Phenylephrine Solution

Phenylephrine 50 u03bcg/mL PS Equity is indicated for the treatment of hypotension during spinal, epidural or general anaesthesia.

Posology

Adults

Normal dose is 50 to 100 micrograms, which can be repeated until the desired effect is obtained. One bolus dose should not exceed 100 micrograms.

Special population

Patients with renal impairment

Lower doses of Phenylephrine 50 u03bcg/mL PS Equity may be required in patients with impaired renal function.

Patients with hepatic impairment

Higher doses of Phenylephrine 50 u03bcg/mL PS Equity may be needed in patients with cirrhosis of the liver.

Elderly patients

Treatment of the elderly should be carried out with care.

Paediatric population

The safety and efficacy of Phenylephrine 50 u03bcg/mL PS Equity in children have not been established. No data are available.

Method of administration

Intravenous bolus injection. Phenylephrine 50 u03bcg/mL PS Equity should only be administered by healthcare professionals with appropriate training and relevant experience. The pre-filled syringe is not suitable for use in a syringe driver.

• Hypersensitivity to phenylephrine hydrochloride or to any of the excipients listed in section 6.1.
• Patients with severe hypertension.
• Patients with peripheral vascular disease, as it can lead to ischaemia with a risk of gangrene or vascular thrombosis.
• Patients with heart-block with or without bradycardia, uncontrolled cardiac failure, bradycardia less than 50 bpm or seriously impaired coronary arterial circulation.
• In combination with indirectly acting sympathomimetic medicines (ephedrine, methylphenidate, pseudoephedrine): risk of vasoconstriction and/or hypertensive crisis.
• In combination with alpha-sympathomimetic medicines (oral and/or nasal use) (etilefrine, midodrine, naphazoline, oxymetazoline, synephrine, tetryzoline, tuaminoheptane, tymazoline): risk of vasoconstriction and/or hypertensive crisis.
• In combination with non-selective monoamine oxidase inhibitors (MAOs) (or within 2 weeks of their withdrawal), due to risk of paroxysmal arterial hypertension and possibly fatal hyperthermia (see section 4.5).
• Patients with severe hyperthyroidism.

Arterial blood pressure should be monitored during treatment. Phenylephrine 50 u03bcg/mL PS Equity should be given with caution to patients with:

• diabetes mellitus
• arterial hypertension
• aneurysm
• uncontrolled hyperthyroidism
• coronary heart disease and chronic heart conditions
• non-severe peripheral vascular insufficiency
• bradycardia
• partial heart block
• tachycardia
• dysrhythmias
• angina pectoris (phenylephrine can precipitate or exacerbate angina in patients with coronary artery disease and history of angina)
• peripheral vascular diseases e.g. Raynaudu2019s phenomenon
• closed angle glaucoma.

Phenylephrine 50 u03bcg/mL PS Equity can induce a reduction in cardiac output. Therefore, care should be exercised in administering to patients with arteriosclerosis, the elderly and to patients with impaired cerebral or coronary circulation. In patients with reduced cardiac output or peripheral or coronary vascular disease, vital organ functions should be closely monitored and dose reduction should be considered when systemic blood pressure is near the lower end of the target range.

In patients with serious heart failure or cardiogenic shock, Phenylephrine 50 u03bcg/mL PS Equity may cause deterioration in the heart failure as a consequence of the induced vasoconstriction (increase in afterload). Particular attention should be paid when administering Phenylephrine 50 u03bcg/mL PS Equity injection to avoid extravasation, since this may cause tissue necrosis. Lower doses may be required in patients with renal impairment (see section 4.2). Higher doses may be required in patients with liver cirrhosis (see section 4.2). Allergic reactions, including anaphylactic shock, may occur in patients with sulphite-sensitivity. Blood pressure response to Phenylephrine 50 u03bcg/mL PS Equity may be increased in patients with autonomic dysfunction.

The administration of Phenylephrine 50 u03bcg/mL PS Equity simultaneously with the following medicines is not recommended, because of the risk of vasoconstriction and/or hypertensive crisis associated with its indirect sympathomimetic effect (see section 4.5):

• dopaminergic ergot alkaloids (bromocriptine, carbergoline, lisuride or pergolide) or vasoconstrictors (dihydroergotamine, ergotamine, or methysergide, methylergometrine).
• in combination with linezolid.

