Phenylephrine Hydrochloride

Registered South African indications:

• Increasing blood pressure in adults with clinically significant hypotension resulting primarily from vasodilation in such settings as septic shock and anaesthesia

Phenylephrine 10mg/ml can only be administered via IV after dilution

Registered South African contraindications

• Hypersensitivity to phenylephrine hydrochloride, or to any of the excipients
• Paediatric use
• Contraindicated in the presence of severe:
  - Uncontrolled hypertension or peripheral vascular disease due to the risk of ischaemic gangrene or vascular thrombosis
  - Hyperthyroidism
  - Heart-block with or without bradycardia
  - Uncontrolled cardiac failure
  - Bradycardia (less than 50 bpm)
  - Seriously impaired coronary arterial circulation
• Phenylephrine should not be used in combination with indirectly acting sympathomimetic medicines (ephedrine, methylphenidate, pseudoephedrine): risk of vasoconstriction and/or hypertensive crisis
• Phenylephrine should not be used 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
• Phenylephrine should not be used 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
• Avoid in patients with prostatic enlargement (10mg/ml)

South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Diabetes
• Arterial hypertension
• Aneurysm
• Uncontrolled hyperthyroidism
• Coronary heart disease and chronic heart disease
• Bradycardia
• Tachycardia
• Dysrhythmia
• Angina pectoris (phenylephrine can precipitate or exacerbate angina in patients with coronary artery disease and history of angina)
• Non-severe peripheral vascular insufficiency
• Closed angle glaucoma

Diminished efficacy

• Sustained intravenous infusion may lead to a decrease in the medicine's effectiveness

Coadministration considerations

• Use of a halogenated volatile anaesthetic (e.g., desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane) with phenylephrine hydrochloride may increase the risk of perioperative hypertensive crisis and dysrhythmia

Cardiac function

• Phenylephrine hydrochloride may cause severe bradycardia and a significant decrease in cardiac output
• Excessive peripheral and visceral vasoconstriction with ischaemia to vital organs may occur, especially in patients with extensive peripheral vascular disease e.g., Raynaud’s phenomenon
• Increased blood pressure may occur and precipitate underlying heart failure, angina in patients with severe arteriosclerosis or past history of angina, and increase pulmonary arterial pressure

Clinical deterioration

• In patients with severe heart failure or cardiogenic shock, the induced vasoconstriction (increased afterload) may cause a worsening or deterioration of the heart condition
• Therefore, it should be administered with extreme caution in patients with atherosclerosis, in the elderly and in patients with impaired cerebral or coronary arterial circulation

Consideration in certain conditions

• Patients with medical conditions such as decreased cardiac output or peripheral or coronary artery disease should have frequent monitoring of vital body functions and lower systemic blood pressure boundary should be considered as a criterion for dose reduction or discontinuation of phenylephrine hydrochloride

Autonomic dysfunction

• Blood pressure response to phenylephrine hydrochloride may be increased in patients with autonomic dysfunction

Administration considerations

• Extravasation: Particular attention must be paid to the injection site to avoid leakage into surrounding tissue, which may cause tissue necrosis

Ocular syndromes (10mg/ml)

• Use in patients with a shallow anterior chamber or history of narrow-angle glaucoma increases the risk of iridocele and floppy iris syndrome

Excipient warnings

Specific to 10mg/ml

• Contains sodium metabisulphite, which may rarely cause severe hypersensitivity reactions and bronchospasm

Specific to 0.1mg/ml

• Contains 3.54mg of sodium per ml, which must be considered in patients on a controlled sodium diet

Effects on ability to drive and use machines

• Phenylephrine hydrochloride can cause undesirable effects (including hypotension with dizziness, fainting, dyspnoea, muscular weakness), which may affect the ability to drive and use machines

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Phenylephrine should only be administered by healthcare professionals with appropriate training and relevant experience in the safe administration of phenylephrine preparations

Increasing blood pressure in adults with clinically significant hypotension resulting primarily from vasodilation in such settings as septic shock and anaesthesia
- Adult patients undergoing surgical procedures with either neuraxial anaesthesia or general anaesthesia (perioperative setting)

• IV: 50-250µg, by intravenous bolus administration; Most frequently reported initial bolus dose is 50µg OR 100µg
• IV: 0.5-1.4µg/kg/min by intravenous continuous infusion, titrated to blood pressure goal

- Adult patients with septic shock

• IV: 0.5-6µg/kg/min by intravenous continuous infusion, titrated to blood pressure goal; Doses above 6µg/kg/min do not show significant incremental increase in blood pressure

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Method of administration (10mg/ml)
Phenylephrine 10mg/ml can only be administered via IV after dilution
Intravenous bolus injection: 10mg of phenylephrine (1ml of phenylephrine 10mg/ml) must be diluted to 200ml of glucose 5% injection or sodium chloride 0.9% injection prior to bolus intravenous injection. This dilution yields a final concentration of 50µg/ml. Withdraw an appropriate dose from the 50µg/ml solution prior to bolus intravenous administration of the diluted solution
Continuous infusion: 10mg of phenylephrine (1ml of phenylephrine 10mg/ml) must be diluted in 500ml of glucose 5% injection or sodium chloride 0.9% injection prior to administration via intravenous infusion

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Method of administration (0.1mg/ml)
Phenylephrine 0.1mg/ml should be administered by slow intravenous bolus injection or continuous intravenous infusion

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The duration of action is short-lived (minutes) and repeat injections are frequently required

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Phenylephrine should be administered in the lowest effective dosage for the shortest possible time. When possible, small doses should be injected initially and subsequent doses determined by pressor response. Patients receiving phenylephrine should be closely monitored

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Treatment with phenylephrine is not a substitute for replacement of blood, plasma, fluids and/or electrolytes. Prior to administration of therapy, hypovolaemia should be corrected. Acidosis may reduce the effectiveness of phenylephrine

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When discontinuing therapy, the dosage should be reduced gradually, since sudden cessation of therapy may result in severe hypotension, intravascular fluid should be administered if necessary to avoid hypotension

• Contraindicated

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Phenylephrine should not be administered to paediatric patients. The safety and efficacy in children have not been established. No data are available

Pregnancy

South African recommendations

• Caution; not recommended
• The safety of phenylephrine hydrochloride 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

Breastfeeding

South African recommendations

• Caution; not recommended
• The safety of phenylephrine hydrochloride 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 hydrochloride should not be used during breastfeeding

Fertility

South African recommendations

• There are no data available regarding fertility, following treatment with phenylephrine

• Caution; dose adjustment recommended
  Lower doses of phenylephrine may be needed in patients with impaired renal function

• Caution; dose adjustment recommended
  Higher doses of phenylephrine may be needed in patients with cirrhosis of the liver

• Caution; no dose adjustment recommended

Immune System Disorders

Less frequent

• Hypersensitivity

Metabolic and Nutrition Disorders

Frequency unknown

• Glucose metabolism abnormal
• Metabolic disorders

Psychiatric Disorders

Less frequent

• Euphoria
• Agitation
• Anxiety
• 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

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 Tissue 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 and urinary retention

General Disorders and Administration Site Conditions

Less frequent

• Extravasation necrosis at injection site

• Non-selective monoamine oxidase inhibitors (MAOIs)
• Iproniazid
• Nialamide
• Phenelzine
• Indirect sympathomimetics medicines
• Ephedrine
• Methylphenidate
• Pseudoephedrine
• Alpha sympathomimetic medicines
• Etilefrine
• Midodrine
• Naphazoline
• Oxymetazoline
• Synephrine
• Tetryzoline
• Tuaminoheptane
• Tymazoline
• Dopaminergic ergot alkaloids
• Bromocriptine
• Cabergoline
• Lisuride
• Pergolide
• Vasoconstrictor ergot alkaloids
• Dihydroergotamine
• Ergotamine
• Methylergometrine
• Methysergide
• Linezolid
• Tricyclic antidepressants
• Desipramine
• Imipramine
• Nortriptyline
• Noradrenergic-serotoninergic antidepressants
• Venlafaxine
• Selective monoamine oxidase inhibitors (MAOs)
• Moclobemide
• Pargyline
• Selegiline
• Toloxatan
• Guanethidine and related products
• Digoxin
• Quinidine
• Halogenated volatile anaesthetics
• Desflurane
• Enflurane
• Halothane
• Isoflurane
• Methoxyflurane
• Sevoflurane
• Antihypertensive and diuretic medicines
• Beta-adrenoceptor-blocking medicines (systemic or ophthalmic)
• Reserpine and other sympatholytic medicines
• Atropine sulphate
• Oxytocic medicines
• Alpha-adrenoceptor-blocking medicines
• Doxazosin
• Labetalol
• Prazosin
• Haloperidol
• Phenothiazines
• Atomoxetine
• Lithium carbonate

• Blood pressure

Specific cases may require

• Electrocardiographic monitoring

Phenylephrine acts predominantly by direct stimulation of alpha1-adrenergic receptors. In therapeutic doses, it has no substantial stimulant effect on the beta-adrenergic receptors of the heart (beta1 adrenergic receptors), but substantial activation of these receptors may occur when larger doses are given. Phenylephrine does not stimulate beta-adrenergic receptors of the bronchi or peripheral blood vessels (beta2-adrenergic receptors). It is believed that alpha1-adrenergic effects result from the inhibition of the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas beta-adrenergic effects result from stimulation of adenyl cyclase activity. Phenylephrine also has an indirect effect by releasing norepinephrine from its storage sites.

The predominant actions of phenylephrine are on the cardiovascular system. Parenteral administration causes a rise in systolic and diastolic pressures. Accompanying the pressor response to phenylephrine is a marked reflex bradycardia that can be blocked by atropine; after atropine, large doses of the medicine increase the heart rate only slightly. Cardiac output is slightly decreased and peripheral resistance is considerably increased. Circulation time is slightly prolonged, and venous pressure is slightly increased; venous constriction is not marked. Most vascular beds are constricted; renal splanchnic, cutaneous and limb blood flows are reduced but coronary blood flow is increased. Pulmonary vessels are constricted, and pulmonary arterial pressure is raised.

Injections (per ml) 10mg

• Hypopress 0.1mg/ml (Umsebe Healthcare)
• Phenylephrine Abbott (Abbott) originator
• Tacyphen (Teva Pharmaceuticals)