Usual Adult Dose for Depression

BUPROPION HYDROCHLORIDE:
Immediate-release tablets:

• Initial dose: 100 mg orally twice a day, increase if necessary after 3 days to 100 mg orally three times a day.
• Maintenance dose: 100 mg orally three times a day
• Maximum dose: 450 mg/day in up to 4 divided doses; single doses should not exceed 150 mg

Sustained-release tablets:

• Initial dose: 150 mg orally once a day in the morning, increase if necessary after 3 days to 150 mg orally twice a day.
• Maintenance dose: 150 mg orally twice a day
• Maximum dose: 400 mg/day; maximum single dose should not exceed 200 mg

Extended-release tablets:

• Initial dose: 150 mg orally once a day in the morning, increase if necessary after 4 days to 300 mg orally once a day.
• Maintenance dose: 300 mg orally once a day
• Maximum dose: 450 mg/day

BUPROPION HYDROBROMIDE:
Extended-release tablets:

• Initial dose: 174 mg orally once a day in the morning, increase if necessary after 4 days to 348 mg orally once a day.
• Maintenance dose: 348 mg orally once a day

Comments:

• Doses of immediate-release oral tablets should be given at least 6 hours apart.
• Doses of sustained-release oral tablets should be given at least 8 hours apart.
• Doses of extended-release oral tablets should be given at least 24 hours apart.
• Dose increases of the immediate-release tablet should not exceed 100 mg per day in a 3-day period.
• So as not to exceed the maximum single dose of 150 mg for immediate-release tablets, a dose of 100 mg orally four times a day (using the 100 mg tablet) may be administered.
• Patients who are taking 300 mg/day for at least 2 weeks (OR are currently taking 450 mg/day) of any formulation may be switched to the extended-release 450 mg dose.
• Bupropion hydrobromide 174 mg oral tablet is equivalent to bupropion hydrochloride 150 mg.
• Patients should be periodically reviewed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Use: Treatment of major depressive disorder

Usual Adult Dose for Seasonal Affective Disorder

BUPROPION HYDROCHLORIDE:
Extended-release tablets:

• Initial dose: 150 mg orally once a day in the morning, increased if necessary after 7 days to 300 mg orally once a day
• Maintenance dose: 150 to 300 mg orally once a day
• Maximum dose: 300 mg/day

BUPROPION HYDROBROMIDE:
Extended-release tablets:

• Initial dose: 174 mg orally once a day, increased if necessary after 7 days to 348 mg orally once a day
• Maintenance dose: 348 mg orally once a day
• Maximum dose: 348 mg/day

Comments:

• Treatment should be initiated in the autumn prior to the onset of depressive symptoms, continued through the winter season, and discontinued in early spring.
• If bupropion hydrochloride 300 mg orally per day is not tolerated, it should be reduced to 150 mg once a day before discontinuing treatment.
• Patients taking bupropion hydrochloride 300 mg orally per day during the autumn-winter season should have their dose tapered to 150 mg once a day for 2 weeks prior to discontinuation.
• When discontinuing bupropion hydrobromide in patients treated with 348 mg orally once a day, the dose should be reduced to 174 mg once a day prior to discontinuation.
• The timing of initiation and treatment duration for seasonal affective disorder should be individualized according to the patient's historical pattern of seasonal major depressive episodes.

Use: Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD)

Usual Adult Dose for Smoking Cessation

BUPROPION HYDROCHLORIDE:
Sustained-release tablets:

• Initial dose: 150 mg orally once a day for 3 days, increased to 150 mg orally twice a day
• Maintenance dose: 150 mg orally twice a day
• Maximum dose: 300 mg/day; maximum single dose should not exceed 150 mg
• Duration of therapy: 7 to 12 weeks

Comments:

• Begin dosing one week before quit day; the target stop date should be set within the first 2 weeks of treatment, preferably in the second week.
• There should be an interval of at least 8 hours between doses.
• May be used with a nicotine transdermal system.
• If there is no effect after 12 weeks, treatment should be discontinued; longer treatment should be guided by the relative benefits and risks for the individual patient.

Use: Aid to smoking cessation treatment

Renal Dose Adjustments

Renal dysfunction (Glomerular filtration rate [GFR] less than 90 mL/min): Consider reducing the dose and/or frequency

Extended-release 450 mg tablets: Not recommended.

Liver Dose Adjustments

BUPROPION HYDROCHLORIDE:
Immediate-release tablets:

• Mild liver dysfunction (Child-Pugh 5 to 6): Consider reducing the dose and/or frequency of dosing.
• Moderate to severe liver dysfunction (Child-Pugh 7 to 15): The maximum dose is 75 mg orally once a day.

