Bupropion Hydrochloride (sr)

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. Bupropion hydrochloride USP appears as a white powder and is soluble in 0.1N Hydrochloric acid, alcohol (96.0%), and water. It has a bitter taste and produces a sensation of local anesthesia on the oral mucosa.

These extended-release tablets are supplied for oral administration as 150-mg (purple), film-coated, sustained-release tablets. Each 150-mg tablet contains the labeled amount of bupropion hydrochloride USP along with inactive ingredients, which include copovidone, cysteine hydrochloride, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, titanium dioxide, FD&C Blue No.2 Lake, and FD&C Red No. 40 Lake. The flavoring agent consists of dextrose, ethyl alcohol, gum arabic, propylene glycol, and silicon dioxide.

Uses and Indications

Bupropion hydrochloride extended-release tablets, USP (SR) are indicated as an aid to smoking cessation treatment. This medication is intended for use in individuals who are motivated to quit smoking and is part of a comprehensive smoking cessation program that may include counseling and support.

Limitations of Use: The safety and efficacy of bupropion hydrochloride extended-release tablets, USP (SR) have not been established in individuals who are not motivated to quit smoking. Additionally, no teratogenic or nonteratogenic effects have been reported in the available data.

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 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 (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, it 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).

Warnings and Precautions

Serious neuropsychiatric adverse events have been reported in patients using Bupropion hydrochloride extended-release tablets, USP (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, USP (SR) for the emergence of these symptoms. Patients should be instructed to discontinue the medication and contact a healthcare provider immediately if they experience any of these adverse events.

The risk of seizures is dose-related; therefore, it is essential to minimize this risk by gradually increasing the dosage and limiting the maximum daily dose to 300 mg. If a seizure occurs, the medication should be discontinued.

Bupropion hydrochloride extended-release tablets (SR) may elevate blood pressure. It is crucial to monitor blood pressure prior to initiating treatment and periodically throughout the treatment course, particularly in patients who are also 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 recommended. Instruct patients to contact a healthcare professional if they experience any neuropsychiatric reactions.

Angle-closure glaucoma has been reported in patients with untreated anatomically narrow angles who are treated with antidepressants. Caution should be exercised in these patients.

There is a WARNING: SUICIDAL THOUGHTS AND BEHAVIORS associated with the use of antidepressants, including Bupropion. There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults. It is imperative to monitor these populations for any worsening or 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 seek emergency medical help if they experience any neuropsychiatric reactions and to discontinue Bupropion hydrochloride extended-release tablets, USP (SR) and contact their healthcare provider if they experience any neuropsychiatric adverse events.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Most common adverse reactions reported 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 careful monitoring. A significant warning is the increased risk of suicidal thoughts and behaviors 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, 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.

There is a dose-related risk of seizures associated with the treatment. To minimize this risk, it is recommended to gradually increase the dose and limit the daily dose to 300 mg. Treatment should be discontinued if a seizure occurs. Additionally, hypertension may occur, necessitating blood pressure monitoring before and during treatment, particularly if the patient is using nicotine replacement therapy.

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 potential for adverse reactions following abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

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 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.

Drug Interactions

CYP2B6 inducers, such as ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin, may necessitate a dose increase of the affected medication based on clinical response. However, it is important that the dosage does not exceed the maximum recommended limit.

Bupropion is known to inhibit CYP2D6, which can lead to increased plasma concentrations of various 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 medications should be considered to mitigate potential adverse effects.

Additionally, bupropion may decrease plasma levels of digoxin; therefore, monitoring of digoxin levels is recommended to ensure therapeutic efficacy and safety.

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

The concomitant use of bupropion hydrochloride extended-release tablets (SR) with dopaminergic drugs, such as levodopa and amantadine, may result in central nervous system (CNS) toxicity, necessitating careful monitoring of patients.

Furthermore, there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (SR) are used in conjunction with monoamine oxidase inhibitors (MAOIs).

Lastly, it is important to note that bupropion hydrochloride extended-release tablets (SR) can cause false-positive results in urine drug tests for amphetamines, which may lead to unnecessary clinical concerns.

Packaging & NDC

The table below lists all NDC Code configurations of Bupropion Hydrochloride (sr) (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 greater sensitivity in some older individuals cannot be ruled out.

Bupropion is extensively metabolized in the liver to active metabolites, which are subsequently metabolized and excreted by the kidneys. Given that elderly patients are more likely to have decreased renal function, the risk of adverse reactions may be heightened in this population. Therefore, it is advisable to consider renal function when selecting a dose for 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 overall increased risk of congenital malformations when administered 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%. While no clear evidence of teratogenic activity was observed in reproductive developmental studies in rats and rabbits, slight increases in fetal malformations and skeletal variations were noted in rabbits at doses approximately two times the maximum recommended human dose (MRHD) and higher. Additionally, decreased fetal weights were observed at doses three times the MRHD and greater. Therefore, bupropion hydrochloride extended-release tablets (SR) should only be used during pregnancy if the potential benefits outweigh the 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 demonstrate an increased risk for malformations overall. 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%. Studies have shown inconsistent findings regarding the association between bupropion exposure and specific cardiovascular malformations, such as left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD). The NBDPS reported an increased risk for LVOTO, while the Slone Epidemiology Study found an increased risk for VSD; however, these findings were limited by small sample sizes and inconsistencies across studies.

