Bupropion hydrochloride

Description

Bupropion Hydrochloride Extended-Release Tablets, USP (SR) are chemically designated as (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. The molecular weight of bupropion hydrochloride is 276.2 g/mol, and its molecular formula is C13H18ClNO•HCl. The powder form of bupropion hydrochloride is white, crystalline, and highly soluble in water. It has a bitter taste and produces a sensation of local anesthesia on the oral mucosa.

These tablets are supplied as 150-mg (purple), film-coated, extended-release tablets. Each 150-mg tablet contains bupropion hydrochloride along with the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, povidone, talc, and titanium dioxide. Additionally, the 150-mg tablet contains FD&C Blue No. 2 aluminum lake and FD&C Red No. 40 aluminum lake.

Uses and Indications

Bupropion Hydrochloride Extended-Release Tablets (SR) are indicated as an aid to smoking cessation treatment.

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 for the first three days. Dosing should commence one week prior to the designated quit day. Following the initial three days, the dose may be increased to 300 mg per day, administered as 150 mg twice daily, with a minimum interval of 8 hours between doses.

For patients with moderate to severe hepatic impairment, the dosing regimen should be adjusted to 150 mg every other day. In cases of mild hepatic impairment, healthcare professionals should consider reducing the dose and/or frequency of administration. Additionally, for patients with renal impairment, a reduction in dose and/or frequency should also be considered to ensure safety and efficacy.

It is essential to increase the dose gradually to minimize the risk of seizures.

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 the risk of seizures.

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 or initiated in patients currently receiving linezolid or intravenous methylene blue.

Known hypersensitivity to bupropion or any other components of Bupropion Hydrochloride Extended-Release Tablets (SR) is also a contraindication.

Warnings and Precautions

Serious neuropsychiatric adverse events have been reported in patients using bupropion hydrochloride extended-release tablets (SR). These events may include significant mood changes such as depression and mania, as well as psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic. Additionally, there is a risk of suicidal ideation, suicide attempts, and completed suicide. Healthcare professionals should closely observe patients attempting to quit smoking with bupropion hydrochloride extended-release tablets (SR) for the emergence of these symptoms. Patients should be instructed to discontinue the medication and contact their healthcare provider immediately if they experience any of these adverse events.

The risk of seizures associated with bupropion hydrochloride extended-release tablets (SR) is dose-related. To minimize this risk, it is recommended to gradually increase the dosage and limit the daily dose to a maximum of 300 mg. If a seizure occurs, the medication should be discontinued.

Bupropion hydrochloride extended-release tablets (SR) may elevate blood pressure. Therefore, it is essential to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course, particularly in patients using nicotine replacement therapies.

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. In the event of psychosis or other neuropsychiatric reactions, patients should be instructed to contact a healthcare professional promptly.

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 (SR).

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. It is crucial to monitor these patients for any worsening of symptoms or the emergence of suicidal thoughts and behaviors.

To ensure safe use, healthcare professionals should monitor blood pressure before starting treatment and periodically during therapy, especially in conjunction with nicotine replacement. Patients should be advised to discontinue bupropion hydrochloride extended-release tablets (SR) and seek medical advice if they experience any neuropsychiatric adverse events or if psychosis and other reactions occur.

Side Effects

Patients receiving Bupropion Hydrochloride Extended-Release Tablets (SR) may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Most common adverse reactions observed in clinical trials include insomnia, rhinitis, dry mouth, dizziness, nervous disturbance, anxiety, nausea, constipation, and arthralgia. These reactions are generally mild to moderate in severity.

Serious adverse reactions warrant particular attention. A WARNING regarding the increased risk of suicidal thoughts and behaviors has been established for children, adolescents, and young adults taking antidepressants, including Bupropion. Patients should be closely monitored for the emergence or worsening of suicidal thoughts and behaviors.

Neuropsychiatric adverse events have been reported, 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 experiencing any of these symptoms should be instructed to contact a healthcare professional immediately.

The risk of seizures is dose-related; therefore, it is recommended to gradually increase the dose and limit the daily dose to 300 mg. If a seizure occurs, discontinuation of the medication is advised. Additionally, Bupropion can increase blood pressure, necessitating monitoring before and during treatment, particularly in patients using nicotine replacement therapies.

Activation of mania or hypomania has been noted, emphasizing the importance of screening patients for bipolar disorder and monitoring for these symptoms. Angle-closure glaucoma has also been reported in patients with untreated anatomically narrow angles who are treated with antidepressants.

