Schedule H

* Oral, Intramuscular (IM), Intravenous (IV)

• Tablet: 5 mg, 10 mg

• Injection: 5 mg/mL (2 mL ampoules)

• Oral solution/syrup: 5 mg/5 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

Route Starting Dose Titration Usual Maintenance Dose Maximum Dose Clinical Notes

Oral/IM/IV 10 mg Not required 10 mg TID (30 mg/day) 30 mg/day Administer 30 minutes before meals and at bedtime if TID dosing

Key Points:

• Give 30 minutes before meals when used for meal-related nausea

• For acute vomiting: single 10 mg dose IM or IV

• Limit duration to shortest period necessary (typically 5–7 days for acute episodes)

1. Gastroparesis (including diabetic gastroparesis)

• Starting dose: 10 mg orally, 30 minutes before each meal and at bedtime (QID)

• Titration: None usually required; assess clinical response at 2–4 weeks

• Usual maintenance dose: 10 mg QID (before meals and bedtime)

• Maximum dose: 40 mg/day

• Duration: Limit to ≤12 weeks due to tardive dyskinesia risk; reassess need at 4–6 week intervals

Clinical consideration: In diabetic patients, improved gastric emptying may affect glycemic control and insulin requirements—monitor blood glucose.

1. Migraine-Associated Nausea (adjunct to analgesics)

• Route: IV or IM preferred

• Dose: 10 mg as single dose at onset of nausea/vomiting

• Titration: Not applicable

• Maximum dose: 10 mg per episode; may repeat after 6–8 hours if needed (max 30 mg/day)

• Notes:

• Enhances gastric emptying and improves oral analgesic absorption

• May be given alongside NSAIDs or specific migraine therapies

• IV administration: give as slow push over 1–2 minutes

Secondary Indications — Adults (Off-label, if any):

• Chemotherapy-Induced Nausea/Vomiting (CINV) — low to moderate emetogenic chemotherapy

• Dose: 10–20 mg IV, administered 30 minutes before chemotherapy

• Duration: Single dose before each chemotherapy cycle, or TID during chemotherapy days

• Specialist only: Oncologist/medical oncologist

• OFF-LABEL (as monotherapy; more commonly used as adjunct to 5-HT3 antagonists)

• Evidence basis: Indian oncology supportive care protocols; commonly used in resource-limited settings when newer antiemetics unavailable

• Functional Dyspepsia with Delayed Gastric Emptying

• Dose: 10 mg orally TID, 30 minutes before meals

• Duration: Short-term (4–6 weeks); reassess need and consider alternative therapies

• OFF-LABEL for functional dyspepsia without proven gastroparesis

• Evidence basis: Indian gastroenterology practice; API Textbook of Medicine references use in dysmotility-like dyspepsia

• Facilitating Small Bowel Intubation (diagnostic procedures)

• Dose: 10 mg IV as single dose before procedure

• OFF-LABEL in current Indian practice, though historically used

• Evidence basis: Older Indian hospital protocols

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

Age/Weight Route Dose Frequency Maximum Daily Dose Maximum Duration

1–18 years (≥10 kg) Oral/IV/IM 0.1–0.15 mg/kg per dose Up to TID 0.5 mg/kg/day (max 30 mg/day) 5 days

<1 year or <10 kg NOT RECOMMENDED except under pediatric specialist supervision — — — —

Safety Monitoring:

• High risk of extrapyramidal symptoms (EPS) in children and adolescents

• Observe closely for dystonic reactions, especially within first 24–48 hours

• Have diphenhydramine or benztropine available for acute dystonia

• Use lowest effective dose for shortest duration

Secondary Indications — Paediatrics (Off-label, if any):

• Chemotherapy-Induced Nausea (adjuvant to primary antiemetics)

• Dose: 0.1–0.15 mg/kg IV, 30 minutes before chemotherapy

• Duration: Single dose or short course during chemotherapy days

• Specialist only: Pediatric oncologist

• OFF-LABEL

• Evidence basis: IAP supportive care protocols for pediatric oncology; commonly used when 5-HT3 antagonists not available

• Gastroesophageal Reflux Disease (GERD) in Infants

• NOT RECOMMENDED in current Indian pediatric practice

• OFF-LABEL and associated with significant neurological adverse effects

• Evidence basis: IAP and WHO no longer support routine use; safer alternatives (e.g., positioning, feed thickening, H2-blockers if needed) preferred

• Avoid except in very specific situations under pediatric gastroenterologist guidance

Required in renal impairment — Metoclopramide and metabolites accumulate; reduce dose and/or frequency:

Hemodialysis: Metoclopramide is minimally dialyzed; give dose after dialysis on dialysis days.

