Bupropion (Wellbutrin) is an NDRI (Norepinephrine dopamine reuptake inhibitor). It is an atypical antidepressant medicine.

Bupropion is used to treat the following conditions:

• Major depressive disorder

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

• As an aid to Smoking cessation (12-hour extended-release [sustained release; Zyban]).

• Off Label Use of Bupropion in Adults:

  • Attention-deficit/hyperactivity disorder;

  • Bipolar depression;

  • Selective serotonin reuptake inhibitor-induced sexual dysfunction, augmentation

Bupropion Dose in Adults

Note:

• It is available as hydrochloride and hydrobromide salts.
• Bupropion hydrochloride 150 mg = 174 mg of bupropion hydrobromide.
• Bupropion is available as immediate-release, 12-hour extended-release (sustained-release), and 24-hour extended-release tablets.

Bupropion Dose in the treatment of Attention-deficit/hyperactivity disorder (off-label):

• 12-hour extended-release (sustained-release):

  • Start with 100 mg orally once a day in the morning.
  • Increase in 100 mg/day increments at intervals of 3 to 4 weeks based on response and tolerability (max 200mg twice daily).

• 24-hour extended-release:

  • 150 mg orally once a day in the morning for 1 week.
  • Increase to 300 mg once daily for 3 weeks (max 450mg/day)

Dose in the treatment of Bipolar depression (off-label):

• 12-hour extended-release (sustained-release):

  • Start with 100 mg orally once a day as an adjunct to a mood stabilizer.
  • Increase based on response and tolerability at 2- week intervals
  • The maximum dose is 450 mg/day in 2 divided doses.

Dose in the treatment of the major depressive disorder (unipolar):

Note: Use the lowest effective dose. Slower dose titrations may be indicated based on the patient care setting, symptom severity, and concern for side effects. May also be used as an alternative agent for patients with SSRI-induced sexual dysfunction.

• Immediate release:

  • Start with 100 mg orally two times a day.
  • The dose may be increased to 100 mg 3 times a day after 3 days.
  • The maximum dose is 450mg/day, not exceeding 150 mg in a single dose.

• 12-hour extended-release (sustained-release):

  • 150 mg orally daily in the morning.
  • If tolerated, after 3 days, may increase to a target dose of 150 mg two times a day
  • The maximum dose is 200mg two times a day, not exceeding 200 mg in a single dose.

• 24-hour extended-release: 

  • Hydrochloride salt:
    • 150 mg orally once a day in the morning.
    • If tolerated, may increase as early as 4th day of dosing to 300 mg once daily.
    • If no clinical improvement after 2 weeks, may increase to 450 mg once daily.
  • Hydrobromide salt:
    • 174 mg orally once daily in the morning.
    • May increase as early as day 4 of dosing to 348 mg once daily (target dose).

Dose in the treatment of Seasonal affective disorder (SAD):

• 24-hour extended-release:
  • Hydrochloride salt:
    • 150 mg orally once a day in the morning.
    • If tolerated, may increase after 7 days to 300 mg once daily in the morning.
  • Hydrobromide salt:
    • 174 mg orally once a day in the morning.
    • If tolerated, may increase after 7 days to 348 mg once daily in the morning.

Note:

• Prophylactic treatment should be reserved for patients with frequent depressive episodes and/or significant impairment.
• Start treatment prior to the onset of symptoms in the autumn, and discontinue in early spring with dose tapering.
• Doses >300 mg daily (hydrochloride salt) or >348 mg daily (hydrobromide salt) have not been studied in SAD.

Dose in the treatment/ augmentation of Selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction (off label):

• 12-hour extended-release (sustained-release):
  • Initial: 150 mg orally once daily for the first 3 days.
  • Increase to 150 mg two times a day, based on response and tolerability.

Dose in the treatment of Smoking cessation:

Note:

• It may be used as monotherapy or in combination with nicotine replacement therapy:

• 12-hour extended-release (sustained-release):

  • 150 mg orally once daily for 3 days.
  • Increase to 150 mg two times a day to a maximum dose of 300 mg/day
  • Consider using 150mg once a day in patients who do not tolerate titration to full dose.

