Presentation and Status in Health Basket
5 x 100 mg / 2 ml
5 x 50 mg/ml
25 x 100 mg / 2 ml
25 x 50 mg/ml
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Relief of Pain
Dosage should be adjusted according to the severity of the pain and the response of the patient.
Adults: The usual dosage is 50 -100 mg, administered intramuscularly or subcutaneously every 3 or 4 hours as necessary.
Children: The usual dosage is 1-1.8 mg/kg body weight, administered intramuscularly or subcutaneously every 3 or 4 hours as necessary. Irrespective of body weight, the adult dose should not be exceeded.
Adults: The usual dosage is 50-100 mg, administered intramuscularly or subcutaneously, 30 to 90 minutes before anesthesia is started.
Children: The usual dosage is 1-2 mg/kg body weight, administered intramuscularly or subcutaneously 30-90 minutes before the start of anesthesia. Irrespective of body weight, the adult dosage should not be exceeded.
Support of Anesthesia: The dose should be titrated to the needs of the patient, according to the premedication and type of anesthetic being employed, the characteristics of the particular patient, and the nature and duration of the operative procedure. Dolestine may be administered intravenously, either by repeated slow injection of fractional doses of a solution diluted to 10 mg/ml, or by infusion as a solution diluted to 1 mg/ml. Dosage may be individualized up to a maximum of 50 mg.
Obstetrical Analgesia: The usual dosage is 50-100 mg, administered intramuscularly or subcutaneously when pain becomes regular. It may be repeated at 1-3 hour intervals.
Relief of severe pain pre-operative medicdbation support of anesthesia obstetrical analgesia.
Known hypersensitivity to the preparation. Pethidine is contraindicated in patients who are receiving monoamine oxidase inhibitors, or those who have recently received such agents. Therapeutic doses of pethidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received monoamine oxidase inhibitors within the last 14 days. The mechanism of these reactions is unclear, but may be related to a preexisting hyperphenylalaninemia. Some have been characterized by coma, severe respiratory depression, cyanosis and hypotension, and have resembled the syndrome of acute narcotic overdose. In other reactions, the predominant manifestations have been hyperexcitability, convulsions, tachycardia, hyperpyrexia, and hypertension. Although it is not known that other narcotics are free of the risk of such reactions, virtually all of the reported reactions have occurred with pethidine. If a narcotic is needed in such patients, a sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while the patient’s condition and vital signs are under careful observation. (Intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of narcotic antagonists in the treatment of these reactions is unknown).
For full details see prescribing information.
Some adverse reactions have been reported more frequently after intravenous administration. Pethidine should only be administered i.v. if a narcotic antagonist and facilities for assisted or controlled respiration are available.
Pethidine should always be administered with caution, and in reduced dosage, to elderly and debilitated patients and patients with head injuries, severe hepatic or renal impairment, biliary tract disorders, hypothyroidism, adrenocortical insufficiency, shock, prostatic hypertrophy, urethral stricture and Addison’s disease.
Supraventricular Tachycardia: Pethidine should be used with caution in patients with atrial flutter and other supraventricular tachycardias because of a possible vagolytic action which may produce a significant increase in the ventricular response rate.
Acute Abdominal Conditions: As with other narcotics, pethidine may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
Convulsions: Pethidine may aggravate preexisting convulsions in patients with convulsive disorders.
Convulsions may occur in individuals without a history of convulsive disorders, following use of a higher than recommended dosage of the drug.
Other Precautions: Caution is also required in patients exhibiting acute alcoholism, raised intracranial pressure or convulsive disorders.
Serious or life-threatening reactions such as respiratory depression, coma, convulsions, possibly due to elevated levels of norpethidine and hypotension have been associated with the use of pethidine.
Pethidine should be used with caution in patients taking other CNS depressant drugs such as hypnotics and sedatives including barbiturates and benzodiazepines, phenothiazines, and other tranquillisers, anaesthetics, alcohol and antidepressants.
Patients with severe pain may tolerate very high doses of pethidine but may exhibit respiratory depression should their pain suddenly subside.
