Consumer medicine information

DBL Pethidine Hydrochloride Injection

Pethidine hydrochloride

BRAND INFORMATION

Brand name

DBL Pethidine Hydrochloride Injection

Active ingredient

Pethidine hydrochloride

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Pethidine Hydrochloride Injection.

SUMMARY CMI

DBL™ Pethidine Hydrochloride Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I being treated with DBL Pethidine Hydrochloride Injection?

DBL Pethidine Hydrochloride Injection contains the active ingredient pethidine hydrochloride. DBL Pethidine Hydrochloride Injection is a pain killer that belongs to a group of medicines called opioid analgesics. It is most commonly used to relieve severe pain. It may also be used just before, or during, an operation, to help the anaesthetic work better.

For more information, see Section 1. Why am I being treated with DBL Pethidine Hydrochloride Injection? in the full CMI.

2. What should I know before treatment with DBL Pethidine Hydrochloride Injection?

Do not use if you have ever had an allergic reaction to pethidine or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before treatment with DBL Pethidine Hydrochloride Injection? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DBL Pethidine Hydrochloride Injection and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is DBL Pethidine Hydrochloride Injection given?

Your doctor will decide what dose of pethidine you will receive. This depends on your condition and other factors, such as your age and weight.

More instructions can be found in Section 4. How is DBL Pethidine Hydrochloride Injection given? in the full CMI.

5. What should I know during treatment with DBL Pethidine Hydrochloride Injection?

Things you should do
  • Remind any doctor, dentist and pharmacist you visit that you are being given pethidine.
  • If you become pregnant while you are being treated with pethidine, tell your doctor immediately.
Things you should not do
  • Do not stop using this medicine suddenly. If you have been using pethidine for more than two weeks, you may experience unpleasant feelings if you stop pethidine suddenly.
Driving or using machines
  • Do not drive a car, operate machinery, or do anything else that could be dangerous until you know how pethidine affects you. Pethidine may cause drowsiness and impair coordination.
Drinking alcohol
  • Do not drink alcohol while you are being treated with pethidine.
Looking after your medicine
  • If you are being given DBL Pethidine Hydrochloride Injection while in hospital, it will be stored in the pharmacy or on the ward. Store below 25°C.

For more information, see Section 5. What should I know during treatment with DBL Pethidine Hydrochloride Injection? in the full CMI.

6. Are there any side effects?

Common side effects are mild and usually short lived. These include drowsiness, dizziness or unsteadiness, light-headedness, sweating or flushing, nausea or vomiting, constipation, hallucinations, pain and irritation at the injection site, blurred vision, dry mouth and mood changes. If you experience serious side effects such as severe drowsiness, slow or rapid heart beat, difficulty in urinating, slow or troubled breathing, severe weakness, agitation, twitching, jerking, seizures (fits), or unconsciousness, you may need urgent medical attention or hospitalisation.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING:

Limitations of use

DBL Pethidine Hydrochloride Injection should only be used when your doctor decides that other treatment options are not able to effectively manage your pain or you cannot tolerate them.

Hazardous and harmful use

DBL Pethidine Hydrochloride Injection poses risks of abuse, misuse and addiction which can lead to overdose and death. Your doctor will monitor you regularly during treatment.

Life threatening respiratory depression

DBL Pethidine Hydrochloride Injection can cause life-threatening or fatal breathing problems (slow, shallow, unusual or no breathing) even when used as recommended. These problems can occur at any time during use, but the risk is higher when first starting pethidine and after a dose increase, if you are older, or have an existing problem with your lungs. Your doctor will monitor you and change the dose as appropriate.

Use of other medicines while using pethidine

Using pethidine with other medicines that can make you feel drowsy such as sleeping tablets (e.g. benzodiazepines), other pain relievers, antihistamines, antidepressants, antipsychotics, gabapentinoids (e.g. gabapentin and pregabalin), cannabis and alcohol may result in severe drowsiness, decreased awareness, breathing problems, coma and death. Your doctor will minimise the dose and duration of use; and monitor you for signs and symptoms of breathing difficulties and sedation. You must not drink alcohol while using pethidine.



FULL CMI

DBL™ Pethidine Hydrochloride Injection

Active ingredient(s): pethidine hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using DBL Pethidine Hydrochloride Injection. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using DBL Pethidine Hydrochloride Injection.

Where to find information in this leaflet:

1. Why am I being treated with DBL Pethidine Hydrochloride Injection?
2. What should I know before treatment with DBL Pethidine Hydrochloride Injection?
3. What if I am taking other medicines?
4. How is DBL Pethidine Hydrochloride Injection given?
5. What should I know during treatment with DBL Pethidine Hydrochloride Injection?
6. Are there any side effects?
7. Product details

1. Why am I being treated with DBL Pethidine Hydrochloride Injection?

DBL Pethidine Hydrochloride Injection contains the active ingredient pethidine hydrochloride. DBL Pethidine Hydrochloride Injection is a pain killer that belongs to a group of medicines called opioid analgesics. Pethidine acts in the brain and the spinal cord.

DBL Pethidine Hydrochloride Injection is most commonly used to relieve severe pain. It may also be used just before, or during, an operation, to help the anaesthetic work better.

Your doctor may have prescribed pethidine for another reason.

Ask your doctor if you have any questions about why pethidine has been prescribed for you.

2. What should I know before treatment with DBL Pethidine Hydrochloride Injection?

If you are not sure whether you should start treatment with pethidine, talk to your doctor or pharmacist.

