Bupropion hydrochloride

Description

Bupropion hydrochloride extended-release tablets (SR) are chemically unrelated to nicotine or other agents used in nicotine addiction treatment. The chemical designation of bupropion hydrochloride is (±)-1-(3-chlorophenyl)-2-(1,1-dimethylethyl)amino-1-propanone hydrochloride. It has a molecular weight of 276.2 g/mol and a molecular formula of 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.

Bupropion hydrochloride extended-release tablets (SR) are supplied for oral administration as 150-mg (purple), film-coated, sustained-release tablets. Each 150-mg tablet contains bupropion hydrochloride along with inactive ingredients, which include colloidal silicon dioxide, ethyl alcohol, hydrochloric acid, hydrogenated vegetable oil, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, povidone, talc, and titanium dioxide. Additionally, the 150-mg tablet contains FD&C blue No. 1 aluminum lake and D&C red No. 27 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 initial three days of treatment. Dosing should commence one week prior to the designated quit day. Following the first 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, nor should an MAOI be initiated within 14 days of discontinuing bupropion hydrochloride extended-release tablets (SR). Additionally, bupropion hydrochloride extended-release tablets (SR) should not be started in patients receiving linezolid or intravenous methylene blue.

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

Warnings and Precautions

The use of bupropion hydrochloride extended-release tablets (SR) 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 Adverse Events Postmarketing reports have indicated serious or clinically significant neuropsychiatric adverse events associated with bupropion hydrochloride extended-release tablets (SR). These events may include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, as well as suicidal ideation, suicide attempts, and completed suicides. Patients attempting to quit smoking while on this medication should be observed for these symptoms. If any adverse events occur, patients should be instructed to discontinue the medication and contact a healthcare provider immediately.

Seizure Risk The risk of seizures 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.

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

Bipolar Disorder Screening Patients should be screened for bipolar disorder prior to treatment, and ongoing monitoring for symptoms of mania or hypomania is advised.

Psychosis and Neuropsychiatric Reactions Patients should be informed to contact a healthcare professional if they experience any neuropsychiatric reactions, including psychosis.

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

Monitoring Parameters Blood pressure should be monitored before initiating treatment and periodically during the course of therapy, especially in conjunction with nicotine replacement.

In the event of neuropsychiatric adverse events, patients must be instructed to discontinue bupropion hydrochloride extended-release tablets (SR) and seek immediate medical assistance.

Side Effects

Patients may experience a range of adverse reactions while taking bupropion hydrochloride extended-release tablets (SR). The most common adverse reactions reported include insomnia, rhinitis, dry mouth, dizziness, nervous disturbance, anxiety, nausea, constipation, and arthralgia.

Serious adverse reactions warrant particular attention. A WARNING: 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 the emergence or worsening of suicidal thoughts and behaviors.

Neuropsychiatric adverse events have been observed, 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 hydrochloride extended-release tablets (SR) may increase blood pressure, necessitating monitoring before and during treatment, particularly if used in conjunction with nicotine replacement therapies.

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

Other important considerations include a history of seizure disorder, current or prior diagnosis of bulimia or anorexia nervosa, and the risks associated with abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Bupropion hydrochloride extended-release tablets (SR) should not be used in conjunction with Monoamine Oxidase Inhibitors (MAOIs) intended for psychiatric disorders or within 14 days of stopping treatment with either medication. Known hypersensitivity to bupropion or its ingredients is also a contraindication.

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 reactions such as fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been documented, particularly in the context of multiple drug overdoses. Fatalities have been reported in patients who ingested large doses of bupropion alone, with multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest occurring prior to death.

Drug Interactions

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

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 a known inhibitor of CYP2D6 and may elevate the plasma 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.

Digoxin Bupropion may decrease plasma levels of digoxin. Therefore, monitoring of digoxin levels is recommended to ensure therapeutic efficacy.

Seizure Threshold Caution is advised when prescribing bupropion to patients taking medications that lower the seizure threshold, as this may increase the risk of seizures.

CNS Toxicity Concomitant use of bupropion with dopaminergic drugs, such as levodopa and amantadine, may lead to central nervous system toxicity. Close monitoring of patients is warranted.

MAOIs The use of bupropion in conjunction with monoamine oxidase inhibitors (MAOIs) may heighten the risk of hypertensive reactions. This combination should be approached with caution.

Urine Drug Testing Bupropion hydrochloride extended-release tablets (SR) can result in false-positive urine test results for amphetamines. This potential outcome should be communicated to patients and healthcare providers to avoid misinterpretation of 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, the use of this medication in children, infants, and adolescents should be approached with caution until further data is available.

