Adrenaline 1mg/1ml (1:1000) & 1mg/10ml (1:10,000), solution for injection in pre-filled syringe Taj Pharma

1.Name of the medicinal product

Adrenaline 1mg/1ml (1:1000) & 1mg/10 ml (1:10,000), solution for injection in pre-filled syringe Taj Pharma

2. Qualitative and quantitative composition

a) Adrenaline 1mg/1ml (1:1000), solution for injection in pre-filled syringe

Each 1ml of solution contains

Adrenaline acid tartrate Equivalent to 1mg of adrenaline

Excipient with known effect:

Sodium metabisulphite

b) Adrenaline 1mg/10 ml (1:10,000), solution for injection in pre-filled syringe

Each ml of solution for injection contains
0.1 mg of adrenaline (as adrenaline tartrate)

Each 10 ml pre-filled syringe contains
1 mg adrenaline (as adrenaline tartrate)

Excipient with known effect: sodium

Each ml of solution for injection contains 3.54 mg equivalent to 0.154 mmol of sodium.

Each 10 ml pre-filled syringe contains

35.4 mg equivalent to 1.54 mmol of sodium.

For a full list of excipients, see section 6.1.

3.Pharmaceutical form

Solution for injection in pre-filled syringe

Clear and colourless solution in a 10 ml pre-filled syringe

pH = 3.0 to 3.4

Osmolarity: 270 – 300 mOsm/l

4.Clinical particulars

4.1 Therapeutic indications

Cardiopulmonary resuscitation

Acute anaphylaxis in adults

4.2 Posology and method of administration

Intravenous adrenaline should only be administered by those experienced in the use and titration of vasopressors in their normal clinical practice.

Cardiopulmonary resuscitation:

10 ml of the 1:10,000 solution (1 mg) by the intravenous or intraosseous route, repeated every 3-5 minutes until return of spontaneous circulation.

Endotracheal use should only be considered as a last resort if no other route of administration is accessible, at a dose of 20 to 25 ml of the 1:10,000 solution (2 to 2.5 mg).

In cardiac arrest following cardiac surgery, Adrenaline should be administered intravenously in doses of 0.5 ml or 1 ml of 1:10,000 solution (50 or 100 micrograms) very cautiously and titrated to effect.

Acute anaphylaxis

Titrate using intravenous boluses of 0.5 ml 1:10,000 solution (0.05 mg) according to response.

Adrenaline 1 mg/10 ml (1:10,000) solution for injection in pre-filled syringe is not recommended for intramuscular use in acute anaphylaxis. For intramuscular administration, a 1 mg/ml (1:1000) solution should be used.

Paediatric Population:

Paediatric population

The following doses of adrenaline 1/1,000 are recommended:

 

AgeDose
Over 12 years0.5 mg IM (0.5ml 1:1000 solution)
6 – 12 years0.3 mg IM (0.3ml 1:1000 solution)
6 months – 6 years0.15 mg IM (0.15ml 1:1000 solution)
Under 6 months0.01mg/kg IM (0.01ml/kg 1:1000 solution)

If necessary, these doses may be repeated at 5-15 -minute intervals according to blood pressure, pulse and respiratory function.

Elderly

The dosage is the same as for younger adults but particular caution is required when administering adrenaline to elderly patients (see section 4.4).

Renal impairment

Adrenaline should be used with caution in patients with severe renal impairment (see section 4.4).

Method of Administration

Adrenaline Injection BP. 1/1000 (1mg/ml) may be administered undiluted by S.C. or IM injection. In the shocked patient, the intramuscular route is recommended as absorption from the intramuscular site is more rapid and reliable than from the subcutaneous site.

This medicinal product is not suitable for delivering a dose of less than 0.5 ml and should therefore not be used by the intravenous or intraosseous route, in neonates and infants with body weight less than 5 kg.

