Schedule H

Oral

• Bupropion hydrochloride immediate-release (IR) tablets: 75 mg, 100 mg

• Bupropion hydrochloride sustained-release (SR) tablets: 150 mg

• Bupropion hydrochloride extended-release (XL) tablets: 150 mg, 300 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Using Extended-Release (XL) Formulation (Preferred):

Parameter Recommendation

Starting dose 150 mg once daily in the morning

Titration Increase to 300 mg once daily after minimum 4 days if tolerated and clinically indicated

Usual maintenance dose 300 mg once daily

Maximum dose 450 mg once daily (specialist supervision only; seizure risk increases significantly above 300 mg)

Using Sustained-Release (SR) Formulation:

Parameter Recommendation

Starting dose 150 mg once daily in the morning

Titration Increase to 150 mg twice daily (minimum 8-hour interval) after 3–4 days

Usual maintenance dose 150 mg twice daily (300 mg/day total)

Maximum dose 200 mg twice daily (400 mg/day total); single dose should not exceed 200 mg

Using Immediate-Release (IR) Formulation:

Parameter Recommendation

Starting dose 100 mg twice daily

Titration Increase to 100 mg three times daily after 3–4 days if needed

Usual maintenance dose 100 mg three times daily (300 mg/day total)

Maximum dose 150 mg three times daily (450 mg/day total); single dose should not exceed 150 mg

Clinical Notes:

• Administer doses in morning and early afternoon to minimise insomnia risk

• Allow minimum 6–8 hours between doses (SR/IR formulations)

• Do not crush, chew, or break SR/XL tablets

• Onset of antidepressant effect typically 2–4 weeks

• May be used as monotherapy or adjunct to SSRIs in treatment-resistant depression

1. Smoking Cessation

Using Sustained-Release (SR) Formulation:

Parameter Recommendation

Starting dose 150 mg once daily for first 3 days

Titration Increase to 150 mg twice daily (minimum 8-hour interval) from day 4

Usual maintenance dose 150 mg twice daily (300 mg/day total)

Maximum dose 300 mg/day

Treatment Protocol:

• Begin treatment 1–2 weeks before target quit date

• Continue for 7–12 weeks; may extend up to 6 months for relapse prevention

• Combine with behavioural support/counselling for optimal outcomes

• May be used with nicotine replacement therapy (monitor blood pressure)

Clinical Notes:

• Set definite quit date within 7–14 days of starting bupropion

• If no significant progress by week 7, reassess continuation

• Specialist initiation recommended for patients with psychiatric comorbidities

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Attention Deficit Hyperactivity Disorder (ADHD) Starting: 150 mg XL once daily; Titration: increase to 300 mg XL once daily after 1 week; Maximum: 450 mg/day Long-term; reassess periodically OFF-LABEL — Specialist only. Modest efficacy demonstrated in RCTs. Consider when stimulants contraindicated or not tolerated. Monitor cardiovascular parameters and anxiety.

Sexual Dysfunction (SSRI-induced) 150–300 mg XL once daily as adjunct Ongoing with SSRI therapy OFF-LABEL — Specialist only. Based on clinical trials showing improvement in SSRI-induced sexual dysfunction. May augment antidepressant effect.

Bipolar Depression (adjunct only) 150–300 mg XL once daily; always with mood stabiliser Duration based on clinical response OFF-LABEL — Specialist only. Never use as monotherapy. Lower switch rate to mania compared to SSRIs per some evidence. Requires careful psychiatric monitoring.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Bupropion is not approved for routine use in children and adolescents in India.

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

ADHD ≥12 years Starting: 1–3 mg/kg/day OR 100–150 mg/day in divided doses; Titration: increase gradually over 2–4 weeks; Maximum: 6 mg/kg/day or 300 mg/day (whichever is lower) OFF-LABEL — Child psychiatrist supervision mandatory. May consider when stimulants contraindicated. Limited efficacy data in paediatric ADHD.

Depression (adolescent) ≥12 years Starting: 150 mg XL once daily; Maximum: 300 mg/day OFF-LABEL — Specialist only. Not first-line; SSRIs preferred. Enhanced suicidality monitoring required per FDA black box warning equivalent.

Minimum Age Statement: Not recommended below 12 years of age. Use in adolescents 12–18 years only under child and adolescent psychiatrist supervision with documented rationale.

