Bupropion hydrochloride

Description

Bupropion hydrochloride is an antidepressant belonging to the aminoketone class, distinguished by its chemical structure, which is unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, or other known antidepressant agents. Its chemical designation is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride, with a molecular weight of 276.2 and a molecular formula of C13H18ClNO•HCl.

The compound appears as a white, crystalline powder that is highly soluble in water, exhibiting a bitter taste and producing a sensation of local anesthesia on the oral mucosa. Bupropion hydrochloride is formulated for oral administration in the form of film-coated tablets, available in strengths of 75 mg and 100 mg. Each tablet contains the specified amount of bupropion hydrochloride along with the following inactive ingredients: FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, hypromellose, microcrystalline cellulose, potassium chloride, pregelatinized starch, stearic acid, titanium dioxide, and triethyl citrate.

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 is 200 mg per day, administered as 100 mg twice daily. To minimize the risk of seizures, the dose should be increased gradually. After an initial period of 3 days, the dose may be escalated 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.

Contraindications

Use of bupropion hydrochloride tablets 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 tablets should not be used in conjunction with MAOIs or within 14 days of discontinuing either treatment. Additionally, bupropion hydrochloride tablets 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 tablets is also a contraindication.

Warnings and Precautions

Patients taking antidepressants, particularly children, adolescents, and young adults, are at an increased risk of suicidal thinking and behavior. It is essential for healthcare professionals to monitor these patients closely for any worsening or emergence of suicidal thoughts and behaviors (5.1).

During smoking cessation, the use of bupropion has been associated with serious neuropsychiatric adverse events. Postmarketing reports indicate that patients may experience significant mood changes, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempts, and completed suicides. Healthcare providers should observe patients attempting to quit smoking with bupropion for these symptoms and instruct them to discontinue the medication and seek immediate medical attention if such adverse events occur (5.2).

The risk of seizures is dose-related when using bupropion. To minimize this risk, it is recommended to gradually increase the dosage and limit the daily dose to a maximum of 450 mg. If a seizure occurs, the medication should be discontinued immediately (4, 5.3, 7.3).

Bupropion hydrochloride tablets may elevate blood pressure. Therefore, it is crucial to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course (5.4). Additionally, patients should be screened for bipolar disorder, and symptoms of mania or hypomania should be closely monitored (5.5).

Healthcare professionals should be vigilant for the occurrence of psychosis and other neuropsychiatric reactions in patients. Patients should be instructed to contact their healthcare provider if they experience any such reactions (5.6). Furthermore, angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants (5.7).

In summary, it is imperative to monitor blood pressure before and during treatment with bupropion (5.4) and to screen for bipolar disorder while observing for symptoms of mania or hypomania (5.5). Patients should be advised to discontinue bupropion and seek medical assistance if they experience neuropsychiatric adverse events (5.2) or if a seizure occurs (4, 5.3).

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.

A significant warning associated with the use of bupropion hydrochloride tablets is the increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults. Patients should be closely monitored for any worsening of symptoms or emergence of suicidal ideation during treatment.

Neuropsychiatric adverse events have been observed 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.

There is a dose-related risk of seizures associated with bupropion hydrochloride tablets. To minimize this risk, 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 lead to increased blood pressure; therefore, blood pressure should be monitored before and periodically during treatment.

Patients with a history of bipolar disorder should be screened and monitored for activation of mania or hypomania. Instructing patients to contact a healthcare professional if they experience psychosis or other neuropsychiatric reactions is essential.

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

Other important considerations include the presence of a seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the 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 bupropion or an MAOI.

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, changes in mental status, sinus tachycardia, ECG changes (such as conduction disturbances and arrhythmias), clonus, myoclonus, and hyperreflexia. Severe reactions such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been noted, particularly in cases involving multiple drug overdoses. Deaths related to bupropion overdose have been documented, often occurring in patients who ingested large doses and experienced multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death.

Drug Interactions

Coadministration of bupropion 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 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 medications should be considered when used concurrently with bupropion.

Digoxin Bupropion may decrease plasma levels of digoxin. It is advisable to monitor digoxin levels closely in patients receiving this combination.

Drugs Lowering Seizure Threshold Caution is warranted when prescribing bupropion in conjunction with drugs that lower the seizure threshold, as this may increase the risk of seizures.

Dopaminergic Drugs Concomitant use of bupropion with dopaminergic medications such as levodopa and amantadine may lead to central nervous system toxicity. Monitoring for adverse effects is recommended.

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

Drug-Laboratory Test Interactions Bupropion hydrochloride tablets 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

Safety and effectiveness in the pediatric population have not been established. Healthcare professionals should refer to the Boxed Warning and Warnings and Precautions (5.1) for further information regarding the use of this medication in children and adolescents. Caution is advised when considering treatment options for pediatric patients.

Geriatric Use

In clinical trials involving approximately 6,000 subjects, 275 participants were aged 65 years and older, with 47 of these individuals aged 75 years and older. The data collected from these trials did not reveal any overall differences in safety or effectiveness between elderly patients and their younger counterparts. However, it is important to note that while clinical experience has not identified significant differences in responses between elderly and younger patients, there remains a possibility of greater sensitivity to treatment in some older individuals.

Elderly patients may be at an increased risk of adverse reactions, particularly those with impaired renal function. Given that this population is more likely to experience decreased renal function, careful consideration should be given to this factor when selecting dosages. It may be beneficial to monitor renal function in geriatric patients to ensure appropriate dosing and to mitigate potential risks associated with treatment.

Pregnancy

Pregnant patients should notify their healthcare provider if they become pregnant or intend to become pregnant during therapy with bupropion hydrochloride tablets. It is important for these patients to discuss the potential risks to the unborn baby associated with the use of bupropion hydrochloride during pregnancy. A pregnancy exposure registry is available to monitor pregnancy outcomes in women exposed to bupropion hydrochloride tablets, and patients are encouraged to participate in this registry if they become pregnant while on treatment.

In the event of pregnancy during treatment, patients should consult their healthcare provider about registering with the National Pregnancy Registry for Antidepressants by calling 1-844-405-6185. Additionally, patients who are breastfeeding or plan to breastfeed should inform their healthcare provider, as bupropion hydrochloride tablets are known to pass into breast milk.

Lactation

Bupropion hydrochloride tablets pass into breast milk. Lactating mothers should consult their healthcare provider to discuss the most appropriate feeding options for their infant during treatment with bupropion hydrochloride tablets.

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 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, including QRS prolongation and arrhythmias. Additional symptoms may encompass clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure, particularly in cases involving multiple drug overdoses.

While the majority of patients have recovered without lasting effects, there have been reports of fatalities linked to bupropion overdose, especially in individuals who ingested large quantities. These cases often involved 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. Contact information for certified poison control centers can be found in the Physician’s Desk Reference (PDR), or by calling 1-800-222-1222 or visiting www.poison.org.

There are no known antidotes for bupropion. Management of an overdose should focus on supportive care, which includes close medical supervision and monitoring. It is essential to consider the possibility of a multiple drug overdose. Healthcare professionals should ensure the maintenance of an adequate airway, oxygenation, and ventilation, while also monitoring cardiac rhythm and vital signs. Induction of emesis is not recommended in cases of bupropion overdose.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice with bupropion at doses of up to 300 mg/kg/day and 150 mg/kg/day, respectively. These doses correspond to approximately 6 and 2 times the maximum recommended human dose (MRHD) on a mg per m² basis. In the rat study, an increase in nodular proliferative lesions of the liver was observed at doses ranging from 100 to 300 mg/kg/day, which is approximately 2 to 6 times the MRHD on a mg per m² basis; lower doses were not evaluated. The potential for these lesions to serve as precursors to liver neoplasms remains unresolved. Conversely, the mouse study did not reveal similar liver lesions, nor was there an increase in malignant tumors in the liver or other organs in either species.

Bupropion demonstrated a positive response in the Ames bacterial mutagenicity assay, with a mutation rate that was 2 to 3 times higher than the control in 2 of 5 strains tested. Additionally, an increase in chromosomal aberrations was noted in 1 of 3 in vivo rat bone marrow cytogenetic studies.

Regarding reproductive toxicity, no adverse effects on male and female fertility were observed when rats were administered oral doses of bupropion up to 300 mg/kg/day (approximately 6 times the MRHD on a mg/m² basis) prior to mating and during gestation or lactation. Males were treated for 60 days prior to and through mating without any noted fertility issues. 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 on the fertility, reproduction, or growth and development of male or female offspring.

Postmarketing Experience

Some patients have reported experiencing changes in mood, including depression and mania, during treatment with bupropion. Additional psychiatric events noted include psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. There have also been reports of suicidal ideation and suicide attempts in individuals attempting to quit smoking while on bupropion. These events were reported voluntarily or identified through surveillance programs.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Medication Guide) thoroughly. Healthcare providers should instruct patients, their families, and caregivers to remain vigilant for the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, and other unusual behavioral changes, as well as worsening depression and suicidal ideation. These symptoms are particularly important to monitor during the initial stages of antidepressant treatment and when dosage adjustments are made. Families and caregivers should observe for these symptoms on a daily basis, as changes may occur abruptly. Any severe, sudden, or previously unreported symptoms should be communicated to the patient’s prescriber or healthcare professional, as they may indicate an increased risk for suicidal thoughts and behaviors, necessitating close monitoring and potential medication adjustments.

Although bupropion hydrochloride tablets are not indicated for smoking cessation, it is important to inform patients that they contain the same active ingredient as ZYBAN®, which is approved for this purpose. Patients should be made aware that some individuals have reported mood changes, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, along with suicidal thoughts and actions when attempting to quit smoking while taking bupropion. Patients should be instructed to discontinue bupropion and contact a healthcare professional if they experience any of these symptoms.

Patients should be educated about the signs of hypersensitivity and instructed to discontinue bupropion hydrochloride tablets if they experience a severe allergic reaction. Additionally, patients must be advised to stop taking bupropion hydrochloride tablets and not to restart them if they experience a seizure during treatment. It is crucial to inform patients that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures, and they should minimize or avoid alcohol consumption.

Patients should be informed that bupropion hydrochloride tablets can cause mild pupillary dilation, which may lead to angle-closure glaucoma in susceptible individuals. It is recommended that patients with a history of glaucoma be evaluated to determine their susceptibility to angle closure and consider prophylactic procedures if necessary.

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

Healthcare providers should advise patients that any CNS-active drug, including bupropion hydrochloride tablets, may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Until patients are certain that bupropion does not adversely affect their performance, they should refrain from driving or operating complex machinery. Patients should also be informed that bupropion may decrease alcohol tolerance.

Patients should notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter medications, as bupropion hydrochloride tablets may interact with other drugs. Additionally, patients should inform their healthcare provider if they become pregnant or plan to become pregnant during treatment, as there is a pregnancy exposure registry that monitors outcomes in women exposed to bupropion during pregnancy.

Patients should be instructed to store bupropion hydrochloride tablets at room temperature, between 20 ºC to 25 ºC (68 ºF to 77 ºF), keeping them dry and protected from light. They should take bupropion hydrochloride tablets in equally divided doses 3 or 4 times a day, ensuring that doses are separated by at least 6 hours to minimize the risk of seizure. If a dose is missed, patients should not take an extra tablet to compensate but should take the next tablet at the regular time. Bupropion hydrochloride tablets should be swallowed whole and not crushed, divided, or chewed, and can be taken with or without food. Patients should also be provided with the Medication Guide separately.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

To ensure product integrity, it is essential to protect the product from light and moisture during storage. Proper handling and storage conditions are critical to maintaining the quality and efficacy of the product.

Additional Clinical Information

Patients should be advised to read the FDA-approved patient labeling (Medication Guide) and to remain vigilant for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, unusual behavioral changes, worsening depression, and suicidal ideation, particularly during the initial stages of treatment or when adjusting the dose. Families and caregivers should monitor for these symptoms daily and report any severe or abrupt changes to the healthcare provider, as they may indicate an increased risk for suicidal thoughts and behaviors.

Patients should be informed that bupropion hydrochloride tablets, while not indicated for smoking cessation, share the same active ingredient as ZYBAN®, which is approved for that purpose. They should discontinue use and contact a healthcare professional if they experience mood changes, psychosis, or seizures. Additionally, patients should be educated about the risk of angle-closure glaucoma and the importance of not combining bupropion with other bupropion-containing products. It is essential to take the medication in divided doses, store it properly, and avoid alcohol to minimize seizure risk. Patients should also notify their healthcare provider of any other medications they are taking and inform them if they become pregnant or plan to become pregnant during treatment.

FDA Insert (PDF)

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

View full prescribing information (PDF)