Intramuscular, Subcutaneous Premedication in surgery, Severe pain
Adult: As morphine sulfate: Usual dose: 10 mg 4 hourly (dose may vary from 5-20 mg) via IM or SC inj. Dosage is individualised based on the severity of pain, patient response, and prior analgesic experience. Elderly: Dose reduction may be needed.
Intraspinal Severe pain
Adult: As morphine sulfate: Initially, 5 mg via epidural inj, if desired pain relief is not achieved within 1 hour, incremental doses of 1-2 mg may be given up to a total dose of 10 mg/24 hours. As continuous epidural infusion: Initially, 3.5-7.5 mg daily in opioid-naïve patients or 4.5-10 mg daily for patients with some degree of opioid tolerance. Dosage is individualised based on the severity of pain, patient response, and prior analgesic experience. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Initiate at the lower end of the dosing range.
Intrathecal Severe pain
Adult: As morphine sulfate: Initially, 0.1-1 mg as a single dose for up to 24 hours. Dosage is individualised based on the severity of pain, patient response, and prior analgesic experience. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Initiate at the lower end of the dosing range.
Intravenous Premedication in surgery, Severe pain
Adult: As morphine sulfate: Initially, 2.5-15 mg 4 hourly via slow inj. Dosage is individualised based on the severity of pain, patient response, and prior analgesic experience. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Dose reduction may be needed.
Oral Moderate to severe pain
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response, opioid tolerance, and prior analgesic experience. Use the lowest effective dose for the shortest treatment duration based on patient’s treatment goals. As conventional preparation: 5-20 mg 4 hourly. As extended-release tab/cap: Recommended initial dose: 10-30 mg 12-24 hourly. Elderly: Dose reduction may be needed.
Rectal Severe pain
Adult: As morphine sulfate supp: Initially, 10-20 mg 4 hourly. Dosage is individualised based on the severity of pain, patient response, and prior analgesic experience. Elderly: Initiate at the lower end of the dosing range.
Renal Impairment
Oral: Moderate to severe pain: Dose reduction may be needed.
Intravenous; Intramuscular; Subcutaneous: Severe pain; Premedication in surgery: Dose reduction may be needed.
Hepatic Impairment
Oral: Moderate to severe pain: Dose reduction may be needed.
Intravenous; Intramuscular; Subcutaneous: Severe pain; Premedication in surgery: Dose reduction may be needed.
Administration
May be taken with or without food. May be taken w/ meals to reduce GI discomfort.
Hypersensitivity. Respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction (including paralytic ileus), suspected surgical abdomen, acute alcoholism, convulsive disorder, head injury, elevated intracranial or cerebrospinal pressure, brain tumour. Intrathecal: Infection at the microinfusion site, concomitant anticoagulant treatment, uncontrolled bleeding diathesis. Concomitant use or within 14 days of discontinuing MAOIs.
Special Precautions
Patient with CV disease (including acute MI), hypovolaemia, biliary tract dysfunction, acute pancreatitis, adrenal insufficiency including Addison disease, cor pulmonale, thyroid dysfunction, impaired respiratory function, decreased respiratory reserve, hypoxia, hypercarbia, seizure disorders, mental health condition (e.g. anxiety disorders, depression, PTSD), toxic psychosis, sleep-related disorders (including sleep apnoea), prostatic hyperplasia, urinary stricture, history of substance abuse disorder; delirium tremens. Obese and debilitated patients. Renal and severe hepatic impairment. Neonates, children, and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: CNS depression, orthostatic hypotension, severe hypotension, syncope, opioid-induced constipation. Cardiac disorders: Chest pain, arrhythmia, tachycardia. Eye disorders: Blurred vision, miosis, nystagmus. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, dry mouth. General disorders and administration site conditions: Asthenia, fatigue, malaise, chills, hypothermia, inj site pain and irritation, drug withdrawal (abstinence) syndrome. Hepatobiliary disorders: Biliary spasm. Metabolism and nutrition disorders: Anorexia, peripheral oedema. Nervous system disorders: Headache, dizziness, drowsiness, somnolence, vertigo, convulsion, agitation, myoclonus, opioid-induced hyperalgesia, increased intracranial pressure. Psychiatric disorders: Confusion, restlessness, mood swings, anxiety, insomnia, hallucination, disorientation, dysphoria, euphoria, tolerance and dependence (long-term use). Renal and urinary disorders: Urinary retention. Reproductive system and breast disorders: Decreased libido, erectile dysfunction, infertility (long-term use). Respiratory, thoracic and mediastinal disorders: Bronchospasm. Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, angioedema, contact dermatitis, facial flushing, hyperhidrosis. Potentially Fatal: Hypersensitivity, respiratory depression.