The elderly demonstrate an increased sensitivity to opioids relative to younger patients. Reduced liver function, renal function and plasma protein binding may contribute to the elevated plasma levels found in elderly subjects. Since pethidine is metabolized in the liver and excreted via the kidneys, the possibility of accumulation of the toxic metabolic norpethidine should be considered in patients with hepatic and/or renal impairment. Reduced cardiac output may lead to reduced hepatic perfusion and diminished metabolism of pethidine leading to accumulation of pethidine with possible toxic results. Pethidine may cause a transient rise in blood pressure and systemic vascular resistance and increased heart rate. Therefore, it is not recommended for pain relief in cardiac infarction. Pethidine in patients with pheochromocytoma may result in a hypertensive crisis. In an individual physically dependent on opioids, the administration of the usual dose of an 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 and only 10 to 20% of the usual initial dose administered. In eclampsia the combination of pethidine with phenothiazines has been reported to induce recurrence of seizures rather than stopping them. Therefore, the use of pethidine in eclampsia and pre-eclampsia is not recommended. Pethidine, while commonly used for pain relief in obstetrics, is known to pass the placenta and may cause neonatal depression, including respiratory depression. An opioid antagonist such as naloxone may be required to reverse such depression. In the neonate, pethidine is excreted and metabolized at a significantly reduced rate compared to adults. Orthostatic hypotension has been reported in ambulatory patients administered pethidine. Pethidine should be given with caution and the initial dose should be reduced in patients with hypothyroidism or Addison’s disease. Pethidine should be used with caution in patients with prostatic hypertrophy or urethral stricture. As opiate agonists may produce hyperglycemia, this effect should be considered when diabetics require pethidine. There are conflicting reports about the effect of pethidine on the eye. Some reports state that pethidine and its congeners produce miosis, whereas others indicate that these drugs tend to produce mydriasis or no pupillary change. Until the effects are better defined intraocular tension should be monitored in patients with glaucoma who received pethidine. Patients may experience drowsiness while receiving pethidine and should therefore be cautioned not to engage in potentially-hazardous activities requiring mental alertness, such as driving a car or operating machinery.
As with other opioid analgesics, respiratory depression is the major hazard associated with parenteral pethidine therapy.
Other adverse reactions include:
More Common Reactions:
Central Nervous System: Lightheadedness, dizziness, sedation, sweating, bizarre feelings, disorientation, hallucinations, psychosis. Some of these effects seem to be more prominent in ambulatory patients and those not experiencing severe pain, and may be relieved by reducing the dose slightly and lying down.
Gastrointestinal: Nausea and vomiting, constipation.
Less Common Reactions
Cardiovascular: Hypotension, vasodilation, hypertension, tachycardia, bradycardia, gangrene, following inadvertent intra-arterial administration.
Dermatological: Rash, pruritus, urticaria, erythema, injection site complications eg: local irritation and induration, fibrosis of muscle tissue with frequent repetition of intramuscular injection.
Gastrointestinal: Decreased gastric emptying.
Genito-urinary: Urinary retention and anuria.
Hepatic: Increased biliary tract pressure, choledochoduodenal sphincter spasm.
Nervous System: Pethidine associated neurotoxicity, or neuropsychiatric toxicity i.e.,auditory and visual hallucinations, irritability, agitation, hypomania, paranoia, delirium and complex partial seizures, vertigo, dizziness, coma, headache, convulsions or tremor, respiratory depression, cold clammy skin, sweating and pallor. Inadvertent injection around a nerve trunk may cause sensory-neural effects, which is usually, but not always transitory.
Psychiatric: Neuropsychiatric toxicity, hyperactivity or agitation, depression, mental clouding, dysphoria.
General: Dry mouth, weakness, hypersensitivity.Pain at injection site; local tissue irritation and induration following subcutaneous injection (particularly when repeated) and antidiuretic effect.
Pethidine has been found to interact with the following drugs:
Barbiturates, Chloral Hydrate, Benzodiazepines: Pethidine enhances the CNS depressant effects of these drugs. In addition, the combination of pethidine and phenobarbitone may reduce the analgesic effect of pethidine in part due to the increased conversion of pethidine to the toxic metabolite, norpethidine.
Phenothiazines: CNS toxicity and hypotension including respiratory depression may occur when given together. In eclampsia the combination has been reported to induce recurrence of seizures.
