Phenergan 10 mg and 25 mg FC tablets.

PHENERGAN has been shown to be of value in many allergic disorders and anaphylactic reactions including hay fever, vasomotor rhinorrhoea, urticaria, angioneurotic oedema and sensitisation reactions to various medicines and other substances. PHENERGAN may be of symptomatic value in relieving pruritus.

Posology
The effect of a single dose of PHENERGAN is maintained for an average of 16 u2013 18 hours. If gastric upset or other side effects occur, it is recommended that PHENERGAN be taken with food or with a well-sweetened drink. The initial PHENERGAN dose should be small and the subsequent doses adjusted to the needs of the patient.

Adults:
The initial daily dose should be one 25 mg tablet given late in the evening. This dose may be increased, if necessary, to 50 mg to 100 mg (two to four 25 mg tablets) on the following evenings. When daytime dosage is indicated, 10 mg three times daily is suggested initially.

As an antihistaminic:
For children 5 u2013 10 years: 10 mg u2013 25 mg. The smaller amount stated is generally sufficient if the dose is to be given twice in 24 hours. PHENERGAN 10 and PHENERGAN 25 is not suitable for children younger than 5 years.

Method of administration
PHENERGAN is given orally.

• Hypersensitivity to promethazine hydrochloride, other phenothiazines or to any of the other ingredients in the formulation of PHENERGAN (see section 6.1).
• PHENERGAN is contraindicated for use in children less than 2 years of age because of the potential for fatal respiratory depression (see section 4.4).
• Children and adolescents with signs and symptoms suggestive of Reyeu2019s syndrome.
• PHENERGAN should be used with care in children, especially those who are acutely ill or dehydrated as these patients have an increased incidence of dystonias.
• Acute asthma attacks.
• PHENERGAN should not be used in patients in a coma or suffering from central nervous system (CNS) depression of any cause.
• Patients taking monoamine oxidase inhibitors up to 14 days previously.

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

PHENERGAN should be avoided in patients with liver or renal dysfunction, Parkinsonu2019s disease, hypothyroidism, cardiac failure, pheochromocytoma, myasthenia gravis, prostate hypertrophy or in patients with a history of narrow angle glaucoma or agranulocytosis.

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

Due to the risk of photosensitivity, exposure to the sun or ultraviolet light should be avoided during or shortly after treatment.

PHENERGAN must not be used in children below two years of age due to the potential for fatal respiratory depression (see section 4.3).

The use of promethazine should be avoided in children and adolescents with signs and symptoms suggestive of Reyeu2019s syndrome.

Phenothiazine derivatives, as contained in PHENERGAN, may potentiate QT interval prolongation which increases the risk of onset of serious ventricular dysrhythmias of the torsades 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. medicine 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).

Prolonged administration of any phenothiazine may result in tardive dyskinesia, particularly in the elderly and children.

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 anaesthetics, or alcohol.

As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8) and requires immediate haematological investigation.

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

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

As with neuroleptics, neuroleptic malignant syndrome (NMS) characterised 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.

PHENERGAN should be used with caution in patients with severe coronary artery disease.

Caution should be exercised in patients with bladder neck or pyloro-duodenal obstruction.

PHENERGAN should be used with caution in patients with epilepsy. PHENERGAN may precipitate epileptiform seizures in patients with focal lesions of the cerebral cortex.

PHENERGAN may delay the early diagnosis of intestinal obstruction or increased intracranial pressure through the suppression of vomiting.

PHENERGAN may mask the warning signs of ototoxicity caused by ototoxic medicines, such as aminoglycoside antibiotics and salicylates.

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

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

PHENERGAN should be discontinued at least three days before the skin test as it may inhibit the cutaneous histamine response thus producing false-negative results.

Medicines known to cause QT prolongation:
Special caution is required when promethazine, as in PHENERGAN, is used concurrently with medicines known to cause QT prolongation (such as antidysrhythmics, antimicrobials, antidepressants or antipsychotics) to avoid exacerbation of the risk of QT prolongation.

PHENERGAN will enhance the action of any anticholinergic medicine, tricyclic antidepressant, sedative or hypnotic.

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.

PHENERGAN is contraindicated in patients taking monoamine oxidase inhibitors within the previous 14 days, and monoamine oxidase inhibitors should be avoided while using PHENERGAN (see section 4.3).

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

Gastrointestinal medicines that are not absorbed:
Reduced gastrointestinal absorption of phenothiazines may occur. Such gastrointestinal medicines should not be taken at the same time as phenothiazines (at least 2 hours apart, if possible).