Cardiac arrest in children:

Intravenous or intraosseous route (above 5 kg only): 0.1 ml/kg of 1:10,000 solution (10 micrograms/kg) to a maximum single dose of 10 ml of 1:10,000 solution (1 mg), repeated every 3-5 minutes until return of spontaneous circulation.

Endotracheal use (any body weight) should only be considered as a last resort if no other route of administration is accessible, at a dose of 1 ml/kg of 1:10,000 solution (100 micrograms/kg) to a maximum of single dose of 25 ml of 1:10,000 solution (2.5 mg).

4.3 Contraindications

Patients with known hypersensitivity to an excipient, where an alternative presentation of adrenaline or alternative vasopressor is available.

4.4 Special warnings and precautions for use

Adrenaline 1 mg/10 ml (1:10,000), solution for injection in pre-filled syringe is indicated for emergency treatment. Medical supervision is necessary after administration.

For intramuscular administration, a 1 mg/ml (1:1000) solution should be used.

In the treatment of anaphylaxis and in other patients with a spontaneous circulation, intravenous adrenaline can cause life-threatening hypertension, tachycardia, arrhythmias and myocardial ischaemia.

Intravenous adrenaline should only be used by those experienced in the use and titration of vasopressors in their normal clinical practice. Patients who are given IV adrenaline require continuous monitoring of ECG, pulse oximetry and frequent blood pressure measurements as a minimum.

The risk of toxicity is increased if the following conditions are pre-existing

  • Hyperthyroidism
  • Hypertension
  • Structural cardiac disease, cardiac arrhythmias, severe obstructive cardiomyopathy,
  • Coronary insufficiency
  • Phaeochromocytoma,
  • Hypokalaemia
  • Hypercalcaemia
  • Severe renal impairment
  • Cerebrovascular disease, organic brain damage or arteriosclerosis
  • Patients taking Monoamine oxidase (MAO) inhibitors (see section 4.5)
  • Patients taking concomitant medication which results in additive effects, or sensitizes the myocardium to the actions of sympathomimetic agents (see section 4.5)

Prolonged use of adrenaline can result in severe metabolic acidosis because of elevated blood concentrations of lactic acid.

Adrenaline may increase intra-ocular pressure in patients with narrow angle glaucoma.

Adrenaline should be used with caution in patients with prostatic hyperplasia with urinary retention.

Adrenaline may cause or exacerbate hyperglycaemia, blood glucose should be monitored, particularly in diabetic patients.

Adrenaline should be used with caution in elderly patients.

Adrenaline should not be used during the second stage of labour (See Section 4.6).

This medicinal product contains 35.4 mg sodium per syringe equivalent to 1.77% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interaction with other medicinal products and other forms of interaction

Volatile halogen anaesthetics: severe ventricular arrhythmia (increase in cardiac excitability).

Imipramine antidepressants: paroxysmal hypertension with the possibility of arrhythmia (inhibition of the entry of sympathomimetics into sympathetic fibres).

Serotoninergic-adrenergic antidepressants: paroxysmal hypertension with the possibility of arrhythmia (inhibition of the entry of sympathomimetics into sympathetic fibres).

Sympathomimetic agents: concomitant administration of other sympathomimetic agents may increase toxicity due to possible additive effects.

Non-selective MAO inhibitors: increased pressor action of adrenaline, usually moderate.

Selective MAO-A inhibitors, Linezolid (by extrapolation from non-selective MAO inhibitors): Risk of aggravation of pressor action.

Alpha-adrenergic blocking agents: Alpha-blockers antagonise the vasoconstriction and hypertension effects of adrenaline, increasing the risk of hypotension and tachycardia.

Beta-adrenergic blocking agents: Severe hypertension and reflex bradycardia may occur with non-cardioselective beta-blocking agents. Beta-blockers, especially non-cardioselective agents, also antagonise the cardiac and bronchodilator effects of adrenaline.

Insulin or oral hypoglycaemic agents: Adrenaline-induced hyperglycaemia may lead to loss of blood-sugar control in diabetic patients treated with insulin or oral hypoglycaemic agents.

