D BL Promethazine Hydrochloride in J
D BL Promethazine Hydrochloride in J
D BL Promethazine Hydrochloride in J
1. PRODUCT NAME
DBL™ Promethazine Hydrochloride Injection, 50 mg/2 mL, solution for injection
• Sodium metabisulfite
3. PHARMACEUTICAL FORM
Solution for injection
4. CLINICAL PARTICULARS
• uncomplicated allergic conditions of the immediate type, e.g., Pruritus, urticaria and
angioedema, when oral therapy is impossible or contraindicated;
• motion sickness;
• 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);
All routes of administration can cause damage to tissues (see section 4.3 and section 4.4).
Promethazine should only be administered intravenously if the benefits outweigh the risks in
an individual patient. This may include emergency situations or 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).
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).
Allergic conditions
Antiemetic
Antiemetics should not be used in vomiting of unknown etiology in children and adolescents
(see section 4.4).
Sedative/hypnotic
Obstetric sedation
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).
• comatose
• after administration of large doses of other CNS depressants (e.g., alcohol general
anaesthetics, opioid analgesics, tranquillisers, etc.)
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’s anti-emetic action may mask the symptoms of acute appendicitis or overdose
of other drugs.
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.
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.
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.
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
Antihypertensive agents
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.
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.
Concurrent use of promethazine with quinidine may result in additive cardiac effect.
Sympathomimetic agents
Tricyclic antidepressants
Concurrent use of tricyclic antidepressants may intensify the anticholinergic effects and
increase the risk of hypotension and extrapyramidal effects.
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.
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.
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 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
For advice on the management of overdose please contact the National Poisons Centre on 0800
POISON (0800 764766).
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.
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.
No data available.
Carcinogenicity
No data available.
No data available.
6. PHARMACEUTICAL PARTICUALRS
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, 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 G, pentobarbitone sodium, phenobarbitone sodium, phenytoin
sodium, piperacillin, sodium bicarbonate, sodium diatizoate, sodium iothalamate,
sulphafurazole, and thiopentone sodium.
8. SPONSOR
Pfizer New Zealand Limited
P O Box 3998
Auckland, New Zealand, 1140
Toll Free Number: 0800 736 363