Consumer medicine information

Morphine MR AN Controlled release tablets

Morphine sulfate pentahydrate


Brand name

Morphine MR AN Controlled release tablets

Active ingredient

Morphine sulfate pentahydrate




Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Morphine MR AN Controlled release tablets.

What is in this leaflet

Read this leaflet carefully before taking your medicine.

This leaflet answers some common questions about MORPHINE MR AN. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is MORPHINE MR AN. It contains the active ingredient morphine sulfate pentahydrate

It is used to treat:

  • chronic severe pain.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

How it works

Opioid analgesics such as morphine sulphate have been used to treat chronic cancer pain for many years. In most cases addiction does not occur. However, over time your body becomes used to taking morphine, so if you suddenly stop taking your MORPHINE MR AN tablets you may experience some symptoms of withdrawal.

It is important that you discuss this issue with your doctor.

Use in children

This medicine must not be used in children under one year of age or weighing less than 25 kg. Safety and effectiveness has not been established in children under one year of age or weighing less than 25kg.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You have or have had any of the following:
  • shallow breathing or other breathing problems, such as severe asthma, impaired lung function or chronic bronchitis
  • severely drowsy or a reduced level of consciousness
  • irregular or rapid heart beats
  • heart disease
  • regularly drinking large amounts of alcohol or have confusion and shaking due to stopping drinking alcohol
  • long lasting pain not due to disease progression and have a history of substance and alcohol abuse
  • fits or convulsions
  • head injury, brain tumour, increased pressure in your head or spine
  • are about to have an operation or have had one within the last 24 hours
  • severe kidney or liver disease or a disease of the brain caused by liver disease
  • severe abdominal pain with bloating, cramps or vomiting
  • a condition where your stomach empties more slowly than it should, your small bowel does not work properly or you have just had an operation on your abdomen
  • taking medicine for depression called a ‘monoamine oxidase inhibitor’ or have taken any in the last two weeks
  • You are pregnant.
  • MORPHINE MR AN may affect your developing baby if you take it during pregnancy.
  • Like most medicines of this kind, MORPHINE MR AN is not recommended to be taken during pregnancy. Your doctor will discuss the risks and benefits of using it if you are pregnant.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.
  • You are hypersensitive or have had an allergic reaction to MORPHINE MR AN, other opioid analgesics, or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting or hayfever-like symptoms.
  • If you think you are having an allergic reaction do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • Please note if you are lactose intolerant that some of the strengths of this medicine also contain lactose (except for 100 mg).

Before you start to take it

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • low blood pressure including from having low blood volume
  • increased prostate size or difficulty passing urine
  • problems or recent surgery of your gall bladder or bile duct
  • inflammation of the pancreas
  • adrenal glands not working properly
  • underactive thyroid gland
  • acute abdominal pain
  • inflammatory bowel disease or recent abdominal surgery.
  1. This medicine is not recommended to be taken during labour.

Morphine given to the mother during labour can cause breathing problems in the newborn.

  1. You are currently breast-feeding or you plan to breastfeed.

Morphine can pass into the breast milk and can affect the baby. Your doctor can discuss with you the risks and benefits involved.

  1. You are planning to have surgery or an anaesthetic.
  2. You are currently receiving or are planning to receive dental treatment.
  3. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines may interact with MORPHINE MR AN. These include:

  • medicines to treat depression, psychiatric or mental disorders. Medicines for depression belonging to a group called monoamine oxidase inhibitors must be stopped 14 days before MORPHINE MR AN tablets are taken.
  • medicines to help you sleep
  • medicines to put you to sleep during an operation or procedure
  • medicines to relax your muscles
  • medicines to prevent or relieve the symptoms of allergy such as antihistamines
  • propranolol or other medicines to lower blood pressure
  • gabapentin or barbiturates to treat seizures
  • medicines to thin the blood e.g. coumarin derivatives such as warfarin
  • medicines used to relieve heartburn or treat stomach ulcers such as cimetidine or antacids (take antacids at least 2 hours after taking MORPHINE MR AN tablets)
  • medicines to treat Parkinson's disease
  • medicines to stop nausea or vomiting e.g. metoclopramide
  • rifampicin, a medicine to treat tuberculosis
  • other pain relievers including other opioids
  • alcohol
  • medicines to treat HIV infection
  • amphetamines

If you are taking any of these you may need a different dose or you may need to take different medicines.