Medicines with anticholinergic properties:
Concomitant use of PHENERGAN with medicines with anticholinergic properties enhances the anticholinergic effect.

PHENERGAN may potentiate the hypotensive effect of some antihypertensive medicines. Some combinations of PHENERGAN and tricyclic antidepressants have resulted in increased plasma concentrations of both medicines.

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

Alcohol should be avoided during treatment. Combination with alcohol enhances the sedative effects of H1 antihistamines.

Pregnancy
Safety in pregnancy and lactation has not been established. The use of PHENERGAN is not recommended during pregnancy.

The use of PHENERGAN is not recommended in the 2 weeks prior to delivery in view of the risk of irritability and excitement in the neonate.

Breastfeeding
PHENERGAN crosses the placenta and is distributed in breast milk. There are risks of neonatal irritability and excitement. PHENERGAN is not recommended for use in breastfeeding.

Fertility
There are no relevant fertility data in animals.

PHENERGAN may cause drowsiness, dizziness and blurred vision and can considerably affect the ability to drive a vehicle and use machines (see section 4.8). Caution is advised before driving a vehicle or operating machinery until the effects of PHENERGAN are known.

The following side effects have been reported and the frequencies may be unknown. PHENERGAN is generally well tolerated at normal dosage levels, but side effects occur in some patients.

Immune system disorders
Frequency unknown: Allergic reactions, including anaphylactic reaction, urticaria, angioedema.

Blood and lymphatic system disorders
Frequency unknown: Blood dyscrasias including haemolytic anaemia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia (including thrombocytopenic purpura).

Metabolism and nutrition disorders
Frequency unknown: Decreased appetite.

Psychiatric disorders
Frequency unknown: Agitation, confusional state, anxiety. Infants, newborns and prematures are susceptible to the anticholinergic effects of PHENERGAN, while other children may display paradoxical hyperexcitability, disorientation.

Nervous system disorders
Frequent: Sedation or somnolence is the most frequent and generally occurs when the medicine is given during the daytime. Other side effects include dizziness, slight disorientation, headache, twitching and jerking of limbs at night and ataxia. Less frequent: Drowsiness, restlessness, nightmares. Frequency unknown: Paradoxical central nervous system stimulation may occur especially in children, with insomnia, nervousness, tachycardia, tremors and convulsions, euphoria. Neuroleptic malignant syndrome, 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. Extrapyramidal effects may occur, including muscle spasm, tic-like movements of the head and face. Anticholinergic effects such as ileus paralytic, risk of urinary retention, dry mouth, constipation, accommodation disorder. The elderly are particularly susceptible to the anticholinergic effects and confusion due to PHENERGAN.

Eye disorders
Frequency unknown: Blurred vision.

Ear and labyrinth disorders
Frequency unknown: Tinnitus.

Cardiac disorders
Frequency unknown: Palpitations, arrhythmias, QT prolongation, torsades de pointes.

Vascular disorders
Frequency unknown: Hypotension.

Respiratory, thoracic and mediastinal disorders
Frequency unknown: Respiratory depression, nasal congestion.

Gastrointestinal disorders
Frequency unknown: Nausea, diarrhoea or constipation, vomiting, increased appetite, epigastric pain, epigastric discomfort, dry mouth.

Hepatobiliary disorders
Frequency unknown: Jaundice cholestatic.

Skin and subcutaneous tissue disorders
Less frequent: Cases of allergic reactions, including urticaria, rash, pruritus and anaphylaxis have been reported. Frequency unknown: Photosensitive skin reactions have been reported; strong sunlight should be avoided during treatment.

Musculoskeletal and connective tissue disorders
Frequency unknown: Muscular weakness, restless legs syndrome.

Renal and urinary disorders
Frequency unknown: Urinary retention.

General disorders and administration site conditions
Frequency unknown: Tiredness.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of PHENERGAN is important. It allows continued monitoring of the benefit/risk balance of PHENERGAN. Health care providers are asked to report any suspected adverse reactions to:
u2022 The Pharmacovigilance Unit at Sanofi: [email protected] (email) or 011 256-3700 (tel), or
u2022 SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

The chief symptom is unconsciousness, commonly delayed. Convulsions have occurred with unconsciousness in the intervening periods. 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. Tachycardia may develop. Cardiorespiratory depression is uncommon. High doses can cause ventricular dysrhythmias including QT prolongation and torsades de pointes (see section 4.8). In the event of overdose of PHENERGAN, take all appropriate measures immediately.