Epidural/IM/IT/IV/Parenteral/PO/Rectal/SC: C (Prolonged use may cause neonatal opioid withdrawal syndrome.)
Patient Counseling Information
This drug may cause CNS depression, if affected, do not drive or operate machinery.
Monitoring Parameters
Closely monitor respiratory status, mental status, blood pressure. Monitor for signs of misuse, abuse, and addiction. Monitor the efficacy of pain control. Monitor for signs of hypogonadism or hypoadrenalism.
Overdosage
Symptoms: Respiratory depression, pneumonia aspiration, pinpoint pupils, skeletal muscle flaccidity, hypotension, hypothermia, cold and clammy skin, bradycardia, somnolence, severe dizziness, severe drowsiness, hallucinations, convulsions (especially in infants and children), rhabdomyolysis leading to renal failure; circulatory failure, apnoea, CNS depression, stupor, coma, cardiac arrest. Management: Supportive treatment. Ensure adequate airway, ventilation and oxygenation. May administer opioid antagonist (e.g. naloxone) as an antidote.
Drug Interactions
Increased CNS depressant effect with other opioids, anxiolytics, sedatives, hypnotics (including benzodiazepines), muscle relaxants, antipsychotics, antidepressants (e.g. TCAs), general anaesthetics (including barbiturates), antiepileptics (e.g. pregabalin), gabapentin, antihypertensives, and centrally acting anti-emetics. Increased serum concentration with cimetidine. Decreased serum concentration with rifampicin, and ritonavir. May decrease the serum concentration of ciprofloxacin. Increased risk of severe constipation with antidiarrhoeal and antiperistaltic agents (e.g. loperamide, kaolin). May increase the anticoagulant effect of coumarin and other anti-coagulants. May delay absorption of mexiletine. May antagonise the gastrointestinal effect of metoclopramide, and domperidone. May decrease the therapeutic effect of diuretics. Potentially Fatal: Enhanced CNS depressant effects with MAOIs.
Food Interaction
Increased bioavailability (oral) with food. Enhanced CNS depressant effect with alcohol.
Lab Interference
May interfere with gastric emptying studies and hepatobiliary imaging using technetium Tc99m diosfenin.
Action
Description: Mechanism of Action: Morphine, a phenanthrene derivative, is an opioid analgesic that acts mainly on the CNS and smooth muscle. It binds to opioid receptors in the CNS causing a decrease in pain impulse transmission and altered pain perception and response. Onset: Approx 30 minutes (conventional tab); 5-10 minutes (IV). Duration: 3-5 hours (immediate-release); 8-24 hours (extended-release tab/cap); 3-7 hours (supp); up to 24 hours (epidural or intrathecal). Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract (oral) and readily absorbed into the blood (SC/IM). Increased bioavailability (conventional preparations) with food. Bioavailability: 17-33% (oral). Time to peak plasma concentration: 1 hour (conventional preparation, epidural); 3-4 hours (extended-release tab); 20-60 minutes (supp); 50-90 minutes (SC); 30-60 minutes (IM); 20 minutes (IV). Distribution: Distributed throughout the body mainly in the kidneys, lungs, liver, and spleen; lower concentration in the skeletal muscle and brain. Crosses the blood-brain barrier and placenta, enters breast milk. Volume of distribution: 1-6 L/kg. Plasma protein binding: 20-35%. Metabolism: Metabolised in the liver and gut via conjugation with glucuronic acid into morphine-3-glucuronide and morphine-6-glucuronide; undergoes extensive first-pass metabolism. Excretion: Via urine (approx 90% of total morphine); faeces (approx 10% as conjugates). Elimination half-life: 2-4 hours (immediate-release).
Chemical Structure
Morphine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5288826, Morphine. https://pubchem.ncbi.nlm.nih.gov/compound/Morphine. Accessed Aug. 16, 2023.
Storage
Tab/cap: Store between 15-30°C. Protect from light and moisture. Oral solution: Store below 30°C. Protect from light. Do not refrigerate. Inj/supp: Store between 20-25°C. Protect from light. Do not freeze. Storage recommendations may vary among individual products. Refer to specific product guidelines.
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