Other medicines not listed above may also interact with MORPHINE MR AN.

How to take this medicine

Follow carefully all directions given to you by your doctor or pharmacist. Their instructions may be different to the information in this leaflet.

How much to take

Your doctor or pharmacist will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

How to take it

MORPHINE MR AN tablets must be swallowed whole. MORPHINE MR AN tablets must not be chewed, crushed or dissolved.

MORPHINE MR AN tablets are only designed to work properly if swallowed whole. The tablets may release all their contents at once if broken, chewed, crushed or dissolved which can be dangerous and cause serious problems, such as an overdose or even death.

If you have trouble swallowing your tablets whole, talk to your doctor.

You must only take MORPHINE MR AN tablets by mouth.

Taking this medicine in a manner other than that prescribed by your doctor can be harmful to your health.

When to take it

MORPHINE MR AN tablets should be taken every 12 hours.

MORPHINE MR AN tablets must be taken regularly to control the pain.

Taking MORPHINE MR AN tablets at regular time intervals means that the onset of pain is prevented.

It is important to take the tablets at the times you have been told to. If, however, you begin to experience pain and you are taking your MORPHINE MR AN as prescribed ('breakthrough pain'), contact your doctor as your dosage may have to be reviewed.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

If you stop taking this medicine suddenly, your pain may worsen and you may experience withdrawal symptoms such as:

  • body aches
  • loss of appetite, nausea, stomach cramps or diarrhoea
  • fast heart rate
  • sneezing or runny nose
  • chills, tremors, shivering or fever
  • trouble sleeping
  • increased sweating and yawning
  • weakness
  • nervousness or restlessness

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If you forget to take a dose, contact your doctor for advice.

Do not take a double dose to make up for missed doses.

This may increase the chance of you experiencing side effects.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints to help you remember.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively go to the Accident and Emergency Department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If someone takes an overdose they may become drowsy, tired, confused, lack muscle tone, have cold or clammy skin, have constricted pupils, have a very low blood pressure or slow heart rate, experience difficulties in breathing and possibly become unconscious or even die.

When seeking medical attention, take this leaflet and any remaining tablets with you to show the doctor. Also, tell them about any other medicines or alcohol which have been taken.

While you are taking this medicine

Things you must do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you become pregnant while taking this medicine, tell your doctor immediately
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.
  • your pain is getting worse or you are having more frequent breakthrough pain.

Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects. Go to your doctor regularly for a check-up.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours
  • Take your medicine to treat any other condition unless your doctor or pharmacist tells you to
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

Over time your body may become used to you taking morphine so if you stop taking it suddenly, your pain may worsen and you may experience withdrawal symptoms. This is called physical dependence.

If you need to stop taking this medicine, your doctor will gradually reduce the amount you take each day, if possible, before stopping the medicine completely.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

Ask your doctor's advice about whether or not it will be safe for you to drive or operate any machinery whilst taking MORPHINE MR AN.

You may feel drowsy when you begin to take MORPHINE MR AN tablets. If you drink alcohol, the drowsiness may be worse.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

You may suffer from nausea or vomiting when taking MORPHINE MR AN tablets. If you vomit 2-3 hours after your dose your pain may come back as you will not have absorbed your morphine. If this happens speak to your doctor. Your doctor may prescribe some medicine to help stop you vomiting.

Constipation can be caused by morphine. You should speak to your doctor about your diet and the proper use of laxatives.

There is potential for abuse of morphine and the development of addiction to morphine. It is important that you discuss this issue with your doctor.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking MORPHINE MR AN tablets or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor or pharmacist if you notice any of the following.

This list includes the more common side effects.

  • constipation
  • drowsiness
  • sweating
  • dizziness
  • nausea or vomiting

Other possible side effects are listed below. Tell your doctor or pharmacist as soon as possible if you notice any of the following:

  • breathing difficulties
  • loss of appetite
  • dry mouth or changes in taste
  • trouble sleeping
  • new problems with your eyesight
  • skin rash, redness in the face or itching
  • faintness
  • irregular periods or sexual problems
  • muscle twitching or muscle tightness
  • swelling of legs or ankles
  • stomach discomfort or cramps, indigestion or abdominal pain
  • abnormal thinking or changes in mood
  • slow or noticeable heartbeats
  • headache, confusion or hallucinations
  • unusual weakness or loss of strength
  • changes in passing urine such as the volume passed, pain or feeling the need to urinate urgently.
  • seizures, fits or convulsions

Other side effects not listed above may occur in some patients.

Allergic reactions

If you think you are having an allergic reaction to MORPHINE MR AN tablets, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • cough, shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue, or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hayfever-like symptoms

Storage and disposal


Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.


If your doctor or pharmacist tells you to stop taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What MORPHINE MR AN looks like

10 mg tablets
Buff coloured, biconvex, smooth, round, film coated tablets with 10 on one face

30 mg tablets
Violet coloured, biconvex, smooth, round, film coated tablets with 30 on one face

60 mg tablets
Orange coloured, biconvex, smooth, round, film coated tablets with 60 on one face

100 mg tablets
Grey coloured, biconvex, smooth, round, film coated tablets with 100 on one face

Available in blister packs of 20, 28 or 60 tablets.

* Not all strengths, pack types and/or pack sizes may be available.


Each tablet contains 10, 30, 60 or 100 mg of morphine sulfate pentahydrate as the active ingredient.

It also contains the following inactive ingredients:

  • lactose (except the 100 mg)
  • hyetellose
  • hypromellose
  • povidone
  • talc – purified,
  • magnesium stearate

The tablet coatings contain a different colourant for each strength, as follows:

  • 10 mg
  • Opadry buff OY-3607
  • 30 mg
  • Opadry violet OY-6708
  • 60 mg
  • Opadry orange OY-3533
  • 100 mg
  • Opadry grey OY-8238

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes. The 100 mg strength is lactose-free.

Australian Registration Numbers

MORPHINE MR AN 10 mg tablets (blisters): AUST R 225425.

MORPHINE MR AN 30 mg tablets (blisters): AUST R 225426.

MORPHINE MR AN 60 mg tablets (blisters): AUST R 225427.

MORPHINE MR AN 100 mg tablets (blisters): AUST R 225428.


Southern Cross Pharma Pty Ltd
Suite 5/118 Church St
Hawthorn VIC 3122

This leaflet was last updated in: June 2017


Brand name

Morphine MR AN Controlled release tablets

Active ingredient

Morphine sulfate pentahydrate




Name of the medicine

Morphine sulfate pentahydrate.


Lactose (except the 100 mg), hyetellose, hypromellose, povidone, purified talc and magnesium stearate. The tablet coating contain a different colourant for each strength, as follows: 10 mg - Opadry; 30 mg - Opadry violet OY-6708; 60 mg - Opadry orange OY-3533; 100 mg - Opadry grey OY-8238.


Chemical name: Di(7,8-didehydro-4,5α-epoxy-17-methylmorphinan-3,6α-diol) sulfate pentahydrate. Molecular formula: C34H40N2O10S.5H2O. Molecular Weight: 759. CAS Number: 6211-15-0.
Morphine sulfate pentahydrate is a white, odourless, crystalline powder or needle-like crystals. It is soluble in water and ethanol. It is practically insoluble in ether or chloroform.
Each modified release tablet contains 10 mg, 30 mg, 60 mg or 100 mg morphine sulfate pentahydrate as the active ingredient. In addition, each modified release tablet contains the following inactive ingredients: lactose (except the 100 mg), hyetellose, hypromellose, povidone, purified talc and magnesium stearate. The tablet coatings contain a different colourant for each strength, as follows:
10 mg - Opadry buff OY-3607.
30 mg - Opadry violet OY-6708.
60 mg - Opadry orange OY-3533.
100 mg - Opadry grey OY-8238.
Morphine sulfate pentahydrate 100 mg corresponds to 75 mg of morphine free base.


Pharmacological actions.

Morphine sulfate pentahydrate is a narcotic analgesic.


Morphine is a phenanthrene alkaloid obtained from opium. Morphine and related compounds interact with specific receptors primarily found in the brain, spinal cord and the myenteric plexus of the gut wall. In humans, the principal pharmacological actions of morphine are in the central nervous system (analgesia, drowsiness, mood changes (including euphoria and dysphoria), mental clouding, respiratory depression, nausea or emesis, miosis) and on smooth muscle (increased gastrointestinal tone with a reduction in propulsive motion, increased biliary pressure and increased tone of the ureter and vesical sphincter).
Morphine induced analgesia is a result of increases in both the pain threshold and pain tolerance. Morphine alters the affective response to pain, in that patients remain aware of its existence but are less distressed. Morphine relieves most types of pain but is more effective against dull constant pain than sharp intermittent pain.



Morphine is readily absorbed from the gastrointestinal tract, nasal mucosa and lung, and after subcutaneous or intramuscular injection. Due to first pass metabolism, the effect of an oral dose is less than that of the same dose given parenterally. The parenteral to oral morphine potency ratio has been reported to range from 1:6 to 1:2. In general, the greatest difference between parenteral and oral potency is seen in acute studies. With chronic dosing, oral morphine is about one-half to one-third as potent as when given by injection.


Following absorption, approximately 30 to 35% of morphine is reversibly bound to plasma proteins. Free morphine readily leaves the circulation and is concentrated in the liver, kidney, lung, spleen and, to a lesser extent, skeletal muscle. In adults, only small quantities of morphine pass the blood-brain barrier.


Conjugation with glucuronic acid is the major metabolic pathway for morphine. The major metabolite is morphine-3-glucuronide. Other metabolites include normorphine, morphine-6-glucuronide, morphine-3,6-diglucuronide and morphine-3-ethereal sulfate. The mean elimination half-life of morphine is two to three hours, with great interpatient variability.


The major route of excretion is via the kidney. Approximately 7 to 10% is excreted in the faeces via the bile. Conjugated morphine excreted in the bile may be hydrolysed and reabsorbed from the large bowel.
At steady state, morphine sulfate SR tablets produce peak morphine concentrations approximately three to five hours postdose, and therapeutic levels tend to persist for a 12 hour period.


Treatment of opioid responsive, chronic severe pain.


Hypersensitivity to opiate narcotics; acute asthma or other obstructive airways disease, acute respiratory depression; cor pulmonale; cardiac arrhythmias; acute alcoholism; delirium tremens; severe CNS depression; convulsive disorders; increased cerebrospinal or intracranial pressure; head injury; brain tumour; suspected surgical abdomen; paralytic ileus, severe liver disease, incipient hepatic encephalopathy; severe renal dysfunction; concurrent (or within 14 days of therapy) monoamine oxidase inhibitors (see Interactions with Other Medicines); children under one year of age; pregnancy. Not recommended for preoperative use or for the first 24 hours postoperatively.
Patients with chronic pain not due to malignancy, who have a prior history of substance and alcohol abuse.


The respiratory depressant effects of morphine and the capacity to elevate cerebrospinal fluid pressure, may be greatly increased in the presence of an already elevated intracranial pressure produced by trauma. Also, morphine may produce confusion, miosis, vomiting and other side effects which obscure the clinical course of patients with head injury. In such patients, morphine must be used with extreme caution and only if it is judged essential.
Morphine should be used with extreme caution in patients with substantially decreased respiratory reserve, pre-existing respiratory depression, hypoxia or hypercapnia. Such patients are often less sensitive to the stimulatory effects of carbon dioxide on the respiratory centre, and the respiratory depressant effects of morphine may reduce respiratory drive to the point of apnoea.
Morphine administration may result in severe hypotension in patients whose ability to maintain adequate blood pressure is compromised by reduced blood volume, or concurrent administration of such drugs as phenothiazines or certain anaesthetics.
Morphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Severe pain antagonises the subjective and respiratory depressant actions of morphine. Should pain suddenly subside, these effects may rapidly become manifest. Patients who are scheduled for cordotomy or other interruption of pain transmission pathways should not receive Morphine MR AN tablets within 24 hours of the procedure. Pain in the immediate preoperative period and any symptoms of opioid withdrawal should be managed with short acting analgesic agents.
Because of the spasmogenic properties of morphine in the biliary tract and sphincter of Oddi, it should be used only when necessary and with caution in biliary colic, operations on the biliary tract and acute pancreatitis.
Decreased gastric emptying associated with morphine may be expected to increase the risks of aspiration either associated with morphine induced CNS depression/coma, or during or after general anaesthesia.
Morphine may cause toxic dilatation in patients with acute ulcerative colitis.
Morphine-6-glucuronide may accumulate in patients with renal failure, leading to CNS and respiratory depression.
Morphine should be used with caution in patients with impaired respiratory function, convulsive disorders, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, hypotension with hypovolaemia, diseases of the biliary tract, pancreatitis and opioid dependency. Where there is a possibility of paralytic ileus occurring, morphine should not be used. Should paralytic ileus be suspected or occur during use, morphine should be discontinued immediately.
Caution is needed when changing between different presentations of morphine, or other potent opioid analgesic preparations, and the patient should be retitrated and clinically reassessed.
Morphine may lower the seizure threshold in patients with a history of epilepsy.

Use in chronic nonmalignant pain.

The use of Morphine MR AN for the treatment of chronic pain which is not due to malignancy should be restricted to situations where:
all other conservative methods of analgesia have been tried and have failed;
the pain is having a significant impact on the patient's quality of life; and
there is no psychological contraindication, drug seeking behaviour or history of drug misuse.
Prior to long-term prescription, a trial of Morphine MR AN or shorter acting opioids should be undertaken. Long-term administration of Morphine MR AN should only occur if this trial demonstrates that the pain is opioid sensitive. Opioid naive patients who require rapid dose escalation with no concomitant pain relief within the trial period should generally be considered inappropriate for long-term therapy.
A single doctor should be responsible for the prescription and monitoring of the patient's opioid use.
Doctors prescribing Morphine MR AN should consult appropriate clinical guidelines on the use of opioid analgesics in such patients (e.g. Australian Pain Society publication in The Medical Journal of Australia 1997;167:30-34).

Drug dependence.

As with other opioids, tolerance and physical dependence tend to develop upon repeated administration of morphine, and there is potential for abuse of the drug and for development of strong psychological dependence. Morphine MR AN should therefore be prescribed and handled with the high degree of caution appropriate to the use of a drug with strong abuse potential.
Drug abuse is not, however, a problem in patients with severe pain in whom morphine is appropriately indicated. On the other hand, in the absence of a clear indication for a strong opioid analgesic, drug seeking behaviour must be suspected and resisted, particularly in individuals with a history of, or propensity for, drug abuse. Withdrawal symptoms may occur following abrupt discontinuation of morphine therapy or upon administration of an opioid antagonist. Therefore, patients on prolonged therapy should be withdrawn gradually from the drug if it is no longer required for pain control. Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.

Special risk groups.

Morphine should be administered with caution and in reduced dosages to elderly or debilitated patients, to patients with severely reduced hepatic or renal function, and in patients with Addison's disease, hypothyroidism, prostatic hypertrophy or urethral stricture.
Patients should be cautioned about the combined effects of morphine with other CNS depressants, including other opioids, phenothiazines, sedative/ hypnotics and alcohol.

Effect on ability to drive or operate machinery.

Morphine may impair the mental and/or physical abilities needed for certain potentially hazardous activities, such as driving a car or operating machinery. Patients should be cautioned accordingly.

Use in pregnancy.

(Category C)
Long-term use in pregnancy may result in neonatal opioid withdrawal state.
Morphine has been associated with fetal CNS defects in rodent studies. In humans it is not known whether morphine can cause fetal harm when administered during pregnancy. Use of morphine sulfate tablets should be avoided to the extent possible in patients who are pregnant.
Prolonged use of opioid drugs may result in impairment of reproductive function, including infertility and sexual dysfunction in both sexes and irregular menses in women.

Use during labour and delivery.

Morphine crosses the placental barrier and its administration during labour can produce respiratory depression in the neonate. These products should only be used during labour after weighing the needs of the mother against the risk to the fetus.

Use in lactation.

Morphine has been detected in human breast milk; caution should be exercised if morphine is administered to a breastfeeding woman and use of morphine sulfate should be avoided to the extent possible.


Generally, the effects of morphine may be antagonised by acidifying agents and potentiated by alkalinising agents. Concurrent administration of antacids may result in a more rapid release of morphine than otherwise expected; dosing should, therefore, be separated by a minimum of two hours.
The analgesic effect of morphine is potentiated by amphetamines, chlorpromazine and methocarbamol. CNS depressants, such as other opioids, anaesthetics, sedatives, hypnotics, barbiturates, phenothiazines, tranquillizers, tricyclic antidepressants, chloral hydrate and glutethimide, may enhance the depressant effects of morphine. Pyrazolidone antihistamines, beta-blockers and alcohol may also enhance the depressant effect of morphine. The interactive effects may include respiratory depression, hypotension, profound sedation and coma. Morphine should be used with caution in patients who are currently taking gabapentin.
Nonselective MAOIs intensify the effects of morphine and other opioid drugs which can cause anxiety, confusion and significant respiratory depression, sometimes leading to coma. Morphine should not be given to patients taking nonselective MAOIs or within 14 days of stopping such treatment. It is unknown whether there is an interaction between the newer selective MAOIs (e.g. moclobemide and selegiline) and morphine, therefore caution is advised with such drug combinations.
Morphine may alter the metabolism of zidovudine by competitively inhibiting glucuronidation or directly inhibiting hepatic microsomal metabolism, therefore this combination should be used with caution.
A potentially lethal interaction between morphine and cimetidine has been reported. The patient exhibited apnoea, a significantly reduced respiratory rate and suffered a grand mal seizure. Naloxone increased respiratory rate, however confusion, disorientation, generalised twitching and periods of apnoea persisted for 80 hours.
Morphine may increase the anticoagulant activity of coumarin and other anticoagulants.
Mixed agonist/ antagonist opioid analgesics (e.g. buprenorphine, nalbuphine, pentazocine) should not be administered to a patient who has received a course of therapy with a pure opioid agonist analgesic.
Available data indicate that ritonavir may increase the activity of glucuronyl transferases. Consequently, coadministration of ritonavir and morphine may result in decreased morphine serum concentrations with possible loss of analgesic effectiveness.
The combination of morphine and propranolol is potentially lethal. Propranolol increases the acute CNS toxicity of morphine.
Medicinal products that block the action of acetylcholine, for example antihistamines, antiparkinsonians and antiemetics, may interact with morphine to potentiate anticholinergic adverse events.
Plasma concentrations of morphine may be reduced by rifampicin.

Adverse Effects

The major hazards associated with morphine, as with other opioid analgesics, are respiratory depression and, to a lesser degree, circulatory depression. Respiratory arrest, shock and cardiac arrest have occurred following oral or parenteral use of morphine.

Most common adverse effects requiring medical attention.

The most frequently observed side effects of opioid analgesics such as morphine are sedation, nausea and vomiting, constipation and sweating.


Most patients experience initial drowsiness, partly for pharmacokinetic reasons and partly because patients often recuperate from prolonged fatigue after the relief of persistent pain. Drowsiness usually clears in three to five days and is usually not a reason for concern providing that it is not excessive, or associated with unsteadiness or confusional symptoms. If excessive sedation persists, the reason for it must be sought. Some of these are: concomitant sedative medications; hepatic or renal failure; exacerbated respiratory failure; higher doses than tolerated in an older patient; or that the patient is actually more severely ill than realised.
If it is necessary to reduce the dose, it can be carefully increased again after three or four days if it is obvious that the pain is not being well controlled. Dizziness and unsteadiness may be caused by postural hypotension, particularly in elderly or debilitated patients. It can be alleviated if the patient lies down. Because of the slower clearance in patients aged over 50 years, an appropriate dose in this age group may be as low as one-half or less the usual dose in the younger age group.

Nausea and vomiting.

Nausea and vomiting occur frequently after single doses of opioids, or as an early unwanted effect of regular opioid therapy. When instituting prolonged therapy for chronic pain, the routine prescription of an antiemetic should be considered. Patients taking the equivalent of a single dose of morphine of 20 mg or more (Morphine MR AN 60 mg every 12 hours) usually require an antiemetic during early therapy. Small doses of prochlorperazine or haloperidol are the most frequently prescribed antiemetics. Nausea and vomiting tend to lessen in a week or so, but may persist due to opioid induced gastric stasis. In such patients, metoclopramide is often useful.


As with all opioid analgesics, constipation is a common occurrence. In some patients, particularly elderly or bedridden patients, faeces may become impacted. It is essential to caution patients in this regard and to institute an appropriate regimen of bowel management at the start of prolonged opioid therapy. Softeners, laxatives and other appropriate measures should be used as required.

Other adverse effects.


Supraventricular tachycardia, hypotension, postural hypotension, bradycardia, palpitations, faintness and syncope.

Central nervous system.

Euphoria, dysphoria, weakness, insomnia, dizziness, vertigo, confusional symptoms, headache, involuntary muscle contractions, asthenia, thought abnormalities, occasionally hallucinations and, uncommonly, agitation, malaise, mood changes, vision abnormalities, paraesthesia and seizure.


Dry mouth, anorexia, dyspepsia, abdominal pain, gastrointestinal disorders, constipation, cramps, taste alterations, ileus, biliary tract cramps and biliary spasm and, uncommonly, elevated hepatic enzymes.


Urinary retention or hesitance, ureteric spasm, amenorrhoea, erectile dysfunction, reduced libido or potency.


Respiratory depression, bronchospasm and cough decreased.


Uncommonly, pulmonary oedema, peripheral oedema and a syndrome of inappropriate antidiuretic hormone secretion characterised by hyponatraemia secondary to decreased free water excretion may be prominent (monitoring of electrolytes may be necessary).


Allergic reaction, anaphylactic and anaphylactoid reaction, drug dependence, drug tolerance, hyperhidrosis, pruritus, urticaria, other skin rashes including contact dermatitis, facial flushing, miosis, hypertonia and oedema.

Withdrawal (abstinence) syndrome.

Physical dependence with or without psychological dependence tends to occur on chronic administration. An abstinence syndrome may be precipitated when opioid administration is discontinued or opioid antagonists administered. Tolerance to the effects of morphine may develop.
The following withdrawal symptoms may be observed after opioids are discontinued: body aches, diarrhoea, gooseflesh, loss of appetite, nervousness or restlessness, runny nose, sneezing, chills, tremors or shivering, stomach cramps, nausea, trouble with sleeping, unusual increase in sweating and yawning, weakness, tachycardia and unexplained fever. With appropriate medical use of opioids and gradual withdrawal from the drug, these symptoms are usually mild.

Dosage and Administration

Administration and dosing of morphine should be individualised, bearing in mind the properties of the drug. In addition, the nature and severity of the pain or pains experienced, and the total condition of the patient must be taken into account. Of special importance is other medication given previously or concurrently.
As with other strong opioid analgesics, use of morphine for the management of persistent pain should be preceded by a thorough assessment of the patient and diagnosis of the specific pain or pains and their causes. Use of opioids for the relief of chronic pain, including cancer pain, important as it is, should be only one part of a comprehensive approach.
Morphine MR AN should be used for the long-term treatment of chronic severe pain only after the pain has been proven to be alleviated by opioids (with a trial of shorter acting opioids or Morphine MR AN itself).

Initial dose in adults.

Individual dosing requirements vary considerably based on each patient's age, weight, severity of pain, and medical and analgesic history. The most frequent initial dose is 30 mg every 12 hours.
Patients aged over 50 years tend to require much lower doses of morphine than the younger age group. In elderly and debilitated patients and those with impaired respiratory function or significantly decreased renal function, the initial dose should be one-half the usual recommended dose.

Initial dose in children.

Over 25 kg.

The initial dose will depend upon the degree of morphine tolerance and should be titrated in accordance with the patient's needs (see Dose titration).

25 kg or less.

There are no controlled trials of the use of morphine sulfate pentahydrate in children weighing 25 kg or less, nor in children with chronic severe nonmalignant pain.
Patients currently receiving other oral morphine formulations may be transferred to Morphine MR AN at the same total daily morphine dosage, equally divided into two Morphine MR AN doses given every 12 hours.
For patients who are receiving an alternate opioid, the oral morphine sulfate pentahydrate equivalent of the analgesic presently being used should be determined. Having determined the total daily dosage of the present analgesic, the following equivalence table can be used to calculate the approximate daily oral morphine sulfate pentahydrate dosage that should provide equivalent analgesia. The total daily oral morphine dosage should then be equally divided into two Morphine MR AN doses given every 12 hours.

Dose titration.

Dose titration is the key to success with morphine therapy. Proper optimisation of doses scaled to the relief of the individual's pain should aim at the regular administration of the lowest dose of morphine which will maintain the patient free of pain at all times. Dose adjustments should be based on the patient's clinical response. Higher doses may be justified in some patients to cover periods of physical activity.
Because of the modified release properties of Morphine MR AN, dosage adjustments should generally be separated by 48 hours. If dose increments are required, they should be proportionately greater at the lower dose level (in terms of percentage of previous dose), than when adjusting a higher dose.
The usual recommended dose (every 12 hours) increments are 5, 10, 15, 20, 30, 40, 60, 90, 120, 150, 180, 200 mg. Above the 200 mg/dose (400 mg/day) increments should be by 30 to 60 mg.
Morphine MR AN tablets are designed to allow dosing every 12 hours. If breakthrough pain repeatedly occurs at the end of a dose interval, it is generally an indication for a dosage increase, not more frequent administration. However, where judged necessary for optimisation of drug effects, Morphine MR AN may be administered every eight hours. More frequent (than every eight hours) administration of Morphine MR AN is neither rational nor recommended.

Dosage adjustment or reduction.

During the first two or three days of effective pain relief, the patient may exhibit drowsiness or sleep for prolonged periods. This can be misinterpreted as the effect of excessive analgesic dosing rather than the first sign of relief in a pain exhausted patient. The dose, therefore, should be maintained for at least three days before reduction, provided the sedation is not excessive or associated with unsteadiness and confusional symptoms, and respiratory activity and other vital signs are adequate. If excessive sedation persists, the reason(s) for such an effect must be sought (see Adverse Effects, Sedation).
Following successful relief of severe pain, periodic attempts to reduce the opioid dose should be made. Smaller doses or complete discontinuation of the opioid analgesic may become feasible due to a change in the patient's condition or improved mental state.


Morphine MR AN tablets should be swallowed intact, not chewed, crushed or broken.



Serious morphine overdosage is characterised by respiratory depression (reduced respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, flaccidity of skeletal muscle, miotic pupils; cold or clammy skin, and sometimes hypotension and bradycardia. Severe overdosage may result in apnoea, pulmonary oedema, circulatory collapse, cardiac arrest and death.


Primary attention should be given to the establishment of adequate respiratory exchange through the provision of a patent airway and controlled or assisted ventilation. The opioid antagonist naloxone hydrochloride (Section 20a) is a specific antidote against respiratory depression due to overdosage or as a result of unusual sensitivity to morphine. An appropriate dose of one of the antagonists should therefore be administered, preferably by the intravenous route. The usual initial intravenous adult dose of naloxone is 0.4 mg or higher. Concomitant efforts at respiratory resuscitation should be carried out. Since the duration of action of morphine, particularly modified release formulations, may exceed that of the antagonist, the patient should be under continued surveillance and doses of the antagonist should be repeated as needed to maintain adequate respiration. An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.
In an individual physically dependent on opioids, the administration of the usual dose of opioid antagonist will precipitate an acute withdrawal syndrome. The severity of this syndrome will depend on the degree of physical dependence and the dose of antagonist administered. The use of opioid antagonists in such individuals should be avoided if possible. If an opioid antagonist must be used to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care by using dosage titration, commencing with 10 to 20% of the usual recommended initial dose.
Gastric lavage with a wide bore tube followed by administration of an activated charcoal suspension will aid the removal of morphine. A saline cathartic or sorbitol added to the first dose of activated charcoal may speed gastrointestinal passage of the product.


Morphine toxicity may result from overdosage, but because of the great interindividual variation in sensitivity to opioids, it is difficult to determine an exact dose of any opioid that is toxic or lethal. Crushing and taking the contents of a modified release dosage form leads to the release of morphine in an immediate fashion; this might result in a fatal overdose.
The presence of pain or tolerance tends to diminish the toxic effects of morphine. Published data suggest that in a morphine naive, pain free individual, the lethal dose would be in excess of 120 mg. Patients on chronic oral morphine therapy have been known to take in excess of 3,000 mg/day with no apparent toxicity.


Morphine MR AN modified release tablets are intended for oral administration.
Each modified release tablet contains 10 mg, 30 mg, 60 mg or 100 mg of morphine sulfate as the active ingredient.

10 mg tablet.

Buff coloured, biconvex, smooth, round, film coated modified release tablets with 10 on one face. Blister Pack (PVC/Aluminium in cartons) of 20, 28 or 60 tablets.

30 mg tablet.

Violet coloured, biconvex, smooth, round, film coated modified release tablets with 30 on one face. Blister Pack (PVC/Aluminium in cartons) of 20, 28 or 60 tablets.

60 mg tablet.

Orange coloured, biconvex, smooth, round, film coated modified release tablets with 60 on one face. Blister Pack (PVC/Aluminium in cartons) of 20, 28 or 60 tablets.

100 mg tablet.

Grey coloured, biconvex, smooth, round, film coated modified release tablets with 100 on one face. Blister Pack (PVC/Aluminium in cartons) of 20, 28 or 60 tablets.


Store below 25°C.

Poison Schedule