Sterile Dopamine 200mg/5ml Concentrate USP in Prefilled Syringes Taj Pharma

Sterile Dopamine 40 mg/1ml; 200mg/5ml Concentrate USP in Prefilled Syringes Taj Pharma

1. Name of the medicinal product

Sterile Dopamine 40mg/1ml; 200mg/5ml Concentrate USP in Prefilled Syringes Taj Pharma

2. Qualitative and quantitative composition

Each 1ml Prefilled Syringe of concentrate contains 40 mg dopamine hydrochloride.

Each 5ml Prefilled Syringe of concentrate contains 200 mg dopamine hydrochloride.

Excipient(s) with known effect

Each Prefilled Syringe contains 50 mg sodium metabisulfite.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Concentrate for solution for infusion in prefilled syringes.

Prefilled Syringe containing a clear colorless or pale-yellow solution.

4. Clinical particulars

4.1 Therapeutic indications

Dopamine is indicated in adults for the correction of haemodynamic imbalance present in:

1) Acute hypotension or shock associated with myocardial infarction, endotoxic septicaemia, trauma and renal failure.

2) As an adjunct after open heart surgery where there is persistent hypotension after correction of hypovolaemia.

3) In chronic cardiac decompensation as in congestive failure.

4.2 Posology and method of administration

Posology

Adults

Where appropriate, the circulating blood volume must be restored with a suitable plasma expander or whole blood, prior to administration of dopamine hydrochloride.

Begin infusion of dopamine hydrochloride solution at doses of 2.5 microgram/kg/min in patients who are likely to respond to modest increments of heart force and renal perfusion.

In more severe cases, administration may be initiated at a rate of 5 microgram/kg/min and increased gradually in 5- to 10 microgram/kg/min increments up to 20 to 50 microgram/kg/min as needed. If doses in excess of 50 microgram/kg/min are required, it is advisable to check urine output frequently.

Should urinary flow begin to decrease in the absence of hypotension, reduction of dopamine dosage should be considered. It has been found that more than 50% of patients have been satisfactorily maintained on doses less than 20 microgram/kg/min.

In patients who do not respond to these doses, additional increments of dopamine may be given in an effort to achieve adequate blood pressure, urine flow and perfusion generally.

Treatment of all patients requires constant evaluation of therapy in terms of blood volume, augmentation of cardiac contractility, and distribution of peripheral perfusion and urinary output.

Dosage of dopamine should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indications for decreasing or temporarily suspending the dosage.

Paediatric population

The safety and efficacy of dopamine in paediatric patients has not been established.

Elderly population

No variation in dosage is suggested for geriatric patients. However, close monitoring is suggested for blood pressure, urine flow and peripheral tissue perfusion.

Method of administration

To be administered by intravenous infusion only after dilution with the appropriate diluents. For instructions on dilution of the medicinal product before administration, see section 6.6.

A suitable metering device is required in the infusion system to control the rate of flow, and this should be adjusted to the optimum patient response and monitored constantly in the light of the individual patient’s response.

4.3 Contraindications

Dopamine is contraindicated in:

– hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

– patients with phaeochromocytoma or hyperthyroidism.

– the presence of uncorrected atrial or ventricular tachyarrhythmias or ventricular fibrillation.

– cyclopropane and halogenated hydrocarbon anaesthetics.

4.4 Special warnings and precautions for use

Warnings:

Dopamine should not be used in the presence of uncorrected tachyarrhythmias or ventricular fibrillation. Nor should it be used in patients with phaeochromocytoma or hyperthroidism. Cyclopropane and halogenated hydrocarbon anaesthetics should be avoided.

Patients who have been treated with MAO inhibitors prior to dopamine should be given reduced doses; the starting dose should be one tenth (¹/₁₀th) of the usual dose.

Excess administration of potassium-free solutions may result in significant hypokalaemia.

The intravenous administration of these solutions can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary oedema.

Precautions:

Hypovolaemia should be corrected where necessary prior to dopamine infusion. Low doses should be used in shock due to acute myocardial infarction.

If a disproportionate rise in diastolic pressure (i.e. a marked decrease in pulse pressure) is observed, the infusion rate should be decreased and the patients observed carefully for further evidence of predominant vasoconstriction activity, unless such an effect is desired.

