Bupropion hydrochloride

Description

Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. It is designated as (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight is 276.21 g/mol, and the molecular formula is C13H18ClNO•HCl. Bupropion hydrochloride powder is white to off-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 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 for the medication is 200 mg per day, administered as 100 mg twice daily. To minimize the risk of seizures, it is advised to increase the dose gradually. After an initial period of 3 days, the dose may be increased to 300 mg per day, given as 100 mg three times daily, ensuring that there is an interval of at least 6 hours between doses. The usual target dose is 300 mg per day, 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 based on individual patient assessment.

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.

The use of bupropion is contraindicated in individuals with a current or prior diagnosis of bulimia or anorexia nervosa due to the potential for increased risk of seizures.

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

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

Known hypersensitivity to bupropion or any of its components is a contraindication for use.

Warnings and Precautions

Neuropsychiatric adverse events have been reported in patients undergoing smoking cessation with bupropion. These events may include significant mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, there have been instances of suicidal ideation, suicide attempts, and completed suicides. It is imperative that healthcare professionals closely observe patients attempting to quit smoking with bupropion for the emergence of these symptoms. Patients should be instructed to discontinue bupropion and promptly contact a healthcare provider if they experience any of these adverse events.

The risk of seizures associated with bupropion is dose-related. To minimize this risk, it is recommended to gradually increase the dosage and limit the maximum daily dose to 450 mg. Should a seizure occur, bupropion must be discontinued immediately.

Bupropion hydrochloride tablets have 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.

Psychosis and other neuropsychiatric reactions may occur; patients should be instructed to contact a healthcare professional if they experience such reactions.

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

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. It is crucial to monitor these populations for any worsening of symptoms or the emergence of suicidal thoughts and behaviors.

To ensure safe use of bupropion, healthcare professionals should monitor blood pressure before treatment initiation and periodically during treatment. Patients must be advised to discontinue bupropion and seek medical attention if they experience any neuropsychiatric adverse events or if a seizure occurs.

Side Effects

Patients may experience a range of adverse reactions while using bupropion hydrochloride tablets. The most common adverse reactions reported include agitation, dry mouth, constipation, headache or migraine, nausea or vomiting, dizziness, excessive sweating, tremor, insomnia, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmias, and auditory disturbances.

Serious warnings associated with bupropion include an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults. Patients should be closely monitored for any worsening or emergence of suicidal thoughts and behaviors during treatment.

Neuropsychiatric adverse events have been observed during smoking cessation, including changes in mood (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. Patients experiencing any of these symptoms should contact a healthcare professional immediately.

The risk of seizures is dose-related; therefore, it is recommended to gradually increase the dose and limit the daily dose to 450 mg. If a seizure occurs, discontinuation of the medication is advised. Additionally, bupropion hydrochloride tablets can increase blood pressure, necessitating monitoring of blood pressure before and during treatment.

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

Other important considerations include the risk of seizures in patients with a seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the potential for serious reactions following 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.

In cases of overdosage, seizures have been reported in approximately one-third of all cases. Other serious reactions associated with bupropion overdose include hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (such as conduction disturbances and 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

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate an increase in dosage 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 elevated concentrations of various medications, including antidepressants (e.g., venlafaxine, nortriptyline), antipsychotics (e.g., haloperidol), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone). Clinicians should monitor patients for potential adverse effects due to these increased concentrations.

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

Caution is warranted when prescribing bupropion hydrochloride tablets alongside drugs that may lower the seizure threshold, as this combination could 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 in conjunction with monoamine oxidase inhibitors (MAOIs).

Lastly, it is important to note that bupropion hydrochloride tablets can lead to false-positive results in urine drug tests for amphetamines, which may require further investigation in clinical settings.

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, as demonstrated in short-term trials. Pooled analyses of 24 placebo-controlled trials involving over 4,400 subjects with major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and other psychiatric disorders indicate that these medications elevate the risk of suicidality in individuals aged 18 to 24.

Healthcare professionals should closely monitor all patients, regardless of age, who are initiated on antidepressant therapy for any worsening of their condition or the emergence of suicidal thoughts and behaviors. It is important to note that while no suicides occurred in the pediatric trials, families and caregivers should be informed of the necessity to observe for signs of agitation, irritability, or unusual behavioral changes. Any concerning symptoms should be reported to healthcare providers immediately.

Geriatric Use

Elderly patients, defined as those aged 65 and older, may experience a reduction in the risk of suicidal thoughts and behaviors when treated with antidepressants, as indicated by short-term clinical trials. In contrast, these trials did not demonstrate an increased risk of suicidality in adults beyond the age of 24 when compared to placebo. However, it is essential to monitor all patients, including geriatric patients, closely for any signs of clinical worsening or the emergence of suicidal thoughts and behaviors, particularly during the initial months of therapy or following any dose adjustments.

Healthcare providers should advise families and caregivers of elderly patients receiving antidepressant therapy about the importance of vigilant observation. They should be informed to monitor for symptoms such as agitation, irritability, and any unusual changes in behavior, as well as the emergence of suicidality. Immediate communication with healthcare providers is crucial should any concerning symptoms arise.

In summary, while elderly patients may benefit from antidepressant therapy with a reduced risk of suicidality, careful monitoring and communication with caregivers are imperative to ensure safety and efficacy in this population.

Pregnancy

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions that should be taken. Healthcare professionals are advised to consider the lack of data when prescribing this medication to pregnant patients and to weigh the potential risks and benefits. Women of childbearing potential should be counseled accordingly, and alternative treatment options should be explored if necessary.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure, assuming a daily consumption of 150 mL/kg, 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. The relationship between bupropion exposure and these seizures remains unclear.

Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the lactating mother's clinical need for bupropion hydrochloride tablets and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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.

Serious adverse reactions associated with bupropion overdose may include hallucinations, loss of consciousness, alterations in mental status, and electrocardiogram (ECG) changes such as conduction disturbances. Additional symptoms that may manifest during an overdose include clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. It is important to note that fatalities have been linked to bupropion overdose, particularly in patients who have ingested large doses, with multiple uncontrolled seizures and cardiac failure being significant contributing factors.

Currently, there are no known antidotes for bupropion overdose. Therefore, the management of such cases relies heavily on supportive care and close medical supervision. In the event of an overdose, it is critical to ensure an adequate airway, oxygenation, and ventilation, while continuously monitoring cardiac rhythm and vital signs.

Healthcare professionals are advised to consult a Certified Poison Control Center for guidance in managing bupropion overdose. Assistance can be obtained by calling 1-800-222-1222.

Nonclinical Toxicology

No teratogenic effects were observed in nonclinical studies. In terms of non-teratogenic effects, oral administration of bupropion at doses up to 300 mg/kg/day (approximately 6 times the maximum recommended human dose MRHD on a mg/m² basis) to female rats prior to mating and continuing through Day 13 of gestation or lactation, as well as to male rats for 60 days prior to and during mating, did not affect male or female fertility. However, doses of 200 mg/kg/day (approximately 4 times the MRHD on a mg/m² basis) or higher resulted in transient ataxia or behavioral changes in adult female rats. Importantly, there were no adverse effects noted on fertility, reproduction, or the growth and development of male or female offspring.

Lifetime carcinogenicity studies conducted in rats and mice involved bupropion doses of up to 300 mg/kg/day and 150 mg/kg/day, respectively, which correspond to approximately 6 and 2 times the 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 (approximately 2 to 6 times the MRHD on a mg/m² basis), while 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 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 reported in 1 of 3 in vivo rat bone marrow cytogenetic studies.

Postmarketing Experience

During postapproval use of bupropion hydrochloride tablets, the following adverse reactions have been identified that are not described elsewhere in the labeling. These reactions have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body (General): Reports include arthralgia, myalgia, and fever accompanied by rash and other symptoms suggestive of delayed hypersensitivity, which may resemble serum sickness.

Cardiovascular: Adverse events such as hypertension (including severe cases), orthostatic hypotension, third-degree heart block, and Brugada pattern/syndrome have been noted.

Endocrine: Instances of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, hyperglycemia, and hypoglycemia have been documented.

Gastrointestinal: Cases of esophagitis and hepatitis have been reported.

Hemic and Lymphatic: Observations include ecchymosis, leukocytosis, leukopenia, and thrombocytopenia. Altered prothrombin time (PT) and/or international normalized ratio (INR) have been infrequently associated with hemorrhagic or thrombotic complications when bupropion was coadministered with warfarin.

Musculoskeletal: Reports of muscle rigidity, fever, rhabdomyolysis, and muscle weakness have been received.

Nervous System: Adverse reactions include aggression, coma, completed suicide, delirium, dream abnormalities, paranoid ideation, paresthesia, parkinsonism, restlessness, suicide attempts, unmasking of tardive dyskinesia, and aseptic meningitis.

Skin and Subcutaneous Tissue Disorders: Serious skin reactions such as Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.

Special Senses: Reports of tinnitus and increased intraocular pressure have also been noted.

Patient Counseling

Healthcare providers should inform patients that the use of antidepressants, including bupropion hydrochloride tablets, is associated with an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults during short-term trials. It is essential to monitor all patients closely for any worsening of their condition or the emergence of suicidal thoughts and behaviors, especially during the initial months of treatment or when there are changes in dosage.

Providers should advise families and caregivers about the importance of close observation and communication with the prescriber. They should be alerted to monitor for signs of agitation, irritability, unusual changes in behavior, and any symptoms indicative of suicidality. Immediate reporting of such symptoms to healthcare providers is crucial.

Prescriptions for bupropion hydrochloride tablets should be written for the smallest quantity necessary to ensure effective patient management, thereby minimizing the risk of overdose. Patients and their caregivers should be instructed to discontinue the medication and contact a healthcare provider immediately if they observe any agitation, depressed mood, or atypical changes in behavior or thinking, or if there are any indications of suicidal ideation or behavior.

Storage and Handling

The product is supplied in a tight, light-resistant container to ensure its integrity. It should be stored at a temperature range of 20ºC to 25ºC (68ºF to 77ºF), with permissible excursions between 15ºC and 30ºC (59ºF to 86ºF) as defined by USP Controlled Room Temperature guidelines. It is essential to protect the product from moisture to maintain its quality and efficacy.

Additional Clinical Information

Bupropion hydrochloride tablets are to be administered whole, without crushing, dividing, or chewing, and can be taken with or without food. The recommended starting dose is 200 mg per day, divided into two doses of 100 mg each. After three days, the dose may be increased to 300 mg per day, administered as 100 mg three times daily, ensuring at least six hours between doses. For patients who do not show clinical improvement after several weeks at 300 mg/day, a maximum dose of 450 mg/day may be considered, with no single dose exceeding 150 mg.

Clinicians should counsel families and caregivers on the importance of close monitoring of patients for any signs of agitation, irritability, behavioral changes, and suicidality, advising them to report any concerning symptoms to healthcare providers immediately. Postmarketing experiences have reported various adverse effects, including arthralgia, myalgia, severe hypertension, hyponatremia, and hypersensitivity reactions. Other serious effects may include muscle rigidity, aggression, and severe skin reactions such as Stevens-Johnson syndrome. Additionally, there have been reports of altered coagulation parameters when bupropion is coadministered with warfarin.

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)