Warnings

Do not use DBL Pethidine Hydrochloride Injection if you:

  • are allergic to pethidine, or any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include:
    - shortness of breath, wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body,
    - rash, itching or hives on the skin
    Always check the ingredients to make sure you can use this medicine.
  • are an asthmatic, have breathing problems or have severe disease relating to the lungs
  • are suffering from a head injury or brain tumour
  • have an irregular heart beat (arrhythmia)
  • are undergoing treatment with, or have finished treatment in the last two weeks with, monoamine oxidase (MAO) inhibitors (e.g. selegiline, phenelzine, tranylcypromine, moclobemide)
  • have severe liver or kidney disease
  • have blood-thinning problems, or are receiving treatment for this disorder (e.g. warfarin)
  • are suffering from acute alcoholism
  • have a blockage in the stomach and intestine (severe constipation) or have severe pain in the stomach with bloating, gut cramps and vomiting (paralytic ileus).

Check with your doctor if you:

  • have or have had any other medical conditions, especially the following
    - lung or breathing problems
    - alcohol abuse
    - gall bladder disease or gallstones
    - under-active thyroid (hypothyroidism)
    - adrenal gland tumour (phaechromocytoma) and/or when the adrenal glands are not working properly (Addison's disease)
    - low or high blood sugar, diabetes
    - epilepsy, convulsions, fits or seizures
    - snoring or sleep apnoea (you temporarily stop breathing or have difficulty breathing while asleep)
  • take any medicines for any other condition
  • have allergies to any other medicines, foods, preservatives or dyes.

If you have not told your doctor or pharmacist about any of the above, tell them before you are given DBL Pethidine Hydrochloride Injection.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Your doctor will discuss the possible risks and benefits of you being given pethidine during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Pethidine passes into breast milk and therefore there is a possibility that your baby may be affected.

Your doctor will discuss the possible risks and benefits of you being given pethidine during breastfeeding.

Addiction

You can become addicted to pethidine even if you use it exactly as prescribed. Pethidine may become habit forming causing mental and physical dependence. If abused it may become less able to reduce pain.

Dependence

As with all other opioid containing products, your body may become used to you using pethidine. Using it for a long time (i.e. more than two weeks) may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop using pethidine suddenly, so it is important to use it exactly as directed by your doctor.

However, it is also important to keep your pain under control. Your doctor can advise you on how to prevent and manage this.

Tolerance

Tolerance to pethidine may develop, which means that the effect of the medicine may decrease. If this happens, more may be needed to maintain the same effect.

Withdrawal

Continue using your medicine for as long as your doctor tells you. If you stop using this medicine suddenly, your pain may worsen and you may experience some or all of the following withdrawal symptoms:

  • nervousness, restlessness, agitation, trouble sleeping or anxiety
  • body aches, weakness or stomach cramps
  • loss of appetite, nausea, vomiting or diarrhoea
  • increased heart rate, breathing rate or pupil size
  • watery eyes, runny nose, chills or yawning
  • increased sweating.

DBL Pethidine Hydrochloride Injection given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with DBL Pethidine Hydrochloride Injection and affect how it works. These include:

  • antidepressants or medicines for anxiety disorders, such as:
    - selective serotonin reuptake inhibitors (SSRIs)
    - serotonin and norepinephrine reuptake inhibitors (SNRIs)
    - tricyclic antidepressants (TCAs)
    - monoamine oxidase inhibitors (MAOIs) e.g. moclobemide, phenelzine, tranylcypromine
  • medicines used for migraines (triptans)
  • medicines used to prevent or treat nausea and vomiting (5-HT3 receptor antagonists)
  • selegiline, a monoamine oxidase inhibitor used to treat Parkinson's disease
  • warfarin, a medicine used to prevent blood clots
  • other medicines which may make you drowsy such as sleeping tablets (e.g. benzodiazepines, hypnotics), tablets to calm your nerves (e.g. sedatives), muscle relaxants, medicines to treat mental disorders, other opioid analgesics or strong painkillers, some antihistamines.

Medicines that may increase the effect of DBL Pethidine Hydrochloride Injection include:

  • macrolide antibiotics (e.g. erythromycin)
  • azole-antifungal agents (e.g. ketoconizole)
  • protease inhibitors or medication for HIV (e.g. ritonavir).

Medicines that may reduce the effect of DBL Pethidine Hydrochloride Injection include:

  • rifampicin (anti-tuberculosis medication)
  • carbamazepine and phenytoin (medicines used to control fits or seizures).

Your doctor will minimise the dose and duration of use; and monitor you for signs and symptoms of breathing difficulties and sedation.

These medicines may be affected by pethidine, or may affect how well it works. You may need different amounts of your medicine, or you may need to take/use different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while you are receiving DBL Pethidine Hydrochloride Injection.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DBL Pethidine Hydrochloride Injection.

4. How is DBL Pethidine Hydrochloride Injection given?

How much is given

  • Your doctor will decide what dose of pethidine you will receive. This depends on your condition and other factors, such as your age and weight.

How is it given

  • Your doctor or nurse will usually give DBL Pethidine Hydrochloride Injection to you.
  • DBL Pethidine Hydrochloride Injection can be given as:
    - an injection into a muscle
    - a slow injection into a vein
    - an injection under the skin or
    - by a method called patient-controlled analgesia.
    -- This method allows you, the patient, to control the amount of pethidine you wish to receive. On experiencing pain, you can press a button which allows a dose of pethidine to be administered to you. To prevent you receiving too much pethidine, there is a "lockout" period built into the pump which prevents continuous injection of pethidine.

Your doctor will decide the appropriate way for you to be given pethidine.

If you use too much (overdose)

DBL Pethidine Hydrochloride Injection is only recommended to be given for a maximum of 24 to 36 hours, however some people may need to receive it for longer.

If you or someone else have received too much (overdose) of DBL Pethidine Hydrochloride Injection and experience one or more of the symptoms below, urgent medical attention is required. Keep the person awake by talking to them or gently shaking them every now and then. You should follow the above steps even if someone other than you have accidentally been given pethidine that was prescribed for you.