Patients with a history of peripheral vascular disease should be closely monitored for any changes in colour or temperature of the skin of the extremities. If change of skin colour or temperature occurs and is thought to be the result of compromised circulation to the extremities, the benefits of continued dopamine infusion should be weighed against the risk of possible necrosis. These changes may be reversed by decreasing the rate or discontinuing the infusion. IV administration of phentolamine mesylate 5-10 mg may reverse the ischaemia.

Dopamine hydrochloride in 5% dextrose injection should be infused into a large vein whenever possible to prevent the possibility of infiltration of perivascular tissue adjacent to the infusion site. Extravasation may cause necrosis and sloughing of the surrounding tissue. Ischaemia can be reversed by infiltration of the affected area with 10-15 ml of saline containing 5 to 10 mg phentolamine mesylate. A syringe with a fine hypodermic needle should be used to liberally infiltrate the ischaemic area as soon as extravasation is noted.

Dopamine should be used with extreme caution in patients inhaling cyclopropane or halogenated hydrocarbon anaesthetics due to the arterial arrhythmogenic potential.

Dextrose solutions should be used with caution in patients with known subclinical or overt diabetes mellitus.

As the effect of dopamine on impaired renal and hepatic function is not known, close monitoring is advised.

Dopamine infusion should be withdrawn gradually, to avoid unnecessary hypotension.

4.5 Interaction with other medicinal products and other forms of interaction

Anaesthetics:

The myocardium is sensitised by the effect of dopamine, cyclopropane or halogenated hydrocarbon anaesthetics, and these should be avoided. This interaction applies both to pressor activity and cardiac beta adrenergic stimulation.

Alpha and Beta Blockers:

The cardiac effects of dopamine are antagonised by β-adrenergic blocking agents such as propranolol and metoprolol, and the peripheral vasoconstriction caused by high doses of dopamine is antagonised by α adrenergic blocking agents. Dopamine-induced renal and mesenteric vasodilation is not antagonised by either α or β-adrenergic blocking agents, but, in animals, is antagonised by haloperidol or other butrophenones, phenothiazines, and opiates.

Monoamine Oxidase (MAO) Inhibitors:

MAO inhibitors potentiate the effect of dopamine and its duration of action. Patients who have been treated with MAO inhibitors prior to administration of dopamine will therefore require a substantially reduced dosage. (The starting dose should be reduced to at least ¹/₁₀th of the usual dose.

Phenytoin:

Administration of IV phenytoin to patients receiving dopamine has resulted in hypotension and bradycardia; some clinicians recommend that phenytoin be used with extreme caution, if at all, in patients receiving dopamine.

Dopamine may increase the effect of diuretic agents.

The ergot alkaloids should be avoided because of the possibility of excessive vasoconstriction. Tricyclic antidepressants and guanethidine may potentiate the pressor response to dopamine.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies have shown no evidence of teratogenic effects with dopamine. However, the effect of dopamine on the human foetus is unknown. Therefore the drug should be used in pregnant women only when the expected benefits outweigh the potential risk to the foetus.

Breast-feeding

It is not known if dopamine is excreted in breast milk, nor is the effect on the infant known.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Adverse reactions to dopamine are related to its pharmacological action.

Frequencies are defined as: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000)

Serious or Life-threatening Reactions:

Gangrene of the feet has occurred following doses of 10-14 microgram/kg/min and higher in a few patients with pre-existing vascular disease.

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

Excessive elevation of blood pressure and vasoconstriction can occur due to the alpha adrenergic actions of dopamine, especially in patients with a history of occlusive vascular disease. If desired, this condition can be rapidly reversed by dose reduction or discontinuing the infusion, since dopamine has a half-life of less than 2 minutes in the body.

Should these measures fail, an infusion of an alpha adrenergic blocking agent, e.g., phentolamine mesylate should be considered.

Dopamine at the infusion site can cause local vasoconstriction hence the desirability of infusing into a large vein. The resulting ischaemia can be reversed by infiltration of the affected area with 10-15 ml of saline containing 5 mg to 10 mg phentolamine mesylate. A syringe with a fine hypodermic needle should be used to liberally infiltrate the ischaemic area as soon as extravasation is noted.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: adrenergic and dopaminergic agents, ATC code: C01CA04

Mechanism of action

Dopamine stimulates adrenergic receptors of the sympathetic nervous system. The drug has principally a direct stimulatory effect on β₁-adrenergic receptors, but also appears to have an indirect effect by releasing norepinephrine from its storage sites. Dopamine also appears to act on specific dopaminergic receptors in the renal, mesenteric, coronary, and intracerebral vascular beds to cause vasodilation. The drug has little or no effect on β₂-adrenergic receptors.