Butyrophenones: The CNS depressant effect of tranquillisers may be increased by pethidine.
Monoamine oxidase inhibitors: Excitation, sweating, rigidity, hypertension or hypotension, coma have occurred with combination. Interaction with furazolidone is not likely until it has been taken for five days. Interaction with selegiline, a MAOI Type B, has been reported as causing delirium, restlessness, sweating and rigidity.
Paracetamol: Absorption may be reduced due to delayed gastric emptying caused by pethidine.
CNS Depressants (Including Alcohol): Depressant effects may be enhanced by pethidine.
Phenytoin: Increased metabolism of pethidine and generation of norpethidine resulting in the possibility of increased CNS effects of norpethidine and reduced analgesia.
Coumarin/Indandione-Derivative The effects of coumarin or indandione – derivative anticoagulants may be increased.
Amphetamines: Concurrent use with amphetamines, which have some MAO inhibiting activity is not recommended because of the risk of serious reactions similar to those reported with other MAO inhibitors.
Cimetidine: Cimetidine inhibits metabolism of pethidine and therefore increases plasma concentration
Anticholinergics: Use of pethidine in prolonged increasing dosage or concomitantly with anticholinergics may result in neurotoxicity in patients with renal failure, cancer or sickle cell anemia.
Acyclovir: Plasma concentrations of pethidine and its metabolite, norpethidine, may be increased by acyclovir, thus caution should be used with concomitant administration.
Ritonavir: Plasma concentrations of the active metabolite norpethidine may be increased by ritonavir, thus concomitant administration should be avoided.
Skeletal Muscle Relaxants: Opioid analgesics, including pethidine, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Pregnancy and Lactation
Pregnancy: Safe use of pethidine prior to the labor period has not been established. Therefore, it should not be used at this time, unless the potential benefits to the mother outweigh the possible hazards to the fetus.
Labor and Delivery: Pethidine crosses the placental barrier and can produce depression of respiration and psychophysiologic functions in the newborn. Resuscitation may be required.Therefore pethidine is not recommended during labor.
Lactation: Pethidine is secreted in breast milk. Therefore, having taken into account the importance of the drug to the mother, either discontinue nursing or discontinue the drug.
Manifestations: Opioid analgesic overdose usually produces central nervous system depression ranging from stupor to a profound coma, respiratory depression which may progress to Cheyne-Stokes respiration and/or cyanosis, cold clammy skin and/or hypothermia, flaccid skeletal muscles, bradycardia and hypotension. In patients with severe overdose, particularly following rapid intravenous administration of an opioid, apnoea, circulatory collapse, cardiac arrest, respiratory arrest and death may occur. Complications such as pneumonia, shock and/or pulmonary oedema may also prove fatal. Although miosis (pupillary constriction) is characteristic of overdose with morphine derivatives and methadone, mydriasis may occur in terminal narcosis or severe hypoxia. Overdose of pethidine may produce mydriasis rather than miosis. Toxic effects of pethidine may be excitatory, especially in patients who have developed tolerance to the depressant effects of the drug. These patients may exhibit dry mouth, increased muscular activity, muscle tremors and twitches, tachycardia, delirium with disorientation, hallucinations and, occasionally, grand mal seizures.
Treatment: In overdose, if necessary, establish an airway and institute assisted or controlled ventilation. Circulation should be maintained with infusions of plasma or suitable electrolyte solution. If consciousness is impaired and respiration depressed, an opioid antagonist should be administered. Naloxone, a pure antagonist, is now the treatment of choice. Consult naloxone (or nalorphine) product information. Administer IV naloxone (eg. 0.4 mg) which may be repeated at 2 to 3 minute intervals. For children, the initial dose recommended is 0.01 mg/kg naloxone. In neonates, a more rapid and improved antagonism was noted after 0.02 mg/kg was administered. A response should be seen after 2 or 3 doses. Note the duration of action of naloxone is usually shorter than that of pethidine and thus the patient should be carefully observed for signs of CNS depression returning. An opioid antagonist should not be administered in the absence of clinical signs of respiratory or cardiovascular depression.
Note: In an individual physically dependent on opioids, the administration of the usual dose of an 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 and only 10 to 20% of the usual initial dose administered.