride extended-release tablets (XL) necessitates careful consideration of several warnings and precautions 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. Healthcare professionals should closely monitor these patients for any worsening of symptoms or emergence of suicidal thoughts and behaviors.

Neuropsychiatric Adverse Events During Smoking Cessation Postmarketing reports have indicated serious neuropsychiatric adverse events associated with smoking cessation using bupropion hydrochloride extended-release tablets (XL). These events may include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal ideation, suicide attempts, and completed suicides. Patients attempting to quit smoking should be observed for these symptoms, and if any occur, they must discontinue the medication and contact a healthcare provider immediately.

Seizure Risk The risk of seizures is dose-related. 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, the medication should be discontinued.

Hypertension Bupropion hydrochloride extended-release tablets (XL) may elevate blood pressure. It is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course.

Activation of Mania/Hypomania Patients should be screened for bipolar disorder prior to treatment, and ongoing monitoring for symptoms of mania or hypomania is advised.

Psychosis and Other Neuropsychiatric 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 professionals are advised to monitor blood pressure before initiating treatment and periodically during the course of therapy. Additionally, screening for bipolar disorder and monitoring for symptoms of mania or hypomania are critical components of patient management.

In the event of neuropsychiatric adverse events, patients must be instructed to discontinue bupropion hydrochloride extended-release tablets (XL) and seek immediate medical attention.

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 significant events.

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

A critical 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 or emergence of suicidal thoughts and behaviors.

Postmarketing reports have indicated serious neuropsychiatric adverse events during smoking cessation, including mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. It is essential to observe patients attempting to quit smoking with bupropion hydrochloride extended-release tablets (XL) for these symptoms and instruct them to discontinue the medication and contact a healthcare provider if such events occur.

The risk of seizures is dose-related, and it is recommended to limit the daily dose to 450 mg and to gradually increase the dose to minimize this risk. If a seizure occurs, the medication should be discontinued immediately. Additionally, bupropion hydrochloride extended-release tablets (XL) can increase blood pressure; therefore, blood pressure should be monitored before and periodically during treatment.

Patients should be screened for bipolar disorder due to the potential activation of mania or hypomania. In the event of psychosis or other neuropsychiatric reactions, patients are advised to contact a healthcare professional.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants, necessitating caution in such individuals.

Overdoses of bupropion have been reported, with doses of 30 grams or more leading to serious reactions in approximately one third of cases, including seizures, hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (such as conduction disturbances or arrhythmias), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. Deaths associated with overdoses of bupropion alone have been documented, with reports of multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest occurring prior to death.

Drug Interactions

Coadministration of bupropion hydrochloride extended-release tablets (XL) with certain drug classes may necessitate careful monitoring and potential dosage adjustments due to significant interactions.

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 required to maintain clinical efficacy. However, the total 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. This includes various antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). A dose reduction of these concomitant medications should be considered to mitigate the risk of adverse effects.

Drugs Lowering Seizure Threshold Caution is advised when prescribing bupropion XL in conjunction with other medications that may lower the seizure threshold. Close monitoring for seizure activity is recommended.

Dopaminergic Drugs The concurrent use of bupropion XL with dopaminergic agents such as levodopa and amantadine may increase the risk of central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is warranted.

Monoamine Oxidase Inhibitors (MAOIs) The combination of bupropion XL with MAOIs can elevate the risk of hypertensive reactions. It is advisable to avoid this combination or to monitor blood pressure closely if coadministration is necessary.

Drug-Laboratory Test Interactions Bupropion XL may interfere with urine drug screening tests, potentially resulting in false-positive results for amphetamines. Clinicians should be aware of this possibility 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 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 subjects 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, the risk of adverse reactions may be heightened in this population. Therefore, it is advisable to consider renal function when selecting a dose for geriatric patients, and monitoring of renal function may be beneficial to ensure safety and efficacy.

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 of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall. However, there are risks to the mother associated with untreated depression. A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The findings indicated that women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than those who continued treatment. Therefore, healthcare providers should consider the risks to the mother of untreated depression and the 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, when given to pregnant rabbits during organogenesis, 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 greater.

