Bupropion hydrochloride

Description

Bupropion hydrochloride extended-release tablets, USP (SR), are an antidepressant belonging to the aminoketone class, chemically distinct from tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, and other known antidepressant agents. The chemical structure 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 active ingredient, bupropion hydrochloride, is presented as a white powder that is soluble in 0.1N HCl, 96% alcohol, and water. It has a bitter taste and can induce a sensation of local anesthesia on the oral mucosa. Bupropion hydrochloride extended-release tablets are formulated for oral administration and are available in three strengths: 100 mg (blue), 150 mg (purple), and 200 mg (pink). Each film-coated tablet contains the specified amount of bupropion hydrochloride along with inactive ingredients, including copovidone, cysteine hydrochloride, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, and titanium dioxide.

The 100 mg tablet incorporates FD&C Blue No. 1 Brilliant Blue FCF Aluminium Lake, the 150 mg tablet contains FD&C Blue No. 2 Indigo Carmine Aluminium Lake and FD&C Red No. 40 Allura Red AC Aluminium Lake, while the 200 mg tablet includes FD&C Red No. 40 Allura Red AC Aluminium Lake. Bupropion hydrochloride extended-release tablets, USP (SR), comply with USP Dissolution Test 2.

Uses and Indications

Bupropion hydrochloride extended-release tablets (SR) 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 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, it is advisable to consider a reduction in dose and/or frequency of dosing to ensure safety and efficacy.

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 within 14 days of stopping an MAOI, nor should an MAOI be initiated within 14 days of stopping bupropion hydrochloride extended-release tablets (SR). Additionally, bupropion should not be started in patients receiving linezolid or intravenous methylene blue.

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

Warnings and Precautions

Increased risk of suicidal thoughts and behaviors has been observed in children, adolescents, and young adults taking antidepressants, including bupropion. Healthcare professionals should closely monitor these populations for any worsening or emergence of suicidal thoughts and behaviors.

Neuropsychiatric adverse events may occur during smoking cessation efforts. Postmarketing reports have indicated serious or clinically significant events, including mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Patients attempting to quit smoking with bupropion should be observed for these symptoms. If any adverse events arise, patients should be instructed to discontinue bupropion and contact a healthcare provider immediately.

The risk of seizures is dose-related. To minimize this risk, it is recommended to gradually increase the dose and limit the daily dose to a maximum of 400 mg. Should a seizure occur, bupropion must be discontinued.

Bupropion hydrochloride extended-release tablets (SR) have the potential to increase blood pressure. Therefore, it is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course.

Patients should be screened for bipolar disorder prior to treatment, as bupropion may activate mania or hypomania. Continuous monitoring for these symptoms is advised.

Instruct patients to report any occurrences of psychosis or other neuropsychiatric reactions to a healthcare professional promptly. Additionally, angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants, necessitating caution in such individuals.

Laboratory tests should include blood pressure monitoring before the initiation of treatment and at regular intervals during therapy to ensure patient safety.

In cases of psychosis or other neuropsychiatric reactions, patients should be advised to seek emergency medical help. Furthermore, if neuropsychiatric adverse events occur during smoking cessation, patients must discontinue bupropion and contact their healthcare provider. Discontinuation of bupropion is also warranted if a seizure occurs.

Side Effects

Patients may experience a range of adverse reactions while using 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 warnings associated with the use of this medication 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, which may include 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 advised to contact a healthcare professional if they experience any of these reactions.

There is a dose-related risk of seizures associated with this medication. To minimize this risk, it is recommended to gradually increase the dose and limit the daily dose to 400 mg. If a seizure occurs, the medication should be discontinued immediately.

Additionally, bupropion hydrochloride extended-release tablets (SR) may increase blood pressure. Blood pressure should be monitored before initiating treatment and periodically during treatment. Patients should also be screened for bipolar disorder due to the potential activation of mania or hypomania, and they should be monitored for these symptoms.

Patients with untreated anatomically narrow angles may be at risk for angle-closure glaucoma when treated with antidepressants. Other important considerations include a history of seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Known hypersensitivity to bupropion or any of its ingredients is also a contraindication for use.

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 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 hydrochloride extended-release tablets (SR) in conjunction with other medications that lower the seizure threshold, as this may increase the risk of seizures.

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

Monoamine Oxidase Inhibitors (MAOIs) The use of bupropion hydrochloride extended-release tablets (SR) with MAOIs can heighten the risk of hypertensive reactions. Caution is advised, and monitoring for hypertensive symptoms should be implemented.

Drug-Laboratory Test Interactions Bupropion hydrochloride extended-release tablets (SR) 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 additional information regarding the use of this medication in children and adolescents. Caution is advised when considering treatment options for pediatric patients.

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 some older individuals may exhibit greater sensitivity to the medication.

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 geriatric patients, and monitoring of renal function may be beneficial to ensure safety and efficacy.

Pregnancy

Data regarding the use of bupropion during pregnancy indicate that it falls under Pregnancy Category C. Epidemiological studies involving pregnant women exposed to bupropion in the first trimester have not demonstrated an overall increased risk of congenital malformations. It is important to note that all pregnancies, irrespective of drug exposure, have a background rate of 2% to 4% for major malformations and 15% to 20% for pregnancy loss.

Reproductive developmental studies in rats and rabbits did not reveal clear evidence of teratogenic activity; however, in rabbits, there were 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 observed at doses twice the MRHD and greater. Therefore, bupropion hydrochloride extended-release tablets (SR) should be prescribed during pregnancy only if the potential benefits outweigh the potential risks to the fetus.

