Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. Initially, 5 mg epidural inj, if desired pain relief is not achieved within 1 hour, incremental doses of 1-2 mg may be given up to 10 mg/24 hour.
Intraspinal Postoperative pain
Adult: As morphine sulfate liposomal inj: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. 10-20 mg for lumbar administration only depending on the type of surgery. Dose adjustments may be required according to individual response.
Intrathecal Moderate to severe pain
Adult: As morphine sulfate: 0.2-1 mg as single dose for up to 24 hours. Dosage is individualised based on the severity of pain, patient response and prior analgesic experience.
Intravenous Moderate to severe pain, Pain associated with myocardial infarction, Postoperative pain, Severe cancer pain
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. As Patient-Controlled Analgesia (PCA): Loading dose: 1-10 mg (Max 15 mg) via IV infusion over 4-5 minutes, then 1 mg on demand with 5-10 minutes lockout time. Elderly: Dose reduction needed.
Oral Moderate to severe pain
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. As conventional preparation: 5-20 mg 4 hourly. As extended-release tab/cap: Recommended initial dose: 1 or 2 (10 mg) tab 12-24 hourly. Child: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. As conventional preparation: 1-5 years 5 mg 4 hourly (Max: 30 mg daily); 6-12 years 5-10 mg 4 hourly (Max: 60 mg daily); ≥13 years Same as adult dose.
Parenteral Severe pain
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. Recommended dose: 10-20 mg 4-6 hourly (dose may vary from 5-20 mg) via SC, IM or IV inj. Elderly: Dose reduction needed.
Parenteral Acute pulmonary oedema, Premedication in surgery
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. Recommended dose: 10 mg 4 hourly if necessary (dose may vary from 5-20 mg) via SC or IM inj. May also be given via IV infusion at a dose corresponding to ¼ - ½ of the IM dose not more than 4 hourly. Elderly: Dose reduction needed.
Parenteral Severe cancer pain, Severe pain
Adult: As morphine tartrate: 5-20 mg 4-6 hourly via SC/IM inj. If rapid onset of action is desired, may give 2.5-15 mg via slow IV inj over 4-5 minutes. As IV Patient-controlled analgesia (PCA): 1 mg/hour administered with a lockout interval of 6-10 minutes and 0.5 (Max of 1.5 mg) demand doses. Child: As morphine tartrate: 0.1-0.2 mg/kg 4-6 hourly via SC/IM inj. Max dose: 15 mg. If rapid of onset is desired, 0.05-0.1 mg/kg via slow IV inj, may titrate dose incrementally over 5-15 minutes.
Rectal Severe pain
Adult: As morphine sulfate: Dosage is individualised based on the severity of pain, patient response and prior analgesic experience. 10-20 mg 4 hourly.
Renal Impairment
Oral Moderate to severe pain: Dose reduction needed.
Parenteral Acute pulmonary oedema; Premedication in surgery; Severe pain; Severe cancer pain: Dose reduction needed.
Intravenous Moderate to severe pain; Pain associated with myocardial infarction; Postoperative pain; Severe cancer pain: Dose reduction needed.
Hepatic Impairment
Oral Moderate to severe pain: Dose reduction needed.
Parenteral Acute pulmonary oedema; Premedication in surgery; Severe pain; Severe cancer pain: Dose reduction needed.
Intravenous Moderate to severe pain; Pain associated with myocardial infarction; Postoperative pain; Severe cancer pain: Dose reduction needed.
Administration
May be taken with or without food. May be taken w/ meals to reduce GI discomfort.
Hypersensitivity. Respiratory depression, obstructive airway disease, paralytic ileus, acute hepatic disease, acute alcoholism, head injuries, increased intracranial pressure, excessive bronchial secretions, acute or severe bronchial asthma, heart failure secondary to chronic lung disease, delayed gastric emptying, GI obstruction, acute abdomen, circulatory shock. Concomitant use during or within 14 days of MAOI therapy.
Special Precautions
Patient with hypovolaemia, CV disease (including acute MI), circulatory shock, adrenal insufficiency, Addison disease, biliary tract dysfunction, acute pancreatitis, delirium tremens, prostatic hyperplasia, urinary stricture, toxic psychosis, myasthenia gravis, mental health conditions (e.g. depression, anxiety, post-traumatic stress disorder), seizure, thyroid dysfunction, history of drug abuse or acute alcoholism, obese. Renal and severe hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: CNS depression, orthostatic hypotension, severe hypotension, syncope constipation. Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Bradycardia, palpitation, tachycardia. Eye disorder: Blurred or double vision, miosis. Gastrointestinal disorders: Abdominal pain, constipation, delayed gastric emptying, diarrhoea, dyspepsia, flatulence, nausea, vomiting, xerostomia, dry mouth, anorexia. General disorders and administration site conditions: Asthenic conditions, hyperhidrosis, withdrawal syndrome. Hepatobiliary disorders: Biliary colic, hypoesthesia, hypokalemia.
Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Dizziness, headache, paresthesia, paralytic ileus, myoclonus.
