Bupropion hydrochloride

Description

Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin reuptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion and is related to phenylethylamines. The chemical designation is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight is 276.2, and the molecular formula is C13H18ClNO•HCl. Bupropion hydrochloride 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 (XL) USP are supplied for oral administration in strengths of 150 mg and 300 mg. These tablets are white, round, and contain the labeled amount of bupropion hydrochloride along with inactive ingredients, which include colloidal silicon dioxide, copovidone, ethyl cellulose, hydroxypropyl cellulose, glyceryl behenate, methacrylic acid copolymer, silicon dioxide, shellac glaze, and iron oxide black. The tablets are printed with edible black ink.

Uses and Indications

Bupropion Hydrochloride Extended-Release Tablets (XL) is indicated for the treatment of major depressive disorder (MDD) in adults. Additionally, this medication is indicated for the prevention of seasonal affective disorder (SAD).

There are no teratogenic or nonteratogenic effects associated with the use of Bupropion Hydrochloride Extended-Release Tablets (XL).

Dosage and Administration

Healthcare professionals are advised to initiate treatment with a gradual increase in dosage to minimize the risk of seizures. It is essential to periodically reassess the patient's dose and the necessity for maintenance treatment.

For the management of Major Depressive Disorder, the recommended starting dose is 150 mg administered once daily. The usual target dose is 300 mg once daily, with the option to increase the dose to 300 mg after a period of 4 days if clinically indicated.

In the case of Seasonal Affective Disorder, treatment should commence in the autumn, prior to the onset of seasonal depressive symptoms. The starting dose is also 150 mg once daily, with a typical target dose of 300 mg once daily. After one week of treatment, the dose may be increased to 300 mg once daily. It is recommended to continue treatment throughout the winter season.

For patients with hepatic impairment, those with moderate to severe conditions should receive a dose of 150 mg every other day. In patients with mild hepatic impairment, consideration should be given to reducing the dose and/or frequency of administration.

In patients with renal impairment, it is advisable to consider a reduction in the dose and/or frequency of dosing based on the severity of the impairment.

Contraindications

Use of bupropion hydrochloride extended-release tablets (XL) 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 extended-release tablets (XL) should not be used within 14 days of stopping an MAOI or initiated in patients currently receiving linezolid or intravenous methylene blue.

Known hypersensitivity to bupropion or any of the other ingredients in bupropion hydrochloride extended-release tablets (XL) is also a contraindication.

Warnings and Precautions

Postmarketing surveillance has identified serious neuropsychiatric adverse events associated with the use of bupropion hydrochloride extended-release tablets (XL) during smoking cessation. These events may include significant mood changes such as depression and mania, as well as psychotic symptoms including hallucinations, paranoia, delusions, and aggressive behaviors. Healthcare professionals should closely observe patients attempting to quit smoking for the emergence of these symptoms. Patients should be instructed to discontinue bupropion hydrochloride extended-release tablets (XL) and seek immediate medical advice if they experience any of these adverse effects.

The risk of seizures is dose-dependent. To mitigate this risk, it is recommended that the daily dose of bupropion hydrochloride extended-release tablets (XL) not exceed 450 mg, and that the dosage be increased gradually. In the event of a seizure, the medication should be discontinued promptly.

Bupropion hydrochloride extended-release tablets (XL) have been associated with an increase in blood pressure. Therefore, it is essential to monitor blood pressure prior to initiating treatment and to conduct periodic assessments throughout the course of therapy.

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

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

There is a risk of angle-closure glaucoma in patients with untreated anatomically narrow angles who are treated with antidepressants, including bupropion hydrochloride extended-release tablets (XL).

It is critical to note the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants. Healthcare providers should monitor these populations closely for any worsening of symptoms or the emergence of suicidal ideation or behaviors.

Side Effects

Patients may experience a range of adverse reactions while using bupropion hydrochloride extended-release tablets (XL). The most common adverse reactions reported include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitations, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash.

Serious adverse reactions warrant particular attention. A WARNING regarding suicidal thoughts and behaviors is indicated, as there is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Patients should be closely monitored 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 advised to contact a healthcare professional if they experience any of these reactions.

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

Activation of mania or hypomania has been reported, particularly in patients with a history of bipolar disorder, and these patients should be screened and monitored for symptoms. Angle-closure glaucoma has also been noted in patients with untreated anatomically narrow angles who are treated with antidepressants.