Human data from 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 indicate an increased risk for malformations overall. Specifically, the rate of cardiovascular malformations in pregnancies with first trimester exposure to bupropion was observed to be 1.3%, which aligns with the background rate of approximately 1%. Furthermore, no increased risk for cardiovascular malformations was noted in additional studies, including the National Birth Defects Prevention Study (NBDPS).

However, findings regarding the association between bupropion exposure during the first trimester and specific cardiovascular defects, such as left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD), are inconsistent. The NBDPS reported an increased risk for LVOTO, while the Slone Epidemiology Study found an increased risk for VSD, but these findings were not corroborated by other studies. The limitations of these studies, including small sample sizes and inconsistent results, suggest that definitive conclusions cannot be drawn regarding these associations.

Animal studies have shown that when bupropion was administered to rats and rabbits during organogenesis, no clear teratogenic effects were observed. However, in rabbits, fetal malformations and skeletal variations were noted at doses starting from the lowest tested dose, which was approximately equal to the MRHD. In contrast, no adverse effects on offspring development were observed in rats administered bupropion at doses up to 300 mg per kg per day throughout pregnancy and lactation.

Healthcare professionals should carefully consider the risks of untreated depression when contemplating the discontinuation or alteration of antidepressant treatment 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.

Caution is advised when administering bupropion hydrochloride extended-release tablets (SR) to lactating mothers due to the potential exposure of breastfed infants to the drug and its metabolites.

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 these cases, seizures occurred in approximately one-third of the patients, highlighting a significant risk associated with excessive intake.

Serious adverse reactions have been observed in individuals who overdosed on bupropion alone. These reactions include hallucinations, loss of consciousness, and sinus tachycardia. Additionally, electrocardiogram (ECG) changes such as conduction disturbances, including QRS prolongation and various arrhythmias, have been reported.

In cases where bupropion was part of a multiple drug overdose, further complications arose. Symptoms such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure were noted. While most patients ultimately recovered without lasting effects, there have been fatalities associated with overdoses of bupropion alone, particularly in those who ingested large quantities of the drug.

In patients who succumbed to bupropion overdose, multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest were reported prior to death. These findings underscore the critical need for prompt recognition and management of bupropion overdose to mitigate potential life-threatening consequences.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice, administering bupropion 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 assessment in rats, conducted at doses up to 300 mg per kg per day, indicated no evidence of impaired fertility.

Postmarketing Experience

Some patients have reported experiencing changes in mood, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and homicidal ideation while using bupropion. Additional symptoms noted include aggression, hostility, agitation, anxiety, panic, and suicidal ideation, particularly during attempts to quit smoking.

Patients are advised to discontinue bupropion and consult a healthcare professional if they encounter any of these symptoms.

Patient Counseling

Advise patients to read the FDA-approved patient labeling, specifically the Medication Guide, to understand the benefits and risks associated with bupropion hydrochloride extended-release tablets (SR). It is essential to counsel patients, their families, and caregivers on the appropriate use of this medication.

Instruct patients, their families, and caregivers to read the Medication Guide thoroughly and assist them in comprehending its contents. Encourage patients to discuss the information within the Medication Guide and to seek clarification on any questions they may have.

Healthcare providers should inform patients about the potential emergence of 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, particularly during the initial stages of treatment or when adjusting the dosage. Families and caregivers should be vigilant in observing for these symptoms on a daily basis, as changes can 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 possible medication adjustments.

Patients should be made aware that some individuals have reported mood changes, psychosis, hallucinations, paranoia, delusions, aggression, and suicidal ideation while attempting to quit smoking while on bupropion. Instruct patients to discontinue the medication and contact a healthcare professional if they experience such symptoms.

Educate patients on the signs of hypersensitivity and advise them to stop taking bupropion hydrochloride extended-release tablets (SR) if they experience a severe allergic reaction. Additionally, patients should discontinue the medication and not restart it if they experience a seizure during treatment. Emphasize that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can heighten the risk of seizures, and patients should minimize or avoid alcohol consumption.

During the initial titration phase, particularly when increasing the dose above 150 mg per day, instruct patients to take bupropion hydrochloride extended-release tablets (SR) in two divided doses, with at least 8 hours between doses, to reduce the risk of seizures. Patients should also be informed that the medication may cause mild pupillary dilation, which could lead to angle-closure glaucoma in susceptible individuals. They may wish to undergo an examination to assess their susceptibility and consider a prophylactic procedure if necessary.

Educate patients that bupropion hydrochloride extended-release tablets (SR) contain the same active ingredient as ZYBAN, which is used for smoking cessation, and should not be used in conjunction with ZYBAN or any other bupropion-containing medications.

Advise patients that bupropion hydrochloride extended-release tablets (SR) may impair their ability to perform tasks requiring judgment, motor, and cognitive skills. Until they are confident that the medication does not adversely affect their performance, patients should refrain from driving or operating complex machinery.

Finally, counsel patients to inform their healthcare provider of any prescription or over-the-counter medications they are currently taking or plan to take, as bupropion hydrochloride extended-release tablets (SR) may interact with other drugs, affecting their metabolism.

Storage and Handling

The product is supplied in a tight, light-resistant container equipped with a child-resistant closure, as required. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the product from light and moisture to maintain its integrity and efficacy.

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 Dr. Reddy’s Laboratories Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)