1. NAME OF THE MEDICINAL PRODUCT

Ephedrine Hydrochloride Injection 30mg/1ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

Ephedrine Hydrochloride 3% w/v.

Each ml of Solution for Injection contains 30 mg ephedrine hydrochloride.

For a full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Clear, colourless solution for Injection

pH = 5.00 – 7.000

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Reversal of hypotension from spinal or epidural anaesthesia.

4.2 Posology and method of administration

Posology

Adults and the elderly

Up to 30 mg in increments of 3 – 7.5 mg.

After the development of hypotension, by slow intravenous administration.

Paediatric Population

0.5 – 0.75 mg / kg body weight or 17 – 25 mg / m2 body surface.

After the development of hypotension, by slow intravenous administration.

4.3 Contraindications

Hypersensitivity to Ephedrine Hydrochloride or to any of the excipients listed in section 6.1

  • In combination with other indirect sympathomimetic agents such as phenylpropanolamine, phenylephrine, pseudoephedrine and methylphenidate.
  • In combination with alpha sympathomimetic agents.
  • In combination with non-selective Monoamine Oxidase Inhibitors (MAOI) or within 14 days of their withdrawal.

4.4 Special warnings and precautions for use

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. Angina 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 beta2 adrenoceptor 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.

Check that the solution is clear and contains no visible particles before infusion.

4.5 Interaction with other medicinal products and other forms of interaction

Contraindicated combinations:

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 (administered concomitantly or within the last 2 weeks)

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 fibres).

Noradrenergic-serotoninergic antidepressants (minalcipran, venlafaxine)

Paroxysmal hypertension with possibility of arrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibres).

Guanethidine and related products

Substantial increase in blood pressure (hyper reactivity 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 agents.

Sibutramine

Paroxysmal hypertension with possibility of arrhythmia (inhibition of adrenaline or noradrenaline entry in sympathetic fibres).

Halogenated volatile anaesthetics

Risk of perioperative hypertensive crisis and serious ventricular arrhythmias.

Combinations requiring precautions for use:

Theophylline

Concomitant 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.

Hypotensive agentsreserpine and methyldopa may reduce the vasopressor action of ephedrine.

4.6 Fertility, pregnancy and lactation

Pregnancy

Studies in animals have shown a teratogenic effect.

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.

Breast-feeding

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.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

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, weakness, insomnia, headache, sweating

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

Symptoms In the event of overdose, the occurrence of nausea, vomiting, fever, paranoid psychosis, ventricular and supraventricular arrhythmias, hypertension, respiratory depression, convulsions and coma is 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.

A benzodiazepine and/or a neuroleptic agent may be required to control CNS stimulant effects.

For severe hypertension, parenteral antihypertensive options include intravenous nitrates, calcium channel blockers, sodium nitroprusside, labetalol or phentolamine. The choice of antihypertensive drug is dependent on availability, concomitant conditions and the clinical status of the patient.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Adrenergic and Dopaminergic Agent.

Ephedrine is a 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.

5.2 Pharmacokinetic properties

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.

5.3 Preclinical safety data

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

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Water for Injections

6.2 Incompatibilities

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

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 25° C.

Keep in outer carton.

Keep out of the sight and reach of children

6.5 Nature and contents of container

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

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Ephedrine Hydrochloride Injection 30mg/1ml

(Ephedrine Hydrochloride)

PACKAGE LEAFLET: INFORMATION FOR THE USER

 (Referred to as “Ephedrine Injection” in this leaflet)

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, please ask your doctor, pharmacist or nurse.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Ephedrine Injection is and what it is used for
2. What you need to know before you are given Ephedrine Injection
3. How Ephedrine Injection is given
4. Possible side effects
5. How to store Ephedrine Injection
6. Contents of the pack and other information

  1. WHAT EPHEDRINE INJECTION IS AND WHAT IT IS USED FOR

Ephedrine belongs to a group of medicines called sympathomimetics. Sympathomimetic drugs affect the part of your nervous system that works automatically.

Ephedrine Injection is used to relieve low blood pressure during spinal or epidural anaesthesia. It raises blood pressure by temporarily reducing the blood supply to small blood vessels.

  1. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN EPHEDRINE INJECTION

You should not be given Ephedrine Injection if:

  • you are allergic to ephedrine hydrochloride or to any of the other ingredients in this medicine, (listed in section 6).
  • you are taking another indirect sympathomimetic agent such as phenylpropanolamine, phenylephrine, pseudoephedrine (medicines used to relieve blocked nose) or methylphenidate (medicine used to treat “attention deficit hyperactivity disorder (ADHD)”)
  • you are taking an alpha sympathomimetic agent (medicines used to treat low blood pressure)
  • you are taking or have taken in the last 14 days a non-selective monoamine oxidase inhibitor (medicines used to treat depression)

Warnings and precautions

Talk to your doctor before using Ephedrine Injection if:

  • you suffer from diabetes
  • you suffer from heart disease or any other heart conditions, including angina;
  • you suffer from weakness in a blood vessel wall leading to a bulge developing (aneurysm);
  • you have high blood pressure;
  • you have a narrowing and/or blockage of blood vessels (occlusive vascular disorders)
  • you have an overactive thyroid gland (hyperthyroidism);
  • you know or suspect that you suffer from glaucoma (increased pressure in your eyes) or prostatic hypertrophy (enlarged prostate gland);
  • you are about to have an operation which requires that you are given an anaesthetic;
  • you are currently taking or have taken within the last 14 days any monoamine oxidase inhibitor medicine used to treat depression.

Other medicines and Ephedrine Injection

Tell your doctor, pharmacist or nurse if you are taking, have recently taken, or might take any other medicines.

Ephedrine Injection must not be used with drugs used to treat severe depression, such as phenelzine or moclobemide, or if you are within 2 weeks of discontinuing them. These drugs are known as monoamine oxidase inhibitors (MAOIs).

Other medicines which may interact with Ephedrine Injection are:

  • methylphenidate, used to treat “attention deficit hyperactivity disorder (ADHD)”;
  • indirect stimulators of the sympathetic nervous system such as phenylpropanolamine or pseudoephedrine (medicines used in nasal decongestant), phenylephrine (a medicine used to treat hypotension);
  • direct stimulators of alpha receptors of the sympathetic nervous system (oral and/or nasal use) that are used to treat hypotension or nasal congestion, among others;
  • anaesthetics that are inhaled, such as halothane;
  • medicines used to treat depression;
  • sibutramine, a medicine used as an appetite suppressant;
  • linezolid, used to treat infections;
  • medicines used to treat asthma such as theophylline
  • corticosteroids, a type of medicine used to relieve swelling in a variety of different conditions;
  • medicines for epilepsy;
  • doxapram, medicines used to treat breathing problems;
  • oxytocin, a medicine used during labour;
  • reserpine and methyldopa and related medicines, used to treat high blood pressure;
  • guanethidine and related medicines, used to treat high blood pressure;
  • Ergot alkaloids, a type of medicines used as vasoconstrictors (narrowing blood vessels) or for their dopaminergic action (increasing the dopamine-related activity in the brain).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before being given this medicine.

Laboratory Testing

This medicinal product contains an active ingredient that can induce positive results in anti- doping controls.

  1. HOW EPHEDRINE INJECTION IS GIVEN

This medicine is an injection and will be given to you by your doctor. Your doctor will determine the dose you require.

The recommended doses are:

Adults, elderly and children over 12 years:

The usual starting dose is 3-7.5mg given slowly into a vein.

Your dose may be repeated until the maximum amount of medicine (30mg) is given.

Use in children:

The paediatric dose will be given as a slow injection into the vein of either 0.5-0.75mg per kg of body weight or 17-25mg per square metre of body surface area.

Patients with kidney or liver disease:

There are no dose adjustments recommended for patients with kidney or liver disease.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

If you think you have been given too much Ephedrine Injection

This medicine is given to you by your doctor so it is unlikely you will receive too much. Your doctor has information on how to recognise and treat an overdose. If you are concerned about your treatment, please talk to your doctor.

If you have any further questions on the use of this product, ask your doctor or nurse.

  1. POSSIBLE SIDE EFFECTS

Like all medicines Ephedrine Injection can cause side effects, although not everybody gets them.

Possible side effects include:

If you get any of the following side effects, stop taking this medicine and seek urgent medical advice straight away:

  • difficulty in breathing
  • abnormal heart rhythm;
  • palpitations, high blood pressure, fast heartbeat, or
  • pain over the heart, slow heartbeat, low blood pressure;
  • heart failure (cardiac arrest);
  • bleeding in the brain;
  • build up of a fluid within the lungs (pulmonary oedema);
  • increased pressure in the eye (glaucoma)
  • difficulty in passing urine

Other side effects that you may experience while taking this medicine are:

Common (may affect up to 1 in 10 people):

  • confusion, feeling worried, depression;
  • nervousness, irritability, restlessness, weakness, sleeping problems, headache, sweating
  • shortness of breath;
  • nausea, vomiting

Not Known (frequency cannot be estimated from the available data):

  • affects blood clotting,
  • allergy (hypersensitivity);
  • changes in your personality or the way you feel/think; fear
  • tremor; excessive saliva production
  • reduced appetite;
  • a decrease in blood potassium levels; changes in blood sugar levels

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE EPHEDRINE INJECTION

Keep out of the sight and reach of children.

You should not be given this medicine if it has passed the expiry date shown on the ampoule label and carton after EXP.

This refers to the last day of that month. Your doctor or nurse will check this.

Do not store above 25°C. Keep in the outer carton in order to protect from light. This medicine will only be used for your treatment. Your doctor will dispose of any left over medicine.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Ephedrine Injection contains

The active ingredient is Ephedrine Hydrochloride 3%w/v, equivalent to 30mg ephedrine hydrochloride in 1ml solution ampoule.

The other ingredient is water for injections.

What Ephedrine Injection looks like and contents of the pack

Ephedrine Injection is a clear, colourless solution for injection supplied to your doctor or pharmacist in a pack of 10 clear glass ampoules, each containing 1ml of medicine.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com