Pethidine Hydrochloride freeze-dried 100mg + Injection water ampule

Pethidine 100mg/vial + 2ml water Solution for Injection

Pethidine Hydrochloride 5% w/v

(50mg in 1ml and 100mg in 2ml total volume)

For the full list of excipients, see section 6.1

Solution for Injection

A clear colourless, particle free solution

Relief of moderate to severe pain.

Premedication.

Obstetric analgesia.

Enhancement of analgesia

Posology

Adults.

For moderate or severe pain.

Normal single dose (usually not to be repeated more often than 4 hourly)

For obstetric analgesia.

By intramuscular or subcutaneous injection repeated 1 – 3 hours later. 50 – 100 mg.

Maximum of 400mg in 24 hours.

As a premedication.

By intramuscular injection one hour prior to the operation. 50 – 100mg

For the enhancement of analgesia.

By slow intravenous injection. 10 – 50mg as required.

Elderly or debilitated patients.

Initial doses should not exceed 25mg as this group of patients may be specially sensitive to the central depressant effect of the drug.

Paediatric population

For moderate or severe pain.

By intramuscular injection. 0.5 – 2 mg per Kg of body weight.

As a premedication.

By intramuscular injection one hour prior to the operation. 1 – 2 mg per kg of body weight.

Method of administration

Intramuscular, intravenous or subcutaneous injection

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Severe respiratory depression, severe obstructive airways disease or acute asthma.

It should not be administered to patients with severe renal impairment or severe hepatic impairment.

Should be avoided in patients with acute alcoholism, delirium tremens, raised intracranial pressure or in those with convulsive states such as status epilepticus.

It should not be administered to patients receiving monoamine oxidase inhibitors ( including moclobemide, and the monoamine B inhibitors selegiline and rasagiline) or within two weeks of their withdrawal.

Pethidine should not be administered to patients receiving ritonavir.

Use of pethidine should be avoided in patients with supraventricular tachycardia.

Use of pethidine in patients with phaechromocytoma may result in hypertensive crisis.

Use of pethidine should be avoided in patients with diabetic acidosis where there is danger of coma.

In comatose patients

In patients with a risk of paralytic ileus

In patients with head injuries.

Pethidine is controlled under the Misuse of Drugs Act 1971 (Schedule 2).

Repeated use may result in dependence of the morphine type.

Pethidine should be used with caution in patients with acute or chronic airflow obstruction including asthma.

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

Pethidine should only be given with caution and in reduced doses to neonates, premature infants, patients who are elderly or debilitated or those with impaired hepatic or renal function. Renal impairment may result in accumulation of the potentially toxic metabolite norpethidine, particularly with repeat dosing All of these patient groups may experience increased or prolonged effects of the product.

Pethidine should be used with caution in patients with shock, hypothyroidism, adreno-corticol insufficiency and a history of convulsive disorders.

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 used with caution in patients with existing hypotension as it may reduce the blood pressure further.

In addition it should be avoided in patients with severe inflammatory bowel disease due to its effects on the gastrointestinal tract where it may precipitate toxic megacolon.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs:

Concomitant use of methadone and sedative medicines such as benzodiazepines or related drugs 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 methadone 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).

Monoamine Oxidase Inhibitors

The concurrent use of MAOIs (including moclobemide) is contra-indicated (see section 4.3) as they may result in CNS excitation or depression.

Pethidine should not be administered to patients receiving monoamine oxidase inhibitors or moclobemide or within two weeks of their withdrawal (see Section 4.3).

CNS depressants

CNS depressants such as alcohol, hypnotics, anxiolytics and sedatives, barbiturates and tricyclic antidepressants may increase the general depressant effects of pethidine and should therefore be used with caution.

Opioid agonists

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

MAO-B inhibitors

Concomitant use of MAO-B inhibitors such as selegiline or rasagiline is contraindicated (see section 4.3) as this may lead to hyperpyrexia and CNS toxicity.

Rasagiline should not be given with pethidine as there is risk of CNS toxicity, its use should be avoided for two weeks after taking rasagiline.

Anticonvulsants

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

Antipsychotics

Concomitant use of phenothiazines and pethidine can induce severe hypotension.

Anti-virals

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 and pethidine should be avoided (see section 4.3).

Histamine H2 antagonists

Cimetidine can reduce the metabolism of pethidine resulting in increased plasma concentration.

Effects of pethidine on other drugs

Pethidine may have an effect on the activities of other drugs, for example domperidone, as a consequence of reduced gastro-intestinal motility.

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

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

Possible increased serotonergic effects when pethidine is given with SSRI’s.

Sedative medicines such as benzodiazepines or related drugs:

The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs 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).

Pregnancy

There is inadequate evidence of safety in human pregnancy, but the drug has been in widely use for many years without apparent ill consequence. 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.

Lactation:

Pethidine crosses the placental barrier and is excreted in breast milk. Patients should be advised to discontinue breast-feeding during treatment with pethidine

Patients should not drive or use machines while taking pethidine as it may cause drowsiness and reduce alertness.

The ability to drive or use machines may be severely affected during and for some time after administration of pethidine. 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

There are no modern clinical studies available that can be used to determine the frequency of undesirable effects. Therefore, all the undesirable effects listed are classified as “frequency unknown” (cannot be estimated from the available data).

The undesirable effects listed below include class effects for opioid analgesics and effects related to the pharmacologically active metabolite, norpethidine.