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 appears as a white to off-white crystalline powder and is highly soluble in water. It has a bitter taste and produces a sensation of local anesthesia on the oral mucosa.

Bupropion hydrochloride is supplied for oral administration as 75-mg (orange) and 100-mg (purple) film-coated tablets. Each 75-mg tablet contains colloidal silicon dioxide, crospovidone, FD&C Yellow #6 Aluminum Lake, fumaric acid granular, hydroxypropyl cellulose, hypromellose, magnesium stearate, methylcellulose, polyethylene glycol, and titanium dioxide. Each 100-mg tablet contains colloidal silicon dioxide, crospovidone, D&C Red #7 Calcium Lake, fumaric acid granular, hydroxypropyl cellulose, hypromellose, magnesium stearate, methylcellulose, polyethylene glycol, and titanium dioxide.

Uses and Indications

Bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD).

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

The recommended starting dose 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, administered in the same manner.

The maximum allowable dose is 450 mg per day, which can be given as 150 mg three times daily. It is important for healthcare professionals to periodically reassess the patient's dose and the necessity for 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. Additionally, for patients with renal impairment, a reduction in dose and/or frequency may also be warranted.

Contraindications

Use of bupropion hydrochloride tablets is contraindicated in the following situations:

Patients with a seizure disorder due to the increased risk of seizures associated with bupropion.

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 also increase seizure risk.

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

Patients with known hypersensitivity to bupropion or any other components of bupropion hydrochloride tablets should not use this medication.

Warnings and Precautions

Patients undergoing smoking cessation with bupropion should be closely monitored for neuropsychiatric adverse events. Postmarketing reports have indicated serious or clinically significant reactions, including 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. Healthcare professionals are advised to observe these patients for the emergence of such symptoms and to instruct them to discontinue bupropion and seek immediate medical attention 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. In the event of a seizure, bupropion should 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 also recommended.

In addition, patients should be informed about the risk of psychosis and other neuropsychiatric reactions. They should be instructed to contact a healthcare professional if they experience any such reactions.

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

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 patients for any worsening of their condition or the emergence of suicidal thoughts and behaviors.

To ensure patient safety, blood pressure should be monitored before starting treatment and periodically during treatment. Patients should be instructed to discontinue bupropion and contact a healthcare provider 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. It is essential to monitor these patients for any worsening or emergence of suicidal thoughts and behaviors.

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 should be instructed to contact a healthcare professional if they experience any of these reactions.

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 before and during treatment.

Activation of mania or hypomania may occur, particularly in patients with a history of bipolar disorder, who should be screened and monitored 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 risk of seizures in patients with a seizure disorder, current or prior diagnoses of bulimia or anorexia nervosa, and the potential for serious reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion hydrochloride tablets should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) intended for psychiatric disorders or within 14 days of stopping treatment with either medication. Known hypersensitivity to bupropion or its ingredients is also a contraindication.

In cases of overdosage, seizures were reported in approximately one-third of all instances. 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

Coadministration of bupropion hydrochloride tablets 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, and phenytoin, an increase in bupropion dosage may be necessary based on clinical response. However, the dosage should not exceed the maximum recommended limit.

CYP2D6 Inhibitors Bupropion is known to inhibit CYP2D6, which can lead to elevated concentrations of various medications, including 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 medications should be considered when used concurrently with bupropion.

Digoxin Bupropion may decrease plasma levels of digoxin. Therefore, it is advisable to monitor digoxin levels closely in patients receiving both medications.

Seizure Threshold Caution is warranted when prescribing bupropion hydrochloride tablets to patients taking other medications that lower the seizure threshold, as this may increase the risk of seizures.

CNS Toxicity Concomitant use of bupropion hydrochloride tablets with dopaminergic drugs, such as levodopa and amantadine, may result in CNS toxicity. Monitoring for adverse effects is recommended.

MAO Inhibitors (MAOIs) The risk of hypertensive reactions may be heightened when bupropion hydrochloride tablets are used in conjunction with MAOIs. Close monitoring of blood pressure is advised in these cases.

Urine Drug Testing Bupropion hydrochloride tablets can cause false-positive results for amphetamines in urine drug tests. This should be taken into account 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

Antidepressants have been associated with an increased risk of suicidal thoughts and behaviors in pediatric patients, including children, adolescents, and young adults, particularly 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 suicidal thinking and behavior in individuals aged 18 to 24.