Other important considerations include the risk of seizures in patients with a seizure disorder, current or prior diagnoses of bulimia or anorexia nervosa, and the potential for serious reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Caution is advised against the use of Monoamine Oxidase Inhibitors (MAOIs) in conjunction with Bupropion or within 14 days of stopping either treatment.

In cases of overdosage, seizures were reported in approximately one-third of all instances. Other serious reactions associated with bupropion overdose include hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes (including conduction disturbances and arrhythmias), clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. Deaths have been reported in patients who ingested large doses of bupropion, often preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest.

Patients should be informed of these potential adverse reactions and the importance of reporting any concerning symptoms to their healthcare provider.

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, or 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, which may lead to elevated plasma concentrations of drugs metabolized by this enzyme, including certain antidepressants, antipsychotics, beta-blockers, and Type 1C antiarrhythmics. A dose reduction of these medications should be considered when used concurrently with bupropion.

Digoxin Bupropion may reduce plasma levels of digoxin. It is advisable to monitor digoxin levels closely in patients receiving this combination to ensure therapeutic efficacy.

Drugs Lowering Seizure Threshold Caution is advised 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 The concomitant use of bupropion with dopaminergic agents such as levodopa and amantadine may result in central nervous system (CNS) toxicity. Monitoring for signs of CNS effects is recommended.

Monoamine Oxidase Inhibitors (MAOIs) The combination of bupropion hydrochloride extended-release tablets (SR) with MAOIs can lead to an increased risk of hypertensive reactions. Caution is warranted, and monitoring for hypertensive symptoms is advised.

Drug-Laboratory Test Interactions Bupropion hydrochloride extended-release tablets (SR) may cause false-positive results in urine drug screenings 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. 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 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, 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 from epidemiological studies indicate that bupropion, classified as Pregnancy Category C, does not show an increased risk of congenital malformations overall when used during the first trimester. The background rate for major malformations in all pregnancies is approximately 2% to 4%, with a pregnancy loss rate of 15% to 20%. In reproductive developmental studies conducted in rats and rabbits, no clear evidence of teratogenic activity was observed; however, rabbits exhibited slightly increased incidences of fetal malformations and skeletal variations at doses approximately two times the maximum recommended human dose (MRHD) and greater. Additionally, decreased fetal weights were noted at doses three times the MRHD and higher.

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 demonstrate an overall increased risk for malformations. Specifically, the rate of cardiovascular malformations in pregnancies exposed to bupropion during the first trimester was 1.3%, which aligns with the background rate of approximately 1%.

Inconsistent findings have been reported regarding the association between bupropion exposure during the first trimester and specific cardiovascular malformations, such as left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD). The United Healthcare database lacked sufficient power to evaluate the LVOTO association, while the National Birth Defects Prevention Study (NBDPS) identified an increased risk for LVOTO (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. For VSD, the Slone Epidemiology Study reported an increased risk (adjusted OR=2.5; 95% CI: 1.3, 5.0), while the NBDPS and United Healthcare database studies did not find an association. These findings are limited by the small number of exposed cases and the potential for chance findings due to multiple comparisons.

Animal studies have shown that bupropion administered during organogenesis in rats and rabbits did not present clear teratogenic effects, although rabbits did show increased fetal malformations and skeletal variations at doses starting from approximately two times the MRHD. No adverse effects on offspring development were observed in rats administered bupropion prior to mating and throughout pregnancy and lactation at doses up to approximately ten times the MRHD.

Given the potential risks, bupropion hydrochloride extended-release tablets (SR) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnant smokers are encouraged to attempt cessation through educational and behavioral interventions prior to considering pharmacological options.

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, to bupropion and its active metabolites 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

There is no specific information regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

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, alterations in mental status, and various cardiac complications. It is important to note that fatalities have been associated with bupropion overdose, particularly in cases involving large doses and multiple uncontrolled seizures.

In the event of an overdose, immediate supportive care is essential. This includes close medical supervision and monitoring of the patient, ensuring that the airway is secure and that adequate oxygenation and ventilation are maintained. Healthcare professionals are advised to consult a Certified Poison Control Center for further guidance in managing 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.

It is critical to recognize that there are no known antidotes for bupropion, and the induction of emesis is not recommended in overdose situations. Proper management and monitoring are vital to mitigate the risks associated with bupropion overdose.

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 10 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 3 to 10 times the MRHD on a mg per m² basis. The implications of these lesions as potential precursors to liver neoplasms remain 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 the 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

Some patients have reported experiencing changes in mood, including depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide during attempts to quit smoking while taking bupropion hydrochloride extended-release tablets (SR).

