- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
|Adults:||Recommended dose 10-20 mg (5-10 ml) every 4 hours. Maximum daily dose: 120 mg per day|
|Children 13-18 years:||Recommended dose 5-20 mg (2.5 10 ml) every 4 hours Maximum daily dose: 120 mg per day|
|Children 6-12 years:||Recommended dose 5-10 mg (2.5-5 ml) every 4 hours Maximum daily dose: 60 mg per day|
|Children 1-5 years:||Recommended dose 5 mg (2.5 ml) every 4 hours Maximum daily dose: 30 mg per day|
|Children under 1 year:||Not recommended|
Method of AdministrationFor oral use.When patients are transferred from other morphine preparations to Oramorph Oral preparations dosage titration may be appropriate.Morphine sulfate is readily absorbed from the gastro-intestinal tract following oral administration. However, when oral Oramorph preparations are 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.
AsthmaIt has been suggested that opioids can be used with caution in controlled asthma. However, opioids are contraindicated in acute asthma exacerbations (see section 4.3).
Head injury and increased intracranial pressureOramorph is contraindicated in patients with increased intracranial pressure, head injuries and coma (see section 4.3). The capacity of morphine to elevate cerebrospinal fluid pressure may be greatly increased in the presence of already elevated intracranial pressure produced by trauma. Also, morphine may produce confusion, miosis, vomiting and other adverse reactions which may obscure the clinical course of patients with head injury.
Abdominal conditionsMorphine sulfate must not be given if paralytic ileus is likely to occur (see section 4.3), or if the patient has bowel or obstructive biliary disease. Should paralytic ileus be suspected or occur during use, Oramorph should be discontinued immediately. Caution should be exercised where there is an obstructive bowel disorder, biliary colic, operations on the biliary tract, acute pancreatitis or prostatic hyperplasia.If constipation occurs this may be treated with the appropriate laxatives. Care should be exercised in patients with inflammatory bowel disease.Morphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions and complications following abdominal surgery.
Hypotensive effectThe administration of morphine may result in severe hypotension in individuals whose ability to maintain homeostatic blood pressure has already been compromised by depleted blood volume or the concurrent administration of drugs such as phenothiazine or certain anaesthetics (see section 4.5).
Drug dependence and abuseTolerance and dependence may occur. Withdrawal symptoms may occur on abrupt discontinuation or on the administration of a narcotic antagonist e.g. naloxone.Morphine sulfate is an opioid agonist and controlled drug. Such drugs are sought by drug abusers and people with addiction disorders. Morphine sulfate can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing morphine in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Morphine should be used with particular care in patients with a history of alcohol and drug abuse.Morphine sulfate may be abused by inhaling or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death.
HypersensitivityHypersensitivity and anaphylactic reactions have both occurred with the use of Oramorph. Care should be taken to elicit any history of allergic reactions to opiates. Oramorph is contraindicated in patients known to be hypersensitive to morphine sulfate (see section 4.3).
Risk in special populationsMorphine is metabolised by the liver and should be used with caution in patients with hepatic disease as oral bioavailability may be increased. It is wise to reduce dosage in chronic hepatic and renal disease, severe hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy or shock (see section 4.2). The active metabolite Morphine-6-glucuronide may accumulate in patients with renal failure, leading to CNS and respiratory depression.
Excipient related warningsPatients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.Oramorph Oral Solution contains the excipients methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which may cause allergic reactions (possibly delayed). Oramorph Oral Solution contains 10 vol % ethanol (alcohol). Each dose contains up to 0.81 g of alcohol which is equivalent to 20 ml beer or 8.3 ml wine. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
Monoamine oxidase inhibitorsMonoamine oxidase inhibitors are known to interact with narcotic analgesics producing CNS excitation or depression with hyper- or hypotensive crisis, therefore their concomitant use with Oramorph is contraindicated (see section 4.3).
GabapentinInteractions have been reported in those taking morphine and gabapentin. Reported interactions suggest an increase in opioid adverse events when co-prescribed, the mechanism of which is not known. Caution should be taken where these medicines are co-prescribed. In a study involving healthy volunteers (N=12), when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Therefore, patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately.
RitonavirAlthough there are no pharmacokinetic data available for concomitant use of ritonavir with morphine, ritonavir may increase the activity of glucuronyl transferases. Consequently, co-administration of ritonavir and morphine may result in decreased serum concentrations of morphine with possible loss of analgesic effectiveness.
RifampicinRifampicin can reduce the serum concentration of morphine and decrease its analgesic effect, the mechanism of which is not known.
CimetidineCimetidine inhibits the metabolism of morphine.
CNS depressantsIt should be noted that morphine potentiates the effects of CNS depressants such as tranquillisers, anaesthetics (see section 4.4), hypnotics, sedatives, antipsychotics, tricyclic antidepressants and alcohol.
EsmololMorphine may increase plasma concentrations of esmolol. Domperidone/metoclopramideOpioid analgesics including morphine may antagonise the actions of domperidone and metoclopramide on gastro-intestinal activity.
MexiletineThe absorption of mexiletine may be delayed by concurrent use of morphine.
Phenothiazine antiemeticsPhenothiazine antiemetics may be given with morphine. However, hypotensive effects have to be considered (see section 4.4).
PregnancyAlthough 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.The quantity of ethanol contained in Oramorph Oral Solution should be considered in pregnant women (See section 4.4).
Breast-feedingAlthough 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.
FertilityLong 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.
|SOC Category||Side effect|
|Immune system disorders||Hypersensitivity Anaphylactic reaction (see section 4.4)|
|Psychiatric disorders||Confusional state Restlessness Altered mood Hallucination Dependence (see section 4.4)|
|Nervous system disorders||Somnolence Headache Increased intracranial pressure (see section 4.4)|
|Ear and labyrinth disorders||Vertigo|
|Respiratory, thoracic and mediastinal disorders||Respiratory depression (see section 4.4 and section 4.6)|
|Cardiac disorders||Bradycardia Tachycardia Palpitations|
|Vascular disorders||Hypotension Flushing|
|Gastrointestinal disorders||Nausea Vomiting Constipation (see section 4.4) Dry mouth|
|General disorders and administration site conditions||Hypothermia Drug tolerance (see section 4.4) Drug withdrawal syndrome (see section 4.4 and section 4.6)|
|Hepatobiliary Disorders||Biliary colic|
|Skin and subcutaneous tissue disorders||Urticaria Pruritus Hyperhidrosis|
|Musculoskeletal and connective tissue disorders||Muscle rigidity|
|Renal and urinary disorders||Dysuria Ureteral spasm Oliguria|
|Reproductive system and breast disorders||Decreased libido Erectile dysfunction|
Reporting of suspected adverse reactionsReporting 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
SymptomsSigns 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.
TreatmentAdults: 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.
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