Peritoneal dialysis: Reduce dose by 75%; give once daily.

• Mild impairment (Child-Pugh A): No dose adjustment usually required

• Moderate impairment (Child-Pugh B):

• Start at lower end of dose range (5 mg per dose)

• Monitor closely for CNS effects and EPS

• Consider reducing frequency to BID

• Severe hepatic impairment (Child-Pugh C):

• Avoid unless benefit clearly outweighs risk

• Specialist supervision required

• Risk of hepatic encephalopathy exacerbation and increased CNS adverse effects

• Pheochromocytoma — risk of hypertensive crisis due to catecholamine release

• Previous tardive dyskinesia related to metoclopramide use

• Mechanical gastrointestinal obstruction, perforation, or active GI hemorrhage — prokinetic effect may worsen these conditions

• Parkinson's disease or parkinsonian syndromes — dopamine antagonism worsens extrapyramidal symptoms

• Known hypersensitivity to metoclopramide or excipients

• Epilepsy or seizure disorders (relative contraindication) — may lower seizure threshold

• Elderly patients: Increased risk of extrapyramidal symptoms, cognitive impairment, sedation, and falls

• Cardiac conduction abnormalities: Risk of QT interval prolongation, particularly with IV use or in combination with other QT-prolonging agents

• Concomitant use with other dopamine antagonists (antipsychotics, some antiemetics) — additive risk of EPS and tardive dyskinesia

• Depression or history of suicidal ideation: Rare reports of worsening depression; monitor mental status

• Avoid chronic use beyond 12 weeks: Risk of tardive dyskinesia increases with duration; document clear indication if use exceeds this period

• Hypertension: May cause transient increase in blood pressure (rare)

• Patients with NADH-cytochrome b5 reductase deficiency: Risk of methemoglobinemia

• Young adults (18–30 years): Higher risk of dystonic reactions compared to middle-aged adults

Overall Assessment: Generally considered safe for short-term use; widely used in Indian obstetric practice for nausea and vomiting

Risk Category:

• Not formally classified in Indian regulatory system

• US FDA former Category B (animal studies show no risk; adequate human studies lacking)

• Large observational studies show no increased teratogenic risk

When It May Be Used:

• Nausea and vomiting of pregnancy when dietary/lifestyle measures fail

• Hyperemesis gravidarum (though other agents may be preferred first-line)

• Short-term use (days to few weeks) preferred

• All trimesters: appears safe based on available data

Preferred Alternatives in Indian Obstetric Practice:

• First-line: Doxylamine + pyridoxine (when available)

• Alternatives: Ondansetron (though first-trimester use debated), vitamin B6, ginger

• Antihistamines (promethazine, cyclizine)

Monitoring:

• Monitor for extrapyramidal symptoms in mother (rare but reported)

• No specific fetal monitoring required for metoclopramide use alone

• If used near term, observe neonate for potential EPS (very rare)

Compatibility: Generally compatible with breastfeeding

Drug Levels in Breast Milk:

• Metoclopramide enters breast milk in low concentrations

• Milk-to-plasma ratio approximately 0.5–2

• Estimated infant dose: 1–10% of maternal weight-adjusted dose

Potential Galactagogue Effect:

• Metoclopramide increases prolactin secretion

• Sometimes used OFF-LABEL to enhance milk production (not standard Indian practice; specialist use only)

Monitoring in Infant:

• Watch for sedation, irritability, or changes in feeding pattern

• Monitor for dystonic reactions (very rare)

• Diarrhea (occasional report)

Preferred Alternatives (if needed):

• For nausea: Ondansetron generally preferred if antiemetic needed in lactating mother

• For reflux/dyspepsia: Antacids, H2-blockers, or PPIs usually safe

Clinical Recommendation: Can be used during breastfeeding for standard short-term indications; use lowest effective dose