4.6 Fertility, pregnancy and lactation

Pregnancy:

Teratogenic effect has been demonstrated in animal experiments.

Adrenaline should only be used during pregnancy if the potential benefits outweigh the possible risks to the foetus. If used during pregnancy, adrenaline may cause anoxia to the foetus.

Adrenaline usually inhibits spontaneous or oxytocin induced contractions of the uterus and may delay the second stage of labour. In dosage sufficient to reduce uterine contractions, adrenaline may cause a prolonged period of uterine atony with haemorrhage. For this reason parenteral adrenaline should not be used during the second stage of labour.

Lactation:

Adrenaline is distributed into breast milk. Breast-feeding should be avoided by mothers receiving adrenaline.

Fertility

No information available concerning impact of adrenaline on fertility.

4.7 Effects on ability to drive and use machines

Not applicable in normal conditions of use.

4.8 Undesirable effects

Metabolism and nutrition disorders:

Frequency not known: hyperglycaemia, hypokalaemia, metabolic acidosis.

Psychiatric disorders:

Frequency not known: anxiety, nervousness, fear, hallucinations.

Nervous system disorders:

Frequency not known: headache, tremors, dizziness, syncope.

Eye disorders:

Frequency not known: mydriasis.

Cardiac disorders:

Frequency not known: palpitations, tachycardia. Takotsubo cardiomyopathy (stress cardiomyopathy) may occur. In high dosage or for patients sensitive to adrenaline: cardiac dysrhythmia (sinus tachycardia, ventricular fibrillation/cardiac arrest), acute angina attacks, and risk of acute myocardial infarction.

Vascular disorders:

Frequency not known: pallor, coldness of the extremities. In high dosage or for patients sensitive to adrenaline: hypertension (with risk of cerebral haemorrhage), vasoconstriction (for example cutaneous, in the extremities or kidneys).

Respiratory, thoracic and mediastinal disorders:

Frequency not known: dyspnoea.

Gastrointestinal disorders:

Frequency not known: nausea, vomiting.

General disorders and administration site conditions:

Frequency not known: sweating, weakness

Repeated local injections may produce necrosis at sites of injection as a result of vascular constriction.

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.

4.9 Overdose

Over dosage or inadvertent intravenous administration of adrenaline may produce severe hypertension. Cerebral, cardiac or vascular accidents which could be potentially fatal may occur as a result (cerebral haemorrhage, dysrhythmias such as transient bradycardia followed by tachycardia that may result in arrhythmia, myocardial necrosis, acute pulmonary oedema, renal insufficiency).

The effects of adrenaline may be counteracted, depending on the condition of the patient, by administration of quick-acting vasodilators, of quick-acting alpha-adrenoreceptor blocking agents (e.g. phentolamine), or beta-adrenoreceptor blocking agents (e.g. propanolol). However, due to the short half-life of adrenaline, treatment with these medicines may not be necessary. In case of prolonged hypotensive reaction, administration of another vasopressive agent such as noradrenaline may be required.

5.Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: adrenergic and dopaminergic agents, adrenaline

Adrenaline is a direct acting sympathomimetic agent, which exerts effects on both α and β adrenoceptors. It has more pronounced effects on β than on α adrenoceptors, although α effects prevail at high doses.

The effects of adrenaline include increased rate and force of cardiac contraction, cutaneous vasoconstriction and broncho-dilatation. With higher doses, stimulation of peripheral α receptors results in an increase in peripheral resistance and in blood pressure.

5.2 Pharmacokinetic properties

Pharmacologically active concentrations of adrenaline are not achieved following oral administration as it is rapidly oxidised and conjugated in the gastrointestinal mucosa and the liver. Absorption from subcutaneous tissue is slow due to local vasoconstriction; effects are produced within 5 minutes. Absorption is more rapid after intramuscular injection than after subcutaneous injection.