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 clinical trials utilizing 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 between these groups, it is important to note that greater sensitivity 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 doses 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 from 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 and specific cardiovascular defects, such as left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD). The United Healthcare database lacked sufficient power to evaluate LVOTO, while the National Birth Defects Prevention Study (NBDPS) suggested 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 indicated an increased risk following first trimester exposure (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 at doses significantly higher than the MRHD, did not produce clear teratogenic effects. However, in rabbits, increased fetal malformations and skeletal variations were noted at lower doses, and decreased fetal weights were observed at higher doses. In rats, no adverse effects on offspring development were seen when bupropion was administered prior to mating and throughout pregnancy and lactation.

Given the available data, 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 has been studied in lactating animals, specifically in rats, where it was administered at oral doses of up to 300 mg per kg per day (approximately 10 times the maximum recommended human dose on a mg per m² basis) prior to mating and throughout pregnancy and lactation. The results indicated no apparent adverse effects on offspring development.

While specific data on excretion in human breast milk and effects on breastfed infants are not provided, healthcare professionals should consider the potential benefits and risks when prescribing bupropion to lactating mothers. Monitoring of breastfed infants for any potential effects is advisable.

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, highlighting the potential neurological risks associated with excessive intake.

Serious adverse reactions stemming from bupropion overdose may include hallucinations, loss of consciousness, sinus tachycardia, and notable changes on the electrocardiogram (ECG). These symptoms indicate the need for immediate medical intervention, as they can escalate rapidly.

Tragically, fatalities linked to bupropion overdose have occurred, frequently associated with multiple uncontrolled seizures and subsequent cardiac failure. This underscores the critical nature of prompt and effective management in overdose situations.

Currently, there are no known antidotes for bupropion. Therefore, the cornerstone of treatment involves supportive care and vigilant medical supervision. Healthcare professionals are advised to monitor the patient closely and manage symptoms as they arise.

In the event of a suspected overdose, it is imperative 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 visiting www.poison.org for further assistance.

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; 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 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

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

New or exacerbated mental health issues, such as changes in behavior or thinking, aggression, hostility, agitation, and suicidal thoughts or actions, have also been documented in some patients taking bupropion hydrochloride extended-release tablets (SR) for smoking cessation.

Serious side effects have been reported, including unusual thoughts or behaviors such as delusions, hallucinations, paranoia, or confusion. The risk of seizures is known to increase with higher doses of bupropion hydrochloride extended-release tablets (SR).

Instances of severe hypertension have been observed in some individuals taking this medication. Furthermore, episodes of mania, characterized by significantly increased energy, severe insomnia, racing thoughts, reckless behavior, grandiosity, excessive happiness or irritability, and rapid speech, have been reported.

Severe allergic reactions to bupropion hydrochloride extended-release tablets (SR) have occurred, 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.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, specifically the Medication Guide, to ensure they understand the medication's use and potential risks. 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, hypomania, mania, and other unusual behavioral changes, as well as worsening depression and suicidal ideation, particularly during the initial stages of antidepressant treatment or when dosage adjustments are made.

Families and caregivers should be encouraged to monitor patients closely for these symptoms on a daily basis, as changes can occur abruptly. Any severe or sudden onset of these symptoms should be reported to the patient's prescriber or healthcare professional. 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). Patients should be instructed to discontinue the medication and contact a healthcare professional if they experience any of these symptoms.

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

Patients should 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. Additionally, patients should be informed that bupropion hydrochloride extended-release tablets (SR) contain the same active ingredient as WELLBUTRIN®, WELLBUTRIN SR®, and WELLBUTRIN XL®, and should not be used in conjunction with any other medications containing bupropion.

Healthcare providers should counsel patients 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 patients are confident that the medication does not adversely affect their performance, they should refrain from driving or operating complex machinery.

Patients should be advised to notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter medications, as interactions may affect drug metabolism. It is also important for patients to inform their healthcare provider if they become pregnant or plan to become pregnant during therapy. Patients should be made aware that bupropion hydrochloride extended-release tablets (SR) are present in human milk in small amounts.

Instruct patients to store bupropion hydrochloride extended-release tablets (SR) at controlled room temperature, between 20° to 25°C (68° to 77°F), and to keep the tablets dry and protected from light. Patients should be advised to swallow the tablets whole to avoid altering the release rate; they should not chew, divide, or crush the tablets, as they are designed for slow drug release.

For patients taking more than 150 mg per day, it is important to instruct them to take bupropion hydrochloride extended-release tablets (SR) in two doses at least 8 hours apart to minimize the risk of seizures. If a patient misses a dose, they should be advised not to take an extra tablet to compensate for the missed dose, but rather 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 packaging that adheres to the National Drug Code (NDC) specifications. It should be stored at a controlled room temperature 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. Proper handling and storage conditions must be observed to ensure optimal product quality.

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 Par Pharmaceutical, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)