Note:

• Therapy should begin at least 1 week before the target quit date.
• Target quit dates are generally in week 2 of the treatment.
• After 7 - 12 weeks If patient successfully quits, may consider ongoing maintenance therapy for up to 1 year(or more based on prior quit attempts) based on individual patient risk: benefit.
• Those who don't show effect by 7th week are less likely to respond, consider using a combination of alternative therapy in those patients.

• ---

  Dosing conversion:

  • Immediate-, 12-hour (SR), and 24-hour (ER) formulations (hydrochloride salt):

    • Convert using same total daily dose, but adjust the frequency as indicated for immediate (3 to 4 times daily), 12-hour extended (SR) (twice daily), or 24-hour extended (once a day) release products.

  • Hydrochloride salt formulation (immediate release, 12-hour (sustained-release), or 24-hour extended-release) to hydrobromide salt formulation (extended-release):

    • Bupropion hydrochloride 150 mg daily = to bupropion hydrobromide 174 mg once daily.
    • Bupropion hydrochloride 300 mg daily = to bupropion hydrobromide 348 mg once daily.
    • Bupropion hydrochloride 450 mg daily = to bupropion hydrobromide 522 mg once daily.

• MAOI recommendations:

  • Switching to or from an MAOI antidepressant:
    • At least a 14 days drug-free interval should be allowed when switching from an MAOI to bupropion and vice versa.
    • Cross titration is contraindicated when switching from an MAOI to an SSRI and vice versa.

• Discontinuation of therapy:

  • Gradual tapering over 2 to 4 weeks is recommended.
  • Withdrawal symptoms from abrupt discontinuation are unlikely as bupropion has minimal serotonergic activity.

Bupropion Dose in Children

Dose in the treatment of Attention-deficit/hyperactivity disorder: 

• Children ≥6 years and Adolescents:

  • Immediate-release, hydrochloride salts:

    • 3 mg/kg/day orally in 2 to 3 divided doses to a maximum initial dose of 150 mg/day.
    • Titrate the dose as needed to a maximum daily dose of 6 mg/kg/day or 300 mg/day with no single dose more than 150 mg.

  • 12-hour sustained-release and 24-hour extended-release, hydrochloride salts:

    • May be used in place of regular tablets once the daily dose is titrated.

Depression, refractory to SSRIs:

Note:

• Maybe most beneficial in patients with comorbid
• ADHD,
• conduct disorder,
• substance abuse problems or
• who want to quit smoking
• Treatment should be periodically evaluated at appropriate intervals to ensure the lowest effective dose is used.

• Immediate release, hydrochloride salt:

  • Children 8 to ≤11 years:
    • 37.5 mg twice a day (max 400mg/day)

12-hour sustained-release, hydrochloride salt:

Children ≥11 years and Adolescents:

• Initial:
  • 2 mg/kg up to 100 mg orally administered as a morning dose.
  • may titrate as needed every 2 to 3 weeks using the following titration schedule:
    • Step 2:
      • Increase up to 3mg/kg every morning
    • Step 3:
      • Increase up to 3 mg/kg every morning & 2 mg/kg at 5 pm
    • Step 4:
      • Increase up to 3 mg/kg/dose 2 times a day; maximum dose: 150 mg;

24-hour extended-release, hydrochloride salt:

Children ≥12 years and Adolescents:

• 150 mg once a day.
• may titrate after 2 weeks to 300 mg once daily (max 400mg/day)

Smoking cessation:

Adolescents more than or equal to 14 years and more than or equal to 40.5 kg:

• 12-hour sustained-release, hydrochloride salt:

  • Initial: 150 mg once a day orally for 3 days
  • Increase to 150 mg two times a day.
  • Initiate while the patient is still smoking in order to allow the drug to reach steady-state levels prior to smoking cessation.
  • Generally, patients should stop smoking during the second week of treatment.
  • The maximum daily dose: 300 mg/day;

Pregnancy Risk Factor: C

• Studies on animal reproduction have shown that there are adverse events.
• In vitro studies showed that Bupropion and its metabolites could cross the placenta.
• Bupropion use during pregnancy has not been associated with an increased risk of congenital malformations. However, there are inconsistent data regarding cardiovascular malformations.
• It is not known if long-term effects of development and behavior will be observed.
• The American Psychiatric Association states that medication treatment can have risks, but should be weighed against untreated depression and other options.
• Patients at high risk should be re-instated on antidepressants immediately after delivery

Breast-Feeding with Bupropion

• Breast milk contains bupropion and active metabolites.
• If the RID for psychotropic drugs is less than 5%, breastfeeding should not be considered.
• Bupropion has been linked to sleep disturbances and seizures in nursing infants.