Additionally, new or exacerbated mental health issues, such as changes in behavior or thinking, aggression, hostility, agitation, and suicidal thoughts or actions, have been noted among individuals using bupropion hydrochloride extended-release tablets (SR) for smoking cessation.

Reports have also included symptoms of mania, characterized by significantly increased energy, severe insomnia, racing thoughts, reckless behavior, unusually grand ideas, excessive happiness or irritability, and accelerated speech.

Unusual thoughts or behaviors, including delusions, hallucinations, paranoia, and confusion, have been documented in some patients taking bupropion hydrochloride extended-release tablets (SR).

Severe allergic reactions to bupropion hydrochloride extended-release tablets (SR) have been reported, manifesting as rash, itching, hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, or difficulty breathing.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Medication Guide) thoroughly. It is important to instruct 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. These symptoms may occur, particularly during the initial stages of antidepressant treatment or when the dosage is adjusted.

Families and caregivers should be encouraged to monitor patients on a daily basis for any abrupt changes in behavior, as these can be significant. Any severe or sudden onset of such symptoms should be reported to the patient’s prescriber or healthcare professional promptly.

Patients should be informed that some individuals may experience 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 when attempting to quit smoking while taking bupropion hydrochloride extended-release tablets (SR). If patients experience any of these symptoms, they should discontinue the medication and contact a healthcare professional immediately.

Education on hypersensitivity symptoms is essential, and patients should be instructed to discontinue bupropion hydrochloride extended-release tablets (SR) if they experience a severe allergic reaction. Additionally, patients must be informed to stop taking the medication and not to restart it if they experience a seizure during treatment.

Healthcare providers should advise patients that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizures, and patients should minimize or avoid alcohol consumption. Patients should also be made aware that bupropion hydrochloride extended-release tablets (SR) can cause mild pupillary dilation, which may lead to an episode of angle-closure glaucoma in susceptible individuals.

It is important to inform patients that bupropion hydrochloride extended-release tablets (SR) contain the same active ingredient (bupropion hydrochloride) found in WELLBUTRIN ®, WELLBUTRIN SR ®, and WELLBUTRIN XL ®, and should not be used in conjunction with any other medications containing bupropion. Patients should be cautioned that any CNS-active drug, including bupropion hydrochloride extended-release tablets (SR), may impair their ability to perform tasks requiring 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, hazardous machinery.

Patients should notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter medications, as bupropion hydrochloride extended-release tablets (SR) and other drugs may interact with each other. Additionally, patients should inform their healthcare provider if they become pregnant or plan to become pregnant during therapy, as bupropion is present in human milk in small amounts.

Storage instructions should be provided, advising patients to keep bupropion hydrochloride extended-release tablets (SR) at room temperature, between 68°F and 77°F (20°C to 25°C), and to keep the tablets dry and out of light. Patients should be instructed to swallow the tablets whole to ensure the release rate is not altered, and they should not chew, divide, or crush the tablets.

For those taking more than 150 mg per day, it is important to instruct patients to take bupropion hydrochloride extended-release tablets (SR) in two doses at least 8 hours apart to minimize the risk of seizures. If a dose is missed, patients should be advised not to take an extra tablet to compensate but to take the next tablet at the regular time due to the dose-related risk of seizure.

Patients should be informed that bupropion hydrochloride extended-release tablets (SR) can be taken with or without food and may have an odor.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and features a child-resistant closure. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as outlined by USP Controlled Room Temperature guidelines.

To ensure product integrity, it must be protected from light and moisture. Additionally, it is crucial to keep the product out of the reach of children.

Additional Clinical Information

Patients and caregivers should be advised to discontinue bupropion hydrochloride extended-release tablets (SR) and contact a healthcare provider immediately if they observe any agitation, depressed mood, or atypical changes in behavior or thinking, including suicidal ideation or behavior. Families and caregivers of patients treated with antidepressants for major depressive disorder (MDD) or other indications should be vigilant for signs of agitation, irritability, and unusual behavioral changes, and report these symptoms to healthcare providers promptly.

Prescriptions for bupropion hydrochloride extended-release tablets (SR) should be limited to the smallest quantity necessary to minimize the risk of overdose. Patients should also be instructed to seek medical advice if they experience neuropsychiatric symptoms such as delusions, hallucinations, or confusion, and to discontinue the medication if they develop any allergic reactions, including skin rash or difficulty breathing. Postmarketing reports indicate that serious neuropsychiatric adverse events, including mood changes, psychosis, and suicidal thoughts, have occurred in patients using this medication for smoking cessation. While some patients experienced resolution of symptoms after discontinuation, others did not, necessitating ongoing monitoring and supportive care.

FDA Insert (PDF)

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

View full prescribing information (PDF)