Starting Dose:

• Begin with 5 mg per dose (rather than standard 10 mg)

• Particularly important in patients >70 years or frail elderly

Titration:

• Slower and more cautious

• Assess response and tolerance after 3–5 days before increasing

• Maximum dose in elderly: 20 mg/day unless clear indication requires higher (specialist decision)

Extra Risks in Elderly:

• Extrapyramidal symptoms: Higher incidence, including parkinsonism, akathisia, dystonia

• Tardive dyskinesia: Risk increases with age and duration of use

• Cognitive effects: Confusion, sedation more common

• Orthostatic hypotension: Increased fall risk

• Reduced renal clearance: Many elderly have reduced eGFR even with normal serum creatinine (use Cockcroft-Gault or eGFR calculation).

Monitoring:

• Assess for involuntary movements before and during therapy

• Monitor for falls, gait disturbance, confusion

• Limit duration to minimum necessary (avoid chronic use)

Route Considerations:

• Prefer oral route when feasible

• If IM required, ensure patient mobile/assisted to reduce orthostatic hypotension risk

Levodopa and Other Dopaminergic Antiparkinson Agents

• Mechanism: Metoclopramide antagonizes dopamine; directly opposes levodopa effect

• Effect: Loss of antiparkinson efficacy; worsening of Parkinson symptoms

• Action: AVOID combination; use alternative antiemetic (e.g., domperidone with caution, ondansetron)

Antipsychotics (typical and atypical)

• Mechanism: Additive dopamine antagonism

• Effect: Increased risk of severe extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia

• Action: Avoid or use with extreme caution; specialist supervision required

QT-Prolonging Agents (e.g., erythromycin, clarithromycin, haloperidol, sotalol, amiodarone, ondansetron, quinolones)

• Mechanism: Additive QT prolongation

• Effect: Risk of torsades de pointes, particularly with IV metoclopramide

• Action: Avoid combination if possible; if essential, baseline and monitoring ECG required; correct electrolytes

MAO Inhibitors (rarely used in India, but includes linezolid)

• Mechanism: Risk of hypertensive crisis, especially in presence of undiagnosed pheochromocytoma

• Effect: Severe hypertension, serotonin syndrome (theoretical)

• Action: Avoid combination; use alternative antiemetic

Anticholinergic Agents (e.g., atropine, dicyclomine, trihexyphenidyl)

• Mechanism: Direct pharmacological antagonism

• Effect: Reduced prokinetic efficacy of metoclopramide

• Action: Avoid concurrent use when treating gastroparesis or dysmotility

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonergic Agents

• Increased risk of serotonin syndrome (rare) and additive EPS risk

• Monitor for tremor, restlessness, confusion if combined

• Usually can be used together with monitoring

CNS Depressants (benzodiazepines, opioids, sedating antihistamines, alcohol)

• Additive sedation and drowsiness

• Counsel patient about activities requiring alertness

• Consider dose reduction of one or both agents

Digoxin

• Metoclopramide may reduce digoxin absorption (accelerated gastric emptying reduces dissolution time)

• Monitor digoxin levels if used chronically together

• Usually not clinically significant with normal formulations

Cyclosporine

• Metoclopramide increases rate of cyclosporine absorption (faster gastric emptying)

• May result in higher peak levels

• Monitor cyclosporine trough levels; dose adjustment rarely needed

Insulin and Oral Hypoglycemic Agents

• Accelerated gastric emptying may alter glucose absorption kinetics

• Risk of hypoglycemia in diabetic gastroparesis patients when gastric emptying improves

• Monitor blood glucose more frequently when initiating metoclopramide in diabetics

Hepatotoxic Drugs (e.g., anti-TB drugs, azoles)

• Additive hepatotoxicity risk (metoclopramide rarely hepatotoxic)

• Monitor liver function if prolonged co-administration

Bromocriptine, Cabergoline (dopamine agonists)

• Metoclopramide may reduce efficacy (dopamine antagonism)

• Usually manageable; monitor clinical response

• Drowsiness and fatigue (10–20% of patients)

• Restlessness and akathisia (motor restlessness, inability to sit still; 5–10%)