Adrenaline is rapidly distributed into the heart, spleen, several glandular tissues and adrenergic nerves. It readily crosses the placenta and is approximately 50% bound to plasma proteins.

Adrenaline is rapidly inactivated in the body, mostly in the liver by the enzymes catechol-O- methyltransferase (COMT) and monoamine oxidase (MAO). Most of a dose of adrenaline is excreted as metabolites in urine.

After intravenous administration, the plasma half-life is about 2-3 minutes.

5.3 Preclinical safety data

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

6.Pharmaceutical particulars

6.1 List of excipients

Sodium chloride

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

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

6.3 Shelf life

Unopened: 24 months.

6.4 Special precautions for storage

Do not store above 25°C.

Do not freeze.

Store in the aluminium pouch in order to protect from light and oxygen.

6.5 Nature and contents of container

10 ml solution in a polypropylene pre-filled syringe without a needle, individually packaged in a transparent blister and overwrapped in an aluminium pouch containing an oxygen absorbing sachet. Available in a box of 1 or 10.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The aluminium pouch and syringe blister should only be opened immediately prior administration.

After opening the pouch the product must be used immediately.

The external surface of the syringe and its content are sterile if the blister is unopened and undamaged.

Strictly respect the protocol below

The pre-filled syringe is for single patient use only. Discard the syringe after use. Do not reuse.

The product should be inspected visually for particles and discolouration prior to administration. Only clear colourless solution free from particles or precipitates should be used.

The product should not be used if the pouch or the blister has been opened or if the tamper evident seal on the syringe (plastic film at the basis of the end cap) is broken.

1) Tear open the aluminium pouch by hand only using the indent(s) Do not use sharp instruments to open the pouch.

2) Withdraw the pre-filled syringe from the sterile blister.

3) Push on the plunger to free the bung. The sterilisation process may have caused adhesion of the bung to the body of the syringe.

4) Twist off the end cap to break the seals. Do not touch the exposed luer connection in order to avoid contamination.

5) Check the syringe seal tip has been completely removed.

If not, replace the cap and twist again.

6) Expel the air by gently pushing the plunger.

7) Connect syringe to vascular access device or to needle. Push the plunger to inject the required volume.

Any unused 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

Adrenaline 1mg/1ml (1:1000) & 1mg/10 ml (1:10,000), solution for injection in pre-filled syringe Taj Pharma

Read all of this leaflet carefully before you start using 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, ask your doctor, pharmacist or nurse.

– This medicine has been prescribed for you only. Do not pass it on to others. It may harm

them, even if their signs of illness are the same as yours.

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

1. What Adrenaline injection is and what it is used for

Adrenaline Injection belongs to a group of medicines called adrenergic and dopaminergic agents.

This medicine is used for:

– Treatment of cardiac arrest (unexpected loss of heart function, breathing and consciousness),

– Treatment of acute anaphylaxis in adults (serious shock or collapse produced by a severe

allergic reaction).

2. What you need to know before you are given Adrenaline injection

You must not be given Adrenaline injection

If you are allergic (hypersensitive) to any ingredients of this medicine (listed in section 6) where an alternative presentation of Adrenaline or alternative vasopressor is available.

Warnings and precautions

Adrenaline injection is indicated for emergency treatment. Continuous medical supervision is necessary after administration.

Precautions for use

The risk of side effects is increased if you:

– have medical history of hyperthyroidism (disease of the thyroid gland),

– have severe renal insufficiency, suffer from hypercalcaemia (increase of calcium concentration in the blood),

– suffer from hypokalaemia (decrease of potassium concentration in the blood),

– have diabetes mellitus,

– have cardiac disease or arterial hypertension,

– have brain damage or hardening of the arteries in the brain,

– have glaucoma (increased pressure in the eye),

– have prostate disorders,

– are elderly,

– are pregnant.

Other medicines and Adrenaline injection

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

Medicines that may interact with Adrenaline injection include:

– Volatile halogen anaesthetics (gas used during anaesthesia),

– Certain antidepressants,

– Drugs to treat high blood pressure, heart conditions,

– Drugs to treat diabetes.

Pregnancy and breast-feeding

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 you are given this medicine.

Driving and using machines

Having Adrenaline injection does not affect your ability to drive or use machines.

Adrenaline injection contains sodium

This medicinal product contains 35.4 mg sodium (main component of cooking/table salt) in each syringe. This is equivalent to 1.77% of the recommended maximum daily dietary intake of sodium for an adult.

3. How Adrenaline injection is given

Adrenaline injection is administered to you by your doctor, nurse or paramedic. They will have to decide the correct amount for you and when and how this should be given.

In case of life threatening allergic reactions (acute anaphylaxis):

Adults will be given a dose of 0.05 mg (0.5 ml of Adrenaline 1:10,000 solution) repeated as necessary until the desired response is achieved.

In case of cardiac arrest:

Adults: 1 mg (10 ml of Adrenaline 1:10,000 solution) is given into a vein or into a bone every

3-5 minutes until the heart starts to work.

Children above 5 kg: 10 micrograms/kg (0.1 ml/kg of Adrenaline 1:10,000 solution) is given into a vein or into a bone every 3-5 minutes every 3-5 minutes until the heart starts to work.

This medicinal product is not suitable for delivering a dose of less than 0,5 ml and should therefore not be used in neonates and infants for which the body weight is less than 5 kg.

4. Possible side effects

Like all medicines this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported:

– anxiety,

– dyspnoea (difficulty in breathing),

– nervousness,

– fear,

– sweating,

– palpitations (irregular or faster heart beat),

– tachycardia (increased heart rate),

– pallor,

– tremors,

– weakness,

– dizziness,

– headache,

– nausea,

– vomiting,

– coldness of the extremities,

– hallucinations,

– syncopes,

– hyperglycaemia (high blood sugar levels),

– hypokalaemia (low potassium levels in the blood),

– metabolic acidosis (increased acidity in the blood),

– mydriasis (dilatation of the pupil).

In high dosages or for patients sensitive to adrenaline, side effects are:

– cardiac dysrhythmia (irregular heartbeats/cardiac arrest),

– hypertension (with risk of cerebral haemorrhage),

– vasoconstriction (narrowing of the blood vessels for example cutaneous, in the extremities or kidneys),

– acute angina attacks,

– risk of acute myocardial infarction.

Repeated local injections may produce necrosis (tissue damage) at the site of injection as a result of vascular constriction (blood vessel constriction).

In all cases, after administration of Adrenaline injection medical supervision is necessary.

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. You can also report side effects directly.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Adrenaline injection

Keep out of the sight and reach of children.

You should not be given this medicine after the expiry date which is stated on the label. The expiry date refers to the last day of the month. Your doctor or nurse will check this.

Store in the aluminium pouch in order to protect from light and oxygen.

Do not store above 25°C.

Do not open the aluminium pouch until use.

After opening the pouch the product must be used immediately.

Do not freeze.

Do not use sharp instruments to open the pouch.

You should not be given Adrenaline injection if it has been partly used or shows signs of

visible damage.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist

how to throw away medicines you no longer use. These measures will help protect the environment.

6. Content of the pack and other information

What Adrenaline injection contains

The active ingredient is adrenaline tartrate:

Each ml of solution for injection contains 0.1 mg of adrenaline (as adrenaline tartrate).

Each 10 ml pre-filled syringe contains 1 mg adrenaline (as adrenaline tartrate).

The other ingredients are sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

What Adrenaline injection looks like and contents of the pack

Adrenaline injection is a clear, colourless solution in a 10 ml polypropylene pre-filled syringe, individually packed in a transparent blister and overwrapped in an aluminium pouch.

The pre-filled syringes are available in boxes of 1 and 10 syringes.

Not all pack sizes may be marketed.

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