Sustained and Extended-release tablets:

• Mild liver dysfunction (Child-Pugh score 5 to 6): Consider reducing the dose and/or frequency of dosing.
• Moderate to severe liver dysfunction (Child-Pugh score 7 to 15): 100 mg orally once a day OR 150 mg orally every other day. The manufacturer product information should be consulted for further guidance.

Extended-release 450 mg tablets: Not recommended.

BUPROPION HYDROBROMIDE:
Extended-release tablets:

• Mild liver dysfunction (Child-Pugh score 5 to 6): Consider reducing the dose and/or frequency of dosing.
• Severe liver dysfunction (Child-Pugh score 7 to 15): 174 mg orally every other day

Dose Adjustments

• Dose adjustments should be made gradually to minimize the risk of seizure.
• Consider reducing the dose and/or frequency in elderly patients.
• Dose adjustments may be necessary when bupropion is coadministered with CYP450 2B6 inhibitors.
• Dosage increases of bupropion may be necessary when coadministered with ritonavir, lopinavir, or efavirenz.
• If bupropion is used concomitantly with a CYP450 inducer, it may be necessary to increase the dose of bupropion.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for extended-release tablet formulations. It includes a medication guide. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
NEUROPSYCHIATRIC REACTIONS DURING SMOKING CESSATION:

• Serious neuropsychiatric reactions have occurred in patients taking bupropion for smoking cessation. The majority of these reactions occurred during bupropion treatment, but some occurred in the context of discontinuing treatment. In many cases, a causal relationship to bupropion treatment is not certain, because depressed mood may be a symptom of nicotine withdrawal. However, some of these symptoms have occurred in patients taking bupropion who continued to smoke.
• The risks of bupropion should be weighed against the benefit of its use. Bupropion has been demonstrated to increase the likelihood of abstinence from smoking for as long as 6 months compared with treatment with placebo. The health benefits of quitting smoking are immediate and substantial.
• Although not all products containing the active ingredient of bupropion are approved as a smoking cessation aid, all patients taking bupropion should be observed for neuropsychiatric reactions and instructed to contact a healthcare provider if such reactions occur.

SUICIDALITY AND ANTIDEPRESSANT DRUGS:

• Although the brands Buproban (R) and Zyban (R) are not indicated for the treatment of depression, they contain the same active ingredient as the antidepressant medications Wellbutrin(R), Wellbutrin SR(R) and Wellbutrin XL(R). Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older.
• In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.
• Advise families and caregivers of the need for close observations and communication with the prescriber.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• All oral formulations should be swallowed whole and not crushed, divided, or chewed.
• Doses may be taken with or without food.

General:

• Give the same total daily dose when possible when switching from immediate-release or sustained-release oral bupropion hydrochloride tablets to extended-release oral bupropion hydrochloride.
• Equivalent daily doses of bupropion hydrobromide and bupropion hydrochloride:
• Bupropion hydrobromide 522 mg is equivalent to 450 mg bupropion hydrochloride.
• Bupropion hydrobromide 348 mg is equivalent to 300 mg bupropion hydrochloride.
• Bupropion hydrobromide 174 mg is equivalent to 150 mg bupropion hydrochloride.
• Periodically review the dose and need for maintenance treatment.
• The full antidepressant effect of this drug may not be evident for 4 weeks or longer.
• Monitoring for potential treatment-emergent elevations of blood pressure is recommended if combination therapy with nicotine transdermal system is used.
• Prophylactic treatment for seasonal affective disorder is not recommended in patients with infrequent episodes or whose seasonal depressive episodes are not associated with significant impairment.
• Patients are more likely to quit smoking and remain abstinent if they are seen frequently and receive support from their physicians or other healthcare professionals. Physicians should also review the patient's overall smoking cessation program.

Monitoring:

• Cardiovascular: Hypertension
• Hepatic: Liver function
• Neurologic: Seizures
• Psychiatric: Suicidal ideation and behavior; re-emergence or worsening of symptoms of depression

Patient advice:

• If you, your family member, or caregiver notice symptoms such as agitation, hostility, depression, thoughts about suicide or dying, or changes in thinking or behavior that are out of character, contact your health provider right away.
• If you are using this medicine to help you quit smoking, only use it as part of a smoking cessation program.
• Do not drive or operate heavy machinery until you know how this drug affects you.

Frequently asked questions

• How long does it take Wellbutrin XL/SR (bupropion) to work?
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