Boxed Warnings
Limitations of use. Because of the risks associated with the use of opioids, morphine should only be used in patients for whom other treatment options, including non-opioid analgesics, are ineffective, not tolerated or otherwise inadequate to provide appropriate management of pain (see Section 4.4 Special Warnings and Precautions for Use).
Hazardous and harmful use. Morphine poses risks of hazardous and harmful use which can lead to overdose and death. Assess the patient's risk of hazardous and harmful use before prescribing and monitor the patient regularly during treatment (see Section 4.4 Special Warnings and Precautions for Use).
Life-threatening respiratory depression. Serious, life-threatening or fatal respiratory depression may occur with the use of morphine. Be aware of situations which increase the risk of respiratory depression, modify dosing in patients at risk and monitor patients closely, especially on initiation or following a dose increase (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant use of benzodiazepines and other central nervous system (CNS) depressants, including alcohol. Concomitant use of opioids with other opioids analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, general anaesthetics, tranquilisers, beta blocker, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required; and monitor patients for signs and symptoms of respiratory depression and sedation. Caution patients not to drink alcohol while using morphine (see Section 4.4 Special Warnings and Precautions for Use).
1 Name of Medicine
Morphine sulfate pentahydrate.
2 Qualitative and Quantitative Composition
Each mL of isotonic preparations of DBL Morphine Sulfate Injection contains morphine sulfate pentahydrate 5 milligram, 10 milligram, 15 milligram or 30 milligram. These are sterile solutions of morphine sulfate pentahydrate and sodium chloride in water for injections. 1 N hydrochloric acid is used to adjust the pH. The pH of these solutions ranges from 3.2 to 4.0.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Solution for injection.
DBL Morphine Sulfate Injection 5 mg/1 mL, 10 mg/1 mL and 15 mg/1 mL: clear slightly yellow, sterile solution.
DBL Morphine Sulfate Injection 30 mg/1 mL: clear yellow, sterile solution.
DBL Morphine Sulfate Injection does not contain any antioxidant or preservative.
4 Clinical Particulars
4.9 Overdose
Symptoms. Overdosage with morphine is characterised by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), pneumonia aspiration, pulmonary oedema, extreme somnolence progressing to stupor or coma, confusion, severe dizziness, severe drowsiness, severe nervousness or restlessness, hallucinations, convulsions (especially in infants and children), skeletal muscle flaccidity, hypothermia, cold and clammy skin, and sometimes bradycardia and hypotension. Rhabdomyolysis, progressing to renal failure, has been reported in overdosage. In severe overdosage, apnoea, circulatory collapse, cardiac arrest and death may occur.
The triad of respiratory depression, coma and constricted pupils is considered indicative of opioid overdosage with dilatation of the pupils occurring as hypoxia develops. Death may occur from respiratory failure.
Treatment. Immediate attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation.
In patients physically dependent on opioids, respiratory support is the first line of treatment. In these patients, the use of naloxone is potentially dangerous.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.
The opioid antagonist, naloxone, is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids. The recommended adult dose of naloxone for the treatment of severe opiate induced respiratory depression is 0.4 to 2 milligram intravenously every 2 to 3 minutes as necessary, simultaneously with assisted respiration.
For children, the initial dose recommended is 0.01 milligram/kg naloxone. A response should be seen after 2 to 3 doses. Note the duration of action of naloxone is usually shorter than that of morphine and thus the patient should be carefully observed for signs of CNS depression returning.
If the response to naloxone is suboptimal or not sustained, additional naloxone may be administered as needed, or given by continuous intravenous infusion to maintain alertness and respiratory function. There is no information available about the cumulative dose of naloxone that may be safely administered.
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to morphine overdosage.
Naloxone should be administered cautiously to persons who are known or suspected to be physically dependent on morphine. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. If it is necessary to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care and by titration with smaller than usual doses of the antagonist.
Morphine toxicity may be a result of overdosage but because of the large inter-individual variation in sensitivity to opioids it is difficult to assess the exact dose of any opioid that is toxic or lethal. The toxic effects of morphine tend to be overshadowed by the presence of pain or tolerance. Patients having chronic morphine therapy have been known to take in excess of 3,000 milligram/day with no apparent toxic effects being present.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. No data available.
Carcinogenicity. No data available.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure. The structural formula of morphine sulfate pentahydrate is shown below:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSMORSUP.gif CAS number. 6211-15-0.
7 Medicine Schedule (Poisons Standard)
S8 - Controlled Drug.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DBLMORST.gif
