This information is intended for use by health professionals

1. Name of the medicinal product

Pethidine 50 mg Tablets

2. Qualitative and quantitative composition

Each tablet contains 50mg pethidine hydrochloride

Excipients with known effect

Each tablet also contains lactose (66.70 mg) and sucrose (4.30mg)

For the full list of excipients, see section 6.1

3. Pharmaceutical form

White or almost white tablet for oral use, with a score line on one side and an imprint of M50 on the reverse side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4. Clinical particulars
4.1 Therapeutic indications

1. Obstetric analgesia.

2. Moderate to severe pain.

3. Premedication and analgesia during anaesthesia.

4.2 Posology and method of administration

Posology

Adults:

The normal single dose, usually not to be repeated more often than four hourly, is as follows: Orally: 50 - 150 mg.

Elderly and debilitated patients

The initial dose should not exceed 50 mg orally as such patients are likely to be particularly sensitive to the central depressant effects of the drug.

Paediatric population:

A single dose of 0.5 - 2 mg / kg body weight orally. This dose may be repeated if clinically necessary but it should not be repeated more often than four hourly.

(As the tablet may not be cut, a child requiring 2mg/kg will need to weigh 25kg, and any child requiring a lower dose will need to be given Pethidine Solution for Injection.)

Method of administration

For oral administration

4.3 Contraindications

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

Not to be given to comatose patients or to patients with respiratory depression, obstructive airways disease or acute asthma. It should not be given to patients who are receiving monoamine oxidase inhibitors or moclobemide, or within two weeks of their withdrawal. For full list of interactions with other medicinal products, see section 4.5. Not to be given to patients with a history of hypersensitivity or idiosyncratic response to the drug or any of its constituents.

Pethidine should be avoided in patients exhibiting acute alcoholism, delirium tremens or convulsive disorders, and paralytic ileus. Pethidine depresses respiratory function and should be avoided in patients with respiratory insufficiency and in patients with head injuries, raised intracranial pressure severe hepatic or renal impairment. Patients with phaechromocytoma should not be treated with pethidine

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

4.4 Special warnings and precautions for use

Pethidine should only be given with caution, and in reduced dosage, to neonates and premature infants, elderly or debilitated patients, hypotension, decreased respiratory reserve, biliary tract disorders, hypothyroidism, adrenal cortical insufficiency, shock, prostatic hypertrophy, and supraventricular tachycardia. Use of cough suppressants containing opioid analgesics is not generally recommended in children and should be avoided altogether in those under at least 1 year.

Repeated administration may induce tolerance to the drug, with a tendency to psychological dependence of the morphine type, with withdrawal symptoms after abrupt cessation of therapy. Cross tolerance between narcotic analgesics can occur. In the case of severe continuing pain it may be advisable to try other treatments. A reduction in dose is advisable in cases of renal disease and chronic hepatic disease.

Pethidine hydrochloride tablets contain lactose and sucrose.

Patients with rare hereditary problems of galactose intolerance, fructose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Alcohol: Enhanced sedative and hypotensive effects.

Antidepressants, SSRI and Tricyclic: The use of pethidine should be avoided in patients receiving monoamine oxidase inhibitors (including moclobemide), or within two weeks of their withdrawal. Increased risk of CNS toxicity. Pethidine may increase potential for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) to cause convulsions.

Anxiolytics and Hypnotics: Sedative effects may be enhanced by simultaneous use of pethidine.

Antipsychotics: Increased risk of convulsions with pethidine

Carbamazepine: Reduces the effects of Pethidine.

Coumarins: Pethidine enhances anticoagulant effects of coumarins.

Digoxin: Risk of digoxin toxicity increased.

Duloxetine: Possible increased serotonergic effects when administered with pethidine.

Selegiline: Caution with pethidine advised by manufacturer of selegiline.

Ciprofloxacin: The manufacturer of ciprofloxacin advises that, if it is used for surgical prophylaxis, opiates should not be used for premedication as this may reduce the plasma concentration of ciprofloxacin.

Cimetidine: The metabolism of pethidine is inhibited (plasma concentrations of pethidine are increased).

Domperidone and metoclopramide: Pethidine antagonises the gastro-intestinal activity of these drugs.

Mexilitine: Pethidine delays the absorption of mexilitine.

Ritonavir: Plasma concentration of pethidine may be increased by ritonavir.

4.6 Fertility, pregnancy and lactation

Pregnancy

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. Nevertheless the established medical practice of prescribing medicaments in early pregnancy should be observed.