Concurrent use with MAO inhibitors may prolong and intensify cardiac stimulation and vasopressor effects because of the release of catecholamines, which accumulate in intraneuronal storage sites during MAO inhibitor therapy; this may result in headache, cardiac dysrhythmias, vomiting or sudden and severe hypertensive or hyper-pyretic crises.

For patients who have been receiving MAO inhibitors 2 to 3 weeks prior to administration of sympathomimetic medicines, the initial dosage should be reduced to be no more than one-tenth of the usual dose (see section 4.5). This medicine contains 37,2 mg sodium per pre-filled syringe, equivalent to 1,9 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Contraindicated combinations (see section 4.3)

• Non-selective monoamine oxidase inhibitors (MAOs) (iproniazid, nialamide, phenelzine) Increased risk of paroxysmal hypertension, hyperthermia possibly fatal. Due to the long duration of action of MAOIs, this interaction is still possible 15 days after discontinuation of the MAOI.
• Indirect sympathomimetics medicines (ephedrine, methylphenidate, pseudoephedrine): Increased risk of vasoconstriction and / or hypertensive crisis.
• Alpha sympathomimetic medicines (oral and/or nasal use) (etilefrine, midodrine, naphazoline, oxymetazoline, synephrine, tetryzoline, tuaminoheptane, tymazoline): Increased risk of vasoconstriction and / or hypertensive crisis.

Combinations not recommended (see section 4.4)

• Dopaminergic ergot alkaloids (bromocriptine, cabergoline, lisuride, pergolide): Increased risk of vasoconstriction and/or hypertensive crisis.
• Vasoconstrictor ergot alkaloids (dihydroergotamine, ergotamine, methylergometrine, methylsergide): Increased risk of vasoconstriction and/or hypertensive crisis.
• Tricyclic antidepressants (desipramine, imipramine, nortriptyline): Increased risk of paroxysmal hypertension with possibility of dysrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibres).
• Noradrenergic-serotoninergic antidepressants (minalcipram, venlafaxine): Increased risk of paroxysmal arterial hypertension with possibility of dysrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibres).
• Selective type A monoamine oxidase inhibitors (MAOs) (moclobemide, pargyline, selegiline, toloxatone): Increased risk of vasoconstriction and/or hypertensive crisis.
• Linezolid: Increased risk of vasoconstriction and/or hypertensive crisis.
• Guanethidine and related products: Substantial increase in blood pressure (hyperreactivity linked to the reduction in sympathetic tone and/or to the inhibition of adrenaline or noradrenaline entry in sympathetic fibres). If the combination cannot be avoided, use with caution lower doses of sympathomimetic medicines.
• Cardiac glycosides, quinidine: Increased risk of dysrhythmias.
• Sibutramine: Paroxysmal hypertension with possibility of dysrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibres).
• Halogenated volatile anaesthetics (desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane): Risk of perioperative hypertensive crisis and dysrhythmia.

The effect of antihypertensive and diuretic medicines used as antihypertensives may be reduced when used concurrently with Phenylephrine 50 u03bcg/mL PS Equity; the patient should be carefully monitored to confirm the desired effect is obtained. Beta-adrenoceptor-blocking medicines, systemic or ophthalmic - concurrent use of Phenylephrine 50 u03bcg/mL PS Equity may result in an exaggeration of the vasoconstriction effects and profound bradycardia. Reserpine and other sympatholytic medicines - concomitant use with Phenylephrine 50 u03bcg/mL PS Equity causes a substantial increase in blood pressure. If the combination cannot be avoided, use with caution. The pressor effect of Phenylephrine 50 u03bcg/mL PS Equity is increased in patients receiving atropine sulphate.

Combinations requiring precautions for use:

• Oxytocic medicines: The effect of pressor-active sympathomimetic amines is potentiated. Thus, some oxytocic medicines may cause severe persistent hypertension and strokes can occur during post-partum period.
• Digoxin: Phenylephrine 50 u03bcg/mL PS Equity may be used with digoxin for therapeutic advantage; caution and close electrocardiographic monitoring are recommended during concurrent use.
• Alpha-adrenoceptor-blocking medicines (doxazosin, labetalol, prazosin, haloperidol, phenothiazines): concurrent use may antagonise the peripheral vasoconstriction effect of Phenylephrine 50 u03bcg/mL PS Equity.

Pregnancy

The safety of Phenylephrine 50 u03bcg/mL PS Equity during pregnancy has not been established. Animal studies are insufficient with respect to effects on pregnancy, embryonal / foetal development, parturition or postnatal development. The potential risk for humans is unknown. Phenylephrine 50 u03bcg/mL PS Equity may be used for the treatment of hypotension during pregnancy. The combination with some oxytocic medicines can cause severe hypertension (see section 4.5).

Breastfeeding

The safety of Phenylephrine 50 u03bcg/mL PS Equity during breastfeeding has not been established. Small amounts of phenylephrine are excreted in human milk. The administration of vasoconstrictors to the mother puts the child at risk for cardiovascular and neurological effects. Phenylephrine 50 u03bcg/mL PS Equity should not be used during lactation. However, in the event of a single bolus administration during childbirth, breastfeeding is possible.

Fertility

There are no data available regarding human fertility, following treatment with Phenylephrine 50 u03bcg/mL PS Equity.

Not relevant.

a. Summary of the safety profile

The most frequent adverse events of Phenylephrine 50 u03bcg/mL PS Equity are bradycardia, hypertensive episodes, nausea and vomiting. Hypertension is more frequent with high doses. The most frequently reported cardiovascular adverse event appears to be bradycardia, likely due to baroreceptor-mediated vagal stimulation and consistent with the pharmacological effect of phenylephrine.

b. Tabulated list of adverse reactions

Immune system disorders

• Less frequent: Hypersensitivity

Metabolism and nutrition disorders

• Frequency unknown*: Abnormal glucose metabolism

Psychiatric disorders

• Less frequent: Anxiety, excitability, agitation, psychotic states, confusion

Nervous system disorders

• Frequent: Headache
• Less frequent: Tingling, fullness head, nervousness or restlessness, insomnia, paraesthesia, tremor

Eye disorders

• Less frequent: Mydriasis, aggravation of pre-existing angle-closure glaucoma

Cardiac disorders

• Less frequent: Anginal pain, reflex bradycardia, tachycardia, ventricular dysrhythmias
• Frequency unknown*: Dysrhythmia, cardiac arrest, palpitations, myocardial ischemia, angina pectoris

Vascular disorders

• Less frequent: Cerebral haemorrhage, hypertension, hypotension with dizziness, hypertensive crisis, pallor
• Frequency unknown*: Fainting, flushing, coldness of skin

Respiratory, thoracic and mediastinal disorders

• Less frequent: Dyspnoea, pulmonary oedema

Gastrointestinal disorders

• Less frequent: Nausea, vomiting
• Frequency unknown*: Hypersalivation

Skin and subcutaneous system disorders

• Less frequent: Piloerection, sweating, skin blanching
• Frequency unknown*: Diaphoresis

Musculoskeletal and connective tissue disorders

• Less frequent: Muscular weakness

Renal and urinary disorders

• Less frequent: Difficulty in micturition, urinary retention

General disorders and administration site conditions

• Less frequent: Extravasation necrosis at injection site

* Frequency cannot be estimated from available data.

c. Description of selected adverse reactions

As Phenylephrine 50 u03bcg/mL PS Equity has been frequently used in the critical care setting in patients with hypotension and shock, some of the reported serious adverse events and deaths are probably related to the underlying disease and not related to the use of phenylephrine (e.g., Phenylephrine 50 u03bcg/mL PS Equity).

d. Other special population(s)

Elderly: risk for phenylephrine toxicity is increased in elderly patients (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are requested to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Symptoms

Symptoms of overdose include headache, nausea, vomiting, paranoid psychosis, hallucinations, hypertension and reflex bradycardia. Cardiac dysrhythmia such as ventricular extrasystoles and short paroxysmal episodes of ventricular tachycardia may occur.

Treatment

Treatment should consist of symptomatic and supportive measures. The hypertensive effects may be treated with an appropriate antihypertensive medicine e.g. magnesium sulfate.