SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Phenylephrine 10 mg/ml Injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 ml ampoule contains 10 mg of the active ingredient phenylephrine hydrochloride.

Excipients with known effect:

Sodium hydroxide solution (q.s.- quantity per ml)

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

A clear, colourless sterile solution

4. CLINICAL PARTICULARS

4.1.    Therapeutic indications

Phenylephrine Injection is indicated in adults and children for the treatment of hypotensive states e.g. circulatory failure, during spinal anaesthesia or drug induced hypotension.

4.2.    Posology and method of administration

Posology

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.

Paediatric population

100 mcg/kg body weight subcutaneously or intramuscularly.

Elderly

There is no need for dosage reduction in the elderly.

Method of administration

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

4.3 Contraindications

Hypersensitivity to phenylephrine or to any of the excipients listed in section 6.1.

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 preexisting 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.

Phenylephrine Injection contains sodium.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

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 is a hypertensive agent and may consequently reverse the action of many antihypertensive drugs. Interactions of phenylephrine with alpha and beta receptor blocking drugs may be complex.

Drugs which have an effect on cq adrenoceptors could potentiate (such as clonidine) or inhibit (such as doxazosin) the vasopressive action of phenylephrine.

Caution should be applied when administering atomoxetine concurrently, as there is potential for synergistic pharmacological effects.

Severe hypertension may occur following the use of phenylephrine and atropine or other antimuscarinics.

The pressor effects of phenylephrine may be slightly reduced by lithium carbonate.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of phenylephrine during pregnancy has not been established. Due to the vasoconstrictive properties of phenylephrine, the product should be used with caution in patients with a history of pre-eclampsia. Administration of phenylephrine in late pregnancy or labour may cause foetal hypoxia and bradycardia.

Breast-feeding

The safety of phenylephrine during lactation has not been established. 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

Immune system disorders Hypersensitivity

Metabolism and nutrition disorders Metabolic disorders

Psychiatric disorders Nervousness, insomnia

Nervous system disorders

Headache, cerebral haemorrhage, paraesthesia

Eye disorders

Mydriasis, angle-closure glaucoma

Cardiac disorders

Pulmonary oedema, bradycardia, tachycardia, arrhythmia, angina pectoris, palpitations, cardiac arrest

Vascular disorders

Hypotension, dizziness, syncope, flushing

Respiratory, thoracic and mediastinal disorders Dyspnoea

Gastrointestinal disorders Vomiting, salivary hypersecretion

Renal and urinary disorders Dysuria, urinary retention

General disorders and administration site conditions Extravasation, infusion site necrosis, hyperhidrosis

Investigations

Increased blood pressure, abnormal blood glucose

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 (website: www.mhra.gov.uk/yellowcard).

4.9 Overdose

Symptoms

Symptoms of overdosage include headache, vomiting, hypertension and reflex bradycardia and other cardiac arrhythmias. In severe cases confusion, hallucinations and seizures may occur.

Management

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

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: adrenergic and dopaminergic agent ATC code: C01CA

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.

Mechanism of action

After injection it produces peripheral vasoconstriction and increased arterial pressure; it also causes reflex bradycardia.

5.2 Pharmacokinetic properties

Absorption

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 about two hours respectively. Intravenous injections are effective for up to about 20 minutes.

B iotransformation

Elimination

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

Sodium Hydroxide solution 1N Hydrochloric Acid -36% 1N Water for injections Nitrogen, liquefied

6.2    Incompatibilities

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

6.3.    Shelf life

2 years.

6.4    Special precautions for storage

Store at 2-25°C. Protect from light

6.5    Nature and contents of container

1 ml neutral glass ampoule with red imprint break ring.

Pack size: 6 x 1ml and 10 x 1ml ampoules

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Amdipharm UK Limited Capital House,

85 King William Street,

London EC4N 7BL, UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 20072/0226

DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 17 November 1999 Date of latest renewal: 18 November 2005

DATE OF REVISION OF THE TEXT

14/09/2016