Symptoms of an overdose may include:

  • slow, unusual or difficult breathing
  • severe drowsiness, dizziness or unconsciousness
  • slow or weak heartbeat
  • nausea or vomiting
  • convulsions or fits (twitching or jerking)
  • severe weakness
  • pale and cold skin.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

When seeking medical attention, take this leaflet and remaining medicine with you to show the doctor. Also tell them about any other medicines or alcohol which have been taken.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know during treatment with DBL Pethidine Hydrochloride Injection?

As pethidine may cause nausea and vomiting, your doctor is likely to prescribe medicine for you to take/receive before the pethidine, to stop you feeling sick.

Pethidine may also cause constipation, so your doctor is likely to prescribe laxatives to prevent this happening.

Things you should do

  • Tell any doctors, dentists and pharmacists who are treating you that you are being given DBL Pethidine Hydrochloride Injection.
  • If you are about to be started on any new medicine, tell your doctor, dentist and pharmacist that you are being given DBL Pethidine Hydrochloride Injection.
  • If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are being treated with DBL Pethidine Hydrochloride Injection.
  • If you become pregnant while you are being treated with pethidine, tell your doctor or pharmacist.
  • Tell your doctor, pharmacist or nurse if you have any concerns about being given pethidine.

Things you should not do

  • Do not give DBL Pethidine Hydrochloride Injection to anyone else, even if they have the same condition as you.
  • Do not use DBL Pethidine Hydrochloride Injection to treat any other complaints unless your doctor or pharmacist tells you to.
  • Do not stop using DBL Pethidine Hydrochloride Injection or lower the dosage without checking with your doctor or pharmacist. If you have been using DBL Pethidine Hydrochloride Injection for more than two weeks, you may experience unpleasant feelings if you stop it suddenly. Your doctor will probably want you to gradually reduce the amount of pethidine you are using, before stopping it completely.
  • Do not take any other medicines, whether they are prescription or over-the-counter medicines, unless they have been prescribed or recommended by a doctor or pharmacist who knows you are being given pethidine.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DBL Pethidine Hydrochloride Injection affects you.

DBL Pethidine Hydrochloride Injection may cause drowsiness and impairment of coordination in some people. Do not drive a car, operate machinery, or do anything else that could be dangerous if you are drowsy or feeling uncoordinated.

Drinking alcohol

Tell your doctor if you drink alcohol.

You must not drink alcohol while using pethidine. Do not drink alcohol while you are undergoing treatment with pethidine unless otherwise advised by your doctor or pharmacist, as drowsiness and coordination impairment may be worse.

Looking after your medicine

If you are being given DBL Pethidine Hydrochloride Injection while in hospital, it will be stored in the pharmacy or on the ward.

DBL Pethidine Hydrochloride Injection should be stored in a cool dry place, protected from light, where the temperature stays below 25°C.

Do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

Do not use this medicine after the expiry date.

DBL Pethidine Hydrochloride Injection should not be given to you if the packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

If your doctor tells you to stop using DBL Pethidine Hydrochloride Injection or the expiry date has passed, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

If you are over 65 years of age you may have an increased chance of getting side effects.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

If you get any side effects, do not stop pethidine without first talking to your doctor or pharmacist.

Common side effects

Common side effectsWhat to do
  • drowsiness
  • dizziness or unsteadiness
  • light-headedness
  • sweating or flushing
  • nausea and/or vomiting
  • constipation
  • hallucinations
  • pain and irritation at the injection site
  • blurred vision
  • dry mouth
  • mood changes

Speak to your doctor if you have any of these common side effects and they worry you.
Mostly they are mild and short lived.

Serious side effects

Serious side effectsWhat to do
  • severe drowsiness
  • slow or rapid heart beat
  • difficulty in urinating
  • slow or troubled breathing
  • severe weakness
  • agitation
  • twitching
  • jerking
  • seizures (fits)
  • unconsciousness

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop treatment with any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What DBL Pethidine Hydrochloride Injection contains

Active ingredient
(main ingredient)		Pethidine hydrochloride
Other ingredients
(inactive ingredients)

Sodium hydroxide

Water for injections

Do not use this medicine if you are allergic to any of these ingredients.

DBL Pethidine Hydrochloride Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

What DBL Pethidine Hydrochloride Injection looks like

DBL Pethidine Hydrochloride Injection is a clear, colourless, sterile solution in ampoules.

It is available in the following strengths:

  • 50 mg/1 mL AUST R 107386
  • 100 mg/2 mL AUST R 107387

Who distributes DBL Pethidine Hydrochloride Injection

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

This leaflet was prepared in February 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

DBL Pethidine Hydrochloride Injection

Active ingredient

Pethidine hydrochloride

Schedule

S8

 

1 Name of Medicine

DBL Pethidine Hydrochloride Injection.

2 Qualitative and Quantitative Composition

DBL Pethidine Hydrochloride Injection is a sterile, clear solution of pethidine hydrochloride in water for injections. The 50 mg/1 mL and 100 mg/2 mL presentations contain sodium hydroxide. The pH of the injection ranges between 3.5 and 6.0.
DBL Pethidine Hydrochloride Injection is a white crystalline powder, very soluble in water and freely soluble in alcohol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Pethidine Hydrochloride Injection is a sterile, clear solution.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Pethidine Hydrochloride Injection is indicated for the short term (24 to 36 hours) management of severe pain for which other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain. It can be given via the following routes of administration: intramuscular, subcutaneous, slow intravenous bolus injection, intravenous infusion and patient controlled analgesia (PCA).
DBL Pethidine Hydrochloride Injection is indicated for administration as an anaesthetic adjunct and for obstetric analgesia.