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, which included 1,213 first trimester exposures, did not show an increased risk for malformations overall. 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%.

Findings regarding the association between bupropion exposure during the first trimester and left ventricular outflow tract obstruction (LVOTO) are inconsistent. The NBDPS found an increased risk for LVOTO, while the Slone Epidemiology case-control study did not find an increased risk. Similarly, findings on the risk for ventricular septal defect (VSD) are also inconsistent, with the Slone Epidemiology Study indicating an increased risk for VSD following first trimester maternal bupropion exposure, while other studies did not find an association.

In studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 mg/kg/day and 150 mg/kg/day, respectively. There was no evidence of fetal malformations in rats, while in rabbits, non-dose-related increases in fetal malformations and skeletal variations were observed at the lowest dose tested and greater. Decreased fetal weights were observed at doses of 50 mg/kg/day and greater, with no maternal toxicity evident at doses of 50 mg/kg/day or less. Additionally, 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.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving ten 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 extended-release tablets (XL) and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

In patients with renal impairment, specifically those with a glomerular filtration rate (GFR) of less than 90 mL/min, consideration should be given to a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (XL). Bupropion and its metabolites are primarily cleared through the kidneys, and in individuals with reduced kidney function, there is a potential for accumulation of the drug and its metabolites.

Healthcare professionals should monitor these patients closely for any adverse reactions that may suggest elevated levels of bupropion or its metabolites, ensuring appropriate management of therapy to mitigate risks associated with increased exposure.

Hepatic Impairment

In patients with moderate to severe hepatic impairment, as defined by a Child-Pugh score of 7 to 15, the maximum recommended dose of bupropion hydrochloride extended-release tablets (XL) is 150 mg every other day. For patients with mild hepatic impairment, indicated by a Child-Pugh score of 5 to 6, it is advisable to consider a reduction in the dose and/or frequency of dosing.

Close monitoring of liver function is recommended in patients with hepatic impairment to ensure safety and efficacy of treatment. Adjustments to the dosing regimen should be made based on the patient's clinical response and any changes in liver function status.

Overdosage

Overdoses of bupropion have been documented, with instances involving doses of 30 grams or more. In approximately one third of these cases, seizures were reported. Other serious adverse reactions associated with bupropion overdose include hallucinations, loss of consciousness, alterations in mental status, sinus tachycardia, and various ECG changes such as conduction disturbances or arrhythmias. Additional symptoms may encompass clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure, particularly in scenarios involving multiple drug overdoses.

While the majority of patients have recovered without lasting effects, there have been fatalities linked to bupropion overdoses, especially in cases where large doses were ingested. Reports indicate that patients who succumbed to overdose experienced multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death.

In the event of a suspected overdose, it is imperative to consult a Certified Poison Control Center for current guidance and recommendations. Healthcare professionals can reach the Poison Control Center at 1-800-222-1222 or visit www.poison.org for further information.

There are no known antidotes for bupropion; therefore, management of an overdose should focus on supportive care. This includes close medical supervision and monitoring of the patient. It is also essential to consider the potential for a multiple drug overdose when assessing the situation.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice, administering bupropion hydrochloride at doses 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 mg/kg/day to 300 mg/kg/day of bupropion hydrochloride, 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, similar liver lesions were not detected in the mouse study, and no increase in malignant tumors of the liver or other organs was noted in either study.

Bupropion demonstrated a positive response in 2 of 5 strains in one Ames bacterial mutagenicity assay, resulting in 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 reported 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

Some patients have reported experiencing changes in mood, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and homicidal ideation while using bupropion hydrochloride extended-release tablets (XL). Additional symptoms noted include aggression, hostility, agitation, anxiety, panic, and suicidal ideation, particularly during attempts to quit smoking.

Patients are advised to discontinue the use of bupropion hydrochloride extended-release tablets (XL) and to contact a healthcare professional if they experience any of these symptoms.

