Consumer medicine information

DBL Promethazine Hydrochloride Injection BP

Promethazine hydrochloride

BRAND INFORMATION

Brand name

DBL Promethazine Hydrochloride Injection BP

Active ingredient

Promethazine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

DBL™ Promethazine Hydrochloride Injection BP

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.

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

DBL Promethazine Hydrochloride Injection BP contains the active ingredient promethazine hydrochloride. DBL Promethazine Hydrochloride Injection BP is used to treat allergic reactions, to relieve nausea, vomiting and dizziness and/or as a sedative.
For more information, see Section 1. Why am I being treated with DBL Promethazine Hydrochloride Injection BP? in the full CMI.

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

Do not use if you have ever had an allergic reaction to promethazine hydrochloride, phenothiazine-derivative medicines 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 Promethazine Hydrochloride Injection BP? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DBL Promethazine Hydrochloride Injection BP 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 Promethazine Hydrochloride Injection BP given?

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight. It must only be given by a doctor or nurse.
More instructions can be found in Section 4. How is DBL Promethazine Hydrochloride Injection BP given? in the full CMI.

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

Things you should do
  • Remind any doctor, nurse, pharmacist or dentist who treat you that you are being given this medicine. Remind them before starting a new medicine, before surgery and blood tests.
  • Use a sunscreen on exposed skin or remain covered if you go outdoors after being given this medicine. DBL Promethazine Hydrochloride Injection BP may cause you to sunburn more easily.
Things to be careful of
  • Be careful before you drive or use any machines or tools until you know how DBL Promethazine Hydrochloride Injection BP affects you.
  • Children should be careful when riding bicycles or climbing trees.
Drinking alcohol
  • Be careful when drinking alcohol while being given this medicine.
  • If you drink alcohol, dizziness or drowsiness may be worse.

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

6. Are there any side effects?

Side effects include: dry mouth, nose or throat, injection site reaction, nausea and vomiting, constipation or diarrhoea, loss of appetite, unusual tiredness or weakness, clumsiness or unsteadiness, feeling faint, difficulty in sleeping, increased sensitivity of the skin to the sun, and skin itch.
Serious side effects include: sore throat and fever, blurred vision, difficult or painful urination, fast or slow heartbeat, severe drowsiness, confusion, tremors or convulsions, muscle spasms in the neck and back, jerky movements of the head and face, shuffling walk, trembling and shaking of hands, ringing or buzzing in ears, unusual excitement, nervousness, restlessness or irritability, hallucinations, trouble breathing, flushing or redness of face, allergic reaction symptoms, severe pain in the stomach with bloating, gut cramps and vomiting, unusual bleeding or bruising, and yellowing of the skin or eyes.
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.



FULL CMI

DBL™ Promethazine Hydrochloride Injection BP

Active ingredient(s): Promethazine hydrochloride (Proe-METH-a-zeen)

Consumer Medicine Information (CMI)

This leaflet provides important information about using DBL Promethazine Hydrochloride Injection BP. 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 Promethazine Hydrochloride Injection BP.

Where to find information in this leaflet:

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

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

DBL Promethazine Hydrochloride Injection BP contains the active ingredient promethazine hydrochloride. DBL Promethazine Hydrochloride Injection BP belongs to a group of antihistamines called phenothiazines (fen-oh-THY-ah-zines). It works by preventing the effects of histamine in the body.

DBL Promethazine Hydrochloride Injection BP is used to treat:

  • allergic reactions,
  • to relieve nausea, vomiting and dizziness
  • as a sedative (to help people go to sleep and control their anxiety) before and after surgery, and during labour.

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

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

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

Warnings

You must not be given DBL Promethazine Hydrochloride Injection BP if:

  1. you are allergic to:
  • any medicine containing promethazine hydrochloride
  • any other phenothiazine-derivative medicines or
  • any of the ingredients listed at the end of this leaflet, such as sulfites.
Some of the symptoms of an allergic reaction may include: shortness of breath, wheezing or difficulty breathing; swelling of the face, lips or 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.
  1. the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.
If it has expired or is damaged return it to your pharmacist for disposal.