4.2 Dose and Method of Administration

Adult dosage.

1. 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 SC injection, every 3 to 4 hours.
25 to 50 mg slow IV injection, every 3 to 4 hours (see Section 4.4 Special Warnings and Precautions for Use).
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 DBL Pethidine Hydrochloride Injection are at particular risk of developing pethidine associated neurotoxicity (PAN). Patients receiving over 800 mg/24 hrs DBL Pethidine Hydrochloride Injection should usually be monitored for early signs of norpethidine toxicity (see Section 4.4 Special Warnings and Precautions for Use).

Note.

Pethidine associated neurotoxicity is dose related, so DBL Pethidine Hydrochloride Injection should not be used for periods greater than 24 to 36 hours (see Section 4.4 Special Warnings and Precautions for Use).
2. Obstetric analgesia. 50 to 100 mg by IM (preferred) or SC injection, administered when pain becomes regular. May be repeated 3 to 4 times at one to three hour intervals if necessary.

Note.

Maximum of 4 doses in 24 hours.
3. 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. See Section 4.4 Special Warnings and Precautions for Use, prior to administering by the IV route. Dosage by this route should not exceed 25 to 50 mg.

Note.

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.
4. 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 DBL Pethidine Hydrochloride Injection 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 DBL Pethidine Hydrochloride Injection have been given via PCA using a lockout interval of 6 to 20 minutes. Along with the self administered dose of DBL Pethidine Hydrochloride Injection, some syringe pumps also deliver a background continuous infusion of DBL Pethidine Hydrochloride Injection 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 DBL Pethidine Hydrochloride Injection 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 DBL Pethidine Hydrochloride Injection are at particular risk of developing DBL Pethidine Hydrochloride Injection associated neurotoxicity (PAN). Patients receiving over 800 mg/24 hrs DBL Pethidine Hydrochloride Injection should usually be monitored for early signs of norpethidine toxicity (see Section 4.4 Special Warnings and Precautions for Use).

Note.

Pethidine associated neurotoxicity is dose related, so DBL Pethidine Hydrochloride Injection should not be used for periods greater than 24 to 36 hours (see Section 4.4 Special Warnings and Precautions for Use).

Paediatric dose.

1. Children.

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.
2. Neonates. (See Section 5 Pharmacological Properties; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy.)
Excretion and metabolism of DBL Pethidine Hydrochloride Injection 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.

Geriatric patients.

Dose reduction to half normal adult dose is recommended in geriatric patients (over 70 years).

Method of administration.

DBL Pethidine Hydrochloride Injection can be given via the following routes of administration: intramuscular, subcutaneous, slow intravenous bolus injection, intravenous infusion and patient controlled analgesia (PCA).
An opioid antagonist and facilities for administration of oxygen and control of respiration should be immediately available during and immediately following intravenous administration of DBL Pethidine Hydrochloride Injection.

Instructions to be given to patient.

CNS depression is increased when DBL Pethidine Hydrochloride Injection is co-administered with CNS depressants, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics (e.g. butyrophenones, phenothiazines), antihistamines, centrally-active anti-emetics, general anaesthetics, tranquilisers, other CNS depressants, and alcohol.
Driving and operating dangerous machinery should not be contemplated until the day following the last dose of DBL Pethidine Hydrochloride Injection.

Dosage adjustments.

Renal impairment.

Due to the possibility of accumulation of norpethidine in patients with renal failure, caution should be exercised when DBL Pethidine Hydrochloride Injection is administered to these patients, especially over prolonged periods of time. Therefore, a decrease in the dose or increase in the dosing interval is recommended (see Section 4.4 Special Warnings and Precautions for Use).

Liver impairment.

Dosage reduction and/or increased dosage intervals are recommended.

Dose conversion.

DBL Pethidine Hydrochloride Injection, when given intramuscularly in a dose of 75 to 100 mg is equivalent in analgesic effect to the following: codeine phosphate 120 mg; fentanyl citrate 200 microgram; morphine 10 mg; methadone hydrochloride 8 to 10 mg.

4.3 Contraindications

Hypersensitivity to DBL Pethidine Hydrochloride Injection.
Severe respiratory disease, acute respiratory disease, respiratory depression, or where respiratory reserve is depleted (acute bronchial asthma, chronic airway disease, severe emphysema, severe chronic bronchitis, kyphoscoliosis).
Head injury, raised intracranial pressure (apart from introducing monitoring and diagnostic problems, hypercapnia associated with respiratory depression can itself result in elevated intracranial pressure), brain tumour.
Cardiac arrhythmias, especially supraventricular tachycardias, cor pulmonale. DBL Pethidine Hydrochloride Injection has a vagolytic action and may produce a significant increase in the ventricular response rate.
Concurrent use of monoamine oxidase inhibitors (MAOIs), including selegiline, or use of MAOIs within two weeks prior. The combination of monoamine oxidase inhibitors and DBL Pethidine Hydrochloride Injection has caused hypotension, hypertension, excitation, rigidity, hyperpyrexia and/or convulsions, and in some cases, fatalities have been reported. This combination should be avoided.
Pre-eclampsia, eclampsia.
Convulsive states such as status epilepticus, tetanus and strychnine poisoning, due to the stimulatory effects of DBL Pethidine Hydrochloride Injection on the spinal cord.
Diabetic acidosis where there is a danger of coma.
Acute alcoholism or delirium tremens.
Severe liver disease, incipient hepatic encephalopathy.
Patients with a low platelet count, coagulation disorders or receiving anticoagulant treatment.
Known or suspected gastrointestinal obstruction, including paralytic ileus (see Section 4.4 Special Warnings and Precautions for Use).

Continuous intravenous infusion.

