SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Promethazine Hydrochloride Injection B.P. 2.5% w/v, 1ml & 2ml.

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1ml of solution contains Promethazine Hydrochloride B.P. 2.5% w/v.

3.    PHARMACEUTICAL FORM

Colourless or almost colourless sterile solution for injection intended for parenteral administration to human beings.

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Promethazine Hydrochloride Injection B.P. 2.5% w/v is indicated

1.    in the management of allergic conditions for its anti-histamine properties,

2.    as an anaesthetic pre-medication for its sedative, anti-emetic and antisecretory effects,

3.    for sedation and hypnosis.

4.2 Posology and method of administration

Method of administration: Deep intramuscular injection. In emergencies, Promethazine Hydrochloride Injection B.P. 2.5% w/v may be administered by slow intravenous injection after dilution (see dosage information).

Adults:

The usual adult dose is 25 to 50mg by deep intramuscular injection.

In emergency situation, a 2.5% w/v solution (equivalent to 25mg Promethazine Hydrochloride in 1ml) may be diluted to 10 times its volume with Water for injection and administered by slow intravenous injection at a rate not exceeding 25mg per minute. The maximum parenteral dose is 100mg.

Elderly:

There is no specific dosage recommendation for elderly patients.

Children:

Children aged 5 to 10 years may be given a dose of 6.25 to 12.5mg by deep intramuscular injection. Not for use in children under 2 years of age (see section 4.3).

4.3 Contraindications

Promethazine Hydrochloride Injection B.P. should not be used in patients who are in coma or suffering from CNS depression of any cause. It must not be given to patients who are hypersensitive to Promethazine or to any of the ingredients in the formulation or to any phenothiazine drug.

Promethazine is contraindicated for use in children less than two years of age because of the potential for fatal respiratory depression.

It should be avoided in patients who have been taking monoamine oxidase inhibitors within the previous 14 days.

4.4 Special warnings and precautions for use

Because promethazine may thicken or dry lung secretions and impair expectoration, it should be used with caution in patients with asthma, bronchitis or bronchiectasis. It should be used with care in patient with severe coronary artery disease, narrow angle glaucoma, epilepsy or hepatic and renal insufficiency. Caution should be exercised in patients with bladder-neck or pyloro-duodenal obstruction.

The use of promethazine should be avoided in children and adolescents with signs and symptoms suggestive of Reye's Syndrome.

Promethazine may mask the warning signs of ototoxicity caused by ototoxic drugs such as salicylates. By suppressing vomiting, promethazine may delay the early diagnosis of intestinal obstruction or raised intracranial pressure. Intravenous injection should be performed with extreme care to avoid extravasation. Accidental intra-arterial injection may lead to peripheral gangrene and necrosis.

If a patient complains of pain during intravenous injection, stop the injection immediately, as this may be a sign of extravasation or inadvertent intra-arterial injection. Intramuscular injection must also be performed carefully to avoid inadvertent subcutaneous injection, which could lead to local necrosis.

Promethazine hydrochloride should not be used in children under the age of two. Caution should be exercised when administering Promethazine HCL medications to paediatric patients two years of age and older.

4.5 Interaction with other medicinal products and other forms of interaction

Promethazine may enhance the action of any anticholinergic agent, tricyclic antidepressant, sedative or hypnotic. Alcohol should be avoided during treatment. Patients, especially if they are elderly, on anti-hypertensive therapy may require adjustment of dosage to avoid postural hypotension.

Promethazine injection increases glucose tolerance.

Promethazine injection may lower the convulsive threshold, and dosage adjustment of anticonvulsant medication may therefore be required.

Promethazine may interfere with immunological urine pregnancy tests and produce false positive or false negative results.

Before commencing skin tests using allergen extracts, promethazine should be discontinued for at least 72 hours as it may inhibit the cutaneous histamine response, thus producing false negative results.

