Summary of Product Characteristics (SmPC) - Promethazine Hydrochloride 25 mg film-coated tablets
1 NAME OF THE MEDICINAL PRODUCT
Promethazine hydrochloride 25mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 25mg of Promethazine hydrochloride.
Excipient with known effect
Each tablet contains 179 mg of lactose monohydrate. For full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Film-coated Tablet
Round, pale blue colored, biconvex, bevelled edge film coated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
As symptomatic treatment for allergic conditions of the upper respiratory tract and skin including allergic rhinitis, urticaria and anaphylactic reactions to drugs and 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
Route of administration: Oral.
Paediatric population
Not for use in children under the age of 6 years (see section 4.3).
As an antihistamine in allergy:
| Children 6-10 years | 25 mg as a single dose*. Maximum daily dose 25 mg. |
| Children over 10 years and adults (including elderly) | 25 mg as a single dose*. Increasing to a maximum of 25 mg twice a day as required. |
*Single doses are best taken at night.
As an antiemetic:
| Children 6-10 years | The use of Promethazine Hydrochloride Liquid is recommended. |
| Children over 10 years and adults (including elderly) | 25 mg to be taken the night before the journey. To be repeated after 6-8 hours as required. |
As a paediatric sedative for short term use and for short term treatment of insomnia in adults:
| Children 6-10 years | 25 mg as a single night time dose. |
| Children over 10 years and adults (including elderly) | 25 or 50 mg as a single night time dose. |
4.3 Contraindications
- Promethazine hydrochloride should not be used in patients in coma or suffering from CNS depression of any cause
- Promethazine hydrochloride should not be given to patients with a known hypersensitivity to the active substance, other phenothiazines or to any of the excipients listed in section 6.1
Promethazine is contraindicated for use in children less than 6 years of age
(see Section 4.4).
- Promethazine hydrochloride 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 hydrochloride use. In case of allergic reaction, treatment with Promethazine hydrochloride must be discontinued and appropriate symptomatic treatment initiated (see Section 4.8).
Promethazine hydrochloride 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 hydrochloride due to the risk of sedation. Combined use with other sedative medicinal products is not recommended (see section 4.5).
Promethazine Hydrochloride 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 Hydrochloride may thicken or dry lung secretions and impair expectoration.
- Severe coronary artery disease
- Narrow angle glaucoma
- Eepilepsy
- Bladder neck or pyloro- duodenal obstruction.
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.
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 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 the 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
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 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 Hydrochloride will enhance the action of any anticholinergic agent, tricyclic anti- depressant, sedative or hypnotic.
Alcohol should be avoided during treatment. Combination with alcohol enhances the sedative effects of H1 antihistamines.
Promethazine Hydrochloride may interfere with immunological urine pregnancy tests to produce false- positive or false-negative results.
Promethazine Hydrochloride 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 other products leading to 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.
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 Hydrochloride should be avoided in patients taking monamine oxidase inhibitors within the previous 14 days, and monamine oxidase inhibitors should be avoided while using Promethazine Hydrochloride.
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 Hydrochloride with drugs with anticholinergic properties enhances the anticholinergic effect.
4.6 Fertility, pregnancy and lactation
Pregnancy
The use of Promethazine Hydrochloride 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 Hydrochloride is excreted in milk (see section 5.2). There are risks of neonatal irritability and excitement. Promethazine Hydrochloride 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, they should not drive or operate heavy machinery.
4.8 Undesirable effects
The following CIOMS frequency rating is used: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10 00 to <1/1000); very rare (<1/10 000), not known (cannot be estimated from the available data).
Immune system disorders
Frequency not known: Allergic reactions, including urticaria, angioedema and anaphylactic reactions.
Skin and subcutaneous tissue disorders
Frequency not known: Rash, Photosensitive skin reactions.
Nervous system disorders
Very common: Sedation or somnolence
Frequency not known:
- Dizziness, headaches, extrapyramidal effects including restless legs syndrome, muscle spasms and tic-like movements of the head and face.
- 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.
- 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.
Frequency not known: children less than 6 years of age also experienced psychomotor
hyperactivity.
Psychiatric disorders
Frequency not known:
- Agitation, confusional state, anxiety.
- Infants (newborn and premature) are susceptible to the anticholinergic effects of promethazine, while other children may display paradoxical hyperexcitability, restlessness, nightmares, and disorientation.
- Children less than 6 years of age also experienced hallucinations and aggression
Eye disorders
Frequency not known: Blurred vision
Gastrointestinal disorders
Frequency not known: Epigastric irritation/discomfort, dry mouth
Renal and urinary disorders
Frequency not known: Urinary retention
Metabolism and nutrition disorders
Frequency not known: Anorexia
Cardiac disorders
Frequency not known: Palpitations, arrhythmias (including QT prolongation and torsade de pointes)
Vascular disorders
Frequency not known: Hypotension
Respiratory, thoracic and mediastinal disorders
Frequency not known: Respiratory depression (see Section 4.4), nasal congestion
Hepatobiliary disorders
Frequency not known: Jaundice cholestatic
Blood and lymphatic system disorders
Frequency not known: Blood dyscrasias including haemolytic anaemia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia (including thrombocytopenic purpura).
General disorders and administration site conditions
Frequency 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 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.
Prolonged QT interval and cases of severe arrhythmias with fatal outcome have been described in overdose of phenothiazines.
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).
Management
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 another suitable anticonvulsant.
In the event of overdose of Promethazine Hydrochloride, take all appropriate measures immediately.
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 pre-clinical data of relevance to the prescriber.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Maize starch
Povidone K30
Magnesium stearate
Colourant: Opadry 03F505142 Blue
Titanium dioxide (E 171)
Hypromellose (E464)
Macrogol/Polyethylene glycol (E1521)
Indigo carmine aluminium lake FD&C Blue no 2 (E132)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store below 30oC. Store in the original package in order to protect from light.
6.5 Nature and contents of container
White opaque PVC-PVDC 250 microns/20 microns Aluminium foil coated with VMCH in blister packs of 28, 56, 84 and 100 tablets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
Noumed Life Sciences Limited
Noumed House, Shoppenhangers Road
Maidenhead, Berkshire, SL6 2RB, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 44041/0236
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
11/06/2024
10 DATE OF REVISION OF THE TEXT
17/04/2025