If you are not sure whether you should be given this medicine, talk to your doctor.

Check with your doctor if you:

  • have any allergies to any other medicines, foods, preservatives or dyes.
  • have or have had any other medical conditions, especially the following:
    - asthma or breathing difficulties
    - bone-marrow depression
    - enlarged prostate
    - epilepsy
    - heart or blood pressure disease
    - irregular heart beat
    - glaucoma, an eye condition
    - liver problems
    - ulcer of the stomach or duodenum
    - kidney or bladder problems
  • take any medicines for any other condition, including sedatives

If you have not told your doctor about any of the above, tell them before you are given promethazine.

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.

DBL Promethazine Hydrochloride Injection BP is not recommended for use during later stages of pregnancy. If there is a need to consider promethazine during pregnancy, your doctor will discuss with you the benefits and risks of being given it.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Promethazine passes into breast milk and there is a possibility that your baby may be affected.

Your doctor or pharmacist will discuss the possible risks and benefits of being given promethazine while you are breastfeeding.

Use in Children

This medicine must not be given to children under the age of 2 years.

Safety and effectiveness in children under the age of 2 years have not been established.

In general, children are more sensitive to the effects of antihistamines, and DBL Promethazine Hydrochloride Injection BP should be administered with caution.

Serious side effects, such as convulsions, are more likely to occur in younger patients and would be of greater risk to infants than to older children or adults. Also, nightmares or unusual excitement, nervousness, restlessness, or irritability may be more likely to occur in children.

The use of this medicine is not recommended in children who have a history of difficulty in breathing while sleeping or a family history of sudden infant death syndrome (SIDS), or in children under 2 years of age.

Children or adolescents who show signs of Reye's syndrome should not be given this medicine.

Uncontrolled movements that may occur with promethazine may be mistakenly confused with symptoms of Reye's syndrome.

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 Promethazine Hydrochloride Injection BP and affect how it works.

These include:

  • anticholinergic medicines, including medicines for stomach spasm
  • anticonvulsants or medicines for epilepsy/fits/seizures
  • beta blockers such as propranolol, medicines used to lower blood pressure
  • bromocriptine, a medicine used to treat Parkinson's disease, acromegaly or to prevent lactation
  • medicines that cause drowsiness or sleepiness such as sedatives, tranquillisers, barbiturates, antihistamines, opioid analgesics (medicine to treat pain), general anaesthetics and alcohol
  • levodopa (medicine for Parkinson's disease)
  • metrizamide, a contrast agent, injected into the spinal cord before an x-ray
  • medicines used to treat depression, especially monoamine oxidase (MAO) inhibitors and tricyclic antidepressants
  • phenothiazine-derivative medicines e.g. chlorpromazine (medicine for thought disorder)
  • quinidine, a medicine for rapid or irregular heartbeat
  • medicines to treat cold and flu
  • appetite suppressants

These medicines may be affected by promethazine or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while being treated with this medicine.

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 Promethazine Hydrochloride Injection BP.

4. How is DBL Promethazine Hydrochloride Injection BP given?

How much is given

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

How it is given

DBL Promethazine Hydrochloride Injection BP is given as:

  • a deep injection into a large muscle or
  • as a slow injection into a vein.

It must only be given by a doctor or nurse.

If you receive too much DBL Promethazine Hydrochloride Injection BP

As DBL Promethazine Hydrochloride Injection BP is given to you under the supervision of your doctor, it is unlikely that you will receive an overdose.

If you experience severe side effects or you think that you have been given too much DBL Promethazine Hydrochloride Injection BP, you may need urgent medical attention.

You should immediately:

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

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

Symptoms of an overdose may include the side effects listed under Section 6. Are there any side effects? but are usually of a more severe nature.

Ask your doctor or pharmacist if you have any concerns.

