Morphine Sulphate

Registered South African indications:

• Intractable pain not controlled with non-narcotic analgesics

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Respiratory depression
• Obstructive airways disease
  - Especially in the presence of cyanosis and excessive bronchial secretion
• Acute alcoholism
• Head injuries
• Seizure disorders
• Conditions of raised intracranial pressure
• Acute bronchial asthma
• Heart failure secondary to chronic lung disease
• Children <1 years
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Acute respiratory depression
• Obstructive airways disease
• Cerebral oedema
• Head injuries
• Coma
• Seizure disorders
• Raised intracranial pressure
• Biliary colic
• Acute alcoholism
• Antibiotic induced pseudomembranous colitis
• Ulcerative colitis
• Phaeochromocytoma
• Paralytic ileus 
• Acute diarrhoea caused by poisoning or invasive pathogens
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use

South African recommendations

• Pregnancy
  - Labour
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Debilitated patients
• Decreased respiratory reserve
• Hypothyroidism
• Adrenocortical insufficiency
• Prostatic hypertrophy
• Myasthenia gravis
• Shock
• Inflammatory or obstructive bowel disorders
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy
• Breastfeeding
• Renal impairment
• Severe hepatic impairment
  - Cirrhosis
• Elderly
• Children<1 years 
• Asthma
• Reduced respiratory reserve
  - Emphysema
  - Chronic cor pulmonale
  - Kyphoscoliosis
  - Excessive obesity
  - Sleep apnoea
• Hypotension​​
• Hypothyroidism
• Adrenocortical insufficiency
• Prostatic hypertrophy
• Urethral stricture
• Shock
• Inflammatory or obstructive bowel disorders
• Debilitated patients
• Biliary disorders
  - Cholecystectomy
  (See additional prescribing points)
• Current or past history of substance misuse disorder
• Current or past history of alcohol abuse
• Prolonged use
• Abrupt withdrawal
• Risk of tolerance
• Risk of physical dependence
• Risk of psychological dependence
• Sickle cell disease
• Coadministration with central nervous system depressants
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

South African Standard Treatment Guidelines indications and dosages

• Click here for the Pain Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2019 Edition)
• Click here for the Sedation Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2019 Edition)
• Click here for the Anaesthesiology and Intensive Care Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2019 Edition)
• Click here for the Medicines Used in Palliative Care Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2019 Edition)

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South African registered indications and dosages

Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with morphine

Intractable pain not controlled with non-narcotic analgesics

• SC/IM: 5-20mg, 4hrly
• IV/SC: Loading dose: Up to 15mg, as a slow intravenous injection OR continuous infusion OR patient controlled infusion; Maintenance: 0.8-80mg/hr, as a continuous intravenous administration OR continuous subcutaneous infusion
• Intrathecal: 0.2-1mg, as a single dose

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

South African Standard Treatment Guidelines indications and dosages

For the different morphine salts, see additional prescribing points

• Click here for the Pain Control Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)
• Click here for the Anaesthetics Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)
• Click here for the Palliative Care Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)

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South African registered indications and dosages

Intractable pain not controlled with non-narcotic analgesics

SC/IM

• Younger than 1 year: Not established for use
• Between 1-5 years: 2.5-5mg
• Between 6-12 years: 5-10mg
• Older than 12 years: No information available

Pregnancy

South African recommendations

• Caution; positive evidence of risk
• The safety of morphine sulphate injection during pregnancy has not been established
• Morphine sulphate injection crosses the placenta, hence risk-benefit must be considered before use during pregnancy
• Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate
• Use during labour may cause respiratory depression in the neonate

Recommendations in other jurisdictions

• Caution; not recommended
• As with all drugs it is not advisable to administer morphine during pregnancy
• Since morphine rapidly crosses the placental barrier, it is not advised to administer morphine during pregnancy and labour
• Morphine sulphate injection may reduce uterine contractions, cause respiratory depression in the foetus and newborn infant, and may have significant effects on foetal heart rate
• Newborns whose mothers received opioid analgesics during pregnancy should be monitored for signs of neonatal withdrawal (abstinence) syndrome. Treatment may include an opioid and supportive care

Breastfeeding

South African recommendations 

• Caution; positive evidence of risk 
• The safety of morphine sulphate injection during breastfeeding has not been established
• Morphine sulphate injection is distributed in breastmilk; hence risk-benefit must be considered before use during breastfeeding

