Oramorph

Overdose

Symptoms

Signs of morphine toxicity and overdosage are likely to consist of pin-point pupils, respiratory depression and hypotension. Circulatory failure and deepening coma may occur in more severe cases. Convulsions may occur in infants and children. Death may occur from respiratory failure.

Treatment

Adults: Administer 0.4-2 mg of naloxone intravenously. Repeat at 2-3 minute intervals as necessary to a maximum of 10 mg, or by 2 mg in 500 ml of normal saline or 5 % dextrose (4 micrograms/ml). Children: 5-10 micrograms per kilogram body weight intravenously. If this does not result in the desired degree of clinical improvement, a subsequent dose of 100 mcg/kg body weight may be administered.

Care should always be taken to ensure that the airway is maintained. Assist respiration if necessary. Maintain fluid and electrolyte levels. Oxygen, i.v. fluids, vasopressors and other supportive measures should be employed as indicated. Peak plasma concentrations of morphine are expected to occur within 15 minutes of oral ingestion. Therefore gastric lavage and activated charcoal are unlikely to be beneficial.

Caution: the duration of the effect of naloxone (2-3 hours) may be shorter than the duration of the effect of the morphine overdose. It is recommended that a patient who has regained consciousness after naloxone treatment should be observed for at least 6 hours after the last dose of naloxone.

Shelf life

The shelf-life expiry date for this product shall not exceed three years from the date of its manufacture for unopened product. The product will be stored according to the provisions specified by the Home Office.

Discard any remaining Oramorph Concentrated Oral Solution 4 months after first opening.

Incompatibilities

None stated.

List of excipients

Disodium Edetate

Sodium Benzoate (E211)

Citric Acid anhydrous

Amaranth (E123)

Purified Water

Undesirable effects

In normal doses, the commonest side effects of morphine sulfate are nausea, vomiting, constipation, drowsiness and confusion. If constipation occurs, this may be treated with appropriate laxatives. The effects of morphine have led to its abuse and misuse. Dependence and addiction may develop with regular, inappropriate use.

Data from clinical trials are not available. Therefore it is not possible to provide information on the frequencies of undesirable effects. A full list of currently known adverse reactions is presented below:

Reporting of suspected adverse reactions

Reporting suspected adverse reaction after authorisation of the medicinal product is important. It allows continued monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

Preclinical safety data

No further relevant preclinical data are available.

Pharmacotherapeutic group

Pharmacodynamic properties

Pharmacotherapeutic group: Natural opium alkaloids. ATC code: NO2AA01

Morphine binds to specific receptors which are located at various levels of the central nervous system and also in various peripheral organs. The pain sensation and the affective reaction to pain is relieved by interaction with the receptors in the central nervous system.

Pharmacokinetic properties

Absorption

Morphine is modestly absorbed from the gastrointestinal tract following oral administration. Following oral administration of radiolabelled morphine to humans, peak plasma levels were reached after approximately 15 minutes. Morphine undergoes significant first pass metabolism in the liver resulting in a systemic bioavailability of approximately 25%.

Distribution

Approximately one third of morphine in the plasma is protein bound after a therapeutic dose.

Biotransformation

Metabolism of morphine principally involves conjugation to morphine 3- and 6- glucuronides. Small amounts are also metabolised by N-demethylation and N-dealkylation. Morphine-6-glucuronide has pharmacological effects indistinguishable from those of morphine. The half-life of morphine is approximately 2 hours. The t1/2 of morphine-6-glucuronide is somewhat longer.

Elimination

A small amount of a dose of morphine is excreted through the bowel into the faeces. The remainder is excreted in the urine, mainly in the form of conjugates. Approximately 90 % of a single dose of morphine is excreted in the first 24 hours. Enterohepatic circulation of morphine and its metabolites can occur, and may result in small quantities of morphine to be present in the urine or faeces for several days after the last dose.

Date of revision of the text

November 2016

Marketing authorisation holder

Boehringer Ingelheim Limited

Ellesfield Avenue

Bracknell

Berkshire

RG12 8YS

United Kingdom

Special precautions for storage

Store below 25 °C. Store in the original container to protect from light.

Nature and contents of container

Amber glass bottle of 30 ml and 120 ml with a tamper evident child resistant closure with an outer overcap in high density polyethylene. A calibrated oral dosing pipette will be enclosed in the carton with each bottle.

Not all pack sizes may be marketed.

Marketing authorisation number(s)

PL 0015/0125

Fertility, pregnancy and lactation

Pregnancy

Although morphine sulfate has been in general use for many years, there is inadequate evidence of safety in human pregnancy.

Morphine is known to cross the placenta. Therefore, Oramorph should not be used in pregnancy, especially the first trimester unless the expected benefit is thought to outweigh any possible risk to the foetus.

Infants born from mothers who have been taking morphine on a chronic basis may exhibit withdrawal symptoms. This should be borne in mind when considering the use of Oramorph in patients during pregnancy.

The risk of gastric stasis and inhalation pneumonia is increased in the mother during labour. Since morphine rapidly crosses the placental barrier it should not be used during the second stage of labour or in premature delivery because of the risk of secondary respiratory depression in the newborn infant.

Breast-feeding

Although morphine sulfate has been in general use for many years, there is inadequate evidence of safety during lactation.

Morphine is not recommended for nursing mothers. Morphine is excreted in breast milk, and may thus cause respiratory depression in the newborn infant.

Fertility

Long term use of opioid analgesics can cause hypogonadism and adrenal insufficiency in both men and women. This is thought to be dose related and can lead to amenorrhoea, reduced libido, infertility and erectile dysfunction.

Effects on ability to drive and use machines

Morphine sulfate is likely to impair ability to drive or use machinery. This effect is even more enhanced, when used in combination with alcohol or CNS depressants.

Patients should be warned not to drive or operate dangerous machinery after taking Oramorph.

This medicine can impair cognitive function and can affect a patient's ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

- The medicine is likely to affect your ability to drive

- Do not drive until you know how the medicine affects you

- It is an offence to drive while under the influence of this medicine

- However, you would not be committing an offence (called 'statutory defence') if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

o It was not affecting your ability to drive safely

Special precautions for disposal and other handling

None stated.

Date of first authorisation/renewal of the authorisation

Date of first authorisation: 16th August 1988

Date of last renewal: 16th August 1993