Lactation

Pethidine crosses the placenta and is also secreted in breast milk. This should be borne in mind when considering its use in patients during pregnancy or 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.

4.7 Effects on ability to drive and use machines

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:

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 table below presents adverse drug reactions by System Organ Class. Within each System Organ Class, the adverse drug reactions are presented by incidence, using the following convention:

Not known (cannot be estimated from the available data).

System Organ Class

Frequency

Adverse Event

Psychiatric disorders

Unknown

Euphoria, hallucinations, dysphoria, mood changes, dependance

Nervous system disorders

Unknown

Central Nervous System

excitation, dizziness, vertigo, drowsiness, headache

Eye disorders

Unknown

Obtund or abolish the corneal reflex, miosis

(pupillary constriction)

Cardiac disorders

Unknown

Bradycardia, tachycardia, palpitations

Vascular disorders

Unknown

Hypotension, facial flushing,

Respiratory, thoracic and mediastinal disorders

Unknown

Respiratory depression

Gastrointestinal disorders

Unknown

Nausea,vomiting, constipation, dry mouth

Hepatobiliary disorders

Unknown

Biliary spasm

Skin and subcutaneous tissue disorders

Unknown

Rashes, urticaria, pruritis

Musculoskeletal and connective tissue disorders

Unknown

Muscle rigidity

Renal and urinary disorders

Unknown

Difficulty in micturition, ureteral spasm

Reproductive system and breast disorders

Unknown

Decreased libido or potency

General disorders and administration site conditions

Unknown

Sweating, hypothermia

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

In acute overdose, the signs may be incoordination, tremors and convulsions followed by respiratory depression and coma.

Management

Gastric lavage should be performed soon after ingestion, and intensive supportive therapy carried out. Naloxone is the preferred antidote. The urinary excretion can be increased by rendering the urine acid by the administration of ammonium chloride. Patients exhibiting symptoms of CNS toxicity should be treated by immediate discontinuation of pethidine, substituting an alternative narcotic for pain, supporting respiratory function and administering an anticonvulsant if seizures occur.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Phenylpiperidine derivatives

ATC code: N02A B02

Pethidine binds to opioid receptors and exerts its chief pharmacological action on the CNS and the neural elements of the bowel. The analgesic effects of pethidine are detectable about 15 minutes after oral administration, reaching a peak in about 2 hours and subsiding gradually over several hours. In equianalgesic doses pethidine depresses respiration to a similar extent to morphine. Pethidine has a spasmogenic effect on certain smooth muscles similar to that observed for other opioids.

Ambulatory patients given pethidine may experience syncope associated with hypotension but symptoms rapidly clear on lying down. Otherwise in therapeutic doses pethidine has no significant untoward effects on the cardiovascular systems, especially if patients are lying down. Pethidine combines analgesic and antispasmodic properties; it is relatively short acting and has little soporific effect. These properties make pethidine particularly useful for pain relief in labour and as an adjunct to nitrous oxide-oxygen anaesthesia.

5.2 Pharmacokinetic properties

Peak plasma concentrations are normally observed between 1 and 2 hours after oral administration. However, only about 50% of the drug escapes first pass metabolism to enter the circulation. About 60% is protein bound in plasma.

Heavy alcohol drinkers have an increased apparent volume of distribution with consequent initially lower pethidine plasma concentrations. Older Patients have higher plasma concentrations and reduced protein binding which may account for the increased response in therapeutic dosages. Pethidine is mainly metabolised in the liver by hydrolysis to pethidinic acid, or by N-demethylation to norpethidine, followed by hydrolysis to norpethidinic acid. Subsequent, partial conjugation with glucuronic acid may also occur.

5.3 Preclinical safety data

None stated

6. Pharmaceutical particulars
6.1 List of excipients

Starch

Lactose

Sucrose

Talc

Magnesium Stearate

Acacia

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years (24 months).

6.4 Special precautions for storage

Store in the original packaging.

Do not store above 25°C.

6.5 Nature and contents of container

A blister strip of 10 tablets, 5 strips per pack.

Pack size of 50 tablets

6.6 Special precautions for disposal and other handling

No special requirement.

7. Marketing authorisation holder

Martindale Pharma

Bampton Road

Romford

RM3 8UG

England.

8. Marketing authorisation number(s)

PL 00156/0031

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 07/08/2008

10. Date of revision of the text

28/12/2017