Morphine Sulfate is indicated for the long-term management of severe and persistent pain that is difficult to control, as well as for the relief of postoperative pain.

Morphine is a phenanthrene derivative that primarily acts on the central nervous system (CNS) and smooth muscles. It binds to opioid receptors in the CNS, altering the perception of pain and the emotional response to it. Its analgesic and euphoric effects, as well as the potential for dependence, are mainly mediated through mu-1 receptors. Respiratory depression and reduced gastrointestinal motility are associated with its action on mu-2 receptors. Additionally, spinal analgesia is produced through its agonist activity at kappa (K) receptors.

15 mg retard tablet:

Adults: A patient presenting with severe pain, uncontrolled by weaker opioids (e.g. dihydrocodeine) should normally be started on 30 mg 12 hourly. Patients previously on normal release oral morphine should be given the same total daily dose as Morphine Sulphate 15 mg tablets but in divided doses at 12-hourly intervals. Increasing severity of pain will require an increased dosage of the tablets. Higher doses should be made, where possible in 30–50% increments as required. The correct dosage for any individual patient is that which is sufficient to control pain with no, or tolerable, side effects for a full 12 hours. Patients receiving Morphine Sulphate 15 mg tablets in place of parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction in analgesic effects associated with oral administration. Usually such increased requirement is of the order of 100%. In patients with advanced cancer pain, adjustments are required.

Children: For children with severe cancer pain, a starting dose in the range of 0.2 to 0.8 mg per kg bodyweight at 12 hourly is recommended. Post-operative pain: Morphine Sulphate 15 mg tablets are not recommended in the first 24 hours post-operatively until normal bowel function has returned; thereafter it is suggested that the following dosage schedule be observed at the physician’s discretion: (a) Morphine Sulphate 30 mg tablets 12 hourly to patients over 70 kg, (b) Elderly – a reduction in dosage may be advisable in the elderly, (c) Children – not recommended. Supplemental parenteral morphine may be given if required but with careful attention to the total dosages of morphine, and bearing in mind the prolonged effects of morphine in this prolonged release formulation.

10 mg tablet:

Adults and children over 12 years: The dosage of Morphine 10 mg tablet is dependent on the severity of pain and the patient’s previous history of analgesic requirements. One Morphine 10 mg tablet to be taken every four hours or as directed by a physician. Increasing severity of pain or tolerance to morphine will require increased dosage of Morphine 10 mg tablet to achieve the desired relief. Patients receiving morphine orally in place of parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction in analgesic effects associated with oral administration. Usually such increased requirement is of the order of 100%. In such patients individual dose adjustments are required.

Elderly: A reduction in adult dosage may be advisable.

Children 3–12 years of age: 3–5 years – 5 mg, 4-hourly; 6–12 years – 5–10 mg, 4-hourly.

Oral Solution:

• Adults: Usual dose 10–20 mg (5–10 ml) every 4 hours.
• Children 13 to 18 years: Maximum single dose 5–20 mg (2.5–10 ml) every 4 hours.
• Children 6–12 years: Maximum dose 5–10 mg (2.5–5 ml) every 4 hours.
• Children 1–5 years: Maximum dose 5 mg (2.5 ml) every 4 hours.
• Children under 1 year: Not recommended.

Dosage can be increased under medical supervision according to the severity of the pain and the patient’s previous history of analgesic requirements. Reductions in dosage may be appropriate in the elderly, patients with moderate-severe renal or hepatic impairment, or where sedation is undesirable.

Morphine Sulfate is readily absorbed from the gastrointestinal tract following oral administration. However, when Oral Solution (5 mg/5 ml) is used in place of parenteral morphine, a 50% to 100% increase in dosage is usually required in order to achieve the same level of analgesia.

Morphine should be used cautiously in patients receiving other central nervous system (CNS) depressants such as sedatives, hypnotics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, antihypertensives, and alcohol. Combined use may lead to enhanced effects such as respiratory depression, hypotension, deep sedation, or even coma. Mixed agonist/antagonist opioids (e.g., buprenorphine, nalbuphine, pentazocine) should not be used in patients already treated with pure opioid agonists. Drugs with anticholinergic effects (e.g., antihistamines, anti-parkinsonian agents, antiemetics) may increase anticholinergic side effects. Cimetidine may inhibit morphine metabolism. Monoamine oxidase inhibitors (MAOIs) may interact with morphine causing CNS excitation or depression and blood pressure instability; therefore, morphine should not be used with MAOIs or within 2 weeks of discontinuation. Rifampicin may reduce morphine levels, while ritonavir may also decrease its plasma concentration by inducing liver enzymes.