Other important considerations include the risk of seizures in patients with a seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the potential for serious reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) intended for psychiatric disorders or within 14 days of stopping treatment with either bupropion or an MAOI.

In cases of overdose, 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 or arrhythmias), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. Deaths have been reported in patients who ingested large doses of bupropion, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Drug Interactions

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate a dose increase of bupropion when coadministered. However, the dosage should not exceed the maximum recommended limit.

Bupropion is a known inhibitor of CYP2D6, which can lead to elevated concentrations of certain medications, including antidepressants (e.g., venlafaxine, nortriptyline), antipsychotics (e.g., haloperidol), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone). A dose reduction of these concomitant medications should be considered to mitigate potential adverse effects.

Caution is warranted when prescribing bupropion hydrochloride extended-release tablets (XL) alongside drugs that may lower the seizure threshold, as this combination could increase the risk of seizures.

The use of bupropion hydrochloride extended-release tablets (XL) in conjunction with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity. Therefore, careful monitoring is advised.

Additionally, there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (XL) are administered with monoamine oxidase inhibitors (MAOIs).

It is important to note that bupropion hydrochloride extended-release tablets (XL) can produce false-positive results in urine tests for amphetamines, which should be taken into consideration during drug screening.

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 of bupropion hydrochloride extended-release tablets (XL) in the pediatric population have not been established. When considering the use of this medication in children or adolescents, healthcare professionals should carefully balance the potential risks against the clinical need for treatment.

Geriatric Use

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

No overall differences in safety or effectiveness were observed between elderly patients and younger subjects in these studies. However, while clinical experience has not identified significant differences in responses between these age groups, it is important to note that greater sensitivity to the drug may be present in some older individuals.

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, careful consideration of renal function is essential in dose selection for this population. Monitoring renal function may be beneficial to mitigate the risk of adverse reactions, which may be heightened in patients with impaired renal function.

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at National Pregnancy Registry for AntidepressantsNational Pregnancy Registry for Antidepressants.

Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall. However, there are risks to the mother associated with untreated depression. A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The findings indicated that women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than those who continued treatment. Therefore, healthcare providers should consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Animal studies have shown that when bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. Conversely, when given to pregnant rabbits during organogenesis, non-dose-related increases in the incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater. Decreased fetal weights were noted at doses twice the MRHD and greater.

The estimated background risk for major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data from an international bupropion Pregnancy Registry, which included 675 first trimester exposures, and a retrospective cohort study using the United Healthcare database, which included 1,213 first trimester exposures, did not show an increased risk for malformations overall. However, the Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. Notably, no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester, with a prospectively observed rate of 1.3%, which is similar to the background rate of approximately 1%.

Study findings regarding bupropion exposure during the first trimester and the risk for left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD) are inconsistent and do not allow for definitive conclusions regarding possible associations. In studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively. There was no evidence of fetal malformations in rats, and in a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day from embryonic implantation through lactation had no effect on pup growth or development.

Lactation

Data from published literature report the presence of bupropion and its metabolites in human milk. In a lactation study involving ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure, assuming a daily consumption of 150 mL/kg, was found to be 2% of the maternal weight-adjusted dose.

There are no data available regarding the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports have not identified a clear association of adverse reactions in breastfed infants. However, it is important to note that postmarketing reports have described seizures in breastfed infants, 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 Extended-Release Tablets (XL) and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

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

Hepatic Impairment

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

Overdosage

Overdoses of bupropion have been documented, with instances involving doses of 30 grams or more. In approximately one third of these cases, seizures have been reported.

Serious adverse reactions associated with bupropion overdose may include hallucinations, loss of consciousness, alterations in mental status, and respiratory failure. These symptoms are particularly concerning in the context of multiple drug overdoses, where the risk of severe complications is heightened.

Fatalities linked to bupropion overdose have also been recorded, often occurring after multiple uncontrolled seizures, which may be accompanied by bradycardia, cardiac failure, and cardiac arrest.

Currently, there are no known antidotes for bupropion overdose. Therefore, the primary approach to management involves supportive care and close medical supervision. Healthcare professionals are advised to consult a Certified Poison Control Center for further guidance in the event of an overdose. The contact number for the Poison Control Center is 1-800-222-1222, and additional resources can be found at www.poison.org.