• Diarrhea or loose stools (prokinetic effect; 5–10%)

• Headache

• Dizziness

• Insomnia or sleep disturbances (paradoxical in some patients)

• Asthenia (weakness)

• Extrapyramidal symptoms (dystonia, parkinsonism, akathisia — more common in young adults and elderly; 1–10% depending on population)

• Tardive Dyskinesia

• Potentially irreversible involuntary movements (tongue protrusion, lip smacking, choreiform movements)

• Risk increases with duration of use (especially >12 weeks) and cumulative dose

• Higher risk in elderly, women, and diabetics

• Action: Discontinue immediately if signs develop; symptoms may persist or worsen after stopping

• Neuroleptic Malignant Syndrome (NMS)

• Rare but life-threatening: hyperthermia, muscle rigidity, altered mental status, autonomic instability

• Action: Discontinue immediately; hospitalize; supportive care

• Acute Dystonic Reactions

• Sudden onset (usually within 24–48 hours): torticollis, oculogyric crisis, opisthotonus, tongue protrusion

• More common in children, young adults, and with IV administration

• Action: IV/IM diphenhydramine (1 mg/kg or 25–50 mg) or benztropine (1–2 mg); symptoms resolve rapidly

• QT Prolongation and Cardiac Arrhythmias

• Torsades de pointes reported, especially with IV use, high doses, or in combination with other QT-prolonging drugs

• Action: Monitor ECG in at-risk patients; correct electrolytes

• Seizures

• Rare; may occur in patients with prior seizure history or in overdose

• Action: Discontinue; manage seizures per standard protocol

• Depression, Suicidal Ideation

• Rare case reports; monitor patients with psychiatric history

• Action: Discontinue if mood changes emerge

• Methemoglobinemia

• Very rare; risk higher in NADH-cytochrome b5 reductase deficiency, infants, or with overdose

• Presents with cyanosis, dyspnea, altered mental status

• Action: Methylene blue if clinically significant (methemoglobin >20–30%)

• Hyperprolactinemia

• Galactorrhea, gynecomastia, menstrual irregularities with chronic use

• Usually reversible upon discontinuation

Baseline (before initiating therapy):

• Neurological examination: check for any pre-existing movement disorders, tremor, rigidity

• ECG if patient has cardiac risk factors, conduction abnormalities, on other QT-prolonging drugs, or if IV metoclopramide planned

• Renal function (serum creatinine, eGFR) — especially in elderly

• Exclude mechanical GI obstruction clinically (and radiologically if uncertain) before using for gastroparesis or dyspepsia

After Initiation / Dose Change:

• Monitor for extrapyramidal symptoms within first 24–72 hours (especially in children, young adults)

• Assess for sedation, dizziness, orthostatic symptoms (particularly elderly)

• Evaluate symptom response (nausea control, gastric emptying improvement)

During Ongoing Therapy:

• Short-term use (<5–7 days): Minimal monitoring; observe for acute EPS

• Prolonged use (>2 weeks):

• Reassess indication and need for continuation every 2–4 weeks

• Monitor for involuntary movements at each visit (early tardive dyskinesia signs)

• If duration approaches or exceeds 12 weeks: document clear rationale and discuss risk/benefit with patient; consider alternative therapies

Laboratory Monitoring (if prolonged use):

• Renal function if elderly or renal impairment present

• Liver function tests if on other hepatotoxic drugs

• Electrolytes (potassium, magnesium) if on diuretics or other QT-prolonging agents

• Serum prolactin if symptoms of hyperprolactinemia

Special Populations:

• Diabetics on insulin: monitor blood glucose more frequently when starting (improved gastric emptying may alter glucose dynamics)

• Perinorm® (IPCA Laboratories)

• Reglan® (Alkem Laboratories)

• Maxolon® (RPG Life Sciences)

• Maxeron® (Glenmark Pharmaceuticals)

• Emekon® (Micro Labs)

• Metpure® (Mankind Pharma)

• Metopar® (Zuventus Healthcare)

• Emitil® (Win-Medicare)

• Multiple generic formulations widely available

Fixed-Dose Combinations (examples):

• Note: Use of FDCs should follow rational prescribing; monotherapy preferred when possible

