- 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. 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
1. Name of the medicinal product
Pethidine Hydrochloride 50mg/ml Solution for Injection
2. Qualitative and quantitative composition
Each 1ml of solution contains 50mg of Pethidine Hydrochloride B.P.
3. Pharmaceutical form
Clear, colourless, sterile solution intended for parenteral administration to human beings.
4. Clinical particulars
4.1 Therapeutic indications
Pethidine hydrochloride may be used as an analgesic for the relief of moderate to severe pain including : obstetric analgesia; pre-operative medication and analgesia during anaesthesia; post-operative analgesia.
4.2 Posology and method of administration
Pethidine Injection may be administered by subcutaneous, intramuscular or slow intravenous injection.Adults : The following single doses may be used and should not usually be repeated more frequently than four hourly; Subcutaneous or intramuscular injection : 25 - 100mg. Intravenous injection : 25 - 50mg.Elderly or debilitated patients : The initial dose should not exceed 25mg, because of the particular sensitivity among elderly or debilitated patients to the central depressant effects of pethidine.Children : The usual single dose is 0.5 to 2mg/kg body weight by intramuscular injection. If necessary, this dose may be repeated, allowing a minimum of four hours between doses. Use of a small graduated syringe is recommended for the accurate administration of dosages in children. In the absence of graduated syringes, the solution should be diluted with Water for Injections before measuring the dose.
History of hypersensitivity to pethidine.Coma. It also contra-indicated in conditions associated with raised intracranial pressure and in head injury (opioid analgesics interfere with pupillary responses vital for neurological assessment). Phaeochromocytoma.Acute respiratory depression and when there is risk of paralytic ileus or obstructive airways disease.Use in patients receiving monoamine oxidase inhibitors or within two weeks following their withdrawal.
4.4 Special warnings and precautions for use
If the intravenous route is being used, pethidine should be given slowly in order to reduce the risk of adverse reactions.Extreme care is required when administering pethidine to patients with asthma, severe cor pulmonale or reduced respiratory function.Pethidine should only be used with caution and in reduced dosage in neonates and premature infants, elderly and debilitated patients and in patients with head injuries, severe hepatic or renal impairment, biliary tract disorders, hypothyroidism, adrenocortical insufficiency, shock, prostatic hypertrophy and supraventricular tachycardia.Caution is also required in patients with acute alcoholism, raised intracranial pressure, or convulsive disorders, hypotension, myasthenia gravis and obstructive or inflammatory bowel disorders.Repeated administration of pethidine may produce physical and psychological dependence of the morphine type, with the development of withdrawal symptoms on abrupt cessation of therapy or on administration of a narcotic antagonist. Repeated administration may also induce tolerance, with a tendency to increase the dose in order to obtain the desired effect.
4.5 Interaction with other medicinal products and other forms of interaction
The central depressant effects of pethidine may be potentiated by the concurrent use of other central nervous system depressants including anxiolytics, hypnotics, antidepressants, other analgesics, alcohol and general anaesthetics; respiratory depression, hypotension and profound sedation or coma may result.Severe hypotension may occur when pethidine is administered to patients whose ability to maintain blood pressure has been compromised by a depleted blood volume or by the administration of drugs such as phenothiazine.Cimetidine inhibits metabolism of pethidine and therefore increases plasma concentration.Very severe reactions including coma, respiratory depression, cyanosis and hypotension have occurred in patients administered monoamine inhibitors (MAOIs). Pethidine should not be administered to patients taking MAOIs or to those who have taken MAOIs within 14 days (see Special Warnings and Precautions for Use). The interaction of pethidine with MAOIs may result in Serotonin syndrome. Pethidine and barbiturates given concomitantly can have CNS depressant effects.Pethidine when given with duloxetine may increase serotonergic effects.The hepatic metabolism of pethidine appears to be enhanced by phenytoinAvoid concomitant use with Ritanovir and isoniazid. Pethidine antagonize effects of domperidone and metoclopramide on gastro-intestinal activity.Use of pethidine in prolonged increasing dosage or concomitantly with anticholinergics may result in neurotoxicity in patients with renal failure, cancer or sickle cell anaemia.
4.6. Pregnancy and lactation
Pethidine crosses the placenta and is excreted in breast milk. This should be borne in mind when considering its use in patients during pregnancy or breast feeding. Administration during labour may cause respiratory depression in the newborn.
