Bupropion hydrochloride

Description

Bupropion hydrochloride USP is an antidepressant of the aminoketone class, chemically unrelated to other known antidepressant agents. It is designated as (±)-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 drug appears as a white, crystalline powder that is highly soluble in water, has a bitter taste, and produces a sensation of local anesthesia on the oral mucosa.

Bupropion hydrochloride extended-release tablets, USP (SR) are supplied for oral administration in strengths of 100 mg (blue), 150 mg (purple), and 200 mg (pink). Each film-coated, sustained-release tablet contains the labeled amount of bupropion hydrochloride along with inactive ingredients, which include microcrystalline cellulose, colloidal silicon dioxide, hydroxy propyl methyl cellulose, diluted hydrochloric acid, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol, and polysorbate 80. The 100 mg tablet contains FD&C Blue No. 1 Aluminum lake, the 150 mg tablet contains FD&C Blue No. 2 Aluminum lake and FD&C Red No. 40 Aluminum lake, and the 200 mg tablet contains FD&C Red No. 40 Aluminum lake.

Uses and Indications

Bupropion hydrochloride extended-release tablets, USP (SR) are indicated for the treatment of major depressive disorder (MDD).

Limitations of Use: There are no teratogenic or nonteratogenic effects associated with the use of this medication as per the available data.

Dosage and Administration

The recommended starting dose is 150 mg per day. To minimize the risk of seizures, the dose should be increased gradually. After an initial period of 3 days, the dose may be increased to 300 mg per day, administered as 150 mg twice daily, with an interval of at least 8 hours between doses. The usual target dose is 300 mg per day, maintained as 150 mg twice daily.

For patients who do not respond adequately to the 300 mg per day regimen, the maximum dose may be increased to 400 mg per day, given as 200 mg twice daily. It is essential to periodically reassess the patient's dose and the necessity for ongoing maintenance treatment.

In patients with moderate to severe hepatic impairment, the recommended dosage is 100 mg daily or 150 mg every other day. For those with mild hepatic impairment, consideration should be given to reducing the dose and/or frequency of administration. Additionally, in patients with renal impairment, a reduction in dose and/or frequency should also be considered.

Contraindications

Use of bupropion hydrochloride extended-release tablets (SR) 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 seizure risk.

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

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

Warnings and Precautions

The use of antidepressants, particularly bupropion, necessitates careful consideration of several warnings and precautions to ensure patient safety.

Suicidal Thoughts and Behaviors There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Healthcare professionals should closely monitor these patients for any worsening of symptoms or the emergence of suicidal thoughts and behaviors.

Neuropsychiatric Events Serious neuropsychiatric events have been reported in patients using bupropion for smoking cessation. It is essential to remain vigilant for any signs of such events.

Seizure Risk The risk of seizures is dose-related. To minimize this risk, healthcare providers should gradually increase the dosage and limit the daily dose to a maximum of 400 mg. If a seizure occurs, the medication should be discontinued immediately.

Hypertension Bupropion hydrochloride extended-release tablets (SR) may elevate blood pressure. Blood pressure should be monitored prior to initiating treatment and periodically throughout the treatment course.

Bipolar Disorder Screening Patients should be screened for bipolar disorder prior to treatment initiation. Continuous monitoring for symptoms of mania or hypomania is also recommended.

Psychosis and Neuropsychiatric Reactions Patients should be instructed to contact a healthcare professional if they experience psychosis or other neuropsychiatric reactions.

Angle-Closure Glaucoma There have been reports of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants. Caution is advised in these patients.

Monitoring Parameters Healthcare professionals are advised to monitor blood pressure before and during treatment to manage the risk of hypertension effectively.

In the event of psychosis or other neuropsychiatric reactions, patients should seek emergency medical help. Additionally, if a seizure occurs, the patient must discontinue the medication and contact their healthcare provider immediately.

Side Effects

Patients may experience a range of adverse reactions while taking the medication. The most common adverse reactions reported include headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitations, myalgia, sweating, rash, and anorexia.

Serious adverse reactions warrant particular attention. There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants, necessitating careful monitoring for the emergence or worsening of these symptoms. Additionally, serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation, highlighting the need for vigilance in this population.

The risk of seizures is dose-related; therefore, it is recommended to gradually increase the dose and limit the daily dose to 400 mg to minimize this risk. If a seizure occurs, discontinuation of the medication is advised. Patients should also be monitored for hypertension, as bupropion hydrochloride extended-release tablets (SR) can elevate blood pressure. Blood pressure should be assessed before initiating treatment and periodically during therapy.