Bupropion Dose in Renal Disease:

Use with caution. No specific recommendations provided. May decrease dose and frequency.

Bupropion dose in liver disease:

• Mild impairment (Child–Pugh score 5-6:
  • Take care.
  • Reduce doses and/or frequency
• Moderate to severe impairment, with severe hepatic dysfunction (Child-Pugh score 7-15)
  • Extreme caution is advised.
  • Do not exceed the following maximum dose:
    • Hydrobromide salt: 174mg every other day
    • Salt of hydrochloride75 mg daily, immediate release
    • Extended 12-hour release (sustained-release).100 mg daily, 150 mg every other days
    • Extended-release 24-hours150 mg every other days

Common side effects of Bupropion (Wellbutrin)

• Cardiovascular:

  • Tachycardia

• Central nervous system:

  • Insomnia
  • headache
  • agitation
  • dizziness

• Dermatologic:

  • Diaphoresis

• Endocrine & metabolic:

  • Weight loss

• Gastrointestinal:

  • Xerostomia
  • Constipation
  • nausea and vomiting

• Neuromuscular & skeletal:

  • Tremor

• Ophthalmic:

  • Blurred vision

• Respiratory:

  • Nasopharyngitis
  • pharyngitis
  • rhinitis

Less common side effects of bupropion:

• Cardiovascular:

  • Palpitations
  • cardiac arrhythmia
  • chest pain
  • flushing
  • hypertension
  • hypotension

• Central nervous system:

  • Lack of concentration
  • confusion
  • anxiety
  • hostility
  • nervousness
  • abnormal dreams
  • abnormal sensory symptoms
  • sleep disorder
  • migraine
  • irritability
  • memory impairment
  • drowsiness
  • pain
  • akathisia
  • central nervous system stimulation
  • paresthesia
  • twitching
  • dystonia
  • abnormality in thinking
  • depression

• Dermatologic:

  • Skin rash
  • pruritus
  • xeroderma
  • urticaria

•  Endocrine & metabolic:

  • Weight gain
  • menstrual disease
  • decreased libido
  • hot flash

• Gastrointestinal:

  • Abdominal pain
  • diarrhea
  • flatulence
  • anorexia
  • dysgeusia
  • increased appetite
  • vomiting
  • dyspepsia
  • oral mucosa ulcer
  • dysphagia

• Genitourinary:

  • Urinary frequency
  • urinary urgency
  • vaginal hemorrhage
  • urinary tract infection

• Hypersensitivity:

  • Hypersensitivity reaction

• Infection:

  • Infection

• Neuromuscular & skeletal:

  • Myalgia
  • arthralgia
  • asthenia
  • neck pain
  • arthritis
  • dyskinesia

• Ophthalmic:

  • Diplopia

• Otic:

  • Tinnitus
  • auditory disturbance

• Renal:

  • Polyuria

• Respiratory:

  • Upper respiratory infection
  • sinusitis
  • cough
  • increased cough
  • epistaxis
  • bronchitis

• Miscellaneous:

  • Accidental injury
  • fever

Contraindications to Bupropion (Wellbutrin)

• Allergy reactions to bupropion and any component of the formulation
• seizure disorder
• History of anorexia/bulimia
• Patients who have had to abruptly stop using ethanol or other sedatives such as benzodiazepines or barbiturates or antiepileptic drugs
• MAO inhibitors should be used in conjunction with therapy within 14 days after the treatment is initiated or stopped.
• Linezolid or intravenous Methylene Blue given to patient
• Arteriovenous malformation
• Head injury can cause severe pain
• Struggling stroke
• CNS Tumor
• CNS infection

Warnings and Precautions

• Major psychiatric Warnings (use for treating psychiatric disorders).

  • Suicidal thoughts/behavior (use in the treatment of psychiatric disorders), especially during the first 1 to 2 months of therapy, or during periods when dosage adjustments (increases and decreases) are made.
  • Families should be in close contact with the doctor and keep them informed.
  • It is possible to discontinue or modify drug therapy if depression is severe and sudden suicidal thoughts are present.
  • Prescribe the lowest amount of medication consistent with good patient care.
  • Beware of adverse side effects

• Stimulation of the CNS:

  • CNS stimulation may cause restlessness, anxiety, insomnia, or anorexia.

• Cognitive impairment:

  • Some patients may experience motor or cognitive impairment, which can impair their physical and mental abilities.
  • Patients should be warned about tasks that require mental alertness, such as operating machinery or driving.

• Hypersensitivity reactions:

  • Anaphylactoid/anaphylactic reactions have been reported, with symptoms such as pruritus and urticaria, angioedema and dyspnea.
  • Rarely, serious reactions such as anaphylactic shock, Stevens-Johnson syndrome, and erythema multiforme have been reported.
  • Reports of myalgia, arthralgia and fever with rash, as well as other symptoms that could be indicative of delayed hypersensitivity, similar to serum sickness, have been made.

• Hypertension:

  • Hypertension and elevated blood pressure can occur.
  • Patients with and without preexisting hypertension have experienced events.
  • The risk is further increased by the use of monoamine oxidase inhibiters, nicotine replacement or other drugs that enhance dopaminergic and noradrenergic activity.
  • Before treatment, monitor blood pressure and take note of it.

• Hypomania/mania:

  • This can lead to a manic, mixed or hypomanic episode, especially for patients with bipolar disorder and those at high risk.
  • Ask about your family's history.
  •  Bupropion for bipolar disorder is not FDA-approved
• Depression.
  • Use in smoking cessation for neuropsychiatric effects:
    • Patients who have taken bupropion to quit smoking have suffered serious neuropsychiatric effects, including seizures.
    • Changes in mood (eg depression, mania)
    • Psychosis
    • Hallucinations
    • Paranoia
    • Delusions
    • Homicide ideation
    • Hostility
    • Agitation
    • Aggression
    • Anxiety
    • Do not panic
    • suicidal ideation
    • Suicide attempt
    • And completed suicide.

• Ocular effects:

  • Mild pupillary dilation may occur, which can in some cases lead to narrow-angle glaucoma.

• Psychosis:

  • Possible delusions, hallucinations and psychosis.
  • This is most common in patients suffering from underlying mental illness.
  • You can reduce or withdraw treatment if symptoms subside.

• Seizures:

  • Could increase the risk of seizures due to high doses.
  • Patients with a history or history of seizures, as well as patients who have been treated for epilepsy, such as patients who have had their medication abruptly stopped.
  • Extended-release formulations that last 24-hours are not recommended for patients who have high seizure risks (eg, severe stroke, CNS cancer, or severe head injury).

• Be carefulConcurrent use

  • Antipsychotics
  • Antidepressants
  • Theophylline
  • Systemic corticosteroids
  • Stimulants (including cocaine)
  • Anorexiants and other sexy people
  • Hypoglycemic agents or
  • Use ethanol
  • Benzodiazepines
  • Sedatives/hypnotics or
  • Opioids.

• Take careSeizure-potentiating metabolic diseases

  • Hypoglycemia
  • Hyponatremia
  • Hepatic impairment severe, and
  • Hypoxia.
  • If a seizure happens during therapy, discontinue use permanently

• Sexual dysfunction:

  • Bupropion has a lower incidence of sexual dysfunction than SSRIs.

• ADHD (off-label usage)

  • Before initiating stimulant medication, all children with ADHD should undergo a complete cardiovascular evaluation to determine if they are at risk for sudden cardiac death.

