Treatment of hypotension from spinal or epidural anaesthesia.

Ephedrine must be used solely by or under the supervision of the anaesthetist.
For intravenous use.
Adults, elderly and children over 12 years
Slow intravenous injection of 3 to 6 mg (maximum 9 mg), repeated as needed every 3-4 min to a maximum of 30 mg. A lack of efficacy after 30 mg should lead to reconsideration of the choice of the therapeutic agent.
Children under 12 years
0.5 - 0.75 mg / kg body weight or 17 - 25 mg / m2 body surface every 3 – 4 minutes according to response.

Use of Ephedrine Hydrochloride Injection 30mg in 1ml is contraindicated in patients with known hypersensitivity to ephedrine or to any of the excipients. Patients receiving treatment with non-selective monoamine oxidase inhibitors (or within 2 weeks of their withdrawal). In combination with other indirect sympathomimetic agents such as phenylpropanolamine, phenylephrine, pseudoephedrine and methylphenidate. • In combination with alpha sympathomimetic agents. Coronary thrombosis, diabetes mellitus, ischaemic heart disease, hypertension, thyrotoxicosis, closed angle glaucoma or, in the case of elderly patients prostatic hypertrophy

Warnings
Ephedrine should be used with caution in patients who may be particularly susceptible to their effects, particularly those with hyperthyroidism. Great care is also needed in patients with cardiovascular disease such as ischaemic heart disease, arrhythmia or tachycardia, occlusive vascular disorders including arteriosclerosis, hypertension, or aneurysms. Anginal pain may be precipitated in patients with angina pectoris.
Care is also required when Ephedrine is given to patients with diabetes mellitus, closed-angle glaucoma or prostatic hypertrophy.
Ephedrine should be avoided or used with caution in patients undergoing anaesthesia with cyclopropane, halothane, or other halogenated anaesthetics, as they may induce ventricular fibrillation. An increased risk of arrhythmias may also occur if Ephedrine is given to patients receiving cardiac glycosides, quinidine, or tricyclic antidepressants.
Many sympathomimetics interact with monoamine oxidase inhibitors, and should not be given to patients receiving such treatment or within 14 days of its termination. It is advisable to avoid sympathomimetics when taking selective MAO inhibitors.
Ephedrine increases blood pressure and therefore special care is advisable in patients receiving antihypertensive therapy. Interactions of Ephedrine with alpha- and beta-blocking drugs may be complex. Propranolol and other beta-adrenoceptor blocking agents antagonise the effects of beta2adrenoceptor stimulants (beta2 agonists) such as salbutamol.
Adverse metabolic effects of high doses of beta2 agonists may be exacerbated by concomitant administration of high doses of corticosteroids; patients should therefore be monitored carefully when the 2 forms of therapy are used together although this precaution is not so applicable to inhaled corticotherapy. Hypokalaemia associated with high doses of beta2 agonists may result in increased susceptibility to digitalis- induced cardiac arrhythmias. Hypokalaemia may be enhanced by concomitant administration of aminophylline or other xanthines, corticosteroids, or by diuretic therapy.

Precautions for use
Ephedrine should be used with caution in patients with a history of cardiac disease.
Athletes should be informed that this preparation contains an active substance which might give a positive reaction in anti-doping tests.

Indirect sympathomimetic agents (phenylpropanolamine, pseudoephedrine, phenylephrine, methylphenidate)
Risk of vasoconstriction and/or of acute episodes of hypertension.
Alpha sympathomimetics (oral and/or nasal route of administration)
Risk of vasoconstriction and/or episodes of hypertension.
Non-selective MAO inhibitors
Paroxysmal hypertension, hyperthermia possibly fatal.
Combinations not recommended: Ergot alkaloids (dopaminergic action)
Risk of vasoconstriction and/or episodes of hypertension.
Ergot alkaloids (vasoconstrictors)

Risk of vasoconstriction and/or episodes of hypertension.
Selective MAO-A inhibitors
Risk of vasoconstriction and/or episodes of hypertension.
Linezolid
Risk of vasoconstriction and/or episodes of hypertension
Tricyclic antidepressants (e.g. imipramine)
Paroxysmal hypertension with possibility of arrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibers).
Noradrenergic-serotoninergic antidepressants (minalcipran, venlafaxine)
Paroxysmal hypertension with possibility of arrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibers).

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 fibers).
If the combination cannot be avoided, use with caution lower doses of sympathomimetic agents.
Sibutramine
Paroxysmal hypertension with possibility of arrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibers).
Combinations requiring precautions for use: Halogenated volatile anaesthetics
Risk of peri-operative hypertensive crisis.

Theophylline
Concomittant administration of ephedrine and theophylline may result in insomnia, nervousness and gastrointestinal complaints.
Corticosteroids
Ephedrine has been shown to increase the clearance of dexamethasone.
Antiepileptics:
Increased plasma concentration of phenytoin and possibly of phenobarbitone and primidone.
Doxapram: risk of hypertension.
Oxytocin: hypertension with vasoconstrictor sympathomimetics.

Pregnancy
PregnancyCategoryC. Ephedrine has been shown to be teratogenic in animals (or shown to have an embryocidal effect or other adverse effect). There are no adequate and well- controlled studies in pregnant women. Ephedrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Clinical data from epidemiological studies on a limited number of women appear to indicate no particular effects of ephedrine with respect to malformation.
Isolated cases of maternal hypertension have been described after abuse or prolonged use of vasoconstrictor amines.
Ephedrine crosses the placenta and this has been associated with an increase in foetal heart rate and beat-to-beat variability.
Therefore, ephedrine should be avoided or used with caution, and only if necessary, during pregnancy.
Lactation
Ephedrine is excreted in breast milk. Irritability and disturbed sleep patterns have been reported in breast-fed infants. There is evidence that ephedrine is eliminated within 21 to 42 hours after administration, therefore a decision needs to be made on whether to avoid ephedrine therapy or lactation should be suspended for 2 days following its administration taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Not known.

Very common: ≥1/10; Common: ≥1/100, <1/10; Uncommon: ≥1/1,000, <1/100; Rare: ≥1/10,000, <1/1,000; Very rare: <1/10,000; Not known: cannot be estimated from the available data
Blood and lymphatic system disorders:
Not known: primary hemostasis modifications
Immune system disorders:
Not known: hypersensitivity
Psychiatric disorders:
Common: confusion, anxiety, depression
Not known: psychotic states, fear
Nervous system disorders:
Common: nervousness, irritability, restlessness, sweating
weakness, insomnia,
headache,
Not known: tremor, hypersalivation

Eye disorders:
Not known: episodes of angle-closure glaucoma
Cardiac disorders:
Common: palpitations, hypertension, tachycardia
Rare: cardiac arrhythmias
Not known: angina pain, reflex bradycardia, cardiac arrest, hypotension
Vascular disorders:
Not known: cerebral haemorrhage
Respiratory, thoracic and mediastinal disorders:
Common: dyspnoea

Not known: pulmonary oedema
Gastrointestinal disorders:
Common: nausea, vomiting Not known: reduced appetite
Renal and urinary disorders:
Rare: acute urinary retention
Investigations:
Not known: hypokalaemia, changes in blood glucose levels
The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

 

Signs
In the event of overdose, the occurrence of nausea, vomiting, fever, paranoid psychosis, ventricular and supraventricular arrhythmias, hypertension, respiratory depression, convulsions and coma are observed.
The lethal dose in humans is approximately 2 g corresponding to blood concentrations of approximately 3.5 to 20 mg/l.
Treatment
The treatment of ephedrine overdose with this product may require intensive supportive treatment.
Slow intravenous injection of labetalol 50-200mg may be given with electrocardiograph monitoring for the treatment of supraventricular tachycardia. Marked hypokalaemia (<2.8mmol.l-1) due to compartmental shift of potassium predisposes to cardiac arrhythmias and may be corrected by infusing potassium chloride in addition to propranolol and correcting respiratory alkalosis, when present.

Adrenergic and Dopaminergic Agent. ATC Code : C01CA26
Ephedrine is sympathomimetic amine acting directly on the alpha and beta receptors
and indirectly by increasing the release of noradrenaline by the sympathetic nerve endings. As with any sympathomimetic agent, ephedrine stimulates the central nervous system, the cardiovascular system, the respiratory system, and the sphincters of the digestive and urinary systems. Ephedrine is also a monoamine oxidase (MAO) inhibitor.

After intravenous administration, ephedrine is completely biologically available, and after oral administration, the bioavailability of ephedrine has been reported to be above 90%.
Excretion depends on urine pH:
From 73 to 99% (mean: 88%) in acidic urine,
From 22 to 35% (mean: 27%) in alkaline urine.
After oral or parenteral administration, 77% of ephedrine is excreted in unchanged form in the urine.
The half life depends on urine pH. When the urine is acidified at pH = 5, the half life is 3 hours; when the urine is rendered alkaline at pH = 6.3, the half life is approximately 6 hours

There is no pre-clinical data of relevance to the prescriber which is additional to that already included in other sections of the SPC.

Water for Injections BP

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

36 months. After opening: the product must be used immediately.

Do not store above 25ºC.
Keep in outer carton in order to protect from light

1 ml in type 1 colourless neutral glass ampoules. Fusion sealed. Packed into cartons of 10 ampoules.

None