4.7 Effects on ability to drive and use machines
Pethidine may impair the mental and/or physical abilities required for driving or for operating machinery; patients should be advised accordingly and warned not to drive or to operate machines if affected. 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|
4.8 Undesirable effects
The most serious adverse effects of pethidine are respiratory depression and hypotension. Rapid intravenous administration of pethidine increases the incidence of these effects and may result in serious respiratory depression and hypotension with tachycardia.The most frequently observed adverse effects include lightheadedness, dizziness, hypothermia, sedation, nausea, vomiting and sweating.Other adverse effects include; Nervous System: Euphoria, dysphoria, weakness, headache, agitation, tremors, uncoordinated muscle movements, convulsions, hallucinations, visual disturbances, confusion, anxiety, nervousness and vertigo.Increased risk of delirium in elderly patients.Gastrointestinal: Dry mouth, constipation, biliary tract spasm.Cardiovascular: Flushing of the face, tachycardia, bradycardia, palpitation, hypotension, syncope.Genitourinary: Urinary retention, difficulty with micturationAllergic: Pruritus, urticaria, other skin rashes, wheal and flare over the vein with intravenous injection.Other: Pain at the injection site and local tissue irritation.
Signs of acute overdosage may include convulsions, respiratory depression, hypotension, shock and coma.Primary attention should be directed at correcting respiratory failure and shock. A patent airway should be established and assisted or controlled ventilation should be provided. Naloxone is a specific antidote used to counteract respiratory depression and coma resulting from opioid overdosage. Intravenous fluids and other supportive measures may be required in the management of shock. An anticonvulsant may be required if seizures occur.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Like other opioids, pethidine binds to opioid receptors and exerts its principal pharmacological actions on the central nervous system where its analgesic and sedative effects are of particular therapeutic value. The respiratory depression produced by pethidine can be antagonised by naloxone and nalorphine.Pethidine has a spasmogenic effect on certain smooth muscles which is qualitatively similar to that of morphine. In equianalgesic doses, pethidine appears to cause less constipation and biliary tract spasm than does morphine.Pethidine, like other opioids, dilates resistance and capacitance vessels and may thereby decrease the capacity of the cardiovascular system to respond to gravitational shifts. In therapeutic doses, the effects of pethidine on the cardiovascular system are generally not of clinical significance, especially when the patient is recumbent. However, rapid intravenous administration, or administration of pethidine to patients with depleted blood volume or in other situations where ability to maintain blood pressure has been compromised, may result in severe hypotension.
5.2 Pharmacokinetic properties
Pethidine hydrochloride is well absorbed by all recommended routes of administration. It is metabolised in the liver by hydrolysis. Following intravenous injection, a rapid decline in plasma concentration occurs due to distribution and this is followed by a slower phase with a half-time of approximately 3 hours. In patients with cirrhosis, the half-life is increased to 6 hours.Approximately 60% of pethidine in plasma is protein-bound. Older patients have decreased binding to plasma proteins and have higher concentrations in plasma, both of which may account for their increased response to therapeutic doses.Pethidine is metabolised in the liver by hydrolysis to pethidinic acid or by demethylation to norpethidine and hydrolysis to norpethidinic acid, followed by conjugation with glucoronic acid. About 1/3 of administered pethidine may be accounted for in the urine as N-demethylated derivatives. The acccumaltion of norpethidine may result in toxicity. The T½ of norpethidine is reported to be up to 20 hours.
5.3 Preclinical safety data
No further relevant information other than that which is included with other sections of the Summary of Product Characteristics.
6. Pharmaceutical particulars
6.1 List of excipients
Sodium Hydroxide B.P.Dilute Hydrochloric Acid B.P.Water for Injections B.P.
There was loss of clarity when intravenous solutions of pethidine hydrochloride were mixed with those of aminophylline, amylobarbitone sodium, heparin sodium, methicillin sodium, morphine sulphate, nitrofurantoin sodium, pentobarbitone sodium, phenobarbitone sodium, phenytoin sodium, sodium bicarbonate, sodium iodide, sulphadiazine sodium, sulphafurazole diethanolamine or thiopentone sodium.
6.3 Shelf life
4 years. If only part used, discard the remaining solution.
6.4 Special precautions for storage
Do not store above 25°C. Keep in outer carton.
6.5 Nature and contents of container
1ml and 2ml clear glass ampoules, glass type 1 Ph. Eur. packed in cardboard cartons to contain 10 x 1ml or 10 x 2ml ampoules.
6.6 Special precautions for disposal and other handling
CD (2)For S/C., I/M., or I/V injection.Use as directed by the physician.
7. Marketing authorisation holder
Mercury Pharma International Ltd4045, Kingswood Road, City West Business Park, Co Dublin, Ireland
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
|Date of first authorisation :||10/05/82|
|Date of renewal :||13/03/97|
10. Date of revision of the text
Concordia International - formerly AMCo
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+44 (0)208 588 9200
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