Schedule H / NDPS (Narcotic Drugs and Psychotropic Substances Act, 1985)

Oral, Intravenous, Subcutaneous, Intramuscular, Epidural, Intrathecal, Rectal

• Immediate-release tablets: 10 mg, 15 mg, 30 mg

• Sustained-release tablets: 10 mg, 30 mg, 60 mg, 100 mg

• Oral solution: 10 mg/5 mL

• Injection (ampoules): 10 mg/mL, 15 mg/mL (1 mL and 2 mL ampoules)

• Epidural/Intrathecal solution: 0.5 mg/mL, 1 mg/mL (specialist use only; limited availability through palliative care centres)

• Rectal suppositories: NOT AVAILABLE in India (limited/unreliable supply)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Moderate to Severe Acute Pain (Postoperative, Trauma, Acute Myocardial Infarction)

Route Starting Dose Titration Usual Maintenance Dose Maximum Dose

IV 2–5 mg every 4 hours PRN Titrate every 1–2 hours based on pain and sedation 5–10 mg every 4 hours No fixed ceiling; titrate to effect with monitoring

SC/IM 5–10 mg every 4 hours PRN Titrate based on clinical response 10–15 mg every 4 hours Titrate to pain control

Clinical notes:

• IV route preferred in acute severe pain for rapid onset

• SC preferred over IM for repeated dosing (less painful, reliable absorption)

• For MI-related chest pain, administer IV morphine 2–4 mg; repeat every 5–15 minutes if needed

1. Chronic Severe Pain — Cancer Pain and Palliative Care

Formulation Starting Dose Titration Usual Maintenance Dose Maximum Dose

Oral IR (opioid-naïve) 5–10 mg every 4 hours Increase by 25–50% of total daily dose every 24–48 hours based on pain Highly variable; 30–180 mg/day typical No ceiling; individualise based on tolerance and response

Oral SR (after stabilisation on IR) 15–30 mg every 12 hours Adjust by 30–50% every 48–72 hours Variable; may exceed 200–300 mg/day in tolerant patients Titrate to pain control

Subcutaneous (continuous or intermittent) 2.5–5 mg every 4 hours Titrate based on pain scores and sedation Variable No ceiling; specialist supervision

Clinical notes:

• SR formulations initiated only after 24–48 hours of stable IR dosing

• Always provide breakthrough doses (10–15% of 24-hour total dose as IR morphine)

• Oral to parenteral conversion: Oral:SC/IM = 3:1; Oral:IV = 3:1 to 2:1

• Follow WHO analgesic ladder; morphine is Step 3 opioid

1. Dyspnoea in Advanced Illness (Palliative Care)

Route Starting Dose Titration Usual Maintenance Dose Maximum Dose

Oral/SC 2.5 mg every 4–6 hours Increase by 25–50% every 24 hours as tolerated 5–10 mg every 4 hours Titrate to symptom control

Clinical notes:

• Low-dose morphine effectively reduces dyspnoea perception

• Does not accelerate death when used appropriately

• Reserved for dyspnoea refractory to disease-specific treatments

Secondary Indications — Adults (Off-label)

1. Severe Intractable Non-Malignant Pain

• Dose: Start 5 mg oral every 4–6 hours; titrate cautiously

• Duration: Short-term only; reassess every 1–4 weeks

• Specialist only: Yes — Pain Medicine specialist

• OFF-LABEL

• Evidence basis: Indian pain clinic practice; international guidelines support cautious use with strict monitoring for addiction risk

1. Severe Refractory Cough in Terminal Illness

• Dose: 2.5–5 mg oral/SC every 4–6 hours

• Duration: As needed in palliative setting

• Specialist only: Yes — Palliative Care

• OFF-LABEL

• Evidence basis: AIIMS Palliative Care protocols; antitussive effect at low doses

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Moderate to Severe Pain (Postoperative, Trauma, Cancer Pain)

Age/Weight Category Route Starting Dose Titration Maximum Single Dose

Neonates (≥37 weeks GA) IV 0.025–0.05 mg/kg every 4–6 hours Increase by 25% every 12–24 hours 0.05 mg/kg

Infants 1–6 months IV 0.05 mg/kg every 4–6 hours Increase by 25% based on pain/sedation 0.1 mg/kg