The administration of DBL Pethidine Hydrochloride Injection via continuous intravenous infusion in patients with renal impairment is contraindicated.

Patient controlled analgesia.

The administration of DBL Pethidine Hydrochloride Injection via patient controlled analgesia (PCA) in young children and adults with poor cognitive function is contraindicated. The administration of DBL Pethidine Hydrochloride Injection via PCA in patients with renal impairment is contraindicated.

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

DBL Pethidine Hydrochloride Injection contains the opioid Pethidine Hydrochloride and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed DBL Pethidine Hydrochloride Injection at recommended doses.
The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed DBL Pethidine Hydrochloride Injection.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Patients should be advised not to share DBL Pethidine Hydrochloride Injection with anyone else.

Accidental ingestion/exposure.

Accidental ingestion or exposure of DBL Pethidine Hydrochloride Injection, especially by children, can result in a fatal overdose of pethidine. Patients and their caregivers should be given information on safe storage and disposal of unused DBL Pethidine Hydrochloride Injection (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Life threatening reactions.

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 DBL Pethidine Hydrochloride Injection. Therefore the recommendations in this section should be carefully observed.

Respiratory depression.

Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of DBL Pethidine Hydrochloride Injection but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients and in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma) and hepatic and renal impairment. Opioids should be used with caution and with close monitoring in these patients (see Section 4.2 Dose and Method of Administration). The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response (see Section 4.2 Dose and Method of Administration).
In addition, large doses and/or rapid intravenous administration of DBL Pethidine Hydrochloride Injection may produce rapid onset respiratory depression including central sleep apnoea (CSA) and sleep related hypoxaemia, apnoea, hypotension, peripheral circulatory collapse, bradycardia (as a result of stimulation of medullary vagal nuclei) or even cardiac arrest. DBL Pethidine Hydrochloride Injection should not be administered by intravenous injection unless an opioid antagonist and facilities for controlled or assisted respiration are available. Consider decreasing the opioid dosage using best practices for opioid taper.
Patients with severe pain may tolerate very high doses of DBL Pethidine Hydrochloride Injection but may exhibit respiratory depression should their pain suddenly subside.

Seizures.

Seizures may result from prolonged exposure or high doses of DBL Pethidine Hydrochloride Injection due to pethidine associated neurotoxicity (PAN). PAN is a recognized clinical entity which is mainly due to the metabolite norpethidine (see Section 4.8 Adverse Effects (Undesirable Effects)). Norpethidine concentrations are enhanced by reduction in renal excretion as in the elderly and the very young and by increased conversion of DBL Pethidine Hydrochloride Injection to norpethidine due to the effects of drugs such as phenobarbitone and phenytoin. Furthermore, DBL Pethidine Hydrochloride Injection associated neurotoxicity is dose related, so DBL Pethidine Hydrochloride Injection should not be used for periods greater than 24 to 36 hours. See DBL Pethidine Hydrochloride Injection associated neurotoxicity (PAN) below.
DBL Pethidine Hydrochloride Injection may aggravate pre-existing convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels because of tolerance development, convulsions may occur in individuals without a history of convulsive disorders.

DBL Pethidine Hydrochloride Injection associated neurotoxicity (PAN).

The risk of DBL Pethidine Hydrochloride Injection associated neurotoxicity (PAN) is increased in a situation in which the patient may receive large doses of DBL Pethidine Hydrochloride Injection, as with patient controlled analgesia (PCA). Caution should therefore be taken in patients receiving DBL Pethidine Hydrochloride Injection by PCA. Frequent clinical assessment and recording of the amount of drug used is required to minimise such risks. Clinical experience suggests that patients with normal renal function receiving more than 1000 mg/24 hrs DBL Pethidine Hydrochloride Injection are at particular risk of developing PAN. Patients receiving over 800 mg/24hrs DBL Pethidine Hydrochloride Injection should be usually monitored for early signs of norpethidine toxicity (e.g. twitching, anxiety).

Serotonin syndrome.

The development of serotonin syndrome (SS), which is potentially life threatening, has been reported with opioid use, including with pethidine. Serotonin syndrome generally occurred when pethidine was used concomitantly with serotonergic drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Serotonin syndrome may include mental status changes (e.g. agitation, hallucinations, coma, confusion), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia, diaphoresis), neuromuscular abnormalities (e.g. hyperreflexia, incoordination, rigidity, tremor, myoclonus), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea).
If serotonin syndrome is suspected, a dose reduction or discontinuation of at least one of the serotonergic medicines being taken should be considered depending on the severity of symptoms.

Patients with head injuries or acute abdominal conditions.

Opioids may obscure the diagnosis and/or mask the clinical course of patients with head injuries or acute abdominal conditions and should not be used unless absolutely necessary in these conditions. The respiratory depressant effects of DBL Pethidine Hydrochloride Injection may be markedly exaggerated in the presence of head injury.

Inadvertent intra-arterial administration.

Inadvertent intra-arterial administration can produce severe necrosis and gangrene.

Reduced cardiac output.

Reduced cardiac output may lead to reduced hepatic perfusion and diminished metabolism of DBL Pethidine Hydrochloride Injection leading to accumulation of pethidine with possible toxic results.

Orthostatic hypotension.

Orthostatic hypotension has been reported in ambulatory patients administered DBL Pethidine Hydrochloride Injection.

Pain relief in cardiac infarction.

DBL Pethidine Hydrochloride Injection 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.

Patients with pheochromocytoma.

DBL Pethidine Hydrochloride Injection in patients with pheochromocytoma may result in a hypertensive crisis.

Patients with eclampsia.

