Pethidine Other names: Pethidine Pethidine Hydrochloride

The central depressant effects of pethidine may be potentiated by the concurrent use of other central nervous system depressants including anxiolytics and sedatives, hypnotics, barbiturates and tricyclic 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.

Enhanced sedative and hypotensive effects.

Pethidine enhances anticoagulant effects of coumarins.

Additive effects on CNS depression, respiratory depression and hypotension can occur with concomitant use of opioid agonist analgesics.

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.

Carbamazepine reduces the effects of pethidine.

Cimetidine inhibits metabolism of pethidine and therefore increases plasma concentration.

The plasma levels of ciprofloxacin may be reduced in the presence of opiate premedicants.

Risk of digoxin toxicity increased.

Pethidine antagonize effects of domperidone and metoclopramide on gastro-intestinal activity.

Pethidine when given with duloxetine (SSRIs) may increase serotonergic effects.

Plasma levels of mexiletine may also be reduced in the presence of opioid analgesics.

Administration of phenytoin may cause an increase in hepatic metabolism of pethidine and subsequently increased levels of norpethidine (a toxic metabolite).

Plasma concentrations of pethidine may be decreased by concomitant administration of ritonavir, however levels of norpethidine (a toxic metabolite) may rise. Concomitant administration of ritonavir, isoniazid and pethidine should be avoided.

Although less spasmogenic than morphine, pethidine may precipitate spasm of the ureter or Sphincter of Oddi. Subsequently it should be used with caution in patients with prostatic hypertrophy and biliary tract disorders including those with pain secondary to gallbladder pathology.

Pethidine should be avoided in patients with obstructive or inflammatory bowel disorders due to its effects on the gastrointestinal tract where it may precipitate toxic megacolon.

Pethidine should be used with caution in patients with, hypothyroidism, adrenocortical insufficiency, shock, and supraventricular tachycardia.

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.

Pethidine should be used with caution or in reduced doses in patients with myasthenia gravis.

There is inadequate evidence of safety of pethidine in human pregnancy, but the drug has been widely used for many years without apparent ill-consequence, and animal studies have not shown any hazard.

As with all drugs during pregnancy care should be taken in assessing the risk to benefit ratio. Administration during labour may cause respiratory depression in the new-born infant.

Pethidine crosses the placenta and is also secreted in breast milk. This should be borne in mind when considering its use in patients during lactation. Administration in labour may cause respiratory depression of the new-born infant.

Fertility

There are insufficient fertility data available to indicate whether pethidine hydrochloride has any effect on fertility.

Pethidine may modify the patient’s reactions to a varying extent, depending on dosage, administration and individual susceptibility. If affected or if you are in any doubt that you may be affected do not drive or operate machinery until any effects have worn off.

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:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
  • It was not affecting your ability to drive safely.