Animal studies have shown that bupropion, administered during organogenesis in rats and rabbits, did not present clear teratogenic effects. In rabbits, increased incidences of fetal malformations were observed at doses starting from 25 mg per kg per day (approximately two times the MRHD), and decreased fetal weights were noted at higher doses. 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.

Given these considerations, healthcare professionals are advised to encourage pregnant smokers to pursue 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, was found to be 2% of the maternal weight-adjusted dose.

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

Renal Impairment

Patients with renal impairment may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with reduced kidney function. Regular monitoring of renal function is advisable to ensure safe and effective use of the medication in this population.

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

In cases of bupropion overdose, significant clinical manifestations can occur, particularly with doses exceeding 30 grams. Seizures are a common complication, occurring in approximately one-third of reported overdose cases.

Clinical Symptoms Serious reactions associated with bupropion overdose may include hallucinations, loss of consciousness, alterations in mental status, and electrocardiogram (ECG) changes such as conduction disturbances. Additional symptoms reported include sinus tachycardia, clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure. It is important to note that fatalities have been documented, particularly in patients who have ingested large doses, with multiple uncontrolled seizures and cardiac failure often preceding death.

Management Recommendations There are currently no known antidotes for bupropion; therefore, supportive care and close medical supervision are critical in managing an overdose. In the event of an overdose, healthcare professionals should ensure the maintenance of an adequate airway, oxygenation, and ventilation, while also monitoring cardiac rhythm and vital signs closely. The induction of emesis is not recommended in cases of bupropion overdose.

For further guidance, it is advisable to consult a Certified Poison Control Center. Healthcare professionals can reach out by calling 1-800-222-1222 or visiting www.poison.org for expert assistance in managing bupropion overdose cases.

Nonclinical Toxicology

Lifetime carcinogenicity studies conducted in rats and mice evaluated the effects of bupropion at doses up to 300 mg per kg per day in rats and 150 mg per kg per day in mice. 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 assessed. 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 in rats administered 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. Suicidal ideation and suicide attempts have also been noted in individuals attempting to quit smoking while using 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 documented among some individuals taking bupropion hydrochloride extended-release tablets (SR) for smoking cessation. These symptoms were reported more frequently in patients with a prior history of mental health disorders compared to those without such a history.

Some individuals may experience episodes of mania while on bupropion hydrochloride extended-release tablets (SR), characterized by symptoms such as significantly increased energy, severe insomnia, racing thoughts, reckless behavior, grandiose ideas, excessive happiness or irritability, and increased talkativeness.

Reports also indicate that some patients may exhibit unusual thoughts or behaviors, including delusions, hallucinations, paranoia, or confusion while taking bupropion hydrochloride extended-release tablets (SR).

Severe allergic reactions to bupropion hydrochloride extended-release tablets (SR) have been observed, with signs 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, or difficulty breathing.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, specifically the Medication Guide, to ensure they are well-informed about their treatment. 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 changes in behavior, as well as worsening depression and suicidal ideation. These symptoms are particularly concerning during the initial stages of antidepressant treatment and when dosage adjustments are made.

Families and caregivers should be encouraged to monitor patients on a daily basis for any abrupt changes in behavior, as these can occur suddenly. Any severe or unexpected symptoms should be reported to the patient's prescriber or healthcare professional promptly. Patients should be informed that some individuals have experienced significant mood changes, including depression and mania, as well as psychosis, hallucinations, paranoia, delusions, and 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.

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

Patients should be made aware that bupropion hydrochloride extended-release tablets (SR) can cause mild pupillary dilation, which may lead to angle-closure glaucoma in susceptible individuals. It is also important to inform patients 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 certain that bupropion does not adversely affect their performance, they should refrain from driving or operating complex 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) may interact with other drugs. 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.

Patients should be instructed to store bupropion hydrochloride extended-release tablets (SR) at room temperature, between 68°F and 77°F (20°C to 25°C), keeping the tablets dry and protected from light. They should swallow the tablets whole to avoid altering the release rate and should not chew, divide, or crush them. For those taking more than 150 mg per day, it is important to take the medication in two doses at least 8 hours apart to minimize the risk of seizures. 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 (SR) can be taken with or without food, and patients should be informed that the medication may have an odor.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at room temperature, ideally between 20° to 25°C (68° to 77°F). Temporary excursions are permissible within the range of 15°C to 30°C (59°F to 86°F).

It is essential to protect the product from light and moisture to maintain its integrity and efficacy. Proper handling and storage conditions are crucial for ensuring the quality of the product throughout its shelf life.

Additional Clinical Information

Patients and caregivers should be advised to discontinue Bupropion hydrochloride extended-release tablets (SR) and seek immediate medical attention if they observe any signs of agitation, depressed mood, or atypical changes in behavior or thinking, including suicidal ideation or behavior. It is also important for patients to contact a healthcare professional if they experience neuropsychiatric symptoms such as delusions, hallucinations, psychosis, concentration disturbances, paranoia, or confusion. Additionally, patients should stop taking the medication and consult a healthcare provider if they develop any allergic reactions, including skin rash, pruritus, hives, chest pain, edema, or shortness of breath.

Postmarketing experience has indicated that serious neuropsychiatric adverse events have occurred in patients using Bupropion hydrochloride extended-release tablets (SR) for smoking cessation. These events include mood changes (such as depression and mania), psychosis, hallucinations, paranoia, delusions, and suicidal behaviors. In a psychiatric cohort, serious neuropsychiatric events were reported in 0.8% of patients treated, all of which resulted in psychiatric hospitalization.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bupropion Hydrochloride (sr) 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)