In eclampsia, the combination of DBL Pethidine Hydrochloride Injection with phenothiazines has been reported to induce recurrence of seizures rather than stopping them. Therefore the use of DBL Pethidine Hydrochloride Injection in eclampsia and pre-eclampsia is not recommended (see Section 4.3 Contraindications).

Pain relief in obstetrics.

DBL Pethidine Hydrochloride Injection, 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, DBL Pethidine Hydrochloride Injection is excreted and metabolised at a significantly reduced rate compared to adults.

Prostatic hypertrophy or urethral stricture.

DBL Pethidine Hydrochloride Injection should be used with caution in patients with prostatic hypertrophy or urethral stricture.

Use in diabetic patients.

As opiate agonists may produce hyperglycaemia, this effect should be considered when diabetics require DBL Pethidine Hydrochloride Injection.

Ophthalmic effects.

There are conflicting reports about the effect of DBL Pethidine Hydrochloride Injection on the eye. Some reports state that DBL Pethidine Hydrochloride Injection 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, intra-ocular tension should be monitored in patients with glaucoma who received DBL Pethidine Hydrochloride Injection.

Tolerance, dependence and withdrawal.

Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid.
Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced. Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
When discontinuing DBL Pethidine Hydrochloride Injection in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Section 4.4 Special Warnings and Precautions for Use, Ceasing opioids; Section 4.2 Dose and Method of Administration).
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.

Ceasing opioids.

Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance, dependence and withdrawal). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been using, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.

Neonatal opioid withdrawal syndrome.

See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy (Category C).

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

Opioid analgesics have an established role in the treatment of acute pain, cancer pain and palliative and end-of-life care. Current evidence does not generally support opioid analgesics in improving pain and function for most patients with chronic non-cancer pain. The development of tolerance and physical dependence and risks of adverse effects, including hazardous and harmful use, increase with the length of time a patient takes an opioid. The use of opioids for long-term treatment of CNCP is not recommended.
The use of an opioid to treat CNCP should only be considered after maximised non pharmacological and non-opioid treatments have been tried and found ineffective, not tolerated or otherwise inadequate to provide sufficient management of pain. Opioids should only be prescribed as a component of comprehensive multidisciplinary and multimodal pain management.
Opioid therapy for CNCP should be initiated as a trial in accordance with clinical guidelines and after a comprehensive biopsychosocial assessment has established a cause for the pain and the appropriateness of opioid therapy for the patient (see Hazardous and harmful use). The expected outcome of therapy (pain reduction rather than complete abolition of pain, improved function and quality of life) should be discussed with the patient before commencing opioid treatment, with agreement to discontinue treatment if these objectives are not met.
Owing to the varied response to opioids between individuals, it is recommended that all patients be started at the lowest appropriate dose and titrated to achieve an adequate level of analgesia and functional improvement with minimum adverse reactions. Immediate-release products should not be used to treat chronic pain, but may be used for a short period in opioid naïve patients to develop a level of tolerance before switching to a modified-release formulation. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment. Discontinue opioid therapy if there is no improvement of pain and/or function during the trial period or if there is any evidence of misuse or abuse. Treatment should only continue if the trial has demonstrated that the pain is opioid responsive and there has been functional improvement. The patient's condition should be reviewed regularly and the dose tapered off slowly if opioid treatment is no longer appropriate (see Ceasing opioids).

Hyperalgesia.

Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance, dependence and withdrawal). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.

Adrenal insufficiency.

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Patients with hypothyroidism or Addison's disease.

DBL Pethidine Hydrochloride Injection should be given with caution and the initial dose should be reduced in patients with hypothyroidism or Addison's disease.

Risks of use in patients with gastrointestinal conditions.

DBL Pethidine Hydrochloride Injection is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
Because of the spasmogenic properties of DBL Pethidine Hydrochloride Injection on the biliary tract and sphincter of Oddi, it should be used only when necessary and then with caution in biliary colic, operations on the biliary tract and acute pancreatitis. DBL Pethidine Hydrochloride Injection may render surgical exploration of the common bile duct difficult.
Decreased gastric emptying associated with DBL Pethidine Hydrochloride Injection may be expected to increase the risks of aspiration either associated with DBL Pethidine Hydrochloride Injection induced CNS depression/coma or during or after general anaesthesia, e.g. a labouring patient going on to caesarean section.

Patients with severe inflammatory bowel disease.

The risk of toxic megacolon may be increased in patients with severe inflammatory bowel disease.

Use in patient controlled analgesia (PCA).

The use of DBL Pethidine Hydrochloride Injection in patient controlled analgesia (PCA) should be reserved for short term (24 to 36 hours) use in patients with normal renal function who have adverse reactions to morphine. Morphine is the opioid of choice for PCA.

Risks of concomitant use or discontinuation of cytochrome P450 3A4 inhibitors and inducers.

Concomitant use of DBL Pethidine Hydrochloride Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g. erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g. ritonavir), may increase plasma concentrations of DBL Pethidine Hydrochloride Injection and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression (see Respiratory depression) particularly when an inhibitor is added after a stable dose of DBL Pethidine Hydrochloride Injection is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in DBL Pethidine Hydrochloride Injection treated patients may increase DBL Pethidine Hydrochloride Injection plasma concentrations and prolong opioid adverse reactions. When using DBL Pethidine Hydrochloride Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in DBL Pethidine Hydrochloride Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of DBL Pethidine Hydrochloride Injection until stable drug effects are achieved (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Concomitant use of DBL Pethidine Hydrochloride Injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease DBL Pethidine Hydrochloride Injection plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to DBL Pethidine Hydrochloride Injection. When using DBL Pethidine Hydrochloride Injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider adjusting the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Risks from concomitant use of benzodiazepines or other CNS depressants.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression including CSA and sleep related hypoxaemia, coma and death. Because of these risks, concomitant prescribing of DBL Pethidine Hydrochloride Injection with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, general anaesthetics, tranquilisers, or other CNS depressants, should be reserved for patients for whom other treatment options are not possible.
If a decision is made to prescribe DBL Pethidine Hydrochloride Injection concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while using DBL Pethidine Hydrochloride Injection.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of medicine-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Advise both patients and caregivers about the risks of respiratory depression including CSA and sleep related hypoxaemia, and sedation when DBL Pethidine Hydrochloride Injection is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery during concomitant use of the benzodiazepine or other CNS depressant. these activities should not be contemplated until the day following the last dose of DBL Pethidine Hydrochloride Injection (see Section 4.7 Effects on Ability to Drive and Use Machines). Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Fatal interaction with monoamine oxidase inhibitors.