Patient Counseling

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

Patients should be instructed to review the Medication Guide, which includes critical topics such as “Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions,” “Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions,” and “What Other Important Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (XL)?” Providers should ensure that patients have the opportunity to discuss the contents of the Medication Guide and to ask any questions they may have.

Healthcare providers should alert patients to be vigilant for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, and other unusual changes in behavior, as well as worsening depression and suicidal ideation, particularly during the initial stages of treatment or when adjusting the dose. Families and caregivers should be encouraged to monitor for these symptoms on a daily basis, as changes can occur abruptly. Any severe or sudden onset of these symptoms should be reported to the prescriber, as they may indicate an increased risk for suicidal thoughts and behaviors, necessitating close monitoring and potential medication adjustments.

Although bupropion hydrochloride extended-release tablets (XL) are not indicated for smoking cessation, it is important to inform patients that it contains the same active ingredient as ZYBAN®, which is approved for this purpose. Patients should be made aware that some individuals have reported mood changes, psychosis, hallucinations, paranoia, delusions, aggression, and suicidal ideation when attempting to quit smoking while taking bupropion. Patients should be instructed to discontinue the medication and contact a healthcare professional if they experience any of these symptoms.

Patients should be educated about the signs of hypersensitivity and advised to discontinue bupropion hydrochloride extended-release tablets (XL) if they experience a severe allergic reaction. Additionally, patients must be instructed to stop taking the medication and not to restart it if they experience a seizure during treatment. They should be informed that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures and should be advised to minimize or avoid alcohol consumption.

It is essential 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 with a history of glaucoma should be evaluated for susceptibility to angle-closure and may consider a prophylactic procedure if indicated.

Patients should be cautioned that bupropion hydrochloride extended-release tablets (XL) contain the same active ingredient as ZYBAN and should not be used in combination with ZYBAN or any other medications containing bupropion hydrochloride, including WELLBUTRIN SR, WELLBUTRIN, and APLENZIN®.

Healthcare providers should advise patients that any CNS-active drug, including bupropion hydrochloride extended-release tablets (XL), may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Until patients are confident that the medication does not adversely affect their performance, they should refrain from driving or operating complex machinery. Additionally, bupropion hydrochloride extended-release tablets (XL) may lead to decreased alcohol tolerance.

Patients should be encouraged to 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. Furthermore, patients should inform their healthcare provider if they become pregnant or plan to become pregnant during treatment, as there is a pregnancy exposure registry monitoring outcomes in women exposed to bupropion hydrochloride extended-release tablets (XL) during pregnancy.

Finally, patients should be instructed to swallow bupropion hydrochloride extended-release tablets (XL) whole to ensure the release rate is not altered. If a dose is missed, patients should be advised not to take an extra tablet to compensate but to take the next dose at the regular 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 various package configurations, with specific NDC numbers available upon request. It should be stored at a controlled room temperature of 25°C (77°F). Temporary excursions are permissible within the range of 15°C to 30°C (59°F to 86°F), in accordance with USP guidelines for controlled room temperature. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients should be advised to read the FDA-approved patient labeling (Medication Guide) for bupropion hydrochloride extended-release tablets (XL) and to discuss its contents with their healthcare provider. It is essential to inform patients, their families, and caregivers about the benefits and risks associated with the treatment, including the potential for suicidal thoughts and behaviors, neuropsychiatric adverse events, and severe allergic reactions. Patients should be vigilant for symptoms such as anxiety, agitation, and unusual changes in behavior, particularly during the initial treatment phase or when adjusting the dose.

Clinicians should counsel patients on the importance of not combining bupropion hydrochloride extended-release tablets (XL) with other bupropion-containing products, including ZYBAN, and to avoid excessive alcohol use due to an increased risk of seizures. Patients should be instructed to swallow the tablets whole and not to crush or chew them. Additionally, they should notify their healthcare provider if they become pregnant or plan to become pregnant during treatment. Regular monitoring and communication with healthcare professionals are crucial for managing any adverse effects or concerns that may arise during therapy.

FDA Insert (PDF)

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

View full prescribing information (PDF)