Children 6 months–12 years IV 0.05–0.1 mg/kg every 4 hours Titrate by 25% increments 0.1–0.15 mg/kg

Children 6 months–12 years Oral IR 0.2–0.3 mg/kg every 4 hours Titrate by 25–50% daily 0.5 mg/kg per dose

Adolescents >12 years IV/Oral Adult dosing with weight consideration As per adult protocol Adult doses

Clinical notes:

• Mandatory continuous respiratory and SpO₂ monitoring for all parenteral use

• Naloxone must be immediately available

• Oral route preferred once pain is controlled and child is tolerating feeds

• Use preservative-free formulations for neonates and epidural/intrathecal use

Secondary Indications — Paediatric Doses (Off-label)

1. Dyspnoea in Terminal Illness (Paediatric Palliative Care)

• Dose: 0.05–0.1 mg/kg SC/oral every 4–6 hours

• Duration: As clinically indicated

• Specialist only: Yes — Paediatric Palliative Care

• OFF-LABEL

• Evidence basis: Adapted from AIIMS Palliative Care protocols; WHO guidelines for paediatric palliative care

Age restrictions:

• Use below 1 month of age only under neonatal/paediatric intensive care or palliative care specialist supervision

• Not recommended for non-terminal pain conditions in children except under specialist pain or oncology protocols

Safety monitoring:

• Respiratory rate, SpO₂, sedation score before each dose

• Bowel function (laxatives mandatory with regular use)

• Signs of tolerance, withdrawal if used >5–7 days

60 No adjustment required

30–60 Reduce dose by 25–50%; extend dosing interval to every 6–8 hours

15–30 Reduce dose by 50–75%; use every 8–12 hours; close monitoring mandatory

<15 or dialysis Avoid morphine; accumulation of active metabolite (morphine-6-glucuronide) causes prolonged sedation and respiratory depression; consider fentanyl or hydromorphone

Note: Morphine is poorly dialysable; not recommended in patients on haemodialysis or peritoneal dialysis.

• Acute respiratory depression (in absence of resuscitation facilities)

• Acute or severe bronchial asthma without monitoring/intervention capability

• Known or suspected paralytic ileus or gastrointestinal obstruction

• Known hypersensitivity to morphine or other opioids

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation

• Acute alcoholism or delirium tremens

• Raised intracranial pressure with impaired consciousness (unless ventilated)

• Renal or hepatic impairment (see adjustment sections)

• Elderly and debilitated patients

• Head injury or intracranial lesions (may obscure neurological assessment)

• History of substance use disorder or addiction

• Hypotension or hypovolaemia

• Biliary tract disorders (may cause sphincter of Oddi spasm)

• Chronic obstructive pulmonary disease or cor pulmonale

• Hypothyroidism, adrenal insufficiency

• Prostatic hypertrophy or urethral stricture

• Inflammatory or obstructive bowel disorders

• Concurrent use of CNS depressants

Parameter Information

Risk category Use only if benefit clearly outweighs risk (Category C equivalent)

Preferred alternatives Paracetamol for mild-moderate pain; regional anaesthesia for labour

When it may be used Short-term acute pain (labour analgesia under supervision); avoid near delivery

What to monitor Fetal heart rate; neonatal respiratory depression and withdrawal symptoms (Neonatal Opioid Withdrawal Syndrome — NOWS) if prolonged maternal use

Parameter Information

Compatibility Compatible with short-term, low-dose use; caution with repeated dosing

Drug levels in milk Low to moderate

Preferred alternatives Paracetamol; short-acting opioids if analgesia required

What to monitor in infant Sedation, poor feeding, respiratory depression, poor weight gain

Note: Avoid high doses or prolonged use. If infant shows excessive sedation or feeding difficulty, discontinue breastfeeding temporarily and consult paediatrician.