DBL Pethidine Hydrochloride Injection is contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitors or those who have recently received such agents. Therapeutic doses of DBL Pethidine Hydrochloride Injection have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 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. Serotonin syndrome with agitation, hyperthermia, diarrhoea, tachycardia, sweating, tremors and impaired consciousness may also occur. In other reactions the predominant manifestations have been hyperexcitability, convulsions, tachycardia, hyperpyrexia, and hypertension.
Do not use DBL Pethidine Hydrochloride Injection in patients taking MAOIs or within 14 days of stopping such treatment.

Use in hepatic/renal impairment.

Since DBL Pethidine Hydrochloride Injection is metabolised in the liver and excreted via the kidneys, the possibility of accumulation of the toxic metabolite norpethidine should be considered in patients with hepatic and/or renal impairment (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

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.

Paediatric use.

Norpethidine concentrations are enhanced by reduction in renal excretion as in the very young and in the elderly (see section above, Seizures and DBL Pethidine Hydrochloride Injection associated neurotoxicity (PAN)). See Section 4.2 Dose and Method of Administration, Paediatric dose.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

DBL Pethidine Hydrochloride Injection has been found to interact with the following drugs:

Barbiturates, chloral hydrate, benzodiazepines.

DBL Pethidine Hydrochloride Injection enhances the CNS depressant effects of these drugs. In addition the combination of DBL Pethidine Hydrochloride Injection and phenobarbitone may reduce the analgesic effect of DBL Pethidine Hydrochloride Injection in part due to the increased conversion of DBL Pethidine Hydrochloride Injection to the toxic metabolite, norpethidine. See Table 1.

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 (see Section 4.4 Special Warnings and Precautions for Use).

Butyrophenones.

The CNS depressant effect of tranquillisers may be increased by DBL Pethidine Hydrochloride Injection.

Paracetamol.

Absorption may be reduced due to delayed gastric emptying caused by DBL Pethidine Hydrochloride Injection.

CNS depressants (including alcohol).

Depressant effects may be enhanced by DBL Pethidine Hydrochloride Injection.

Phenytoin.

Increased metabolism of DBL Pethidine Hydrochloride Injection and generation of norpethidine resulting in the possibility of increased CNS effects of norpethidine and reduced analgesia.
The effects of coumarin or indandione derivative anticoagulants may be increased.
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.

Serotonergic drugs.

The concomitant use of opioids including pethidine, with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome (see Section 4.4 Special Warnings and Precautions for Use). Drugs that affect the serotonergic neurotransmitter system include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, and MAOIs. See Table 2.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C1)
Opioid analgesics may cause respiratory depression in the newborn infant. These products should therefore only be used after weighing the needs of the mother during labour against the risk to the fetus (see Section 5 Pharmacological Properties).
Prolonged use of opioid analgesics during pregnancy can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhoea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Animal reproduction studies have not been conducted with DBL Pethidine Hydrochloride Injection and safe use in pregnancy prior to labour has not been established with regard to possible adverse effects on fetal development.
1 Category C = drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.
 DBL Pethidine Hydrochloride Injection is excreted in breast milk, however, clinical data on the rate of excretion or concentration of DBL Pethidine Hydrochloride Injection in breast milk is not available. The clinical significance of these findings is yet to be determined. It is not recommended that DBL Pethidine Hydrochloride Injection be administered to nursing mothers.

4.7 Effects on Ability to Drive and Use Machines

Since DBL Pethidine Hydrochloride Injection may cause drowsiness and general impairment of coordination, ambulatory patients should be cautioned against driving or operating machinery.
Driving and operating dangerous machinery should not be contemplated until the day following the last dose of DBL Pethidine Hydrochloride Injection.

4.8 Adverse Effects (Undesirable Effects)

As with other opioid analgesics, respiratory depression is the major hazard associated with parenteral DBL Pethidine Hydrochloride Injection therapy. Other adverse reactions include:

More common effects.

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 effects.

Cardiovascular.

Hypotension, vasodilation, hypertension, tachycardia, bradycardia, gangrene following inadvertent intra-arterial administration.

Dermatological.

Rash, pruritus, urticaria, erythema, injection site complications, e.g. local irritation and induration, fibrosis of muscle tissue with frequent repetition of intramuscular injection.

Gastrointestinal.

Decreased gastric emptying.

Genitourinary.

Urinary retention and anuria.

Hepatic.

Increased biliary tract pressure, choledochoduodenal sphincter spasm.

Nervous system.

DBL Pethidine Hydrochloride Injection associated neurotoxicity (see Section 4.4 Special Warnings and Precautions for Use), 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. 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.

Vascular.

Pallor.

General.

