SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Promethazine Hydrochloride 50mg Film-coated Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each film-coated tablet contains 50 mg of the active substance promethazine hydrochloride equivalent to 44.31 mg promethazine.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet

White coloured, oval shaped, 12.3 x 7.8 mm biconvex, film coated tablets debossed with "C50" on one side and plain on other side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For short term use:

-    Treatment of insomnia in adults.

-    As a paediatric sedative in children over 10 years.

4.2 Posology and method of administration

Posology

Paediatric population

Promethazine 50 mg film-coated tablets are not recommended for use in children under 10 years.

Promethazine is contraindicated in children under the age of 2 years (see section 4.3).

Short term use as a paediatric sedative:

Method of administration

Oral.

4.3 Contraindications

Promethazine film-coated tablets are contraindicated:

-    in patients with hypersensitivity to the active substance or to any of the excipients listed in section 6.1

-    in patients in coma or suffering from CNS depression of any cause

-    in patients taking monoamine oxidase inhibitors up to 14 days previously

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

4.4 Special warnings and precautions for use

Promethazine may thicken or dry lung secretions and impair expectoration. It should therefore be used with caution in patients with asthma, bronchitis or bronchiectasis.

Use with care in patients 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.

There have been case reports of drug abuse with promethazine. The risk of abuse is greater in patients with a history of drug abuse.

As with neuroleptics, Neuroleptic Malignant Syndrome (NMS) characterized by hyperthermia, extrapyramidal disorders, muscle rigidity, altered mental status, autonomic nervous instability and elevated CPK, may occur. As this syndrome is potentially fatal, promethazine must be discontinued immediately and intensive clinical monitoring and symptomatic treatment should be initiated.

Promethazine may mask the warning signs of ototoxicity caused by ototoxic drugs e.g. salicylates. It may also delay the early diagnosis of intestinal obstruction or raised intracranial pressure through the suppression of vomiting.

Paediatric population

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

4.5 Interaction with other medicinal products and other forms of interaction

Promethazine will enhance the action of any anticholinergic agent, tricyclic antidepressant, sedative or hypnotic.

Alcohol should be avoided during treatment.

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

Promethazine should be discontinued at least 72 hours before the start of skin tests as it may inhibit the cutaneous histamine response thus producing false-negative results.

4.6 Fertility, pregnancy and lactation

Pregnancy

Promethazine should not be used in pregnancy unless the physician considers it essential. The use of promethazine is not recommended in the 2 weeks prior to delivery in view of the risk of irritability and excitement in the neonate.

Breast-feeding

Available evidence suggests that the amount excreted in milk is insignificant. However, there are risks of neonatal irritability and excitement.

Fertility

No data available.

4.7 Effects on ability to drive and use machines

Because the duration of action may be up to 12 hours, patients should be advised that if they feel drowsy they should not drive or operate heavy machinery.

4.8 Undesirable effects

Side effects may be seen in a few patients: drowsiness, dizziness, restlessness, headaches, nightmares, tiredness, and disorientation. Anticholinergic side effects such as blurred vision, dry mouth and urinary retention occur occasionally.

Infants are susceptible to the anticholinergic effects of promethazine, while other children may display paradoxical hyperexcitability.

The elderly are particularly susceptible to the anticholinergic effects and confusion due to promethazine.

Other side-effects include urticaria, rash, pruritus, anorexia, gastric irritation, palpitations, hypotension, arrhythmias, extrapyramidal effects, muscle spasms and tic-like movements of the head and face. Anaphylaxis, jaundice and blood dyscrasias including haemolytic anaemia rarely occur. Photosensitive skin reactions have been reported. Strong sunlight should be avoided during treatment.

Neuroleptic Malignant Syndrome has been reported with an unknown frequency (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Yellow Card Scheme

Website: www.mhra.gov .uk/yellowcard

4.9 Overdose

Symptoms of severe overdosage are variable. They are characterised in children by various combinations of excitation, ataxia, incoordination, athetosis and hallucinations, while adults may become drowsy and lapse into coma. Convulsions may occur in both adults and children: coma or excitement may precede their occurrence. 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 otherwise supportive with attention to maintenance of adequate respiratory and circulatory status. Convulsions should be treated with diazepam or other suitable anticonvulsant.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihistamines for systemic use; Phenothiazine derivatives, ATC code: R06AD02

Potent, long acting, antihistamine with additional anti-emetic central sedative and anti-cholinergic properties.

5.2 Pharmacokinetic properties

Promethazine is distributed widely in the body. It enters the brain and crosses the placenta. Promethazine is slowly excreted via urine and bile. Phenothiazines pass into the milk at low concentrations.

5.3 Preclinical safety data

No additional preclinical data of relevance to the prescriber.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Tablet core:

Microcrystalline cellulose

Calcium hydrogen phosphate dihydrate

Sodium starch glycolate (Type A)

Stearic acid Magnesium stearate

Tablet Coating:

Hypromellose (E464)

Macrogol 8000 (E1521)

Titanium dioxide (E171)

Talc

6.2    Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

6.5 Nature and contents of container

Promethazine 50 mg film-coated tablets are available in blister packs (White opaque PVC/ ACLAR forming foil and lidding plain push through aluminium foil or PVC/PCTFE/PVC foil and lidding aluminum foil) of 5, 7, 8, 10, 14, 15, 16, 20, 30 and 56 film- coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements

7    MARKETING AUTHORISATION HOLDER

Caduceus Pharma Ltd.

6^th floor, 94 Wigmore Street

London

W1U 3RF

UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 24668/0197

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

02/06/2016

10 DATE OF REVISION OF THE TEXT

02/06/2016