BUPROPION HYDROCHLORIDE SR- bupropion hydrochloride tablet, film coated, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

BUPROPION HYDROCHLORIDE (UNII: ZG7E5POY8O) (BUPROPION - UNII:01ZG3TPX31)

Available from:

Preferred Pharmaceuticals, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Bupropion hydrochloride extended-release tablets (SR) is indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). The efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with MDD [see Clinical Studies ( 14)] . The efficacy of bupropion hydrochloride extended-release tablets (SR) in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial [see Clinical Studies ( 14)] . Pregnancy Exposure Registry There is an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to any antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-4056185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants. Risk Summary Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data) . There are risks to the mother associated with untreated depression in pregnancy (see Clinical Considerations) . When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 11 times the maximum recommended human dose (MRHD) of 400 mg/day. When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations, and skeletal variations were observed at doses approximately equal to the MRHD and greater. Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data) . The estimated background risk for major birth defects and miscarriage is unknown for the indicated population. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: 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 women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. 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. Data Human Data: Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database, which had a limited number of exposed cases with cardiovascular malformations, and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) of self-reported bupropion use from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7), and the Slone Epidemiology case control study did not find increased risk for LVOTO. Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. Animal Data: In studies conducted in rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 11 and 7 times the MRHD, respectively, on a mg/m 2 basis). There was no evidence of fetal malformations in rats. When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the MRHD on a mg/m 2 basis) and greater. Decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the MRHD on a mg/m 2 basis) and greater. No maternal toxicity was evident at doses of 50 mg/kg/day or less. In a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 4 times the MRHD on a mg/m 2 basis) from embryonic implantation through lactation had no effect on pup growth or development. Risk Summary Data from published literature report the presence of bupropion and its metabolites in human milk (see Data) . There are no data on 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 the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bupropion hydrochloride extended-release tablets (SR) and any potential adverse effects on the breastfed child from bupropion hydrochloride extended-release tablets (SR) or from the underlying maternal condition. Data In a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants. The relationship of bupropion exposure and these seizures is unclear. Safety and effectiveness in the pediatric population have not been established [see  Boxed Warning, Warnings and Precautions ( 5.1)] . Of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. In addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see Dosage and Administration ( 2.3), Use in Specific Populations ( 8.6), Clinical Pharmacology ( 12.3)]. Consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (SR) in patients with renal impairment (GFR: less than 90 mL per min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see Dosage and Administration ( 2.3), Clinical Pharmacology ( 12.3)] . In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of bupropion hydrochloride extended-release tablets (SR) is 100 mg per day or 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [ see Dosage and Administration ( 2.2), Clinical Pharmacology ( 12.3)] . Bupropion is not a controlled substance. Humans Controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity. In a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like activity as compared with placebo on the Morphine Benzedrine Subscale of the Addiction Research Center Inventories (ARCI) and a score greater than placebo but less than 15 mg of the Schedule II stimulant dextroamphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug liking which are often associated with abuse potential. Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose trials does suggest that the recommended daily dosage of bupropion when administered orally in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs. Bupropion hydrochloride extended-release tablets (SR) are intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has been reported. Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. Animals Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavior response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models assessing the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

Product summary:

Bupropion hydrochloride extended-release tablets, USP (SR), 200 mg of bupropion hydrochloride, are pink, blackberry flavored, round, biconvex, film coated tablets, debossed with ‘SG, 176’ on one side and plain on other side in Bottles of 20 (NDC 68788-7807-2) Tablets Bottles of 30 (NDC 68788-7807-3) Tablets Bottles of 60 (NDC 68788-7807-6) Tablets Bottles of 90 (NDC 68788-7807-9) Tablets Bottles of 100 (NDC 68788-7807-1) Tablets Bottles of 120 (NDC 68788-7807-8) Tablets Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure (as required). Protect from light and moisture.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

BUPROPION HYDROCHLORIDE SR- BUPROPION HYDROCHLORIDE TABLET, FILM
COATED, EXTENDED
RELEASE
Preferred Pharmaceuticals, Inc.
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MEDICATION GUIDE
Bupropion Hydrochloride Extended-Release Tablets, USP (SR)
(bue proe' pee on hye'' droe klor' ide)
IMPORTANT: Be sure to read the three sections of this Medication
Guide. The first section is about the
risk of suicidal thoughts and actions with antidepressant medicines;
the second section is about the risk of
changes in thinking and behavior, depression and suicidal thoughts or
actions with medicines used to quit
smoking; and the third section is entitled “What Other Important
Information Should I Know About
bupropion hydrochloride extended-release tablets, (SR)?”
Antidepressant Medicines, Depression and Other Serious Mental
Illnesses, and Suicidal Thoughts or
Actions
This section of the Medication Guide is only about the risk of
suicidal thoughts and actions with
antidepressant medicines.
What is the most important information I should know about
antidepressant medicines, depression and
other serious mental illnesses, and suicidal thoughts or actions?
1.
Antidepressant medicines may increase the risk of suicidal thoughts or
actions in some children,
teenagers, or young adults within the first few months of treatment.
2.
Depression or other serious mental illnesses are the most important
causes of suicidal thoughts and
actions. Some people may have a particularly high risk of having
suicidal thoughts or actions.These
include people who have (or have a family history of) bipolar illness
(also called manic- depressive
illness) or suicidal thoughts or actions.
3.
How can I watch for and try to prevent suicidal thoughts and actions
in myself or a family member?
o
Pay close attention to any changes, especially sudden changes, in
mood, behaviors, thoughts,
or feelings. This is very important when an antidepressant medicine is
started or when the
dose is changed.
o
Call your healthcare provider right away to report new or sudden
changes in mood, behavior,
thoughts, or

Summary of Product characteristics

BUPROPION HYDROCHLORIDE SR- BUPROPION HYDROCHLORIDE TABLET, FILM
COATED, EXTENDED RELEASE
PREFERRED PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BUPROPION
HYDROCHLORIDE EXTENDED-RELEASE TABLETS (SR) SAFELY AND EFFECTIVELY.
SEE FULL
PRESCRIBING INFORMATION FOR BUPROPION HYDROCHLORIDE EXTENDED-RELEASE
TABLETS
(SR).
BUPROPION HYDROCHLORIDE EXTENDED-RELEASE TABLETS (SR), FOR ORAL USE
INITIAL U.S. APPROVAL: 1985
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS;
_ SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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INDICATIONS AND USAGE
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
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CONTRAINDICATIONS
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INCREASED RISK OF SUICIDAL THINKING AND BEHAVIOR IN CHILDREN,
ADOLESCENTS, AND
YOUNG ADULTS TAKING ANTIDEPRESSANTS. ( 5.1)
MONITOR FOR WORSENING AND EMERGENCE OF SUICIDAL THOUGHTS AND
BEHAVIORS. ( 5.1)
Bupropion hydrochloride extended-release tablets, (SR) are an
aminoketone antidepressant,
indicated for the treatment of major depressive disorder (MDD). ( 1)
Starting dose: 150 mg/day ( 2.1)
General: Increase dose gradually to reduce seizure risk. ( 2.1, 5.3)
After 3 days, may increase the dose to 300 mg/day, given as 150 mg
twice daily at an interval of at
least 8 hours. ( 2.1)
Usual target dose: 300 mg/day as 150 mg twice daily. ( 2.1)
Maximum dose: 400 mg/day, given as 200 mg twice daily, for patients
not responding to 300 mg/day.
( 2.1)
Periodically reassess the dose and need for maintenance treatment. (
2.1)
Moderate to severe hepatic impairment: 100 mg daily or 150 mg every
other day. ( 2.2, 8.7)
Mild hepatic impairment: Consider reducing the dose and/or frequency
of dosing. ( 2.2, 8.7)
Renal impairment: Consider reducing the dose and/or frequency. ( 2.3,
8.6)
Tablets: 100 mg, 150 mg, 200 mg. ( 3)
Seizure disorder. ( 4, 5.3)
Current or prior diagnosis of bulimia or anorexia nervosa. ( 4, 5.3)
Abrupt discontinuation of alcohol, benzodiazepines, barbiturates,