Psychiatric disorders: Anxiety, confusion, dependence, insomnia hallucination, euphoria, agitation, mood altered. Renal and urinary disorders: Bladder spasm, oliguria, urinary retention. Reproductive system and breast disorders: Decreased libido or potency (long term use). Respiratory, thoracic and mediastinal disorders: Dyspnea, hypoxia, rigors, bronchospasm, pulmonary oedema. Skin and subcutaneous tissue disorders: Pruritus, skin rash, urticaria, sweating. Vascular disorders: Hypertension, facial flushing. 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
Monitor efficacy of pain control, vital signs, respiratory and mental status. Assess physical and/or psychological dependence. Monitor signs or symptoms of hypogonadism or hypoadrenalism.
Overdosage
Symptoms: Respiratory depression, pinpoint pupils, hypoxia, hypothermia, severe dizziness, severe drowsiness, hypotension, bradycardia, circulatory failure pulmonary oedema, severe nervousness or restlessness, hallucinations, convulsion (especially in infants and children); skeletal muscle flaccidity, cold and clammy skin. Management: Ensure adequate airway, ventilation and oxygenation. Administration of opioid antagonist e.g. naloxone may be given as an antidote.
Drug Interactions
Increased depressant effects with other CNS depressants (e.g. sedatives, hypnotics, general anaesthesia, phenothiazines, tranquilisers). May enhance the neuromuscular blocking action of skeletal muscle relaxants. Reduced analgesic effect with mixed agonist/antagonist opioid analgesics (e.g. buprenorphine, nalbuphine, pentazocine). Increased plasma concentrations with cimetidine. Reduced plasma concentration with rifampicin, ritonavir. Decreased therapeutic effect of diuretics. Increased plasma concentration with cisapride. Increased risk of orthostatic hypotension with antihypertensive agents. Increased risk of severe constipation and CNS depression with antidiarrhoeal agents Potentially Fatal: Enhanced depressant effect with MAOIs.
Food Interaction
Alcohol enhances the CNS depressant effect of morphine. Increased bioavailability with food (oral).
Lab Interference
May interfere with gastric emptying studies and with hepatobiliary imaging using technetium Tc99m diosfenin.
Action
Description: Morphine, an opioid analgesic, is a phenanthrene derivative which acts mainly on the CNS and smooth muscles. It binds to opiate receptors in the CNS altering pain perception and response by modulating the descending inhibitory pathways from the brain. Analgesia, euphoria and dependence are thought to be due to its action at the µ-1 receptors while respiratory depression and inhibition of intestinal movements are due to action at the µ-2 receptors. Spinal analgesia is mediated by morphine agonist action at the κ receptor. 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 (single dose epidural or intrathecal). Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract (oral) and into the blood (SC/IM). Increased bioavailability with food. Bioavailability: 17-33 % (oral). Time to peak plasma concentration: 1 hour (conventional tab, epidural); 3-4 hours (extended-release tab); 20-60 minutes (supp); 50-90 minutes (SC); 30-60 minutes (IM); 20 minutes (IV). Distribution: Widely distributed throughout the body mainly in the kidneys, liver, lungs and spleen, with lower concentrations in the brain and muscles. Crosses the blood-brain barrier and placenta; enters breast milk. Volume of distribution: 1-6 L/kg. Plasma protein binding: Approx 35%. Metabolism: Metabolised in the liver and gut via glucuronidation to produce morphine-3-glucoronide and morphine-6-glucoronide; undergoes extensive first-pass metabolism. Excretion: Via urine [approx 60% (oral); approx 90% (parenteral)]; faeces (10%, as conjugates). Elimination half-life: Approx 2 hours (morphine); 2.4-6.7 hours (morphine-3-glucoronide).
Chemical Structure
Morphine Source: National Center for Biotechnology Information. PubChem Database. Morphine, CID=5288826, https://pubchem.ncbi.nlm.nih.gov/compound/Morphine (accessed on Jan. 23, 2020)
Storage
Store between 20-25°C. Protect from light and moisture.
N02AA01 - morphine ; Belongs to the class of natural opium alkaloids. Used to relieve pain.
References
Anon. Morphine (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/08/2018.Anon. Morphine Sulfate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 07/08/2018.Buckingham R (ed). Morphine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/08/2018.Depodur (Endo Pharmaceuticals Inc.). U.S. FDA. https://www.fda.gov/. Accessed 21/09/2018.Depodur Injection, Lipid Complex (Pacira Pharmaceuticlas Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/07/2014.Duramorph (Baxter Healthcare Corporation). U.S. FDA. https://www.fda.gov/. Accessed 21/09/2018.Joint Formulary Committee. Morphine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/08/2018.Morphine Sulfate Capsule, Extended Release (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/08/2018.Morphine Sulfate Injection (West-Ward Pharmaceuticals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/08/2018.Morphine Sulfate Suppository (Paddock Laboratories, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/08/2018.Morphine Sulfate Tablet, Film Coated, Extended Release (Watson Laboratories, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/08/2018.
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