Morphine Sulfate is contraindicated in patients with hypersensitivity to morphine, respiratory depression, head injury, obstructive airway disease, paralytic ileus, acute abdominal conditions, delayed gastric emptying, acute liver disease, or those receiving MAO inhibitors. It is not recommended during pregnancy or in children below 3 years.

At usual doses, the most frequently reported side effects of morphine include nausea, vomiting, constipation, and drowsiness. During long-term use, nausea and vomiting are less common with morphine sulphate tablets; however, if they occur, an antiemetic may be administered if necessary. Constipation can be managed with appropriate laxatives. Psychiatric disorders: Common – confusion, insomnia. Nervous system disorders: Common – dizziness, headache, involuntary muscle contractions, drowsiness. Gastrointestinal disorders: Very common – constipation, nausea; Common – abdominal pain, loss of appetite, dry mouth, vomiting. Skin and subcutaneous tissue disorders: Common – excessive sweating (hyperhidrosis), rash. General disorders: Asthenia, pruritus.

Morphine is not recommended during pregnancy or labor due to the risk of neonatal respiratory depression. It is excreted in breast milk and should not be used during breastfeeding. Withdrawal symptoms may occur in newborns of mothers using morphine chronically.

The primary risk associated with opioid overdose is respiratory depression. As with all narcotic agents, dose reduction may be necessary in elderly patients, those with hypothyroidism, and individuals with renal or chronic hepatic impairment. Caution is required in patients with impaired respiratory function, severe bronchial asthma, convulsive disorders, acute alcoholism, delirium tremens, increased intracranial pressure, hypotension with hypovolaemia, severe cor pulmonale, opioid dependence, and in patients with a history of substance abuse, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, or adrenocortical insufficiency. Morphine sulphate tablets should not be used in cases where paralytic ileus is suspected or present. If paralytic ileus occurs during treatment, the medication should be discontinued immediately. Morphine may reduce the seizure threshold in patients with epilepsy. Individuals with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication. Tolerance to morphine may develop with prolonged use, requiring higher doses to maintain adequate pain control. Long-term use may also result in physical dependence, and abrupt discontinuation can lead to withdrawal symptoms; therefore, gradual dose reduction is recommended when stopping therapy. Hyperalgesia that does not respond to dose escalation may require dose reduction or switching to an alternative opioid. Although rare, high doses of morphine sulphate may cause hyperalgesia. Morphine has a known potential for abuse similar to other strong opioids and may be sought or misused by individuals with substance use disorders. There is a risk of developing psychological dependence (addiction) to opioid analgesics, including morphine. Extra caution is advised in patients with a history of alcohol or drug misuse. Misuse of oral formulations through parenteral administration can lead to severe adverse events, including fatal outcomes.

Symptoms of morphine toxicity and overdose include pinpoint pupils, skeletal muscle flaccidity, bradycardia, respiratory depression, hypotension, drowsiness, and central nervous system depression that may progress to stupor or coma. In severe cases, circulatory failure and worsening coma may occur. Rhabdomyolysis leading to renal failure has also been reported. Management should prioritize securing a patent airway and providing assisted or controlled ventilation. Activated charcoal (50 g for adults, 1 g/kg for children) may be administered if a significant overdose is suspected within one hour, provided the airway is protected. Naloxone is a specific antidote for opioid overdose. In cases of severe overdose, administer naloxone 0.8 mg intravenously, repeating every 2–3 minutes as necessary, or by infusion (2 mg in 500 mL normal saline or 5% dextrose, equivalent to 0.004 mg/mL), adjusted according to patient response. Due to the relatively short duration of action of naloxone, patients should be closely monitored until normal respiration is consistently maintained. In less severe cases, naloxone 0.2 mg intravenously may be given, followed by incremental doses of 0.1 mg every 2 minutes if required. Naloxone should not be used in the absence of clinically significant respiratory or circulatory depression due to opioid overdose. Naloxone should be administered cautiously in individuals with known or suspected physical dependence on opioids, as rapid or complete reversal of opioid effects may precipitate acute withdrawal symptoms.

Opioid analgesic

Store in a cool, dry place and protect from light.