Recommendations in other jurisdictions

• Caution 
• The amount of morphine secreted in breast milk after a single-dose administration seems to be compatible with breastfeeding and insufficient to cause major problems or dependence
• However long-term treatment with morphine in high doses may cause significant plasma concentrations. That is why caution is advised on the use of morphine in breastfeeding patients and the benefit must outweigh the risk to the infant
• If breastfeeding is continued, the infant should be observed for possible adverse effects

Fertility

South African recommendations

• No information available

Recommendations in other jurisdictions

• Animal studies have shown that morphine may reduce fertility

South African recommendations

• Caution; dose adjustment recommended
  Morphine sulphate must be used with caution, or in reduced doses, in patients with impaired renal function
  *No specific dose adjustment has been provided by the manufacturer

Recommendations in other jurisdictions

• eGFR>10ml/min/1.73m²: Caution; no dose adjustment recommended
  No specific dose adjustment has been provided by the manufacturer. It is recommended to start cautiously with lower doses; titrating slowly while carefully monitoring renal function parameters
• eGFR<10ml/min/1.73m²: Caution; not recommended 

South African recommendations

• Caution; dose adjustment recommended
  Morphine sulphate must be used with caution, or in reduced doses, in patients with impaired hepatic function
  *No specific dose adjustment has been provided by the manufacturer

Recommendations in other jurisdictions

• Mild to Moderate (Child-Pugh classes A or B): No dose adjustment recommended 
• Severe impairment (Child-Pugh class C) or cirrhosis: Caution; dose adjustment recommended 
  Caution is advised when giving morphine to patients with impaired hepatic function due to its hepatic metabolism, and reduction in dosage should be considered
  *No specific dose adjustment has been provided by the manufacturer

South African recommendations

• Caution; dose adjustment recommended
  The dosage should be reduced in the elderly and debilitated patient
  *No specific dose adjustment has been provided by the manufacturer

Recommendations in other jurisdictions

• Caution; dose adjustment recommended 
  As with all narcotics, a reduction in dosage may be advisable in the elderly
  It is recommended to start cautiously with lower doses; titrating slowly while carefully observing for signs of toxicity. Use is not recommended in elderly patients with hepatic and/or renal impairments
  *No specific dose adjustment has been provided by the manufacturer

Central Nervous System Disorders

• Confusion
• Drowsiness
• Headache
• Hallucinations
• Altered mood
  - Mood swings
• Drug dependence
  - Psychological dependence (addiction)
  - Physical dependence
  (See additional prescribing points)
• Seizures
• Hyperalgesia
• Restlessness
• Allodynia
• Fatigue
• Myoclonus
• Increased intracranial pressure
• Coma
• Hyperaesthesia
• Medicine tolerance
• Medicine withdrawal syndrome
• Neonatal medicine withdrawal syndrome

Cardiovascular Disorders

• Palpitations
• Bradycardia
• Tachycardia
• Facial flushing
• Hypotension
• Orthostatic hypotension
• Circulatory failure

Respiratory Disorders

• Respiratory depression
• Bronchospasm (potentially fatal outcomes)
• Pulmonary oedema (potentially fatal outcomes)
• Respiratory failure (potentially fatal outcomes)

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting
• Dry mouth
• Paralytic ileus
• Intestinal functional disordes
• Narcotic bowel syndrome

Hepatobiliary Disorders

• Biliary spasm
• Increased hepatic enzymes
• Spasm of the sphincter of oddi

Genitourinary Disorders

• Urethral spasm (inj)
• Urinary retention
• Decreased libido
• Erectile dysfunction

Endocrine and Metabolic Disorders

• Hypothermia
• Increased serum prolactin
• Reversible adrenal insufficiency
  (See additional prescribing points)

Musculoskeletal Disorders

• Muscle rigidity
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Pruritis
• Urticaria
• Contact dermatitis
• Injection site pain
• Injection site irritation

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reaction
• Anaphylactoid reaction
• Hypersensitivity
• Angioedema