Nonclinical Toxicology

Lifetime carcinogenicity studies were conducted in rats and mice, administering bupropion hydrochloride at doses up to 300 mg/kg/day and 150 mg/kg/day, respectively. These doses correspond to approximately 7 and 2 times the maximum recommended human dose (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 of bupropion hydrochloride, which is approximately 2 to 7 times the MRHD on a mg/m² basis. Lower doses were not evaluated in this study. 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 2 of 5 strains in one Ames bacterial mutagenicity assay, resulting in a mutation rate that was 2 to 3 times higher than the control. However, it yielded negative results in another assay. 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/kg/day indicated no evidence of impaired fertility.

Postmarketing Experience

Postmarketing experience has revealed that some patients have reported changes in mood, including depression and mania, as well as symptoms such as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. These symptoms have been observed in individuals attempting to quit smoking while using bupropion.

Additionally, new or exacerbated mental health issues, including changes in behavior or thinking, aggression, hostility, agitation, depression, and suicidal thoughts or actions, have been documented. Some patients experienced these symptoms upon initiation of bupropion therapy, while others developed them after several weeks of treatment or following discontinuation of the medication.

Patients are advised to discontinue bupropion hydrochloride extended-release tablets (XL) and contact their healthcare provider immediately if they experience a seizure. It is important to avoid reinitiating treatment with bupropion hydrochloride extended-release tablets (XL) after a seizure event.

Reports have also indicated that some individuals may experience significant increases in blood pressure while taking bupropion hydrochloride extended-release tablets (XL), particularly if they are concurrently using nicotine replacement therapy, such as nicotine patches, to assist with smoking cessation.

Furthermore, some patients may experience episodes of mania while on bupropion hydrochloride extended-release tablets (XL), characterized by symptoms such as heightened energy levels, severe insomnia, racing thoughts, reckless behavior, grandiose ideas, and excessive happiness or irritability.

Unusual thoughts or behaviors, including delusions, hallucinations, paranoia, and confusion, have also been reported among patients taking bupropion hydrochloride extended-release tablets (XL).

Severe allergic reactions to bupropion hydrochloride extended-release tablets (XL) have been noted, with symptoms including rash, itching, hives, fever, swollen lymph nodes, painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, and difficulty breathing. Patients experiencing these symptoms should discontinue use and seek immediate medical attention.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Medication Guide) thoroughly. It is important for patients, their families, and caregivers to be vigilant for the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior, as well as worsening depression and suicidal ideation, particularly during the initial stages of antidepressant treatment and when dosage adjustments are made.

Families and caregivers should monitor patients closely 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. Such symptoms may indicate an increased risk for suicidal thoughts and behaviors, necessitating close monitoring and potential medication adjustments.

Patients should be informed that some individuals have reported mood changes (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal thoughts and actions when attempting to quit smoking while using bupropion. If patients experience any of these symptoms, they should discontinue Bupropion Hydrochloride Extended-Release Tablets and contact a healthcare professional immediately.

Patients should be educated about the signs of hypersensitivity and instructed to discontinue bupropion hydrochloride extended-release tablets (XL) if they experience a severe allergic reaction. Additionally, if a patient experiences a seizure while on treatment, they should stop taking bupropion hydrochloride extended-release tablets (XL) and not restart them.

Patients should be cautioned 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. It is also important to inform patients that bupropion hydrochloride extended-release tablets (XL) may cause mild pupillary dilation, which could lead to an episode of angle-closure glaucoma in susceptible individuals.

Patients should be made aware that bupropion hydrochloride extended-release tablets (XL) contain the same active ingredient (bupropion) found in ZYBAN, which is used for smoking cessation, and that these medications should not be used together or with any other products containing bupropion hydrochloride.

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

Patients should notify their healthcare provider of any prescription or over-the-counter medications they are taking or plan to take, as bupropion hydrochloride extended-release tablets (XL) 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 hydrochloride extended-release tablets (XL) during pregnancy.

Patients should be instructed to swallow bupropion hydrochloride extended-release tablets (XL) whole to ensure the release rate is not altered. If a dose is missed, patients should not take an extra tablet to compensate but should take the next tablet at the regular time due to the dose-related risk of seizure. Bupropion hydrochloride extended-release tablets (XL) should be taken in the morning and may be consumed with or without food.

Storage and Handling

The product is supplied in a well-closed container to protect it from light. 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. Proper storage conditions are essential to maintain the integrity 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)