Pethidine is indicated for the short-term (24–36 hours) management of moderate to severe pain. It can be administered via intramuscular, subcutaneous, slow intravenous bolus injection, intravenous infusion, or patient-controlled analgesia (PCA).

Pethidine is also used as an adjunct to anesthesia and for pain relief during labor (obstetric analgesia). During and immediately after intravenous administration, an opioid antagonist, oxygen supply, and facilities for respiratory support should be readily available.

Pethidine is a phenylpiperidine derivative opioid analgesic that primarily acts as a mu-opioid receptor agonist. Like other opioids, it mimics naturally occurring (endogenous) opioids by activating receptors in both the central and peripheral nervous systems. It reduces the release of neurotransmitters and decreases the activity of postsynaptic neurons in the spinal cord, thereby inhibiting the transmission of pain signals.

Adult Dosage:

Analgesia:

• Dosage should be adjusted according to the severity of pain and the response of the patient and also depends on patient profile e.g. age, weight, sex, previous exposure to narcotics.
• 25 to 100 mg by IM (preferred) or S.C. injection, every 3 to 4 hours.
• 25 to 50 mg slow IV injection, every 3 to 4 hours.
• Usual dose is 200 mg/day by the IV route. Intravenous injection should be made very slowly, preferably using a diluted solution.
• For continuous intravenous infusion adequate analgesia should be established prior to commencement of the infusion. A dosage of 0.3 mg/kg/hr is recommended as the initial intravenous infusion rate.
• Clinical experience suggests that patients with normal renal function receiving more than 1000 mg/24 hrs pethidine are at particular risk of developing pethidine-associated neurotoxicity (PAN). Patients receiving over 800 mg/24 hrs pethidine should usually be monitored for early signs of norpethidine toxicity.

Obstetrical Analgesia:

50 to 100 mg by IM (preferred) or S.C. injection, administered when pain becomes regular. May be repeated 3 to 4 times at one or three hour intervals if necessary. Maximum of 4 doses in 24 hours

Anaesthesia Adjunct:

As premedication, intramuscular (preferred) or subcutaneous, 50 to 100 mg thirty to ninety minutes prior to anaesthesia. As an adjunct to anaesthesia, intravenous, by repeated slow injection of fractional doses of a solution diluted to 10 mg per mL. Dosage by this route should not exceed 25 to 50 mg. Dosage must be titrated to the needs of the patient, depending on the premedication given, the type of anaesthesia, and the nature and duration of the surgical procedure.

Patient-Controlled Analgesia:

• Patient-controlled analgesia (PCA) allows patients to assess their own level of pain and consequently titrate the amount of pethidine they require for adequate pain control against sedation and other side effects. Adequate analgesia should be established prior to commencement of PCA.
• The dosages and time intervals are preset into a microprocessor-controlled infusion pump. When the patient experiences pain, a button is depressed by the patient and a dose of pethidine is administered intravenously. If the patient should depress the button before the preset time interval (lockout interval) has elapsed, no extra drug is administered. For adults, demand doses, of 5 mg to a maximum of 20 mg pethidine have been given via PCA using a lockout interval of 6 to 20 minutes. Along with the self-administered dose of pethidine, some syringe pumps also deliver a background continuous infusion of pethidine at a basal rate. Some PCA pumps allow a maximum dosage over a defined period to be preset in order to avoid patient overdosage.
• The demand dosage and lockout interval should be determined according to the patient's analgesic requirements. Patients receiving a background infusion of pethidine should generally receive a smaller demand dose relative to equivalent patients utilising a demand dose only.
• Clinical experience suggests that patients with normal renal function receiving more than 1000 mg/24 hrs pethidine are at particular risk of developing pethidine-associated neurotoxicity (PAN). Patients receiving over 800 mg/24 hrs pethidine should usually be monitored for early signs of norpethidine toxicity. Pethidine-associated neurotoxicity is dose related, so pethidine should not be used for periods greater than 24 to 36 hours

Paediatric Dose:

• Analgesia: Intramuscular (preferred) or subcutaneous, 0.5 to 2 mg per kg of body weight, not to exceed 100 mg, every three to four hours as needed.
• Preoperative: Intramuscular (preferred) or subcutaneous, 1 to 2 mg per kg of body weight, not to exceed 100 mg, thirty to ninety minutes prior to anaesthesia.
• Neonates: Excretion and metabolism of pethidine in the neonate is reduced compared with adults. Safety has not been established in neonates and due to lack of data, no dosage regimen can be recommended.

Pethidine metabolite levels may increase when used with drugs such as aciclovir, cimetidine, and ritonavir. Its analgesic effectiveness may be reduced when combined with phenytoin or barbiturates. Concurrent use with alcohol, barbiturates, benzodiazepines, phenothiazines, tricyclic antidepressants (TCAs), or other CNS depressants may result in additive sedative and respiratory depressive effects.

Hypersensitivity to pethidine.

Respiratory depression, or conditions where respiratory reserve is significantly reduced, such as acute bronchial asthma, chronic airway disease, severe emphysema, severe chronic bronchitis, or kyphoscoliosis.

Head injury, increased intracranial pressure (in addition to difficulties in monitoring and diagnosis, hypercapnia due to respiratory depression may further increase intracranial pressure), and brain tumours.