Sensory Disorders

• Miosis
• Blurred vision
• Nystagmus
• Vertigo

• Monoamine oxidase inhibitors
• Selegiline
• Moclobemide
• Linezolid
• Central nervous system depressants
  (See additional prescribing points)
• Concomitant opioids
• Hypnotics
• Sedatives
• Benzodiazepines
• Tricyclic antidepressants
• Antipsychotics
• Sedating antihistamines
• Cimetidine
• Antibacterial agents
• Rifampicin
• Ritonavir
• Metoclopramide
• Domperidone
• Antiarrhythmics
• Mexiletine
• Anxiolytics
• Antidiarrhoeal and antiperistaltic agents
• Loperamide
• Kaolin
• Antimuscarinics
• Atropine
• ciprofloxacin
• Oral P2Y12 inhibitors
  (See additional prescribing points)

Other interactions

• Alcohol

• Respiratory function
• Blood pressure
• Oxygenation
• Level of consciousness
• Urine drug testing

Additional observations

• Signs and symptoms
  - Hypogonadism
  - Hypoadrenalism
  - Misuse, abuse, and addiction
• Mental status
• Pain control

Morphine salts available in South Africa

Morphine Sulphate	Morphine Hydrochloride	Morphine Tartrate
Slow release tablet; Injection	Powder (Discontinued)	Combination preparation, see Morphine/ Cyclizine

Additional warning

• Morphine is a potent medicine but with considerable potential for harmful effect, including addiction. It should be used only if other agents with fewer hazards are inadequate, and with the recognition that it may possibly mask significant manifestations of disease which should be identified for proper diagnosis and treatment

Adrenal insufficiency

• Opioid analgesics may cause reversible adrenal insufficiency requiring monitoring and glucocorticoid replacement therapy
• Symptoms of adrenal insufficiency may include e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure

Drug abuse, dependence and withdrawal (abstinence) syndrome

• Morphine has an abuse potential similar to other strong agonist opioids, and should be used with special caution in patients with a history of alcohol or drug abuse
• Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance
• The risk increases with the time the agent is used, and with higher doses
• Symptoms can be minimised with adjustments of dose or dosage form, and gradual withdrawal of morphine
• Hyperalgesia that does not respond to a further dose increase of morphine may occur in particular in high doses
• A morphine dose reduction or change in opioid may be required
• An unexplained increase in abdominal pain associated with disturbed intestinal motility, symptoms of constipation, bloating, abdominal distension and increased gastroesophageal reflux during treatment with morphine sulphate, may indicate the development of opioid-induced bowel dysfunction or narcotic bowel syndrome
• In such situations consider the use of alternative analgesics and a morphine detoxification

Biliary disorders

• Opioids such as morphine should either be avoided in patients with biliary disorders or they should be given with an antispasmodic
• Morphine can cause an increase in intrabiliary pressure as a result of effects on the sphincter of Oddi; therefore in patients with biliary tract disorders morphine may exacerbate pain (use in biliary colic is a contraindication)
• In patients given morphine after cholecystectomy, biliary pain has been induced

Coadministration with central nervous system depressants

• Coadministration of morphine sulphate and sedative medicines such as benzodiazepines or related agents may result in sedation, respiratory depression, coma and death
• Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible
• If a decision is made to prescribe morphine sulphate concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible
• The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD)

• Due to a possible association between ACS and morphine use in SCD patients treated with morphine during a vaso-occlusive crisis, close monitoring for ACS symptoms is warranted

Oral P2Y12 inhibitors

• A delayed and decreased exposure to oral P2Y12 inhibitor antiplatelet therapy has been observed in patients with acute coronary syndrome treated with morphine
• This interaction may be related to reduced gastrointestinal motility and apply to other opioids
• The clinical relevance is unknown, but data indicate the potential for reduced P2Y12 inhibitor efficacy in patients coadministered morphine and a P2Y12 inhibitor
• In patients with acute coronary syndrome, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered

Morphine is a narcotic analgesic obtained from opium, which acts mainly on the central nervous system and smooth muscle.

Injection (per ml) 10mg

• Morphine Sulphate Fresenius PF 10mg/1ml (Fresenius) originator
• Mylan Morphine ( Mylan)
• Pharma-Q Morphine 10mg Injection (Pharma-Q)
• Sabax Morphine 1ml (Adcock)

Injection (per ml) 15mg

• Morphine Sulphate Fresenius PF 15mg/1ml (Fresenius) originator
• Mylan Morphine (SCP Pharmaceuticals)
• Pharma-Q Morphine 15mg Injection (Pharma-Q)
• Sabax Morphine 1ml (Adcock)