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

Dosing should be initiated at a low level and increased gradually to minimize the risk of seizures. Healthcare professionals are advised to periodically reassess the patient's dose and the necessity for ongoing maintenance treatment.

For the management of Major Depressive Disorder, the recommended starting dose is 150 mg administered once daily. The usual target dose is 300 mg once daily, with the option to increase the dose to 300 mg after 4 days if clinically indicated.

In the treatment of Seasonal Affective Disorder, therapy should commence in the autumn, prior to the onset of seasonal depressive symptoms. The initial dose is also 150 mg once daily, with a typical 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 150 mg every other day. In cases of mild hepatic impairment, it is advisable to consider a reduction in dose and/or 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 adverse effects.

Patients who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, as this may also increase the risk of seizures.

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

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

Warnings and Precautions

Patients undergoing treatment with bupropion hydrochloride should be closely monitored for a range of potential neuropsychiatric adverse events. Postmarketing reports have indicated serious or clinically significant reactions, including mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and aggressive behaviors. Notably, there have been instances of suicidal ideation, suicide attempts, and completed suicides. It is imperative that healthcare providers observe patients attempting to quit smoking with bupropion hydrochloride for the emergence of these symptoms. Patients should be instructed to discontinue the medication and seek immediate medical advice if they experience any of these adverse events.

The risk of seizures associated with bupropion hydrochloride is dose-dependent. To mitigate 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 immediately.

Bupropion hydrochloride has the potential to 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 may activate mania or hypomania. Continuous monitoring for these symptoms is advised.

Additionally, there is a risk of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants.

Healthcare professionals should be particularly vigilant regarding the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants, including bupropion. Regular monitoring for any worsening or emergence of suicidal thoughts and behaviors is crucial.

In the event of neuropsychiatric adverse events, patients must be instructed to discontinue bupropion hydrochloride and contact their healthcare provider. This includes any occurrence of psychosis or other neuropsychiatric reactions, as well as the necessity to stop the medication if a seizure occurs. Regular blood pressure monitoring is also recommended to ensure patient safety throughout treatment.

Side Effects

Common adverse reactions observed in clinical trials, occurring in at least 5% of patients and at a rate greater than twice that of placebo, include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitations, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash.

Serious adverse reactions warranting caution include an 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 ideation or behavior.

Neuropsychiatric adverse events have been reported during smoking cessation, with serious manifestations 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. Patients experiencing any of these symptoms should be instructed to contact a healthcare professional immediately.

The risk of seizures is dose-related; therefore, 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. Additionally, bupropion hydrochloride may elevate blood pressure, necessitating monitoring before and during treatment.

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

Other important considerations include the contraindications for patients with a seizure disorder, current or prior diagnoses of bulimia or anorexia nervosa, and those who have abruptly discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. The use of monoamine oxidase inhibitors (MAOIs) in conjunction with bupropion hydrochloride extended-release tablets (XL) is contraindicated, as is the initiation of bupropion hydrochloride extended-release tablets (XL) within 14 days of stopping an MAOI or in patients receiving linezolid or intravenous methylene blue. Known hypersensitivity to bupropion or its components is also a contraindication.

In cases of overdose, seizures were reported in approximately one third of instances. Other serious reactions associated with bupropion overdose include 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 have been reported in patients who ingested large doses of bupropion, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Drug Interactions

Coadministration of bupropion hydrochloride with certain drug classes may lead to significant interactions that require careful consideration of dosage adjustments and monitoring.

CYP2B6 Inducers When bupropion is administered alongside CYP2B6 inducers such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, or phenytoin, an increase in bupropion dosage may be necessary to maintain clinical efficacy. However, the dosage should not exceed the maximum recommended limit.

CYP2D6 Substrates Bupropion is a known inhibitor of CYP2D6 and may elevate the 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 That Lower Seizure Threshold Bupropion hydrochloride should be used with caution in patients taking other medications that lower the seizure threshold, as this may increase the risk of seizures.

Dopaminergic Drugs Concomitant use of bupropion with dopaminergic agents such as levodopa and amantadine may lead to central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is advised.

Monoamine Oxidase Inhibitors (MAOIs) The use of bupropion in conjunction with MAOIs can heighten the risk of hypertensive reactions. Close monitoring is recommended if these agents are used together.

Drug-Laboratory Test Interactions Bupropion hydrochloride may cause false-positive results in urine tests for amphetamines. This potential interaction should be communicated to healthcare providers conducting such tests.

Packaging & NDC

The table below lists all NDC Code configurations of Bupropion Hydrochloride, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Antidepressants have been associated with an increased risk of suicidal thoughts and behaviors in pediatric patients, including children and adolescents under 18 years, as demonstrated in pooled analyses of short-term placebo-controlled trials. While no suicides occurred in any of the pediatric trials, it is crucial for healthcare providers to monitor these patients closely for any worsening of symptoms or the emergence of suicidal thoughts and behaviors upon initiation of antidepressant therapy.

Families and caregivers are advised to maintain vigilant observation and communication with the prescriber regarding the patient's condition. They should be particularly alert for signs of agitation, irritability, unusual changes in behavior, and any indications of suicidality. Immediate reporting of such symptoms to healthcare providers is essential to ensure the safety and well-being of pediatric patients undergoing treatment with antidepressants.

Geriatric Use

Elderly patients, defined as those aged 65 and older, do not exhibit an increased risk of suicidal thoughts and behavior when treated with antidepressants, according to short-term clinical trials. Furthermore, these studies indicate that there is a reduction in the risk of suicidality in this age group when antidepressants are compared to placebo.