Cardiac arrhythmias, particularly supraventricular tachycardia and cor pulmonale. Pethidine has a vagolytic effect and may increase the ventricular response rate.

Concurrent use of monoamine oxidase inhibitors (MAOIs), including selegiline, or use within the previous two weeks. The combination of MAOIs and pethidine may lead to hypotension, hypertension, excitation, rigidity, hyperpyrexia, convulsions, and in some cases, death. This combination should be avoided.

Pre-eclampsia and eclampsia.

Convulsive conditions such as status epilepticus, tetanus, and strychnine poisoning, due to the stimulatory effect of pethidine on the spinal cord.

Diabetic acidosis where there is a risk of coma.

Acute alcoholism or delirium tremens.

Severe liver disease and early hepatic encephalopathy.

Patients with low platelet count, coagulation disorders, or those receiving anticoagulant therapy.

Continuous intravenous infusion: The use of pethidine via continuous intravenous infusion is contraindicated in patients with renal impairment.

Patient-controlled analgesia (PCA): The use of pethidine via PCA is contraindicated in young children and in adults with impaired cognitive function. It is also contraindicated in patients with renal impairment.

Central Nervous System: Lightheadedness, dizziness, sedation, sweating, abnormal sensations, confusion, hallucinations, and psychosis. These effects may be more noticeable in mobile patients and those without severe pain, and may improve with dose reduction and rest.

Gastrointestinal: Nausea, vomiting, and constipation.

Pregnancy: Pethidine Hydrochloride is classified as Pregnancy Category C. Opioid analgesics, including pethidine, may cause respiratory depression in newborn infants if used during labour. Therefore, its use should be carefully considered by balancing the mother’s need for pain relief against the potential risks to the fetus. Animal studies on reproduction have not been conducted with pethidine, and its safety during pregnancy before labour has not been clearly established, particularly regarding possible effects on fetal development.

Breast-feeding: Pethidine is known to pass into breast milk, although detailed information on its concentration or rate of excretion is not available. The clinical impact of this on nursing infants remains uncertain. For this reason, the use of pethidine is generally not recommended in breastfeeding mothers.

The use of Pethidine may be associated with serious or life-threatening effects such as respiratory depression, coma, convulsions, hypotension, and increased levels of its metabolite norpethidine. Therefore, all recommended precautions and warnings should be strictly followed.

Pethidine should be used cautiously in patients taking other central nervous system depressants, including sedatives, hypnotics, barbiturates, benzodiazepines, phenothiazines, tranquilizers, anesthetics, alcohol, and antidepressants, due to the risk of enhanced sedation and respiratory depression.

Patients experiencing severe pain may tolerate higher doses of pethidine; however, if the pain suddenly decreases, they may become more susceptible to respiratory depression.

Elderly patients are generally more sensitive to opioids. Age-related decline in liver and kidney function, as well as changes in protein binding, may lead to higher drug levels in the body.

Since pethidine is metabolized in the liver and eliminated through the kidneys, accumulation of the toxic metabolite norpethidine may occur in patients with liver or kidney impairment.

Reduced cardiac output can decrease liver blood flow, slowing the metabolism of pethidine and increasing the risk of drug accumulation and toxicity.

Pethidine may temporarily increase blood pressure, vascular resistance, and heart rate; therefore, it is not recommended for use in patients with myocardial infarction.

In patients with pheochromocytoma, pethidine may trigger a hypertensive crisis.

In individuals who are physically dependent on opioids, the use of opioid antagonists may cause acute withdrawal symptoms. If necessary, antagonists should be used with extreme caution and at reduced doses.

Pethidine may worsen seizures in patients with seizure disorders. High doses, especially beyond recommended limits, may also induce seizures in individuals without prior history.

In cases of eclampsia, the combination of pethidine with phenothiazines may increase the risk of seizures rather than control them. Therefore, it is not recommended in eclampsia or pre-eclampsia.

Pethidine crosses the placenta and may cause respiratory depression in newborns when used during childbirth. Neonates metabolize and eliminate the drug more slowly than adults, and treatment with an opioid antagonist such as naloxone may be required.

Orthostatic hypotension has been reported in patients receiving pethidine.

Caution is advised and dose adjustment may be necessary in patients with hypothyroidism or Addison’s disease.

Pethidine should be used carefully in patients with prostate enlargement or urethral obstruction.

Opioids may increase blood sugar levels; therefore, this effect should be considered in diabetic patients receiving pethidine.

There are inconsistent findings regarding the effects of pethidine on the eyes. Some reports indicate pupil constriction, while others suggest dilation or no change. Until more information is available, intraocular pressure should be monitored in patients with glaucoma.

Geriatric Patients: Start with half the usual adult dose.
Hepatic Impairment: Dose reduction or increased dosing interval is recommended.
Renal Impairment: Use cautiously due to risk of metabolite accumulation; dose adjustment is required.

Symptoms: CNS and respiratory depression, dilated pupils, slow heart rate, pulmonary edema, tremors, excitability, and seizures.
Treatment: Symptomatic management. Naloxone may be used to reverse opioid effects but should not be used for pethidine-induced seizures.

Opioid analgesic

Store at room temperature. Protect from light and do not freeze.