Healthcare professionals are advised to closely monitor all patients, regardless of age, who are initiated on antidepressant therapy for any worsening of symptoms or the emergence of suicidal thoughts and behaviors. Families and caregivers should be informed of the importance of observing patients for signs of agitation, irritability, or unusual changes in behavior. Immediate reporting of such symptoms to healthcare providers is crucial for ensuring patient safety during treatment.

Geriatric Use

Elderly patients, defined as those aged 65 and older, may experience a reduction in the risk of suicidal thoughts and behavior when treated with antidepressants, as evidenced by clinical trials. These trials indicated that while there was no increase in the risk of suicidality in adults beyond age 24, a notable reduction in risk was observed in the geriatric population.

It is essential for healthcare providers to monitor all patients receiving antidepressants for any indication, including major depressive disorder (MDD) and other psychiatric or nonpsychiatric conditions. Close observation is particularly critical during the initial months of treatment or when there are changes in dosage, whether increases or decreases.

Families and caregivers of elderly patients should be informed of the importance of monitoring for signs of clinical worsening, suicidality, agitation, irritability, and any unusual changes in behavior. They should be encouraged to conduct daily observations and report any concerning symptoms to healthcare providers immediately. This proactive approach is vital to ensure the safety and well-being of geriatric patients undergoing antidepressant therapy.

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 on the absence of established safety information and the importance of discussing any potential pregnancy with their healthcare provider.

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, 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 tablets and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

Dosage adjustments may be necessary for patients with renal impairment. It is essential to monitor renal function in these patients prior to and during treatment. Patients with severe renal impairment, defined as a creatinine clearance of less than 30 mL/min, should not use this medication. For patients with moderate renal impairment, characterized by a creatinine clearance between 30-60 mL/min, a reduced dose should be considered.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Overdoses of bupropion have been documented, with instances involving amounts of 30 grams or more. In approximately one-third of these cases, seizures have been reported as a significant complication.

Serious adverse reactions associated with bupropion overdose may include hallucinations, loss of consciousness, alterations in mental status, and various cardiac issues. It is important to note that fatalities linked to bupropion overdose have occurred, particularly in patients who have experienced multiple drug overdoses.

Currently, there are no known antidotes for bupropion. Therefore, the management of overdose cases relies heavily on supportive care and close medical supervision. Healthcare professionals are advised to monitor the patient closely for any emerging symptoms and to provide appropriate interventions as necessary.

In the event of a bupropion overdose, it is crucial to consult a Certified Poison Control Center for expert guidance. Healthcare providers can reach out to the Poison Control Center by calling 1-800-222-1222 for assistance in managing the overdose effectively.

Nonclinical Toxicology

There were no teratogenic effects observed in the studies conducted. Non-teratogenic effects were noted in a fertility assessment where 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 adversely 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. Additionally, there were no adverse effects on the fertility, reproduction, or growth and development of male or female offspring.

Lifetime carcinogenicity studies were conducted in rats and mice with 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. In contrast, 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. Furthermore, an increase in chromosomal aberrations was observed 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 reported.

Gastrointestinal: Cases of esophagitis and hepatitis have been documented.

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

Musculoskeletal: Adverse reactions include muscle rigidity, fever, rhabdomyolysis, and muscle weakness.

Nervous System: Reports of aggression, coma, completed suicide, delirium, dream abnormalities, paranoid ideation, paresthesia, parkinsonism, restlessness, suicide attempts, and unmasking of tardive dyskinesia have been received.

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: Instances of tinnitus and increased intraocular pressure have been documented.

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 signs of clinical worsening 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 maintaining close observation and open communication with the prescriber. They should be alerted to monitor for any signs of agitation, irritability, or unusual changes in behavior, as well as the emergence of suicidality. Any concerning symptoms should be reported to healthcare providers immediately.

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 without delay if they notice any agitation, depressed mood, or atypical changes in behavior or thinking, or if suicidal ideation or behavior develops.

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 should be administered whole, without crushing, dividing, or chewing, 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. It is essential for them to monitor patients for signs of agitation, irritability, unusual behavioral changes, and any emergence of suicidality, reporting such symptoms to healthcare providers immediately.

Postmarketing experience has revealed various adverse effects associated with bupropion use. These include arthralgia, myalgia, fever with rash, severe hypertension, orthostatic hypotension, and cardiac issues such as third-degree heart block and Brugada syndrome. Other reported conditions include hyponatremia, hyperglycemia, esophagitis, hepatitis, and hematological changes like leukocytosis and thrombocytopenia. Serious neuropsychiatric events such as aggression, delirium, and suicidal behavior have also been noted, alongside dermatological reactions like Stevens-Johnson syndrome and DRESS. Additionally, patients may experience tinnitus and increased intraocular pressure.

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)