4.6. Pregnancy and Lactation

Promethazine should not be used in pregnancy unless considered essential by the physician. Use of promethazine in the two weeks prior to delivery is not recommended in view of the risk of irritability and excitement in the neonate. Although available evidence suggests that the amount excreted in milk is insignificant, there are risks of neonatal irritability and excitement.

4.7 Effects on ability to drive and use machines

Ambulant patients receiving promethazine for the first time should not be in control of vehicles or machinery for the first few days until it is established that they are not hypersensitive to the central nervous effects of the drug and do not suffer from disorientation, confusion or dizziness.

Promethazine may impair the mental and/or physical abilities required for driving or operating machinery. Concomitant administration of other central nervous system depressants, including alcohol, may have an additive effect. Patients should be warned accordingly.

Undesirable effects

Side effects may be seen in a few patients: drowsiness, dizziness, restlessness, headache, nightmares, tiredness and disorientation. Anticholinergic side-effects such as blurred vision, dry mouth and urinary retention occur occasionally. Newborn and premature infants are susceptible to the anticholinergic effects of promethazine while other children may display paradoxical hyperexcitability. The elderly are particularly susceptible to anticholinergic effects and confusion due to promethazine. Other side effects include anorexia, gastrointestinal disturbance, palpitation, hypotension, arrhythmias, extrapyramidal effects, muscle spasm and tic-like movement of the head and face. Anaphylaxis, jaundice and blood dyscrasias including haemolytic anaemia rarely occur. Very rare cases of allergic reactions, including urticaria, rash and pruritus have been reported.

Photosensitivity skin reaction have been reported and strong sunlight should be avoided during treatment. The preservatives in promethazine hydrochloride Injection B.P. have been reported to cause hypersensitivity reactions, characterised by circulatory collapse with CNS depression, in certain susceptible individuals with allergic tendencies.

4.9 Overdose

Symptoms of severe overdosage are variable. Children may display various combinations of excitation, ataxia, in-coordination, athetosis and hallucination, whereas adults may become drowsy and lapse into coma. Convulsion may occur in adults or children and may be preceded by coma or excitement. Cardiorespiratory depression is uncommon. If the patient is seen soon enough after ingestion, it should be possible to induce vomiting with ipecacuanha despite the antiemetic effect of promethazine; alternatively, gastric lavage may be used.

Treatment is symptomatic and supportive and attention should be given for maintaining adequate respiratory and circulatory status. Convulsions may be controlled with diazepam or other suitable anticonvulsant.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Promethazine is a long-acting antihistamine with additional anti-emetic, anticholinergic and sedative effects. It has a phenothiazine derivative.

5.2 Pharmacokinetic properties

Promethazine Hydrochloride is well absorbed after intramuscular administration. It is widely distributed in the body and it enters the brain and crosses the placenta. The drug is highly plasma protein bound. Promethazine is

metabolised in the liver and is slowly excreted via urine and bile. Phenothiazines pass into the breast milk at low concentrations.

5.3. Pre-Clinical Safety Data

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

6. PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Sodium Metabisulphite B.P.

Sodium Sulphite B.P.

Sodium Chloride B.P.

Hydrochloric Acid B.P.

Water for Injections B.P.

6.2. Incompatibilities

Solutions of promethazine hydrochloride are incompatible with alkaline substances, which precipitate the insoluble promethazine base.

6.3. Shelf Life

Unopened : 3 years (36 months)

After reconstitution : not applicable After first opening : not applicable*

* If only part of an ampoule is used, discard the remaining solution.

6.4. Special Precautions for Storage

Protect from light.

Store below 25°C.

Nature and Contents of Container

6.6. Instructions for Use, Handling and Disposal

For deep intramuscular injection.

Use as directed by the physician.

Keep out of reach of children.

If only part used, discard the remaining solution.

7    MARKETING AUTHORISATION HOLDER

Mercury Pharma International Ltd 4045, Kingswood Road,

City West Business Park,

Co Dublin, Ireland

8.    MARKETING AUTHORISATION NUMBER

PL 2848/0121.

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

18/9/1989.

10 DATE OF REVISION OF THE TEXT

23/08/2012