Schedule H

Oral

• Tablets: 4 mg

⚠️ Note: Reboxetine has limited availability in India and may not be widely marketed. Confirm availability through pharmacy sources before prescribing.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD) in Adults

Parameter Recommendation

Starting dose 4 mg twice daily (morning and evening)

Titration May increase by 2 mg/day increments after 3–4 weeks if response inadequate

Usual maintenance dose 8–10 mg/day in 2 divided doses

Maximum dose 12 mg/day

Clinical notes:

• Activating antidepressant — administer earlier in the day to minimise insomnia

• Therapeutic effect may take 2–4 weeks to manifest

• Gradual tapering recommended on discontinuation

• Particularly useful when fatigue and psychomotor retardation are prominent symptoms

Secondary Indications – Adults Only (Off-label, if any)

1. Attention Deficit Hyperactivity Disorder (ADHD) in Adults — OFF-LABEL

• Dose: 4 mg twice daily; may titrate to 8–10 mg/day

• Duration: Individualised; reassess response every 3 months

• Specialist only

• Evidence: Small RCTs and case series; not first-line

1. Panic Disorder — OFF-LABEL

• Dose: Start 2 mg twice daily; titrate to 4–6 mg twice daily over 2–4 weeks

• Duration: Minimum 8–12 weeks trial

• Specialist only

• Evidence: Limited controlled data; may be considered when SSRIs not tolerated

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Reboxetine is not approved for paediatric use in India.

Secondary Indications – Paediatrics (Off-label, if any)

Not recommended — Insufficient safety and efficacy data in children and adolescents.

Age restriction: Not recommended below 18 years. No robust paediatric dosing guidelines available. Use only under exceptional specialist psychiatric supervision if no alternatives exist.

• Hypersensitivity to reboxetine or any excipient

• Concomitant use with MAO inhibitors or within 14 days of MAOI discontinuation

• Narrow-angle glaucoma (untreated)

• Urinary retention (acute)

• History of seizures or conditions lowering seizure threshold

• Suicidal ideation — heightened risk in early treatment phase

• Prostatic hypertrophy — risk of urinary retention

• Cardiovascular disease — may increase heart rate and blood pressure

• Bipolar disorder — risk of manic switch; screen before initiating

• Hypokalemia or hypomagnesemia — correct before starting

• Elderly patients — increased sensitivity to adverse effects

• Concurrent use of other noradrenergic agents

• Avoid abrupt discontinuation

Parameter Recommendation

Risk category Limited human data; avoid unless essential

Preferred alternatives Sertraline generally preferred in Indian obstetric practice

When may be used Only if benefit clearly outweighs risk; specialist psychiatric supervision mandatory

Monitoring Neonatal adaptation syndrome if used near term; monitor fetal growth

Parameter Recommendation

Compatibility Not recommended — insufficient safety data

Preferred alternatives Sertraline (better studied in lactation)

Levels in milk Unknown; presumed low based on pharmacokinetics

Infant monitoring Sedation, irritability, poor feeding, weight gain

• Starting dose: 2 mg twice daily

• Titration: Slow — increase at intervals of 2 weeks or longer

• Maximum dose: Generally limit to 8 mg/day

• Extra risks:

• Orthostatic hypotension

• Urinary retention

• Falls

• Cognitive effects

• Reduced renal clearance may increase drug exposure

Interacting Drug Effect/Risk Management

MAO inhibitors (phenelzine, tranylcypromine, selegiline) Risk of hypertensive crisis and serotonin syndrome Contraindicated; 14-day washout required

Linezolid MAOI-like effect; hypertensive crisis risk Avoid combination

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) Increased reboxetine levels and toxicity Reduce reboxetine dose; monitor closely

Ergot derivatives Enhanced vasoconstrictive effects Avoid combination

Interacting Drug Effect/Risk Management

Carbamazepine, phenytoin CYP3A4 induction reduces reboxetine levels Monitor efficacy; may need dose increase

Rifampicin Reduced reboxetine efficacy Consider alternative antidepressant

Fluoxetine, paroxetine CYP2D6 inhibition may increase reboxetine levels Monitor for toxicity

Beta-blockers Potential additive effects on heart rate and blood pressure Monitor cardiovascular parameters

Anticholinergics Additive urinary retention and cognitive effects Minimise combined use

Potassium-depleting diuretics May worsen hypokalemia Monitor electrolytes

• Dry mouth

• Constipation

• Insomnia

• Sweating (hyperhidrosis)

• Dizziness

• Tachycardia

• Urinary hesitancy

• Nausea

• Headache

Note: Most adverse effects are dose-dependent and may attenuate with continued therapy.

• Seizures — discontinue immediately

• Acute urinary retention — may require catheterisation

• Hypertensive crisis (especially in overdose or with interacting drugs)

• Manic or hypomanic switch — discontinue and reassess

• Suicidal ideation or behaviour — especially in younger adults; requires close monitoring

• Allergic reactions (rare)

Phase Parameters

Baseline Blood pressure, heart rate, psychiatric history (bipolar screening, suicidality), renal and hepatic function, electrolytes

After initiation BP and heart rate at 1–2 weeks; assess for suicidal ideation weekly for first month; urinary symptoms

Long-term Periodic BP monitoring; weight; mood assessment; urinary function in at-risk patients

⚠️ Limited Availability

• Edronax® (reported but availability unconfirmed)

• Norebox® (Intas) — verify current availability

Note: Market presence is limited; confirm with local distributors before prescribing for long-term therapy.

• Not listed in NLEM 2022

• Not under DPCO price control

• Limited availability in government supply chains

• Pricing may vary significantly by region and supplier

• Selective noradrenergic mechanism — useful when SSRIs cause sedation, sexual dysfunction, or weight gain

• Activating profile — beneficial for depression with fatigue and anergy; avoid in anxious or agitated depression

• Administer doses in morning and early afternoon to minimise insomnia

• Higher rates of dry mouth and urinary hesitancy compared to SSRIs — counsel patients

• Less effective for comorbid anxiety compared to SSRIs or SNRIs

• No significant QT prolongation risk — relatively cardiac-safe option apart from BP/HR effects

• Due to limited availability in India, ensure reliable supply before initiating long-term therapy

reboxetine; antidepressant; NaRI; noradrenaline reuptake inhibitor; depression; ADHD; limited availability India; activating antidepressant; urinary retention; psychiatry

RxIndia v0.2 — 13 Jan 2025

• CDSCO database (formulation registration — limited)

• Indian Pharmacopoeia

• NLEM 2022 — NOT listed

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition

• AIIMS Psychiatry protocols

• International RCTs for off-label indications (ADHD, panic disorder)