Despite the absence of increased risk in geriatric patients, it is imperative that all patients receiving antidepressants for any indication are monitored closely. This includes vigilant observation for clinical worsening, suicidality, and any unusual changes in behavior, particularly during the initial months of treatment or when there are adjustments in dosage, whether increases or decreases.

Families and caregivers of elderly patients undergoing treatment with antidepressants for major depressive disorder or other psychiatric and nonpsychiatric indications should be informed of the importance of monitoring for signs of agitation, irritability, and other behavioral changes. They should also be alert to the emergence of suicidality and are encouraged to report any concerning symptoms to healthcare providers immediately. Daily observation by families and caregivers is recommended to ensure the safety and well-being of geriatric patients during treatment.

Pregnancy

The available data regarding the use of this medication during pregnancy is limited. There are no specific safety concerns outlined in the prescribing information, nor are there any dosage modifications recommended for pregnant patients. Additionally, no special precautions for the use of this medication during pregnancy have been provided.

Healthcare professionals should consider the potential risks and benefits when prescribing this medication to women of childbearing potential. It is advisable to monitor any pregnant patients closely and to discuss the lack of specific data regarding the safety of this medication during pregnancy.

Lactation

It is not known whether bupropion is excreted in human milk. Caution should be exercised when bupropion is administered to a nursing woman. The effects of bupropion on milk production and the potential for excretion in breast milk have not been studied. Therefore, the decision to discontinue nursing or to discontinue the drug should be made, taking into account the importance of the drug to the mother.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be warranted in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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 were reported as a significant adverse effect. Other serious reactions associated with bupropion overdoses 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, and hyperreflexia.

In cases where bupropion was part of a multiple drug overdose, more severe complications have been observed, including fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. While most patients have recovered without lasting effects, fatalities have been reported in individuals who ingested large doses of bupropion alone. In these instances, multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest were noted prior to death.

In the event of a bupropion overdose, it is crucial to provide supportive care, which includes close medical supervision and monitoring of the patient. There are currently no known antidotes for bupropion, and healthcare professionals should consider the possibility of a multiple drug overdose when assessing the patient.

For immediate guidance and advice, it is recommended to consult a Certified Poison Control Center by calling 1-800-222-1222 or visiting www.poison.org.

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 to 300 mg/kg/day of bupropion hydrochloride, which is approximately 2 to 7 times the MRHD on a mg/m² basis. The implications of these lesions as potential precursors to liver neoplasms remain 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, 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 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

Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports include changes in mood such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, instances of suicidal ideation, suicide attempts, and completed suicides have been documented. Neuropsychiatric adverse events have occurred in patients both with and without pre-existing psychiatric conditions, with some patients experiencing a worsening of their psychiatric illnesses.

Patients should be monitored for the occurrence of neuropsychiatric adverse events. It is advised that patients and caregivers be informed to discontinue bupropion hydrochloride and contact a healthcare provider immediately if symptoms such as agitation, depressed mood, or atypical changes in behavior or thinking arise, or if suicidal ideation or behavior develops. In many postmarketing cases, resolution of symptoms was reported following the discontinuation of bupropion; however, in some instances, symptoms persisted, necessitating ongoing monitoring and supportive care until resolution.

Anaphylactoid and anaphylactic reactions have been documented during clinical trials with bupropion, characterized by pruritus, urticaria, angioedema, and dyspnea, which required medical intervention. Additionally, rare spontaneous postmarketing reports have indicated occurrences of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. Reports of arthralgia, myalgia, fever with rash, and other symptoms suggestive of serum sickness indicative of delayed hypersensitivity have also been noted.

Patient Counseling

Healthcare providers should advise patients and their families about the increased risk of suicidal thoughts and behaviors associated with the use of antidepressants, particularly in children, adolescents, and young adults during short-term trials. It is essential to monitor patients of all ages who are initiated on antidepressant therapy closely for any worsening of their condition, as well as for the emergence of suicidal thoughts and behaviors.

Providers should emphasize the importance of families and caregivers being vigilant in observing patients for signs of agitation, irritability, or any unusual changes in behavior. They should be informed about the necessity of reporting any concerning symptoms, including the emergence of suicidality, to healthcare providers immediately. This monitoring should involve daily observation by families and caregivers to ensure the patient's safety and well-being.

Additionally, when prescribing bupropion hydrochloride, healthcare providers should write prescriptions for the smallest quantity of tablets that is consistent with effective patient management. This practice is crucial in minimizing the risk of overdose and ensuring patient safety.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. It is essential to protect the product from light to maintain its integrity and efficacy.

Additional Clinical Information

Bupropion hydrochloride extended-release tablets (XL) should be administered whole, without crushing, dividing, or chewing, preferably in the morning, and can be taken with or without food. Clinicians are advised to counsel families and caregivers on the importance of close observation and communication with the prescriber for patients initiating antidepressant therapy. They should be vigilant for signs of agitation, irritability, unusual behavioral changes, and the emergence of suicidality, reporting any such symptoms to healthcare providers promptly.

Patients are instructed to discontinue bupropion hydrochloride and seek medical advice if they experience any allergic or anaphylactoid/anaphylactic reactions during treatment. Additionally, postmarketing experience has revealed serious neuropsychiatric adverse events associated with bupropion use for smoking cessation, including mood changes, psychosis, hallucinations, and suicidal ideation, which have occurred in both patients with and without pre-existing psychiatric conditions, sometimes leading to a worsening of their psychiatric illnesses.

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)