Promethazine hydrochloride 25 mg tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Promethazine hydrochloride 25 mg tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 25 mg of the active substance promethazine hydrochloride.

Excipient(s) with known effect

Also contains 35.44 mg of lactose monohydrate and 51.50 mg of sucrose. For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Sugar coated tablet

Blue sugar-coated tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

As symptomatic treatment of allergic conditions of the upper respiratory tract and skin including allergic rhinitis, urticaria and anaphylactic reactions to drug or foreign proteins.

As an antiemetic

For short term use:

• Treatment of insomnia in adults
• As a paediatric sedative

4.2 Posology and method of administration

Posology

Paediatric population:

Not for use in children under 6 years of age (see section 4.3).

As an antihistamine in allergy:

*Single doses are best taken at night.

As an antiemetic:

As a paediatric sedative for short term use and for short term treatment of insomnia in adults:

Method of

administration

For oral use.

4.3 Contraindications

Promethazine should not be given to patient with a known hypersensitivity to the active substance, other promethazine or to any of the excipients listed in section 6.1.

Promethazine should not be used in patients in coma or suffering from CNS depression of any cause.

Promethazine is contraindicated for use in children less than 6 years of age because of the potential for fatal respiratory depression.

Promethazine should be avoided in patients taking monoamine oxidase inhibitors up to 14 days previously.

4.4 Special warnings and precautions for use

Hypersensitivity reactions including anaphylaxis, urticaria and angioedema have been reported with Promethazine use. In case of allergic reaction, treatment with Promethazine must be discontinued and appropriate symptomatic treatment initiated (see Section 4.8).

Promethazine should be avoided in patients with liver or renal dysfunction, parkinson’s disease, hypothyroidism, cardiac failure, pheochromocytoma, myasthenia gravis, or prostate hypertrophy, or in patients with a history of narrow angle glaucoma or agranulocytosis.

Caution must be exercised when using H₁-antihistamines such as Promethazine due to the risk of sedation. Combined use with other sedative medicinal products is not recommended (see section 4.5).

Promethazine should not be used for longer than 7 days without seeking medical advice.

Caution should be used in patients with:

• asthma, bronchitis or bronchiectasis. Promethazine may thicken or dry lung secretions and impair expectoration,
• severe coronary artery disease,
• narrow angle glaucoma,
• epilepsy,
• hepatic or renal insufficiency,
• bladder neck or pyloroduodenal obstruction.

Ototoxicity

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.

QT interval

As phenothiazines can prolong the QT interval, caution is advised in treated patients with pronounced bradycardia, cardiovascular disease, with a hereditary form of prolongation of the QT interval and concomitant use with other products leading to QT prolongation.

QT Prolongation

Phenothiazine derivatives may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalaemia, and acquired (i.e. drug induced) QT prolongation. If the clinical situation permits, medical and laboratory evaluations should be performed to rule out possible risk factors before initiating treatment with a phenothiazine derivative and as deemed necessary during treatment (see section 4.8).

Photosensitivity reactions

Due to risk of photosensitivity, exposure to strong sunlight or ultraviolet light should be avoided during or shortly after treatment (see section 4.8).

Paediatric population

Promethazine must not be used in children less than six years of age due to the potential for fatal respiratory depression, psychiatric and CNS events (see Section 4.3 and Section 4.8).

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

Excipient(s) with known effect

This medicine contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Alcohol and alcohol-containing medicines should be avoided while on this medicine (see section 4.5).

Phenothiazines may be additive with, or may potentiate the action of, other CNS depressants such as opiates or other analgesics, barbiturates or other sedatives, general anesthetics, or alcohol.

The occurrence of unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8) and requires immediate hematological investigation.

All patients should be advised that, if they experience fever, sore throat or any other infection, they should inform their physician immediately and undergo a complete blood count. Treatment should be discontinued if any marked changes (hyperleucocytosis, granulocytopenia) are observed in the blood count.

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. Combination with alcohol enhances the sedative effects of H₁ antihistamines.

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.

Special caution is required when promethazine is used concurrently with drugs known to cause QT prolongation including medicinal products such as antipsychotics, i.e., some phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, amisulpride, tiapride), pimozide, haloperidol, droperidol, citalopram, halofantrin, methadone, pentamidine, and moxifloxacine to avoid exacerbation of risk of QT prolongation.

Cytochrome P450 2D6 Metabolism: Some phenothiazines are moderate inhibitors of CYP2D6. There is a possible pharmacokinetic interaction between inhibitors of CYP2D6, such as phenothiazines, and CYP2D6 substrates. Co administration of promethazine with amitriptyline/amitriptylinoxide, a CYP2D6 substrate, may lead to an increase in the plasma levels of amitriptyline/amitriptylinoxide. Monitor patients for dose-dependent adverse reactions associated with amitriptyline/amitriptylinoxide.

Promethazine should be avoided in patients taking monamine oxidase inhibitors within the previous 14 days, and monamine oxidase inhibitors should be avoided while using Promethazine.

Seizure threshold-lowering drugs: Concomitant use of seizure-inducing drugs or seizure threshold-lowering drugs should be carefully considered due to the severity of the risk for the patient (see section 4.4).

Gastro-intestinal agents that are not absorbed (magnesium, aluminium and calcium salts, oxides and hydroxides): Reduced gastro-intestinal absorption of phenothiazines may occur. Such gastro-intestinal agents should not be taken at the same time as phenothiazines (at least 2 hours apart, if possible).