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

Things you should do

  • Remind any doctor, nurse, pharmacist or dentist who treat you that you are being given DBL Promethazine Hydrochloride Injection BP.
    If you are about to start taking any new medicine, tell your doctor and pharmacist that you are being given DBL Promethazine Hydrochloride Injection BP.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.
    It may affect other medicines used during surgery.
  • If you are about to have any blood tests, tell your doctor that you are being given this medicine.
    It may interfere with the results of some tests including pregnancy, glucose and skin allergen tests.
  • Use a sunscreen on exposed skin or remain covered if you go outdoors after being given DBL Promethazine Hydrochloride Injection BP.
    This medicine may cause you to sunburn more easily.

Things to be careful of

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

DBL Promethazine Hydrochloride Injection BP may cause drowsiness, dizziness or sleepiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Children should be careful when riding bicycles or climbing trees.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while being given this medicine.

If you drink alcohol, dizziness or drowsiness may be worse.

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.

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

Side effects

Side effectsWhat to do
General
  • dry mouth, nose or throat
  • injection site reaction
Stomach related issues
  • nausea and vomiting
  • constipation or diarrhoea
  • loss of appetite
Central Nervous System
  • unusual tiredness or weakness
  • clumsiness or unsteadiness
  • feeling faint
  • difficulty in sleeping
Skin related issues
  • increased sensitivity of the skin to the sun
  • skin itch
Speak to your doctor, nurse or pharmacist if you have any of these side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
General
  • sore throat and fever
Eye issues
  • blurred vision
Urinary related issues
  • difficult or painful urination
Heart related issues
  • fast or slow heartbeat
Central nervous system
  • severe drowsiness
  • confusion
  • tremors or convulsions
  • muscle spasms in the neck and back
  • jerky movements of the head and face
  • shuffling walk
  • trembling and shaking of hands
  • ringing or buzzing in ears
Changes in behaviour, thinking or mood
  • unusual excitement, nervousness, restlessness or irritability
  • hallucinations
Respiratory issues
  • trouble breathing
Skin issues
  • flushing or redness of face
Allergic reaction symptoms
  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips or tongue or other parts of the body
  • rash, itching or hives on the skin.
Stomach related issues
  • severe pain in the stomach with bloating, gut cramps and vomiting
Blood related issues
  • unusual bleeding or bruising
Liver related issues
  • yellowing of the skin or eyes (jaundice)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these side effects.
These may be serious side effects. You may need urgent medical attention.

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. Some side effects may only be found when your doctor does tests from time to time to check your progress.

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 Promethazine Hydrochloride Injection BP contains

Active ingredient
(main ingredient)		promethazine hydrochloride
Other ingredients
(inactive ingredients)		disodium edetate
glacial acetic acid
sodium acetate
sodium metabisulfite
water for injections

DBL Promethazine Hydrochloride Injection BP contains 50 mg/2 mL of promethazine hydrochloride.

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

This medicine does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

What DBL Promethazine Hydrochloride Injection BP looks like

DBL™ Promethazine Hydrochloride Injection BP is a clear, colourless solution. (Aust R 16255).

How DBL Promethazine Hydrochloride Injection BP is stored

DBL Promethazine Hydrochloride Injection BP will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Who distributes DBL Promethazine Hydrochloride Injection BP

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

This leaflet was prepared in January 2022.

™ Trademark

© Pfizer Australia Pty Ltd 2021

Published by MIMS March 2022

BRAND INFORMATION

Brand name

DBL Promethazine Hydrochloride Injection BP

Active ingredient

Promethazine hydrochloride

Schedule

S4

 

1 Name of Medicine

Promethazine hydrochloride.

2 Qualitative and Quantitative Composition

Each mL of the solution contains 25.0 mg promethazine hydrochloride, 0.10 mg disodium edetate, 1.30 microlitre glacial acetic acid, 27.2 mg sodium acetate and 1.32 mg sodium metabisulfite in water for injections.

Excipient(s) with known effect.

