SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Phenylephrine 10 mg/ml Solution for Injection or Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Phenylephrine hydrochloride Ph Eur 1.0% w/v Each 1 ml ampoule contains 10 mg phenylephrine.

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Solution for injection, or concentrate for solution for injection or infusion. Clear, colourless, sterile, solution.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of hypotensive states, e.g. circulatory failure, during spinal anaesthesia or drug-induced hypotension.

4.2 Posology and method of administration

For subcutaneous, intramuscular or slow intravenous injection or by intravenous infusion.

Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.

Adults

Phenylephrine injection may be administered subcutaneously or intramuscularly in a dosage of 2 to 5 mg with further doses of 1 to 10 mg if necessary according to response, or in a dose of 100 to 500 micrograms by slow intravenous injection as a 0.1% solution, repeated as necessary after at least 15 minutes.

Alternatively, 10 mg in 500 ml of glucose 5% injection or sodium chloride 0.9% injection may be infused intravenously, initially at a rate of up to 180 micrograms per minute, reduced according to response to 30-60 micrograms per minute.

Children

100 micrograms/kg bodyweight subcutaneously or intramuscularly. Elderly

There is no need for dosage reduction in the elderly.

4.3 Contraindications

Hypersensitivity to phenylephrine or to any of the excipients.

Patients taking monoamine oxidase inhibitors, or within 14 days of ceasing such treatment.

Severe hypertension and hyperthyroidism.

4.4 Special warnings and precautions for use

Great care should be exercised in administering Phenylephrine Injection to patients with pre-existing cardiovascular disease such as ischaemic heart disease, arrhythmias, occlusive vascular disease including arteriosclerosis, hypertension or aneurysms. Anginal pain may be precipitated in patients with angina pectoris.

Care is also required when given to patients with diabetes mellitus or closed-angle glaucoma.

Keep all medicines out of the reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

Phenylephrine may interact with cyclopropane and halothane and other halogenated inhalational anaesthetics, to induce ventricular fibrillation.

An increased risk of arrhythmias may also occur if phenylephrine injection is given to patients receiving cardiac glycosides, quinidine or tricyclic antidepressants.

Phenylephrine may increase blood pressure and consequently reverse the action of many antihypertensive agents.

Interactions of phenylephrine with alpha and beta receptor blocking drugs may be complex. Drugs which have an effect on a₁- adrenoreceptors could potentiate (such as ganisetron) or inhibit (such as doxazosin or buspirone) the vasopressive action of phenylephrine.

4.6 Pregnancy and lactation

The safety of phenylephrine during pregnancy and lactation has not been established. Administration of phenylephrine in late pregnancy or labour may cause foetal hypoxia and bradycardia.

Excretion of phenylephrine in breast milk appears to be minimal.

4.7 Effects on ability to drive and use machines

No adverse effects known.

4.8 Undesirable effects

Extravasation of Phenylephrine injection may cause tissue necrosis. Phenylephrine will cause a rise in blood pressure with headache and vomiting and this may produce cerebral haemorrhage and pulmonary oedema. There may also be a reflex bradycardia or tachycardia, other cardiac arrhythmias, anginal pain, palpitations and cardiac arrest, hypotension with dizziness, and fainting and flushing may occur.

Phenylephrine may induce difficulty in micturition and urinary retention, mydriasis, dyspnoea, altered metabolism including disturbances of glucose metabolism, sweating, hypersalivation, transient tingling and coolness of the skin and temporary fullness of the head. Phenylephrine is without significant stimulating effects on the central nervous system at usual doses.

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.

4.9 Overdose

Symptoms of overdosage include headache, vomiting, hypertension and reflex bradycardia and other cardiac arrhythmias.

Treatment should consist of symptomatic and supportive measures. The hypertensive effects may be treated with an alpha-adrenoceptor blocking drug, such as phentolamine, 5 to 60 mg i.v. over 10-30 minutes, repeated as necessary.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Adrenergic and dopaminergic agents.

ATC code: C01C A06

Phenylephrine hydrochloride is a sympathomimetic agent with mainly direct effects on adrenergic receptors. It has predominantly alpha-adrenergic activity and is without

significant stimulating effects on the central nervous system at usual doses. After injection it produces peripheral vasoconstriction and increased arterial pressure. It also causes reflex bradycardia.

5.2 Pharmacokinetic properties

When injected subcutaneously or intramuscularly, phenylephrine takes 10 to 15 minutes to act. Subcutaneous and intramuscular injections are effective for up to about one and up to two hours respectively. Intravenous injections are effective for up to about 20 minutes. Phenylephrine is metabolised in the liver by monoamine oxidase. The metabolites, their route and rate of excretion have not been identified.

5.3 Preclinical safety data

Phenylephrine has been used to induce cardiac myocyte hypertrophy in cultures of rat neonatal mycocytes at doses of 100 pM and 10 pM. To the best of our knowledge there have been no human studies associating therapeutic phenylephrine use with the development of cardiac myocyte hypertrophy.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

N/1 Sodium Hydroxide

N/1 Hydrochloric Acid Water for Injections Ph Eur

6.2 Incompatibilities

Phenylephrine Injection has been stated to be incompatible with alkalis, ferric salts, phenytoin sodium and oxidising agents.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Keep out of sight and reach of children.

Store below 25°C. Store in the original package.

6.5 Nature and contents of container

1 ml neutral glass ampoule with ceramic break ring.

Pack size: 10 ampoules

6.6 Special precautions for disposal

Not applicable.

7 MARKETING AUTHORISATION HOLDER

Beacon Pharmaceuticals Ltd.

85, High Street, Tunbridge Wells Kent TN1 1YG, UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 18157/0223

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/03/2011

10    DATE OF REVISION OF THE TEXT

04/11/2015