• Cardiovascular disease

  • Patients with history of hypertension or cardiovascular disease should be cautious.
  • There have been reports of bupropion-induced hypertension, including some severe cases, with both bupropion alone or in combination with nicotine transdermal system.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious; you may need to reduce the dose or frequency.

• Renal impairment

  • Patients with impaired renal function should be cautious. Consider reducing the dose or frequency.

• For the elderly:

  • Be careful with the elderly.
  • Chronic dosing may pose a greater risk to elderly patients.
  • Reduce the dose.

• Missuse/abuse

  • Doses higher than the prescribed dose may cause increased motor activity, agitation/excitement and euphoria.

• Electroconvulsive therapy, ECT:

  • May increase the risk associated with ECT
  • If possible, consider quitting ECT treatment before you start it 

Bupropion: Drug Interaction

Monitoring Parameters:

• Weight of the body
• Depression and mental health
• Suicidal ideation, especially at the beginning of therapy and when dosages are increased or reduced
• Anxiety
• Social functioning
• Mania,
• Panic attacks
• Blood pressure (baseline, periodically especially when used with nicotine transdermal substitute);
• Hepatic and renal function
• If ADHD treatment is being used, it is important to assess the cardiovascular risk.

Monitor

• Heart rate
• Blood pressure and
• Consider getting an ECG before you start.

How to administer bupropion?

• You can take it orally, without any consideration for meals.

Release immediately:

• Take 3-4 doses daily, with at least 6 hours between each one Maximum single dose is 150mg

Extended 12-hour release (sustained-release).

• Take 2 doses daily, with at least 8 hours between each one. Maximum single dose is 200mg

Extended-release 24-hours

• Take one dose daily, with at most 24 hours between each subsequent dose.

Administration: Children

• You can take it orally, without any consideration for meals. Take the tablet whole.
• The extended-release tablet's insoluble shell may be left intact during GI transit, but is eventually eliminated by the feces.

Release immediately:

• Between each dose, wait at least 6 hours.

Sustained-release

• You should usually take 2 doses daily, with at least 8 hours between each one.

Extended-release

• Take one dose daily, with at most 24 hours between each subsequent dose 

Mechanism of action of Bupropion:

MOA is still not fully understood. It acts as a weak inhibitor on neuronal dopamine uptake ( NDRI), but does not inhibit MAO, or the reuptake serotonin.

The beginning of action1 to 2 Weeks

Time of action1 to 2 Days

AbsorptionRapid

Protein binding84%

Metabolism: Hepatic.

Distribution: 3-4 hours

Excretion

Salt of Bupropion Hydrochloride: 21 Hours after multiple dosing (+-9 hours);

• After a single dose, metabolites:
  • Hydroxybupropion: 20 +- 5 Hours
  • Erythrohydrobupropion: 33 +- 10 Hours
  • Threohydrobupropion37 +- 13 Hours

Salt of hydrobromide: 21 +- 7 Hours

• Metabolites
  • Hydroxybupropion: 24+- 5 hours
  • Erythrohydrobupropion: 31 +- 8 Hours
  • Threohydrobupropion: 51 +- 9 Hours

Time until peak serum concentration

• Bupropion: Immediate Release:
  • Within 2 hours
• Extended-release:
  • 12-hour
• Sustainable-release
  • Within 3 hours
• Extended-release
  • 24-hour
• Hydroxybupropion is the Metabolite
  • Instant-release: 3 Hours
  • Extended-release: 6 to 7 hours

Excretion: Urine 87%, feces 10%  

Bupropion International brands:

ACT BuPROPion XL MYLAN-BuPROPion XL NOVO-BuPROPion SR PMS-BuPROPion SR RATIO-BuPROPion SR SANDOZ BuPROPion Wellbutrin SR Wellbutrin XL Abstain SR Betetrim Bupep SR Buprotrin Buxon Deppreo Elontril Fumipan Funnix Le Fu Ting Nicopion Nicostop Prewell Prexaton Quomen Vixadep Wellbutrin Wellbutrin Retard Wellbutrin SR Wellbutrin XL Wellbutrin XR Wellinta Yue Ting Zyban LP Zyban SR Zyban Sustained-Release Zylexx SR Zyntabac 

Bupropion brands in Pakistan: