Morphine 10 Mg/15 Mg/20 mg Injection

MORPHINE UNIMED is an analgesic for the symptomatic relief of severe pain especially that associated with neoplastic disease, myocardial infarction and surgery.

The usual dose by subcutaneous or intramuscular injection is 5 to 20 mg every 4 hours.
Paediatric population
Children up to 1 month of age may be given 150 u03bcg per kg body mass every 4 hours; those aged 1 to 12 months: 200 u03bcg per kg; 1 to 5 years: 2,5 to 5 mg; 6 to 12 years: 5 to 10 mg.
Elderly or debilitated patients
The dosage should be reduced in elderly and debilitated patients. Doses of up to 15 mg have been given by slow intravenous injection sometimes as a loading dose for continuous or patient-controlled infusion. For continuous intravenous administration, maintenance doses have generally ranged from 0,8 to 80 mg per hour although some patients have required and been given much higher doses.
Method of administration
By subcutaneous, intramuscular or slow intravenous administration.

MORPHINE UNIMED is contraindicated in:

• Hypersensitivity to morphine sulphate or to any of the excipients of MORPHINE UNIMED (see section 6.1)
• Patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment.
• Morphine Unimed is contra-indicated in respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion.
• In the presence of acute alcoholism, convulsive disorders, head injuries, comatose patients and conditions in which intracranial pressure is raised.
• During an attack of bronchial asthma or in heart failure secondary to chronic lung disease.
• Biliary colic (see section 4.4)
• Paralytic ileus.
• Phaeochromocytoma
• Acute diarrhoeal caused by poisoning or invasive pathogens.

MORPHINE UNIMED is liable to be subject to abuse, the euphoric activity of morphine has led to its abuse. Dependence and tolerance to Morphine Unimed may occur.
MORPHINE UNIMED should be used with extreme caution in patients with decreased respiratory reserve. It should be given with extreme care to newborn or premature infants for other conditions. It should be given with caution or in reduced doses to patients with hypotension, hypothyroidism, convulsive disorders, adrenocortical insufficiency, myasthenia gravis, urethral stricture, impaired kidney or liver function, prostatic hypertrophy, or shock or inflammatory or obstructive bowel disorders. Larger doses produce respiratory depression and hypotension, with circulatory failure and deepening coma. Convulsions may occur in infants and children. Death may occur from respiratory failure. Toxic doses vary considerably with the individual.
Biliary Disorders
Opioids such as MORPHINE UNIMED should either be avoided in patients with biliary disorders or they should be given with an antispasmodic. MORPHINE UNIMED 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 contraindicated, see section 4.3). In patients given MORPHINE UNIMED after cholecystectomy, biliary pain has been induced.
Risk from concomitant use of sedative medicines such as benzodiazepines or medicines:
Concomitant use of MORPHINE UNIMED and sedative medicines such as benzodiazepines or related medicines 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 UNIMED 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 (see section 4.5).
Oral P2Y12 inhibitor antiplatelet therapy
Within the first day of concomitant P2Y12 inhibitor and morphine treatment, reduced efficacy of P2Y12 inhibitor treatment has been observed (see section 4.5).
Palliative Care
In the control of pain in terminal illness, these conditions should not necessarily be a deterrent to use.
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.
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.
Decreased Sex Hormones and Increased prolactin
Long-term use of opioid analgesics may be associated with decreased sex hormone levels and increased prolactin. Symptoms include decreased libido, impotence or amenorrhea.
Dependence and withdrawal (abstinence) syndrome
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 medicine is used, and with higher doses. Symptoms can be minimised with adjustments of dose or dosage form, and gradual withdrawal of morphine. For individual symptoms, (see section 4.8). Hyperalgesia that does not respond to a further dose increase of morphine may occur, particularly at high doses. A dose reduction or change in opioid may be required.
Mental health disorders or Psychological dependence (addiction)
MORPHINE UNIMED should be used with particular care in patients with a personal or family history of substance abuse or mental health disorders including, but not limited to major depression, anxiety and alcohol and drug abuse.
MORPHINE UNIMED contains sodium. MORPHINE UNIMED contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free.
Note: Facilities for administration of oxygen and assisted respiration should be available if morphine is given intravenously.

Alcohol: Enhanced sedative and hypertensive effects.
Dysrhythmics: There may be delayed absorption of mexiletine.
Antibacterials: The opioid analgesic papaveretum has been shown to reduce plasma ciprofloxacin concentration. The manufacturer of ciprofloxacin advises that premedication with opioid analgesics be avoided.
Antidepressants: The depressant effects of MORPHINE UNIMED are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, tricyclic antidepressants and phenothiazines.
Antipsychotics: Possible enhanced sedative and hypotensive effect.
Antidiarrhoeal and antiperistaltic agents (such as loperamide and kaolin): Concurrent use may increase the risk of severe constipation.
Antimuscarinics: Medicines such as atropine antagonise morphine-induced respiratory depression and can partially reverse biliary spasm but are additive to the gastrointestinal and urinary tract effects. Consequently, severe constipation and urinary retention may occur during intensive antimuscarinic analgesic therapy.
Metoclopramide and domperidone: There may be antagonism of the gastrointestinal effects of metoclopramide and domperidone.
Sedative medicines such as benzodiazepines or related medicines: The concomitant use of opioids with sedative medicines such as benzodiazepines or related medicines increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).
Cimetidine: Inhibits the metabolism of morphine.
Rifampicin: Plasma concentrations of morphine may be reduced by rifampicin.
Ritonavir: Although there are no pharmacokinetic data available for concomitant use of ritonavir with morphine, ritonavir induces the hepatic enzymes responsible for the glucuronidation of morphine and may possibly decrease plasma concentrations of morphine.
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.

Pregnancy: The safety of MORPHINE UNIMED during pregnancy has not been established. Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. The administration of opioid analgesics during labour may cause respiratory depression in the newborn infant.
Lactation: The safety of MORPHINE UNIMED has not been established in breastfeeding women.

Drowsiness may affect the ability to perform skilled tasks. Those affected should not drive a vehicle or operate machinery.

Table 1: Tabulated list of adverse reactions
System Organ Class Frequency Adverse effect
Immune system disorders Frequent Histamine release (decreased blood pressure, fast heartbeat, increased sweating, redness or flushing of the face, wheezing or troubled breathing)
Less Frequent Allergic reaction (skin rash, hives and/or itching, swelling of face).
Metabolism and nutritional disorder Less Frequent Loss of appetite
Psychiatric disorders Less Frequent False sense of wellbeing, general feeling of discomfort or illness, nervousness or restlessness, insomnia, confusion, hallucinations, mental depression. Decreased libido, mood swings restlessness. Frequency not known Nightmares or unusual dreams
Nervous system disorders Frequent Drowsiness, hyperhidrosis
Less Frequent Headache, paradoxical CNS stimulation (unusual excitement or restlessness, especially in children), vertigo
Frequency not known Convulsions, allodynia
Eye disorders Less Frequent Miosis, nystagmus
Frequency not known Blurred or double vision or other changes in vision
Ear and labyrinth Frequency not known Tinnitus (ringing or buzzing in the ears).
Cardiac Disorders Less Frequent Bradycardia, tachycardia, pounding heartbeat
Frequency not known Palpitations
Vascular Disorders Less Frequent Dizziness, feeling faint or light-headedness, hypotension, orthostatic hypotension
Frequency not known Increased Blood Pressure
Respiratory, thoracic and mediastinal disorders Less Frequent Atelectasis, bronchospastic allergic reaction, laryngeal oedema, allergic laryngospasm, respiratory depression
Gastrointestinal disorders Frequent Nausea and vomiting, constipation.
Less Frequent Dry mouth, gastrointestinal irritation (stomach cramps or pain), paralytic ileus or toxic megacolon.
Frequency Unknown Intestinal functional disorder, narcotic bowel syndrome
Hepato-billary disorders Less Frequent Biliary spasm, hepatic enzyme increase.
Frequency not known Hepatotoxicity, spasm of the sphincter of Oddi
Musculoskeletal and connective tissue disorders Less Frequent Muscle rigidity (especially in muscles of respiration), trembling or uncontrolled muscle movements.
Frequency unknown Rhabdomyolysis
Renal and urinary disorders Frequent Urinary retention
Less Frequent Ureteral spasm (difficult or painful urination, frequent urge to urinate), antidiuretic effect.
Frequency unknown Renal Failure
Skin and subcutaneous tissue disorders Frequent pruritus, sweating, facial flushing
Less Frequent Urticaria, rash, angioedema, contact dermatitis
Reproductive system and breast disorders Frequent Erectile dysfunction
General disorders and administrative site conditions Frequent Unusual tiredness or weakness, medicine tolerance
Less Frequent Redness, swelling, pain burning at the site of injection, medicine withdrawal (abstinence) syndrome (babies born to opioid-dependent mothers also at risk of present withdrawal syndrome
Description of selected adverse reactions: Dependence and withdrawal (abstinence) syndrome. Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. An abstinence syndrome may be precipitated when opioid administration is suddenly discontinued, or opioid antagonists administered, or can sometimes be experienced between doses. For management, see section 4.4 Physiological withdrawal symptoms include: Body aches, tremors, restless legs syndrome, diarrhoea, abdominal colic, nausea, flu-like symptoms, tachycardia and mydriasis. Psychological symptoms include dysphoric mood, anxiety and irritability. In dependence, u201cdrug cravingu201d is often involved.
Post-marketing data Less frequent: increased risk of abdominal pain, including pancreatitis has been reported.
Reporting of suspected adverse reactions Reporting suspected adverse reactions 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 Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc-org) found on SAHPRA website.

Symptoms and signs
Signs and symptoms of overdose indicating need for medical attention: cold clammy skin; confusion; convulsions; severe dizziness; severe drowsiness; low blood pressure; nervousness or severe restlessness; pinpoint pupils of eyes; slow heartbeat; slow or troubled breathing; unconsciousness; severe weakness (see section 4.8).
Management of overdose
Intensive supportive therapy may be required to correct respiratory failure and shock. Death may occur from respiratory failure. The specific antagonist, naloxone hydrochloride, is used. A dose of 0,4 to 2 mg is given intravenously, repeated at intervals of 2 to 3 minutes if necessary, up to 10 mg. For children, the initial dose is 0,01 mg/kg. Naloxone may also be given by subcutaneous or intramuscular injection. The effect of naloxone may be of shorter duration than that of the opioid analgesic and additional doses may be required to prevent relapses. The circulation should be maintained with infusions of dextrose injection and suitable electrolyte solutions. Assisted respiration may be necessary. The use of opioid antagonists such as naloxone, nalorphine, and levallorphan in persons physically dependent on morphine or related medicines may induce withdrawal symptoms.