Sodium metabisulfite.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
DBL Promethazine Hydrochloride Injection BP is a clear, colourless solution of pH 5.0 to 6.0.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Promethazine Hydrochloride Injection BP is indicated for the following conditions:
Treatment of allergic reactions such as: uncomplicated allergic conditions of the immediate type, e.g. pruritus, urticaria and angioedema, when oral therapy is impossible or contraindicated.
Treatment and prevention of vomiting including: motion sickness; drug induced nausea; prevention and control of nausea and vomiting associated with certain types of anaesthesia and surgery, such as procedures with a high incidence of post-operative vomiting (e.g. gynaecological surgery, strabismus or middle ear surgery, and electroconvulsive therapy); in patients with a past history of motion sickness or post-operative vomiting; and in patients in whom avoidance of vomiting is crucial (e.g. neurosurgery and eye surgery).
Promethazine has sedative effects and it is also used in: pre-operative, post-operative and obstetric (during labour) sedation.

4.2 Dose and Method of Administration

Dosage.

Allergic conditions.

Adults.

25 mg to 50 mg by deep intramuscular injection or slow intravenous injection; may be repeated within two hours if necessary. Maximum dose up to 150 mg daily.
Antiemetic. Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see Section 4.4 Special Warnings and Precautions for Use).
In established nausea or vomiting due to causes other than motion sickness.

Adults.

12.5 to 25 mg, by intramuscular or intravenous injection, every four hours as needed.

Children.

5 to 12 yrs old - 12.5 mg by intramuscular injection.
Sedative/hypnotic.

Adults.

25 to 50 mg by intramuscular or intravenous injection.

Children.

When oral route is not possible;
2 to 5 yrs old - 7.5 to 10 mg by intramuscular injection.
6 to 10 yrs old - 10 to 12.5 mg by intramuscular injection.
Pre-operative and post-operative sedation.

Adults.

25 to 50 mg by intramuscular or intravenous injection, usually with pethidine and atropine.
Obstetric sedation. Early stages of labour: 50 mg, by intramuscular injection. Established labour: 25 to 75 mg, by intramuscular or intravenous injection, with an appropriately reduced dose of an opioid analgesic. May be repeated once or twice at four hourly intervals during the course of the labour, if necessary. Total dose should not exceed 100 mg in 24 hours.

Method of administration.

All routes of administration can cause damage to tissues (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
Deep Intramuscular Injection is the preferred route of administration of DBL Promethazine Hydrochloride Injection BP.
Promethazine should only be administered intravenously if the benefits outweigh the risks in an individual patient. This may include emergency situations or situations where IM injections are contraindicated (see Section 4.4 Special Warnings and Precautions for Use). Extreme care must be taken to avoid extravasation or intra-arterial injection. Injections should be stopped immediately if a patient complains of pain during injection (see Section 4.4 Special Warnings and Precautions for Use).
If venous administration is required, a large vein should be used. Administration via a venous site in the hand or wrist should be avoided if possible due to an increased risk of tissue injury.
When given intravenously, DBL Promethazine Hydrochloride Injection BP 50 mg/2 mL should be diluted 1 in 10 with water for injections or preferably given through the tubing of a freely flowing IV infusion. It should be injected slowly at a rate of administration not greater than 25 mg/minute (i.e. 10 mL/minute of dilute solution).
Rapid intravenous infusion may cause a transient fall in blood pressure and may increase the risk of severe tissue injuries. Promethazine should not be given intra-arterially or subcutaneously (see Section 4.3 Contraindications).

4.3 Contraindications

Promethazine is contraindicated for use in paediatric patients less than two years of age because of the potential for fatal respiratory depression. Post marketing cases of respiratory depression including fatalities have been reported with the use of promethazine in paediatric patients less than two years of age. A wide range of weight-based doses of promethazine have resulted in respiratory depression in these patients (see Section 4.4 Special Warnings and Precautions for Use).
Promethazine is contraindicated in patients who have exhibited hypersensitivity to the drug or other phenothiazine derivatives.
Promethazine is also contraindicated in the following patients: comatose; after administration of large doses of other CNS depressants (e.g. alcohol, general anaesthetics, opioid analgesics, tranquillisers, etc.).
Intra-arterially administration of DBL Promethazine Hydrochloride Injection BP is contraindicated due to the likelihood of severe arteriospasm and the possibility of resultant gangrene.
Subcutaneous administration of DBL Promethazine Hydrochloride Injection BP is contraindicated, as the solution is an irritant and may produce necrotic lesions.

4.4 Special Warnings and Precautions for Use

This product should not be used in children under 2 years of age due to the potential for fatal respiratory depression (see Section 4.3 Contraindications).
Antiemetics are not recommended for treatment of uncomplicated vomiting in paediatric patients, and their use should be limited to prolonged vomiting of known etiology.
As a result of its anticholinergic actions, promethazine should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder neck obstruction. It should also be used with caution in patients with bone marrow depression, jaundice, impaired liver function, epilepsy, asthmatic attack, or cardiovascular disorders.
Promethazine may mask the adverse effects of ototoxic medications, e.g. tinnitus, dizziness. Concurrent use of promethazine and other hypotension producing medications may produce additive hypotensive effects. Concurrent use of promethazine with other hepatotoxic medications may increase the potential for hepatotoxicity, and patients should be carefully monitored.
Promethazine's antiemetic action may mask the symptoms of acute appendicitis or overdose of other drugs.
QT interval prolongation has been reported with phenothiazines.
The concomitant administration of alcohol, sedative-hypnotics, general anaesthetics, opioids, tranquillisers or other CNS depressants may have an additive sedative effect. Patients should be warned accordingly.
DBL Promethazine Hydrochloride Injection BP contains sodium metabisulfite, which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes, in certain susceptible people.

Intravenous use.

Promethazine is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration can cause severe tissue injury including gangrene, which may require surgical intervention including fasciotomy, skin graft, and/or amputation. Severe tissue injury may result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Prescribes should be aware of early sign of tissue injury including burning or pain at the injection site, phlebitis, swelling and blistering. Injections should be stopped immediately if any of these symptoms occur.
If venous administration is required, a large vein should be used. Administration via a venous site in the hand or wrist should be avoided if possible due to an increased risk of tissue injury.

Use in the elderly.

No data available.

Paediatric use.

Caution should be exercised when administering promethazine to paediatric patients two years of age or older, because the potential for fatal respiratory depression, including central and obstructive apnoea and reduced arousal. Respiratory depression and apnoea, sometimes fatal, are associated with promethazine even if individualised weight-based dosing is used. It is recommended that the lowest effective dose of promethazine be used in paediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided.
Use of promethazine should be avoided in acutely ill or dehydrated children, since these patients have an increased susceptibility to dystonias. Use of the drug should also be avoided in children and adolescents with signs and symptoms which suggest Reye's syndrome, since the potential extrapyramidal effects produced by the drug may obscure the diagnosis of, or be confused with the CNS signs and symptoms of this condition or other hepatic diseases. Excessively large doses in children may cause hallucinations, convulsions and sudden death. Children may experience paradoxical excitation with promethazine.

Effects on laboratory tests.

Promethazine may interfere with diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG, and may cause an increase in glucose tolerance. Promethazine may produce false negative results in skin tests using allergen extracts. It is recommended that antihistamines are discontinued at least 72 hours before testing begins.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticholinergics.

Anticholinergic effects may be potentiated when these medications are used concurrently with promethazine. Patients should be advised to report occurrence of gastrointestinal problems promptly, since paralytic ileus may occur with concurrent therapy.

Anticonvulsants.

As promethazine may lower the convulsion threshold, dosage adjustment of anticonvulsant medication may be required.

Antihypertensive agents.

Concurrent use of promethazine with beta blockers, especially propranolol, may result in increased plasma concentrations of each agent because of inhibition of metabolism. This may result in additive hypotensive effects, irreversible retinopathy, cardiac arrhythmias and tardive dyskinesia.
The neuronal uptake of guanethidine may be inhibited when used with promethazine, causing a decrease in the antihypertensive effect.

Bromocriptine.

Increase serum prolactin concentrations, thereby interfering with the effects of bromocriptine. Dosage adjustments of bromocriptine may be necessary.

CNS depressants.

Promethazine may potentiate the sedative action of other CNS depressants such as barbiturates, antihistamines, tranquillisers, opioids, general anaesthetics, or alcohol.

Levodopa.

The antiparkinsonian effects of levodopa may be inhibited when used concurrently with promethazine because of blockade of dopamine receptors in the brain.

Metrizamide.

Concurrent use of intrathecal metrizamide with promethazine may lower the seizure threshold. Promethazine should be discontinued at least 48 hours before, and not resumed for at least 24 hours following myelography.

Monoamine oxidase (MAO) inhibitors.

Concurrent use of MAO inhibitors with promethazine may prolong and intensify the anticholinergic and CNS depressant effects, and may increase the risk of hypotension and extrapyramidal reactions.

Phenothiazine derivatives.

Concurrent use of other phenothiazine derivatives may increase the severity and frequency of extrapyramidal effects.

Quinidine.

Concurrent use of promethazine with quinidine may result in additive cardiac effects.

Sympathomimetic agents.

The alpha adrenoceptor agonist effects of adrenaline may be blocked when it is used concurrently with promethazine, possibly resulting in severe hypotension and tachycardia. The alpha adrenoceptor blocking activity of promethazine may also decrease the pressor response to ephedrine, metaraminol and methoxamine; decrease the stimulant effects of amphetamines; and antagonise the anorectic effect of the centrally acting appetite suppressants.

Tricyclic antidepressants.

Concurrent use of tricyclic antidepressants may intensify the anticholinergic effects and increase the risk of hypotension and extrapyramidal effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C1)
When given in high doses during late pregnancy, phenothiazines have caused prolonged extrapyramidal disturbances in the child.
1Category 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.
 The exact amount of promethazine excreted into breast milk is unknown, but amounts are usually small. Promethazine should be used with caution in nursing women. The infant should be observed for side effects, especially sedation.

4.7 Effects on Ability to Drive and Use Machines

Promethazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a vehicle or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

CNS.

Sedation is the most prominent CNS effect of promethazine. Extrapyramidal reactions may occur with high doses and usually subside with dosage reduction. Other reported reactions include dizziness, lassitude, tinnitus, confusion, disorientation, incoordination, fatigue, blurred vision, euphoria, diplopia, nervousness, irritability, tremors, convulsions, oculogyric crises, excitation, catatonic-like states, and hysteria.

Cardiovascular.

Tachycardia, bradycardia, faintness, dizziness, transient minor increases in blood pressure, and hypotension have been reported following the use of DBL Promethazine Hydrochloride Injection BP. Venous thrombosis at the injection site has been reported.

Gastrointestinal.

Nausea and vomiting have been reported, usually in association with surgical procedures and combination drug therapy. Loss of appetite, epigastric distress, constipation and diarrhoea have also been reported.

Allergic.

Urticaria, dermatitis, pruritus, asthma, photosensitivity, and angioneurotic oedema have been reported.

Other reported reactions.

Leukopenia and agranulocytosis, usually when promethazine has been used in association with other known toxic agents; anaphylaxis; thrombocytopenic purpura; obstructive jaundice; tissue necrosis following subcutaneous injection; nasal stuffiness; and dry mouth.

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.

Symptoms of overdose range from mild depression of the CNS and cardiovascular system (drowsiness, bradycardia, tachycardia, and transient increases in blood pressure) to profound hypotension, respiratory depression, and unconsciousness. Paradoxical CNS stimulation (hallucinations, seizures, nightmares and trouble in sleeping) may be evident, especially in children and the elderly. Anticholinergic symptoms (severe dryness of mouth, nose or throat, flushing or redness of face, trouble in breathing), and extrapyramidal effects (muscle spasms, especially of the neck and back, restlessness, tic-like movements of head and face, trembling of hands) may occur.