Activation of mania or hypomania has been observed, necessitating screening for bipolar disorder and monitoring for these symptoms. Patients should be instructed to contact a healthcare professional if they experience psychosis or other neuropsychiatric reactions.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants, which requires careful consideration in susceptible individuals.

In cases of overdose, seizures were reported in approximately one-third of all instances. Other serious reactions associated with bupropion overdose include hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances or arrhythmias. Severe outcomes such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been noted, particularly in the context of multiple drug overdoses. Deaths associated with bupropion overdose have been documented, often occurring in patients who ingested large doses, with reports of multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest preceding death.

Drug Interactions

Coadministration of bupropion hydrochloride extended-release tablets (SR) with certain drug classes may lead to significant interactions that require careful consideration.

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: venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline.

• Antipsychotics: haloperidol, risperidone, and thioridazine.

• Beta-blockers: metoprolol.

• Type 1C antiarrhythmics: propafenone and flecainide. It is advisable to consider dose reductions for these medications when used concurrently with bupropion.

Seizure Threshold Caution is warranted when prescribing bupropion hydrochloride extended-release tablets (SR) to patients who are taking medications that lower the seizure threshold, as this may increase the risk of seizures.

CNS Toxicity The concomitant use of bupropion hydrochloride extended-release (SR) with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity. Monitoring for adverse effects is recommended.

MAOIs The use of bupropion hydrochloride extended-release tablets (SR) in conjunction with monoamine oxidase inhibitors (MAOIs) can heighten the risk of hypertensive reactions. Close monitoring is advised in such cases.

Urine Drug Testing It is important to note that bupropion hydrochloride extended-release tablets (SR) may cause false-positive results in urine tests for amphetamines. This should be considered when interpreting drug screening results.

Packaging & NDC

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

Pediatric Use

Safety and effectiveness in the pediatric population have not been established. Therefore, caution is advised when considering the use of this medication in children, infants, and adolescents. Further studies are needed to determine appropriate dosing and outcomes in these age groups.

Geriatric Use

Clinical trials involving bupropion sustained-release tablets included approximately 6,000 subjects, of which 275 were aged 65 years and older, and 47 were aged 75 years and older. Additionally, several hundred subjects aged 65 years and older participated in trials using the immediate-release formulation of bupropion for depression.

No overall differences in safety or effectiveness were observed between elderly patients and younger subjects. However, while clinical experience has not identified significant differences in responses, it is important to note that greater sensitivity in some older individuals cannot be ruled out.

Bupropion is extensively metabolized in the liver to active metabolites, which are subsequently metabolized and excreted by the kidneys. Given that elderly patients are more likely to have decreased renal function, the risk of adverse reactions may be heightened in this population. Therefore, it is advisable to consider renal function when selecting a dose for elderly patients, and monitoring of renal function may be beneficial to ensure safety and efficacy.

Pregnancy

Pregnancy Category C. Data from epidemiological studies involving pregnant women exposed to bupropion during the first trimester indicate no overall increased risk of congenital malformations. The background rate for major malformations in all pregnancies is approximately 2% to 4%, with a pregnancy loss rate of 15% to 20%. Reproductive developmental studies in rats and rabbits did not demonstrate clear teratogenic activity; however, rabbits exhibited slightly increased incidences of fetal malformations and skeletal variations at doses approximately equal to the maximum recommended human dose (MRHD) and higher. Additionally, decreased fetal weights were noted at doses twice the MRHD and above.

The international bupropion Pregnancy Registry, which included 675 first trimester exposures, and a retrospective cohort study using the United Healthcare database with 1,213 first trimester exposures did not reveal an increased risk for malformations overall. Specifically, no increased risk for cardiovascular malformations was observed following bupropion exposure during the first trimester, with a prospectively observed rate of 1.3% (9 cardiovascular malformations out of 675 exposures), consistent with the background rate of approximately 1%.

Inconsistent findings regarding the association between bupropion exposure during the first trimester and left ventricular outflow tract obstruction (LVOTO) have been reported. The United Healthcare database lacked sufficient power to evaluate this association, while the National Birth Defects Prevention Study (NBDPS) identified an increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7). Conversely, the Slone Epidemiology case-control study did not find an increased risk for LVOTO. Similarly, findings related to ventricular septal defect (VSD) are inconsistent, with the Slone Epidemiology Study indicating an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0), while the NBDPS and United Healthcare database studies did not find an association. Limitations in these studies include small sample sizes and the potential for chance findings due to multiple comparisons.

