DBL™ Promethazine hydrochloride

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Promethazine hydrochloride 25 mg/mL;  
Available from:
Pfizer New Zealand Limited
INN (International Name):
Promethazine hydrochloride 25 mg/mL
Dosage:
50 mg/2mL
Pharmaceutical form:
Solution for injection
Composition:
Active: Promethazine hydrochloride 25 mg/mL   Excipient: Glacial acetic acid Sodium acetate trihydrate Sodium edetate Sodium metabisulfite Water for injection
Units in package:
Ampoule, glass, 5 x 2mL, 10 mL
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Sigma-Aldrich Ireland Ltd
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, eg. Pruritus, urticaria and angioedema, when oraltherapy 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 postoperative vomiting (eg. 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 (eg. Neurosurgery and eye surgery); Promethazine has sedative effects and it is also used in: preoperative, postoperative and obstetric (during labour) sedation.
Product summary:
Package - Contents - Shelf Life: Ampoule, glass, 2mL - 5 dose units - 36 months from date of manufacture stored at or below 25°C protect from light
Authorization number:
TT50-4275
Authorization date:
1989-09-07

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NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

Promethazine Hydrochloride Injection, 50 mg/2 mL, solution for injection

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 injection.

Excipient with known effect

Sodium metabisulfite

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Solution for injection

DBL Promethazine Hydrochloride Injection is a clear, colourless solution of pH 5.0 - 6.0.

4.

CLINICAL PARTICULARS

4.1 Therapeutic indications

DBL Promethazine Hydrochloride Injection 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 postoperative 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:

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preoperative, postoperative and obstetric (during labour) sedation.

4.2 Dose and method of administration

Dose

All routes of administration can cause damage to tissues (see section 4.3 and section 4.4).

The preferred route of administration of DBL Promethazine Hydrochloride Injection is by deep

intramuscular injection. Intramuscular injection may be painful.

Promethazine should only be administered intravenously if the benefits outweigh the risks in

individual

patient.

This

include

emergency

situations

situations

where

intramuscular injections are contraindicated (see section 4.4). 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).

If intravenous 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 25 mg/1 mL should be

diluted 1 in 10 with water for injections or preferably given through the tubing of a freely

flowing I.V. infusion. It should be injected slowly at a rate of administration not greater than

25 mg/minute (ie. 10 mL/minute) of dilute solution.

Rapid intravenous infusion may cause a transient fall in blood pressure and may increase the

risk

severe

tissue

injuries.

Promethazine

should

given

intra-arterially

subcutaneously (see section 4.3).

Allergic conditions

Adults:

25 mg - 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).

In established nausea or vomiting due to causes other than motion sickness:

Adults:

12.5 - 25 mg, by intramuscular or intravenous injection, every four hours as

needed.

Children:

5 - 12 yrs old 12.5mg by intramuscular injection.

Sedative/hypnotic

Adults:

25 - 50 mg by intramuscular or intravenous injection.

Children:

When oral route is not possible:

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2 - 5 yrs old

7.5 - 10 mg by intramuscular injection

6 - 10 yrs old

10 - 12.5 mg by intramuscular injection

Preoperative and postoperative sedation

Adults:

25 - 50 mg by intramuscular or intravenous injection, usually with pethidine

and atropine one hour before surgery.

Obstetric sedation

Early stages of labour: 50 mg, by intramuscular injection. Established labour: 25 - 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.

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).

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-arterial administration of DBL Promethazine Hydrochloride Injection is contraindicated

due to the likelihood of severe arteriospasm and the possibility of resultant gangrene.

Subcutaneous

administration

Promethazine

Hydrochloride

Injection

contraindicated, as the solution is irritant and may produce necrotic lesions.

4.4 Special warnings and precautions for use

Antiemetics are not recommended for treatment of uncomplicated vomiting in paediatric

patients, and their use should be limited to prolonged vomiting of known aetiology.

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.

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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

promethazine

with

other

hepatotoxic

medications may increase the potential for hepatotoxicity, and patients should be carefully

monitored.

Promethazine’s anti-emetic action may mask the symptoms of acute appendicitis or overdose

of other drugs.

QT interval prolongation has been reported with phenothiazines.

DBL Promethazine Hydrochloride Injection 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. Prescribers should be aware of early signs 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 intravenous 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.

Paediatric 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).

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.

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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 Interaction with other medicines and other forms of interaction

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.

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.

Monoamine oxidase (MAO) inhibitors

Concurrent

inhibitors

with

promethazine

prolong

intensify

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.

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Quinidine

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

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

Fertility

No data available.

Pregnancy

Category C

When given in high doses during late pregnancy, phenothiazines have cause prolonged

extrapyramidal disturbances in the child.

Lactation

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 machinery

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. 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.

4.8 Undesirable effects

CNS

: Sedation is the most prominent CNS effect 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.

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Cardiovascular:

Tachycardia, bradycardia, faintness, dizziness, transient minor increases in

blood pressure, and hypotension have been reported following the use of promethazine

hydrochloride injection. 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; anaphalaxis; thrombocytopenic

purpura;

obstructive

jaundice;

tissue

necrosis

following

subcutaneous

injection;

nasal

stuffiness; and dry mouth.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are

asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

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

used

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 advice on the management of overdose please contact the National Poisons Centre on 0800

POISON (0800 764766).

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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 H

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.

5.2 Pharmacokinetic properties

Promethazine is well absorbed following intramuscular and intravenous injection 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 2-8 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.

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Reproductive and developmental toxicity

No data available.

6.

PHARMACEUTICAL PARTICUALRS

6.1 List of excipients

Glacial acetic acid

Sodium acetate

Disodium edetate

Sodium metabisulfite

Water for injection

6.2 Incompatibilities

Solutions of promethazine hydrochloride are incompatible with alkaline substances, which

precipitate

insoluble

promethazine

base.

Promethazine

been

reported

incompatible

with

solutions

containing

following

compounds:

aminophylline,

benzylpenicillin

salts,

cefepime

hydrochloride,

cefotetan

disodium,

cephazolin,

chloramphenicol

sodium

succinate,

chloroquine

phosphate,

chlorothiazide

sodium,

dexamethasone sodium phosphate, dextran, dimenhydrinate, flocloxacillin 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

pentobarbitone

sodium,

phenobarbitone

sodium,

phenytoin

sodium,

piperacillin,

sodium

bicarbonate,

sodium

diatizoate,

sodium

iothalamate,

sulphafurazole, and thiopentone sodium.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store at or below 25°C. Protect from light.

6.5 Nature and contents of container

DBL Promethazine Hydrochloride Injection (50 mg/2 mL) is available in 5 × 2 mL Ampoules.

6.6 Special precautions for disposal

Any unused medicine or waste material should be disposed of in accordance with local

requirements.

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7.

MEDICINE SCHEDULE

Prescription Medicine

8.

SPONSOR

Pfizer New Zealand Limited

P O Box 3998

Auckland, New Zealand, 1140

Toll Free Number: 0800 736 363

9.

DATE OF FIRST APPROVAL

07 September 1989

10. DATE OF REVISION OF THE TEXT

13 August 2019

Summary table of changes

Section changed

Summary of new information

1, 2, 4.4, 4.5, 4.7,

6.1, 6.4, 6.5, 7, 9

Minor editorial modifications related to reformatting.

Added safety information regarding respiratory depression in children under 2

two years of age which was previously present in section 4.4.

Added safety information regarding potential for fatal respiratory depression in

children under two years of age. Also, additional safety information was added

in subsection ‘Paediatric Use’.

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