Pharmacodynamic effects

In IV doses of 0.5-2 microgram/kg per minute, the drug acts predominantly on dopaminergic receptors; in IV doses of 2-10 microgram/kg per minute, the drug also stimulates β₁-adrenergic receptors. In higher therapeutic doses, α-adrenergic receptors are stimulated and the net effect of the drug is the result of α-adrenergic, β₁-adrenergic, and dopaminergic stimulation. The main effects of dopamine depend on the dose administered. In low doses, cardiac stimulation and renal vascular dilation occur and in larger doses vasoconstriction occurs. It is believed that α-adrenergic effects result from inhibition of the production of cyclic adenosine -31, 51-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas β-adrenergic effects result from stimulation of adenyl cyclase activity.

5.2 Pharmacokinetic properties

Absorption:

Orally administered dopamine is rapidly metabolised in the G.I. tract. Following IV administration, the onset of action of dopamine occurs within 5 minutes, and the drug has duration of action of less than 10 minutes.

Distribution:

The drug is widely distributed in the body but does not cross the blood-brain barrier to a substantial extent. It is not known if dopamine crosses the placenta.

Elimination:

Dopamine has a plasma half-life of about 2 minutes. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-0-methyltransferase to the inactive compounds homovanillic acid (HVA) and 3, 4-dihydroxyphenylacetic acid. In patients receiving MAO inhibitors, the duration of action of dopamine may be as long as 1 hour. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals.

Dopamine is excreted in urine principally as HVA and its sulfate and glucuronide conjugates and as 3, 4-dihydroxyphenylacetic acid. A very small fraction of a dose is excreted unchanged. Following administration of radio labelled dopamine, approximately 80% of the radioactivity reportedly is excreted in urine within 24 hours.

5.3 Preclinical safety data

There is 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 metabisulfite, Water for injections

6.2 Incompatibilities

Dopamine Sterile Concentrate should not be added to any alkaline intravenous solutions, i.e. sodium bicarbonate. Any solution which exhibits physical or chemical incompatibility through a colour change or precipitate should not be administered.

It is suggested that admixtures containing gentamicin sulfate, cephalothin sodium, cephalothin sodium neutral or oxacillin sodium should be avoided unless all other viable alternatives have been exhausted.

Admixtures of ampicillin and dopamine in 5% glucose solution are alkaline and incompatible and result in decomposition of both drugs. They should not be admixed.

Admixtures of dopamine, amphotericin B in 5% glucose solution are incompatible as a precipitate form immediately on mixing.

6.3 Shelf life

As packaged for sale: 3 years.

Following dilution in the recommended diluents (see section 6.6), chemical and physical in-use stability has been demonstrated for 48 hours at a temperature not above 25°C.

However, from a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to used are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Do not store above 30°C. Keep container in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Clear, type I, glass Prefilled Syringe.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

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

Do not use if the solution is discoloured.

Preparation of Infusion Solutions

Dilution:

Aseptically transfer Dopamine Sterile Concentrate into the IV solution as shown in the following table:-

Dopamine hydrochloride can be diluted with:-

Sodium chloride (0.9%) intravenous infusion

Dextrose (5%), sodium chloride (0.45%) solution

Sodium lactate intravenous infusion, compound (Hartmann’s Solution for Injection)

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

Sterile Dopamine 40 mg/1ml; 200mg/5ml Concentrate USP in Prefilled Syringes 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.

 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 Dopamine Sterile Concentrate is and what it is used for
2. What you need to know before you use Dopamine Sterile Concentrate
3. How to use Dopamine Sterile Concentrate
4. Possible side effects
5. How to store Dopamine Sterile Concentrate
6. Contents of the pack and other information
7. What Dopamine Sterile Concentrate is and what it is used for

Dopamine is a medicine that stimulates the heart and has effects on the blood vessels.

Dopamine Sterile Concentrate can be used in adults:

 to treat low blood pressure or shock (reduction of blood flow through the body

tissues) after a heart attack, blood poisoning, trauma (injury) or kidney failure

 in combination with other treatments where low blood pressure occurs after open heart surgery

 in congestive heart failure (heart failure due to a build up of fluid/blood)

2. What you need to know before you use Dopamine Sterile Concentrate

Do not use Dopamine Sterile Concentrate

 if you are allergic to dopamine hydrochloride or any of the other ingredients of this medicine (listed in section 6)

 if you have a tumour that causes an increase in blood pressure

 if you have an overactive thyroid gland

 if you have irregular or rapid heartbeats

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Dopamine Sterile Concentrate

 if you have diabetes

 if you have kidney or liver problems

 if you have a history of blood circulation problems (you will be monitored for any

changes in colour or temperature of your fingers or toes)

If possible, tell your doctor if any of the above applies to you before this medicine is used.

Other medicines and Dopamine Sterile Concentrate

Tell your doctor if you have been taking, have recently taken or might take any other medicine, for example:

 anaesthetics (dopamine should not be used with cyclopropane and halogenated

hydrocarbon anaesthetics)

 alpha- and beta-blockers, e.g. propranolol (medicines which are often used for

treating blood pressure and heart disorders)

 monoamine oxidase inhibitors (anti-depressant medicines)

 phenytoin (a medicine used to treat epilepsy)

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 or pharmacist for advice before taking this medicine.

Driving and using machines

Do not drive or use machines if you experience any side effects (e.g. dizziness or difficulty seeing in bright light) which may lessen your ability to do so.

Dopamine Sterile Concentrate contains sodium

This medicine contains sodium metabisulfite which, rarely, may cause severe hypersensitivity (severe allergy) reactions and bronchospasm (breathing difficulties).

This medicine contains less than 1 mmol (23 mg) sodium per ampoule, i.e. essentially ‘sodium free’.

3. How to use Dopamine Sterile Concentrate

This medicine will be diluted before it is given to you. It will be given as an infusion (drip) into a vein.

Dose

If your blood volume is low, you may be given a transfusion of blood or a plasma expander before dopamine is given.

Your doctor will work out the recommended dose of dopamine for you and how often it must be given. The dose will depend upon your medical condition and your size.

The rate of administration will be carefully controlled and adjusted according to your response. During treatment your heart rate, blood pressure and urine output will be measured to check how you are responding.

If you use more Dopamine Sterile Concentrate than you should

This medicine will be given to you in a hospital, under the supervision of a doctor. It is

unlikely that you will be given too much or too little, however, tell your doctor or nurse if you have any concerns.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If any of the following happen, tell your doctor immediately:

Uncommon: may affect up to 1 in 100 people:

 severe allergic reaction – you may experience a sudden itchy rash (hives), swelling of

the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint

 pain or poor circulation in your fingers or toes (you may notice a change in skin colour)

 pain or swelling at the injection site during or immediately after the injection

 severe palpitations

These are serious side effects. You may need urgent medical attention.

If any of the following happen, tell your doctor as soon as possible:

Common: may affect up to 1 in 10 people:

 irregular, rapid or slow heart beats

 chest pain

 shortness of breath

 low blood pressure (you may feel dizzy or faint, particularly when standing up or getting out of bed)

 feeling or being sick

 headache

 dilation of the pupil of the eye (mydriasis) which may cause difficulty seeing in bright light

 goose pimples

Dopamine may lead to changes in your blood chemistry. Your doctor may take blood samples to monitor for these.

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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Dopamine Sterile Concentrate

Keep this medicine out of the sight and reach of children.

Expiry date

This medicine must not be used after the expiry date which is stated on the ampoule and carton after ‘EXP’. Where only a month and year is stated, the expiry date refers to the last day of that month.

Storage conditions

Do not store above 30°C. Keep the Prefilled Syringe in the outer carton in order to protect from light.

Prepared infusions should be used immediately, however, if this is not possible they can be stored for up to 48 hours provided they have been prepared in a way to exclude microbial contamination.

Do not use this medicine if you notice an opaque, cloudy or discoloured solution.

6. Contents of the pack and other information

What Dopamine Sterile Concentrate contains

The active substance is dopamine hydrochloride. Each millilitre (ml) of concentrate contains

40 milligrams (mg) of dopamine hydrochloride.

The other ingredients are sodium metabisulfite and water for injections (see section 2

Dopamine Sterile Concentrate contains sodium).

What Dopamine Sterile Concentrate looks like and contents of the pack

Dopamine Sterile Concentrate is a clear, colourless or pale-yellow concentrate for solution for infusion which comes in glass containers called Prefilled Syringe.

It may be supplied in packs containing:

 5 x 200 mg/5 ml Prefilled Syringe

 50 x 200 mg/5 ml Prefilled Syringe

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