Drugs with anticholinergic properties: Concomitant use of Promethazine with drugs with anticholinergic properties enhances the anticholinergic effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of Promethazine is not recommended during pregnancy and in women of childbearing potential not using contraception, unless the potential benefits outweigh the potential risks. When promethazine has been given in high doses during late pregnancy, promethazine has caused prolonged neurological disturbances in the infant.

Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise patients to avoid becoming pregnant while receiving this medicine. Advise female patients of reproductive potential to use effective contraception.

There are no available animal studies regarding reproductive toxicity. Breast-feeding

Promethazine is excreted in breast milk (see section 5.2). There are risks of neonatal irritability and excitement. Promethazine is not recommended for use in breast-feeding.

Fertility

There are no relevant fertility data in animals.

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, dizzy and have blurred vision, they should not drive or operate heavy machinery.

4.8 Undesirable effects

The following CIOMS frequency raiting is used: Very common (≥1/10); commom (≥1/100 to 1/10); uncommon (≥1/1,000 to 1/100); rare (≥1/10,00 to 1/1,000); vary rare (<1/10,000), not known (cannot be estimated from the available data).

Immune System disorders

Not known: Allergic reactions, including urticaria, angioedema, and anaphylactic reactions have been reported.

Skin and subcutaneous tissue disorders

Not known: Rash, Photosensitive skin reactions have been reported.

Nervous system disorders

Very common: Sedation or Somnolence

Not known: Dizziness, headaches, extrapyramidal effects including restless legs syndrome, muscle spasms and tic-like movements of the head and face.

Not known: Dystonia, including oculogyric crisis, usually transitory are commoner in children and young adults, and usually occur within the first 4 days of treatment or after dosage increases.

Not known: Anticholinergic effects such as ileus paralytic, risk of urinary retention, dry mouth, constipation, accommodation disorder, neuroleptic malignant syndrome, psychomotor hyperactivity.

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

Not known: children less than 6 years of age also experienced psychomotor hyperactivity.

Psychiatric disorders

Not known: Agitation, confusional state, anxiety, hallucinations, aggression. Not known: Infants (newborn and premature) are susceptible to the anticholinergic effects of promethazine, while other children may display paradoxical hyperexcitability, restlessness, nightmare and disorientation.

Not known: children less than 6 years of age also experienced aggression and hallucination.

Eye disorders

Not known: Blurred vision

Gastrointestinal disorders

Not known: Epigastric irritation/discomfort, dry mouth

Renal and urinary disorders

Not known: Urinary retention

Metabolism and nutrition disorders

Not known: : Decrease appetite

Cardiac disorders

Not known: Palpitations, arrhythmias includingQT prolongation and torsade de pointes

Vascular disorders

Not known:Hypotension

Respiratory, thoracic and mediastinal

disorders

Not known: Respiratory depression (see Section 4.4), nasal congestion

Hepatobiliary disorders

Not known Jaundice, cholestatic

Blood and lymphatic system disorders

Not known: Blood dyscrasias including haemolytic anaemia rarely occur. Agranulocytosis, leukopenia, eosinophilia, thrombocytopenia (including thrombocytopenia purpura).

General and administration site conditions

Not known: Tiredness

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Symptoms of severe overdosage are variable. They are characterised in children by various combinations of excitation, ataxia, incoordination, athetosis and hallucinations, intellectual disability and cognition deficit in children less than 6 years of age while adults may become drowsy and lapse into coma. Convulsions may occur in both adults and children. Coma or excitement may precede their occurrence. Tachycardia may develop. Cardiorespiratory depression is uncommon.

High doses (supratherapeutic doses) can cause ventricular arrhythmias including QT prolongation and torsade de pointes (see section 4.8).

Prolonged QT interval and cases of severe arrhythmias with fatal outcome have been described in overdose of phenothiazines.

Management

If the patient is seen soon enough after ingestion, it should be possible to induce vomiting with ipecacuanha despite the anti-emetic 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.

In the event of overdose of Promethazine, take all appropriate measures immediately.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Promethazine hydrochloride is a potent, long acting, antihistaminic 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

Core tablets:

Lactose Monohydrate

Maize Starch

Starch Pregelatinised

Magnesium Stearate (E572)

Coating:

Shellac (E904)

Purified Talc (E553b)

Titanium Dioxide (E171)

Povidone

PB-605010 (Indigo Carmine Aluminum Lake (E132) and Titanium Dioxide (E171))

Sucrose

Beeswax Yellow (E901)

Carnauba Wax (E903)

6.2 Incompatibilities

Promethazine hydrochloride is incompatible with alkaline substances that precipitate Promethazine Base.

6.3 Shelf life

Polystyrene/polypropylene containers - 36 months

PVC/Aluminium blister-packs - 36 months

6.4 Special precautions for storage

Blister Packs:

Store below 25°C. Store in the original package. Protect from light..

Container:

Store below 25°C. Keep the container tightly closed. Protect from light. Keep the container in the outer carton.

6.5 Nature and contents of container

High-density polystyrene with polythene lids and/or polypropylene containers with polypropylene or polythene lids and polyurethane/polythene inserts. Packs of 100, 500 and 1000.

or

PVC/Aluminium foil blister-packs of 10, 14, 28, 30 and 56

6.6 Special precautions for disposal

Not applicable.

7 MARKETING AUTHORISATION HOLDER

Chelonia Healthcare Limited

Boumpoulinas 11, 3^rd Floor

NICOSIA

CYPRUS

P.C. 1060

CYPRUS

8 MARKETING AUTHORISATION NUMBER(S)

PL 33414/0092

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

10 August 1990 / Renewed 03 December 1998

10 DATE OF REVISION OF THE TEXT

03/04/2025