Safety Monitoring:

• Weekly assessment for suicidal ideation during first month

• Seizure risk assessment before initiation

• Blood pressure monitoring

• Growth and weight monitoring

• Behavioural changes and mood assessment

Note: Active metabolites (hydroxybupropion) accumulate in renal impairment and may increase seizure and adverse effect risk.

• Seizure disorder (current or history of any seizure type)

• Conditions that lower seizure threshold: CNS tumours, severe head trauma, history of CNS infection

• Current or prior diagnosis of bulimia nervosa or anorexia nervosa

• Abrupt discontinuation of alcohol in alcohol-dependent patients

• Abrupt discontinuation of benzodiazepines, barbiturates, or antiepileptic drugs

• Concurrent use of MAO inhibitors (including linezolid, methylene blue IV) — minimum 14-day washout required

• Concurrent use of other bupropion-containing products

• Known hypersensitivity to bupropion or any excipient

• Severe hepatic impairment (Child-Pugh C)

• Hypertension (pre-existing or treatment-emergent) — monitor blood pressure regularly

• Cardiovascular disease — limited safety data; use with caution

• History of psychiatric conditions: bipolar disorder, psychosis, severe anxiety — may precipitate manic episode or worsen symptoms

• Elderly patients — increased sensitivity to CNS effects; start low

• Renal impairment — accumulation of active metabolites

• Mild-moderate hepatic impairment — requires dose reduction

• Diabetes mellitus on insulin or oral hypoglycaemics — bupropion may affect glucose control; dose adjustments of antidiabetic agents may be needed

• Patients with factors predisposing to seizures: concurrent medications lowering seizure threshold, excessive alcohol use, stimulant use, history of head trauma

• Angle-closure glaucoma — mydriatic effect reported rarely

• Concomitant use with nicotine replacement therapy — monitor blood pressure

Parameter Recommendation

Safety Category Limited human data; animal studies do not indicate direct teratogenicity; some observational data suggest possible increased risk of cardiac malformations (inconclusive)

Preferred Alternatives Sertraline, escitalopram (SSRIs) are preferred first-line antidepressants during pregnancy per Indian obstetric and psychiatric practice

When to Use May be considered if patient was stable on bupropion pre-conception or if SSRIs contraindicated/ineffective; requires psychiatry and obstetric input

Monitoring Fetal cardiac assessment (if exposed in first trimester); neonatal monitoring for irritability or feeding difficulties if used near term

Parameter Recommendation

Breastfeeding Compatibility Use with caution; bupropion and metabolites are excreted in breast milk

Drug Levels in Milk Low to moderate; relative infant dose estimated 0.2–2%

Preferred Alternatives Sertraline, paroxetine preferred for breastfeeding mothers with depression

Infant Monitoring Monitor for irritability, poor feeding, seizures (rare), and sleep disturbances

Parameter Recommendation

Starting dose 150 mg once daily (XL) or 100 mg once daily (IR); lower than standard adult dose

Titration Slower titration over 1–2 weeks; assess tolerance before increasing

Additional Risks Increased sensitivity to CNS effects (agitation, insomnia, confusion); higher risk of seizures; impaired renal function leading to metabolite accumulation; hypertension; falls risk

Monitoring Blood pressure, renal function, mental status, sleep quality

Interacting Drug Mechanism/Effect Management

MAO inhibitors (phenelzine, tranylcypromine, selegiline, linezolid, IV methylene blue) Risk of hypertensive crisis and serotonin toxicity Contraindicated; minimum 14-day washout before or after MAOI

Drugs lowering seizure threshold (tramadol, meperidine, antipsychotics, systemic corticosteroids, theophylline, quinolones) Additive seizure risk Avoid combination if possible; if essential, use lowest effective bupropion dose with close monitoring

Tamoxifen Bupropion inhibits CYP2D6; reduces conversion of tamoxifen to active metabolite (endoxifen) Avoid concurrent use; consider alternative antidepressant (venlafaxine, escitalopram)

Alcohol Increased seizure risk; may lower seizure threshold Avoid excessive alcohol; warn against binge drinking; abrupt alcohol cessation also contraindicated

Thioridazine CYP2D6 inhibition by bupropion increases thioridazine levels; risk of QT prolongation and arrhythmias Avoid concurrent use

Interacting Drug Effect Management

SSRIs (fluoxetine, paroxetine, sertraline) Combination may increase efficacy in resistant depression but increases seizure risk and serotonergic effects May be combined under specialist supervision; monitor for agitation, tremor, seizures

CYP2B6 inducers (carbamazepine, phenytoin, phenobarbital, rifampicin) Increased bupropion metabolism; reduced efficacy May need higher bupropion doses; monitor clinical response; alternative inducers-free regimens preferred

CYP2D6 substrates (metoprolol, propafenone, flecainide, atomoxetine, desipramine, venlafaxine) Bupropion inhibits CYP2D6; increased levels of these drugs Reduce dose of CYP2D6 substrate if initiating bupropion; monitor for toxicity

Nicotine replacement therapy Additive effect on blood pressure Monitor blood pressure; beneficial combination for smoking cessation

Warfarin Potential for altered INR (mechanism unclear) Monitor INR closely when initiating or discontinuing bupropion

Levodopa, amantadine Additive dopaminergic effects; increased risk of neuropsychiatric adverse effects Use with caution; monitor for agitation, restlessness, psychosis

Ritonavir May decrease bupropion levels through CYP induction Monitor antidepressant efficacy

• Insomnia (most common; dose-related)

• Dry mouth

• Headache

• Nausea

• Dizziness

• Agitation or anxiety (usually transient)

• Tremor

• Constipation

• Excessive sweating

• Weight loss (or weight neutrality)

• Tachycardia

Adverse Effect Clinical Significance

Seizures Dose-dependent; risk ~0.4% at 300 mg/day, increases significantly above 450 mg/day; immediate discontinuation required; hospitalisation for evaluation

Neuropsychiatric events Psychosis, hallucinations, paranoia, mania/hypomania; discontinue and refer for psychiatric evaluation

Suicidal ideation Particularly in young adults and adolescents; enhanced monitoring required in first weeks of therapy

Severe hypersensitivity reactions Stevens-Johnson syndrome (rare), angioedema, urticaria, serum sickness-like reaction; immediate discontinuation required

Hypertensive crisis Rare; particularly with MAOI combination; requires emergency management

Angle-closure glaucoma Rare; presents with eye pain, visual changes, nausea; urgent ophthalmology referral

Baseline:

• Blood pressure

• Mental health assessment including suicide risk evaluation

• Seizure risk assessment (history, medications, alcohol/substance use)

• Renal function (if impairment suspected)

• Hepatic function (if impairment suspected)

• Weight

After Initiation/Dose Change:

• Mental status assessment at 1–2 weeks (mood, anxiety, suicidal ideation)

• Blood pressure at 1–2 weeks

• Sleep quality assessment

• Adverse effect review

Long-term:

• Blood pressure every 3–6 months

• Weight monitoring (usually stable or decreased)

• Mental health review every 3–6 months

• Reassessment of treatment need annually

• Periodic review of seizure risk factors

• Bupron SR® (Sun Pharma) — 150 mg sustained-release tablets

• Bupron XL® (Sun Pharma) — 150 mg, 300 mg extended-release tablets

• Zyban® (GlaxoSmithKline) — 150 mg sustained-release tablets (limited availability)

• Aplenzin® equivalent — NOT AVAILABLE in India

• Wellbutrin® — NOT AVAILABLE in India (not marketed)

Note: No fixed-dose combinations with bupropion are marketed in India.

• Not included in NLEM

• Not under NPPA price control

• Limited availability in government hospital formularies; primarily available through private purchase

• Sexual dysfunction advantage: Bupropion has minimal sexual side effects compared to SSRIs — consider as first-line when sexual dysfunction is a significant concern or as adjunct when SSRI-induced sexual dysfunction occurs

• Weight consideration: Unlike most antidepressants, bupropion is associated with weight loss or weight neutrality — useful in patients where weight gain is problematic

• Seizure threshold: Never exceed 450 mg/day; avoid in any patient with elevated seizure risk; single doses should not exceed 150 mg (IR) or 200 mg (SR)

• Timing of doses: Always prescribe morning doses; evening dosing worsens insomnia significantly

• Smoking cessation protocol: Start 1–2 weeks before quit date; combine with behavioural support; duration 7–12 weeks; may use with nicotine patches if blood pressure monitored

• Formulation matters: SR and XL formulations are NOT interchangeable on a mg-to-mg basis; XL once-daily dosing improves adherence

bupropion; depression; MDD; smoking cessation; NDRI; seizure-risk; sexual-dysfunction; weight-neutral; psychiatry; tobacco-dependence

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychiatry Drug Formulary

• NIMHANS Clinical Practice Guidelines

• ICMR Guidelines on Tobacco Cessation

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs on ADHD indication (off-label reference only)