Animal studies have shown that bupropion, administered orally during organogenesis in rats and rabbits at doses up to 450 mg/kg and 150 mg/kg per day, respectively (approximately 11 and 7 times the MRHD on a mg/m² basis), did not provide clear evidence of teratogenicity. However, in rabbits, increased incidences of fetal malformations and skeletal variations were noted at the lowest tested dose (25 mg/kg per day, approximately equal to the MRHD on a mg/m² basis) and higher. Decreased fetal weights were observed at doses of 50 mg/kg and above. In rats, administration of bupropion at doses up to 300 mg/kg per day (approximately 7 times the MRHD on a mg/m² basis) prior to mating and throughout pregnancy and lactation did not result in apparent adverse effects on offspring development.

Bupropion hydrochloride extended-release tablets (SR) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinicians should consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Lactation

Bupropion and its metabolites are present 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 per kg, was found to be 2% of the maternal weight-adjusted dose.

Exercise caution when administering bupropion hydrochloride extended-release tablets (SR) to lactating mothers.

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 to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring of these patients.

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, highlighting the potential neurological risks associated with excessive intake.

Serious adverse reactions stemming from bupropion overdose may include hallucinations, loss of consciousness, and cardiovascular complications such as sinus tachycardia. Additionally, electrocardiogram (ECG) changes, including conduction disturbances and arrhythmias, have been observed in affected individuals. It is important to note that fatalities have occurred, particularly in cases involving large doses, where multiple uncontrolled seizures and cardiac failure were significant 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. Healthcare professionals are advised to monitor the patient closely for any emerging symptoms and complications.

In the event of a bupropion overdose, it is crucial to consult a Certified Poison Control Center for expert guidance. Healthcare providers can reach the Poison Control Center by calling 1-800-222-1222 or by visiting www.poison.org for additional resources.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice with bupropion administered at doses of up to 300 mg per kg per day and 150 mg per kg per day, respectively. These doses correspond to approximately 7 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 per kg per day, which is approximately 2 to 7 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.

A fertility study conducted in rats at doses up to 300 mg per kg per day indicated no evidence of impaired fertility.

Postmarketing Experience

Serious neuropsychiatric reactions have been reported in patients taking bupropion for smoking cessation. The majority of these reactions occurred during treatment, although some were noted upon discontinuation. While a causal relationship to bupropion treatment is not definitively established, it is important to consider that depressed mood may be a symptom of nicotine withdrawal. Notably, some cases involved patients who continued to smoke while on bupropion.

Reported neuropsychiatric symptoms include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, as well as suicidal ideation, suicide attempts, and completed suicides.

Anaphylactoid and anaphylactic reactions have also been documented during clinical trials with bupropion, characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical intervention. Additionally, rare spontaneous postmarketing reports have indicated occurrences of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion.

Further reports have included arthralgia, myalgia, fever with rash, and other serum sickness-like symptoms suggestive of delayed hypersensitivity. It is recommended that all patients be monitored for these reactions and instructed to contact a healthcare provider if they occur.

Patient Counseling

Healthcare providers should inform patients that the use of antidepressants 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 once they begin antidepressant therapy. Providers should advise families and caregivers about the importance of close observation and maintaining open communication with the prescriber regarding any changes in the patient's condition.

Additionally, healthcare providers should be aware that serious neuropsychiatric reactions have been reported in patients taking bupropion for smoking cessation. It is crucial to observe all patients for any signs of neuropsychiatric reactions and instruct them to contact their healthcare provider immediately if such reactions occur.

Families and caregivers of patients receiving antidepressants for major depressive disorder (MDD) or other indications should be alerted to monitor for signs of agitation, irritability, unusual changes in behavior, and any emergence of suicidality. They should be encouraged to report these symptoms to healthcare providers without delay.

Finally, when prescribing bupropion hydrochloride extended-release tablets (SR), healthcare providers should write prescriptions for the smallest quantity of tablets necessary for effective patient management. This practice is intended to minimize the risk of overdose.

Storage and Handling

Bupropion hydrochloride extended-release tablets, USP (SR) are supplied in a tight-light resistant container as defined by the United States Pharmacopeia (USP).

For optimal storage, these tablets should be maintained at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential to ensure the integrity and efficacy of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)