• Tablet 10 mg: ₹1.50–₹5 per tablet (strip of 10: ₹15–₹50)

• Injection 5 mg/mL (2 mL ampoule): ₹4–₹12 per ampoule

• Oral syrup/solution 5 mg/5 mL: ₹20–₹40 per 60 mL bottle; ₹35–₹60 per 100 mL bottle

Pricing Notes:

• Generic formulations at lower end of range

• Branded products (Perinorm, Reglan, etc.) at mid-to-upper range

• Not included in National List of Essential Medicines (NLEM) 2022 — not under NPPA price control

• Available in government hospitals and primary health centers; often dispensed free or at minimal cost

1. Route and Timing Matter for Efficacy:

• For nausea/vomiting with oral intolerance: prefer IM or IV route initially

• For gastroparesis/dysmotility: oral route 30 minutes before meals optimizes prokinetic effect

• In migraine: IV/IM not only treats nausea but enhances absorption of subsequently given oral analgesics (NSAIDs, triptans)

1. Extrapyramidal Risk Stratification:

• Highest risk: Children, adolescents, young adults (18–30 years), elderly, females

• Acute dystonia (within hours to 2 days): Have diphenhydramine or promethazine readily available, especially when using IV metoclopramide in young patients

• Tardive dyskinesia (after weeks to months): Irreversible in many cases — strictly limit duration to <12 weeks

1. Always Exclude Mechanical Obstruction:

• Before prescribing for "gastroparesis" or persistent vomiting, ensure no bowel obstruction (clinical exam, consider imaging if red flags)

• Metoclopramide in mechanical obstruction can worsen perforation risk

1. IV Administration Technique:

• Give as slow IV push over 1–3 minutes (not rapid bolus)

• Rapid injection increases risk of akathisia, anxiety, and transient hypotension

• Can also dilute in 50 mL NS and infuse over 15 minutes to minimize adverse effects

1. Not First-Line for All Nausea:

• For chemotherapy-induced nausea: 5-HT3 antagonists (ondansetron, granisetron) are more effective for moderate-high emetogenic chemo; metoclopramide adjunct or alternative in resource-limited settings

• For pregnancy nausea: try dietary measures, ginger, vitamin B6 first; then doxylamine+pyridoxine if available; metoclopramide if others fail or unavailable

1. Switching from Metoclopramide:

• If prolonged use needed (chronic gastroparesis): consider domperidone (less CNS penetration, lower EPS risk but has cardiac QT concerns) or other prokinetics under specialist guidance

• If EPS emerge: stop metoclopramide immediately; do not rechallenge

1. Documentation for Chronic Use:

• If prescribing beyond 12 weeks (exceptional cases): document clear indication, failure of alternatives, patient informed of tardive dyskinesia risk, and regular reassessment plan in medical record

antiemetic; prokinetic; nausea; vomiting; gastroparesis; diabetic-gastroparesis; migraine-adjunct; dopamine-antagonist; extrapyramidal-risk; tardive-dyskinesia; pediatric-caution; pregnancy-compatible; renal-dose-adjustment; Schedule-H; India

RxIndia v1.0 — 15 May 2025

• Central Drugs Standard Control Organisation (CDSCO) — Product information and approved indications

• Indian Pharmacopoeia Commission — Metoclopramide monograph

• Association of Physicians of India (API) Textbook of Medicine, 11th Edition — Use in gastroparesis, functional dyspepsia, and nausea/vomiting management

• Indian Academy of Pediatrics (IAP) Guidelines — Pediatric dosing for antiemetics and chemotherapy supportive care

• ICMR-National Cancer Grid Guidelines — Supportive care in oncology (CINV management)

• All India Institute of Medical Sciences (AIIMS) Hospital Formulary — Adult and pediatric dosing protocols

• Indian Council of Medical Research (ICMR) — Rational use of antiemetics

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition — Pharmacology, adverse effects, drug interactions

• Harrison's Principles of Internal Medicine, 21st Edition — Clinical use in GI motility disorders

• MoHFW (Ministry of Health and Family Welfare) Essential Medicines List for India — Availability and use in public health system

• Indian specialist practice consensus: Gastroenterology, Medical Oncology, and General Medicine departments — common dosing practices and off-label use patterns in Indian hospitals