• Starting dose: Reduce by 25–50% (e.g., IV 1–2.5 mg; oral 2.5–5 mg)

• Titration: Extend dosing intervals; titrate slowly over 48–72 hours

• Extra risks:

• Enhanced CNS sensitivity (increased sedation, confusion, delirium)

• Higher fall risk

• Reduced renal clearance even with normal serum creatinine

• Increased constipation requiring prophylactic laxatives

• Respiratory depression at lower doses

Interacting Drug/Class Effect Recommendation

MAO inhibitors (phenelzine, tranylcypromine, moclobemide) Severe, potentially fatal reactions (serotonin syndrome, respiratory depression, hypotension) Contraindicated; avoid within 14 days of MAOI use

Benzodiazepines and other sedative-hypnotics Profound sedation, respiratory depression, coma, death Avoid combination unless no alternative; if essential, use lowest doses with intensive monitoring

Alcohol Enhanced CNS and respiratory depression Avoid concurrent use

Other opioid analgesics Additive respiratory depression Use with caution; adjust doses

Naltrexone/Naloxone (chronic use) Opioid antagonism; may precipitate withdrawal or block analgesia Avoid naltrexone; naloxone reserved for overdose reversal only

Interacting Drug/Class Effect Recommendation

Gabapentin, pregabalin Additive CNS depression; increased respiratory depression risk Monitor closely; consider dose reduction of one or both

Anticholinergic drugs Increased constipation, urinary retention, confusion Coadminister laxatives; monitor

Rifampicin Induces morphine metabolism; reduced efficacy May need increased morphine dose; monitor pain control

Cimetidine Reduced morphine clearance; increased sedation Monitor for excessive sedation

SSRIs/SNRIs Rare serotonin syndrome risk; additive sedation Monitor for serotonergic symptoms

Tricyclic antidepressants Additive CNS depression, anticholinergic effects Use with caution; monitor elderly

Antihypertensives Additive hypotension Monitor blood pressure

Muscle relaxants (baclofen, tizanidine) Enhanced sedation Monitor

• Constipation (>80%; universal with chronic use)

• Nausea and vomiting (especially initial doses)

• Sedation and drowsiness

• Dizziness

• Dry mouth

• Pruritus (especially with neuraxial administration)

• Urinary retention

• Postural hypotension

• Miosis

• Respiratory depression — dose-dependent; potentially fatal; requires immediate intervention

• Severe hypotension and circulatory shock — especially with IV bolus in hypovolaemic patients

• Seizures — rare; may occur with high doses or renal impairment

• Neurotoxicity — myoclonus, hyperalgesia, delirium; particularly in renal failure or high-dose therapy

• Opioid use disorder and physical dependence — with prolonged use

• Severe constipation progressing to ileus — especially in debilitated patients

• Anaphylactoid reactions — rare; histamine release more common

After initiation/dose change Respiratory rate, SpO₂, sedation scale every 1–4 hours for first 24–48 hours (parenteral use)

Ongoing (chronic use) Pain scores; bowel function (daily); signs of tolerance, dependence, or misuse; renal function periodically

Palliative setting Symptom control scores; sedation scale; quality of life indicators

• Morphine Sulphate Injection (Sun Pharma, Neon Labs, Rusan Pharma)

• MST Continus (sustained-release tablets) — limited availability via government/palliative care channels

• Morcontin (sustained-release) — Wockhardt

• Morphine Oral Solution — available through select palliative care centres

Note: All morphine formulations are controlled under NDPS Act. Procurement requires NDPS licence. Prescription must comply with state-specific NDPS regulations and maintain register/logbook documentation.

• Included in NLEM 2022

• Available free at government palliative care centres and pain clinics

• Private availability restricted due to NDPS licensing requirements

• Start prophylactic laxatives (bisacodyl, lactulose, or polyethylene glycol) whenever initiating morphine — constipation is inevitable and does not develop tolerance

• Tolerance develops to sedation, nausea, and respiratory depression but NOT to constipation or miosis

• Oral bioavailability is approximately 30% — adjust doses when converting between routes

• In cancer pain, titrate morphine upward until pain is controlled or unacceptable side effects occur — there is no ceiling dose

• Always have naloxone available when using parenteral morphine in opioid-naïve patients

• Document NDPS prescription requirements as per local regulations — failure to maintain records is a legal offence

opioid; morphine; cancer pain; palliative care; NDPS India; NLEM; respiratory depression; renal adjustment; postoperative pain; Schedule H

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• NLEM 2022

• ICMR Guidelines for Palliative Care

• AIIMS Palliative Care Protocols

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses

• Harrison's Principles of Internal Medicine