Dry mouth, weakness, hypersensitivity.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Opioid analgesic overdosage 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 overdosage, 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 overdosage with morphine derivatives and methadone, mydriasis may occur in terminal narcosis or severe hypoxia. Overdosage of DBL Pethidine Hydrochloride Injection may produce mydriasis rather than miosis.
Toxic effects of DBL Pethidine Hydrochloride Injection 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 overdosage, 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 (e.g. 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 DBL Pethidine Hydrochloride Injection 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

DBL Pethidine Hydrochloride Injection is a synthetic opioid analgesic which produces a pattern of effects similar to morphine, the standard against which opioid analgesics are compared. In addition to analgesia, the effect of DBL Pethidine Hydrochloride Injection on the central nervous system causes respiratory depression, drowsiness, sedation, change in mood, euphoria, dysphoria, mental clouding, nausea, vomiting and electroencephalographic changes. Large doses of DBL Pethidine Hydrochloride Injection may induce excitation or convulsions. DBL Pethidine Hydrochloride Injection is not effective in the management of cough or diarrhoea.
As a general rule, 75 to 100 mg DBL Pethidine Hydrochloride Injection (parenterally) is equivalent to 10 mg morphine with respect to analgesic effect, euphoria and respiratory depression.
DBL Pethidine Hydrochloride Injection has local anaesthetic activity but may be irritant when applied locally.
Opioids exert their pharmacological actions by interaction with stereo-specific opiate receptors located in the central and peripheral nervous systems.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

DBL Pethidine Hydrochloride Injection may be administered as an intramuscular, intravenous or subcutaneous injection. Variable absorption has been observed in some cases following intramuscular administration. It has been found that 80% or more of a 100 mg dose of DBL Pethidine Hydrochloride Injection administered intramuscularly is absorbed over six hours with a mean time of maximum plasma concentration at approximately 24 minutes.
Analgesia may persist for two to four hours following intramuscular, intravenous and subcutaneous administration.

Distribution.

There is no specific information on the distribution of DBL Pethidine Hydrochloride Injection, but data indicate that DBL Pethidine Hydrochloride Injection is extensively distributed extravascularly, primarily into rapidly perfused tissues.
The apparent volume of distribution is estimated as 4.17 L/kg. Plasma protein binding has been estimated to be 64.3%. Because of the large volume of distribution of DBL Pethidine Hydrochloride Injection, displacement of DBL Pethidine Hydrochloride Injection from plasma proteins is not likely to cause a significant increase in free DBL Pethidine Hydrochloride Injection concentration.

Metabolism.

DBL Pethidine Hydrochloride Injection is extensively metabolised in the liver. It undergoes transformation primarily by hydrolysis to pethidinic acid, followed by partial conjugation with glucuronic acid. DBL Pethidine Hydrochloride Injection also undergoes N-demethylation to norpethidine, followed by hydrolysis and partial conjugation. In vitro data show DBL Pethidine Hydrochloride Injection is metabolized to norpethidine in liver mainly by CYP3A4 and CYP2B6.
Norpethidine, a major metabolite, is estimated to be half as active as DBL Pethidine Hydrochloride Injection as an analgesic but twice as potent as a convulsive agent as DBL Pethidine Hydrochloride Injection.
Accumulation of DBL Pethidine Hydrochloride Injection can occur in patients with hepatic dysfunction. Adjustment in dose, frequency and/or duration of DBL Pethidine Hydrochloride Injection therapy is recommended.

Excretion.

The mean plasma clearance of DBL Pethidine Hydrochloride Injection following IV injection is 1.06 L/min (range 0.71 to 1.32) but only 3.8% of the dose is excreted unchanged (range 2.2 to 6.9%). Plasma clearance is significantly reduced with hepatic dysfunction.
Elimination half-life of DBL Pethidine Hydrochloride Injection has been estimated to be approximately 3.5 hours. This can be prolonged to 7 to 11 hours in cirrhotic patients and patients with acute viral hepatitis, see Metabolism for advice on dosage adjustment.
In patients with impaired renal function, persons over 60 years and the neonate, the elimination half-life of norpethidine is prolonged from the normal range of 8 to 21 hours to longer than 30 hours which may lead to accumulation and toxic side effects such as seizures, agitation, irritability, tremors, twitches and myoclonus. The half-life of norpethidine in pregnant women averages 20.6 hours.
DBL Pethidine Hydrochloride Injection and norpethidine accumulate in maternal plasma following multiple doses of DBL Pethidine Hydrochloride Injection during labour and maximum exposure of the foetus will result because of a continued diffusion gradient from mother to foetus. Elimination of both DBL Pethidine Hydrochloride Injection and norpethidine is prolonged and with long drug to delivery intervals and/or multiple doses the levels of norpethidine in the newborn may become clinically significant.
The urinary excretion of DBL Pethidine Hydrochloride Injection and norpethidine may be enhanced with acidification of the urine.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium hydroxide, water for injections.

6.2 Incompatibilities

The mixing of thiopentone solutions with DBL Pethidine Hydrochloride Injection results in the formation of a pharmacologically inactive complex. A loss of clarity of solution was noted when solutions of DBL Pethidine Hydrochloride Injection were mixed with the following: aminophylline, heparin, amobarbital (amylobarbitone) sodium, methicillin sodium, morphine sulphate, phenobarbital (phenobarbitone) sodium, phenytoin sodium, sodium bicarbonate or sodium iodide.
DBL Pethidine Hydrochloride Injection is also incompatible with alkalis, iodine and iodides.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Pethidine Hydrochloride Injection is available in the following presentations and pack sizes:

Presentations.*

50 mg in 1 mL: 5 and 50 ampoules.
100 mg in 2 mL: 5 and 50 ampoules.
*Not all presentations or pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: ethyl 1-methyl-4-phenylpiperidine-4-carboxylate hydrochloride.
Molecular weight: 283.8.

CAS number.

50-13-5.

7 Medicine Schedule (Poisons Standard)

Schedule 8 (controlled drug).

Summary Table of Changes