Treatment.

Treatment of promethazine overdosage is similar to that of other phenothiazine derivatives. Symptomatic supportive therapy is indicated and general physiologic measures such as maintenance of adequate ventilation should be instituted if necessary. Analeptics may cause convulsions and should not be used. Convulsions may be controlled with diazepam or barbiturates. Anticholinergic antiparkinsonism agents may be used to treat severe extrapyramidal reactions. Severe hypotension may respond to administration of noradrenaline or phenylephrine, but should not be treated with adrenaline because it may lower the blood pressure further.
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.

Promethazine is a phenothiazine derivative with potent antihistaminic and sedative-hypnotic effects. It also has antiemetic, antivertigo, anti-motion sickness, anticholinergic effects and local anaesthetic actions.
Antihistamines competitively and reversibly antagonise the effects of histamine at the H1-receptor sites on effector cells which are responsible for vasodilatation, increased capillary permeability, flare and itch reactions in the skin, and to some extent for contraction of smooth muscle in the bronchi and gastrointestinal tract.
The precise mechanism of the CNS effects of promethazine is unknown. The sedative effects may involve antagonism at central histamine, serotonin and acetylcholine receptors, or central alpha adrenergic stimulation. However, paradoxical CNS stimulation may occur, especially in children, and at high doses may be attributable to antimuscarinic activity. The antiemetic, anti-motion sickness and antivertigo effects of promethazine are possibly a result of central anticholinergic actions on the vestibular apparatus and the integrative vomiting centre and medullary chemoreceptive trigger zone of the midbrain.
The anticholinergic (antimuscarinic) actions of promethazine provide a drying effect on the oral and nasal mucosa.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Promethazine is well absorbed from parenteral sites and the onset of antihistaminic properties occurs about 20 minutes after intramuscular injection and 3 to 5 minutes after intravenous injection. It has a prolonged antihistamine action, which may persist for 12 hours or more. The duration of sedative effects may range from 2 to 8 hours depending on the dose and route of administration.
Promethazine is widely distributed within body tissues. Promethazine crosses the blood-brain barrier, and the placenta and is excreted in breast milk. It is metabolised by the liver and excreted slowly in the urine and faeces mainly as inactive promethazine sulphoxide and glucuronides; elimination half lives of 7 to 14 hours have been reported.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Disodium edetate, glacial acetic acid, sodium acetate, sodium metabisulfite, water for injections.

6.2 Incompatibilities

Solutions of promethazine hydrochloride are incompatible with alkaline substances which precipitate the insoluble promethazine base. Promethazine has been reported to be incompatible with solutions containing the following compounds: aminophylline, benzylpenicillin salts, cefepime hydrochloride, cefotetan disodium, cephazolin, chloramphenicol sodium succinate, chloroquine phosphate, chlorothiazide sodium, dexamethasone sodium phosphate, dextran, dimenhydrinate, flucloxacillin sodium, foscarnet, frusemide, heparin sodium, hydrocortisone sodium succinate, ketorolac tromethamine, meglumine diatrizoate, meglumine iodipamide, methicillin sodium, methohexitone sodium, methotrexate sodium, morphine sulfate, nalbuphine hydrochloride (some formulations only), nitrofurantoin, penicillin G, pentobarbitone sodium, phenobarbitone sodium, phenytoin sodium, piperacillin, sodium bicarbonate, sodium diatrizoate, sodium iothalamate, sulphafurazole, thiopentone sodium.

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 Promethazine Hydrochloride Injection BP is available as follows:

Strength.

50 mg/2 mL.

Pack.

5 x 2 mL coloured glass ampoules.

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

Molecular formula: C17H20N2S.HCl. Molecular weight. 320.9.

Chemical structure.


CAS number.

58-33-3.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes