Schedule H

Oral

• Tablets: 50 mg, 100 mg

• Extended-release formulations: NOT AVAILABLE in India

• Oral suspension: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Obsessive-Compulsive Disorder (OCD)

Fluvoxamine is considered first-line SSRI for OCD in many guidelines due to strong efficacy data.

Parameter Recommendation

Starting dose 50 mg once daily at bedtime

Titration Increase by 50 mg every 4–7 days based on response and tolerability

Usual maintenance dose 100–200 mg/day

Maximum dose 300 mg/day (doses >150 mg/day should be given in divided doses)

Clinical Notes:

• Therapeutic response may take 4–8 weeks; full response often requires 10–12 weeks

• Continue treatment for minimum 1–2 years after symptom control

• Higher doses (200–300 mg/day) often required for optimal OCD response

• Administer larger dose at bedtime if using divided dosing; sedative effect can aid sleep

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 50 mg once daily at bedtime

Titration Increase by 50 mg every 7 days based on response and tolerability

Usual maintenance dose 100–200 mg/day

Maximum dose 300 mg/day (divided doses recommended above 150 mg/day)

Clinical Notes:

• Not typically first-line SSRI for MDD in Indian practice (sertraline, escitalopram preferred)

• May be preferred when significant anxiety, insomnia, or agitation accompanies depression (sedative properties)

• Therapeutic effect typically observed within 2–4 weeks

• Continue for minimum 6 months after remission; longer in recurrent depression

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Social Anxiety Disorder Starting: 50 mg/day at bedtime; Titration: increase by 50 mg/week; Maintenance: 100–200 mg/day; Maximum: 300 mg/day Minimum 12 weeks; continue based on response OFF-LABEL — Specialist only. Supported by international RCTs. Limited routine use in Indian practice.

Panic Disorder Starting: 25–50 mg/day; Titration: increase by 25–50 mg/week; Maintenance: 100–200 mg/day; Maximum: 300 mg/day Long-term; reassess periodically OFF-LABEL — Specialist only. Start at lower dose to avoid initial anxiety exacerbation. Based on international RCT evidence.

Post-Traumatic Stress Disorder (PTSD) Starting: 50 mg/day; Maintenance: 100–200 mg/day; Maximum: 300 mg/day Long-term OFF-LABEL — Specialist only. Sertraline/paroxetine preferred as first-line for PTSD.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Obsessive-Compulsive Disorder (OCD)

Fluvoxamine is one of the preferred SSRIs for paediatric OCD based on efficacy data. Use under child psychiatrist supervision only.

Age-based Dosing:

8–11 years 25 mg once daily at bedtime Increase by 25 mg every 4–7 days 50–150 mg/day 200 mg/day (divided doses above 50 mg)

12–17 years 25–50 mg once daily at bedtime Increase by 25–50 mg every 4–7 days 100–200 mg/day 300 mg/day (divided doses above 100 mg)

Clinical Notes:

• Therapeutic response may take 8–12 weeks in children

• Doses above 50 mg/day should be divided (give larger portion at bedtime)

• Continue for at least 1 year after symptom control

Minimum Age Statement: Not recommended in children below 8 years of age. Use in patients 8–17 years only under child and adolescent psychiatrist supervision.

Safety Monitoring:

• Weekly assessment for suicidal ideation, self-harm behaviour, and mood changes during first 4 weeks, then monthly for 3 months

• Monitor for behavioural activation, agitation, hostility, emotional lability

• Height and weight monitoring every 3 months

• Review treatment need every 6 months

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Major Depressive Disorder ≥12 years Starting: 25 mg/day; Titration: as for OCD; Maximum: 200 mg/day OFF-LABEL — Specialist only. Not first-line; fluoxetine is preferred for paediatric depression. Enhanced suicidality monitoring mandatory.

Anxiety Disorders (GAD, Social Anxiety) ≥8 years Starting: 25 mg/day; Titration: as per tolerability; Maintenance: 50–150 mg/day OFF-LABEL — Specialist only. Limited data in children.

• Known hypersensitivity to fluvoxamine or any excipient

• Concurrent use with monoamine oxidase inhibitors (MAOIs) including phenelzine, tranylcypromine, selegiline, moclobemide; minimum 14-day washout required before or after MAOI

• Concurrent use with linezolid or intravenous methylene blue (MAOI activity)

• Concurrent use with tizanidine (potent CYP1A2 inhibition by fluvoxamine causes dangerous elevation of tizanidine levels with severe hypotension and sedation)

• Concurrent use with pimozide, thioridazine, or alosetron (CYP inhibition leading to dangerous plasma level elevations)

• Severe hepatic impairment

• History of seizure disorder — may lower seizure threshold; use with caution

• Suicidal ideation — enhanced risk in first weeks of treatment, especially in patients under 25 years; close monitoring required

• Bipolar disorder — risk of precipitating manic/hypomanic episode; use with mood stabiliser

• Bleeding disorders or concurrent anticoagulant/antiplatelet/NSAID therapy — SSRI-induced platelet dysfunction increases bleeding risk

• Hyponatraemia risk — especially in elderly, patients on diuretics, or those with SIADH history

• Narrow-angle glaucoma — may increase intraocular pressure

• Hepatic or renal impairment — requires dose adjustment/caution

• Cardiac disease — limited data on cardiac effects

• Diabetes mellitus — may alter glycaemic control

• Concurrent use with drugs metabolised by CYP1A2 or CYP2C19 — fluvoxamine is potent inhibitor of both

• History of mania — may precipitate switch

• Abrupt discontinuation — risk of discontinuation syndrome; always taper

• Concurrent use with serotonergic drugs — risk of serotonin syndrome

Parameter Recommendation

Safety Category Limited human data; some observational studies suggest possible increased risk of cardiovascular malformations (inconclusive); risk of neonatal adaptation syndrome and persistent pulmonary hypertension of newborn (PPHN) with third-trimester exposure

Preferred Alternatives Sertraline is preferred first-line SSRI during pregnancy in Indian obstetric psychiatry practice; fluoxetine is alternative

When to Use May be considered if patient was stable on fluvoxamine pre-conception or if preferred SSRIs have failed; requires joint obstetric-psychiatry decision

Monitoring Standard fetal anomaly scanning; neonatal monitoring for irritability, feeding difficulties, respiratory distress if exposed in third trimester

Parameter Recommendation

Breastfeeding Compatibility Compatible with caution; low to moderate infant exposure reported

Drug Levels in Milk Low to moderate (relative infant dose approximately 1–2%)

Preferred Alternatives Sertraline and paroxetine have more safety data and lower milk levels; preferred if initiating SSRI during breastfeeding

Infant Monitoring Monitor for drowsiness, sedation, irritability, poor feeding, and adequate weight gain

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Slower titration at 2-week intervals; increase by 25 mg increments

Maximum dose 200 mg/day (consider lower maximum)

Additional Risks Increased susceptibility to hyponatraemia (SIADH); sedation; cognitive impairment; falls risk; drug interactions due to polypharmacy; GI bleeding risk if on NSAIDs/anticoagulants

Monitoring Serum sodium (baseline and periodic); mental status; fall risk assessment; review of concurrent medications for CYP interactions

Interacting Drug Mechanism/Effect Management

MAOIs (phenelzine, tranylcypromine, selegiline, moclobemide) Risk of life-threatening serotonin syndrome Contraindicated; 14-day washout required

Linezolid, IV methylene blue MAOI activity; serotonin syndrome risk Avoid concurrent use; if linezolid essential, discontinue fluvoxamine and monitor

Tizanidine Fluvoxamine potently inhibits CYP1A2; massively increased tizanidine levels causing severe hypotension, bradycardia, sedation Contraindicated

Theophylline, aminophylline CYP1A2 inhibition; 3–4 fold increase in theophylline levels; risk of theophylline toxicity (seizures, arrhythmias) Avoid combination; if essential, reduce theophylline dose by 66% and monitor levels closely

Clozapine CYP1A2 inhibition; significantly increased clozapine levels; risk of sedation, seizures, hypotension Reduce clozapine dose by 50–66% when initiating fluvoxamine; monitor clozapine levels

Olanzapine CYP1A2 inhibition; increased olanzapine levels Monitor for sedation and metabolic effects; may need olanzapine dose reduction

Pimozide, thioridazine Increased plasma levels via CYP inhibition; risk of QT prolongation and arrhythmias Contraindicated

Alosetron Markedly increased alosetron levels Contraindicated

Ramelteon CYP1A2 inhibition; massive increase in ramelteon levels Avoid concurrent use

Interacting Drug Effect Management

Warfarin Inhibition of warfarin metabolism (CYP1A2, CYP2C9); increased anticoagulant effect; bleeding risk also increased via platelet serotonin depletion Monitor INR closely; may need warfarin dose reduction

NSAIDs (ibuprofen, diclofenac, aspirin) Additive GI bleeding risk via platelet dysfunction Use with caution; consider gastroprotection; avoid long-term combination

Caffeine CYP1A2 inhibition; reduced caffeine clearance; increased CNS stimulation, anxiety, insomnia Advise limiting caffeine intake

Benzodiazepines (alprazolam, diazepam, midazolam) Fluvoxamine inhibits metabolism (CYP3A4, CYP2C19); increased benzodiazepine levels and sedation Reduce benzodiazepine dose by 50%; monitor for excessive sedation; lorazepam/oxazepam less affected

Propranolol CYP1A2 inhibition; increased propranolol levels Monitor for bradycardia and hypotension; may need propranolol dose reduction

Carbamazepine May reduce fluvoxamine levels (CYP inducer); also, fluvoxamine may increase carbamazepine epoxide levels Monitor clinical response and carbamazepine levels

Phenytoin CYP2C19 inhibition; increased phenytoin levels and toxicity risk Monitor phenytoin levels closely

Lithium Possible enhanced serotonergic effects; rare reports of increased lithium levels Monitor for serotonin syndrome and lithium toxicity

Tramadol Serotonin syndrome risk; also CYP2D6 interaction Use with caution; monitor closely

Triptans (sumatriptan, etc.) Additive serotonergic effects; serotonin syndrome risk Use with caution; monitor for serotonin syndrome

Methadone CYP inhibition; increased methadone levels; QT prolongation risk Monitor ECG and for opioid toxicity

Rifampicin CYP induction; may significantly reduce fluvoxamine levels Monitor antidepressant efficacy; may need higher fluvoxamine dose

Tacrine, donepezil CYP1A2 inhibition; increased levels Monitor for cholinergic adverse effects

• Nausea (very common; usually transient over first 1–2 weeks)

• Vomiting

• Somnolence, sedation, drowsiness (common; may be therapeutic for insomnia)

• Headache

• Dizziness

• Dry mouth

• Constipation

• Diarrhoea

• Dyspepsia

• Insomnia or sleep disturbance (less common than with activating SSRIs)

• Agitation, nervousness (early treatment)

• Asthenia, fatigue

• Excessive sweating

• Sexual dysfunction (decreased libido, anorgasmia, delayed ejaculation)

• Tremor

• Anorexia

Adverse Effect Clinical Significance

Serotonin syndrome Life-threatening; characterised by hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes; discontinue immediately; supportive care and cyproheptadine

Suicidal ideation/behaviour Increased risk in adolescents and young adults; enhanced monitoring required in first weeks

Hyponatraemia (SIADH) Particularly in elderly; presents with confusion, seizures; check sodium; discontinue if severe

Seizures Dose-related risk; discontinue if seizure occurs

Mania/hypomania May precipitate in bipolar patients; discontinue and initiate mood stabiliser

Bleeding (GI, ecchymoses, intracranial) Due to platelet serotonin depletion; increased risk with concurrent anticoagulants/NSAIDs

Hepatotoxicity Rare elevation of liver enzymes; very rare hepatic failure; monitor if symptomatic

Stevens-Johnson Syndrome/TEN Rare but serious; discontinue immediately if mucocutaneous reaction occurs

QT prolongation Primarily at high doses or with interacting drugs; ECG monitoring if concerned

Discontinuation syndrome Common with abrupt cessation; symptoms include dizziness, sensory disturbances, anxiety, nausea, irritability; always taper gradually

Akathisia Restlessness; may be mistaken for worsening anxiety

Angle-closure glaucoma Rare; presents with eye pain, visual changes

Baseline:

• Comprehensive psychiatric evaluation including suicide risk assessment

• Serum sodium (especially in elderly or those on diuretics)

• Liver function tests (if hepatic disease suspected)

• Weight

• Review of concurrent medications for CYP1A2/2C19 interaction potential

• ECG if using with QT-prolonging drugs or at high doses

After Initiation/Dose Change:

• Mental status, mood, and suicidal ideation assessment at 1, 2, and 4 weeks

• Assess for emergent anxiety, agitation, or insomnia

• Monitor for nausea (most common early adverse effect)

• Serum sodium at 2–4 weeks in high-risk patients

• Review adverse effects including sedation

Long-term:

• Weight and metabolic parameters every 3–6 months

• Sexual function assessment periodically

• Serum sodium periodically in elderly

• Liver function tests if on long-term therapy or symptomatic

• Review of concurrent medications (especially narrow therapeutic index drugs metabolised by CYP1A2)

• Annual review of continued treatment need

• Gradual taper plan when discontinuing (over 4+ weeks)

• Uvox® (Abbott)

• Fluvoxin® (Intas)

• Faverin® (Solvay/Abbott)

• Favoxil® (Sun Pharma)

• Fluvox® (Torrent)

• Suvoxil® (Sun Pharma)

• Luvox® (Limited availability)

Note: Fixed-dose combinations with fluvoxamine are not commonly marketed in India.

• Not included in NLEM

• Not under NPPA price control

• Available in some government psychiatric hospitals and district mental health programme supply

• Significant price variation between brands

• OCD preference: Fluvoxamine is one of the most well-studied SSRIs for OCD and may be preferred first-line for this indication; higher doses often needed (200–300 mg/day)

• Sedation advantage: More sedating than most SSRIs — therapeutically useful when prominent anxiety, agitation, or insomnia accompanies depression/OCD; dose at bedtime

• CYP1A2 inhibition: Strongest CYP1A2 inhibitor among SSRIs — causes unique and clinically significant interactions with theophylline, clozapine, tizanidine, caffeine; always review concurrent medications

• Nausea management: Nausea is very common initially; advise taking with food; usually resolves within 1–2 weeks; starting at lower dose (25 mg) may help

• Discontinuation: Taper over 4+ weeks to avoid discontinuation syndrome; reduce by 25–50 mg every 1–2 weeks

• Sexual dysfunction: Like other SSRIs, sexual dysfunction is common but may be slightly less than paroxetine; discuss proactively with patients

fluvoxamine; SSRI; OCD; depression; anxiety; CYP1A2-inhibitor; serotonin syndrome; suicidality-monitoring; paediatric-OCD; psychiatry; pregnancy-caution

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychopharmacology Protocols

• Indian Psychiatric Society — Clinical Practice Guidelines for OCD

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Manufacturer product inserts (India-licensed)

• International RCTs (for social anxiety disorder, panic disorder — off-label indications only)