1. Name of the medicinal product

Dopamine Hydrochloride injection USP 200mg/5ml Taj pharma.
Dopamine Hydrochloride injection USP 400mg/10ml Taj pharma.

  1. Qualitative and quantitative composition

a)Dopamine Hydrochloride injection USP 200mg/5ml.
Each ml contains:
Dopamine Hydrochloride 40mg (equivalent to 32.3mg Dopamine Base),
Sodium metabisulfite                       9mg
Citric acid                                        10mg
Sodium Citrate                                   5mg
Water for Injection                            q.s

b)Dopamine Hydrochloride injection USP 400mg/10ml.
Each ml contains:
Dopamine Hydrochloride 40mg (equivalent to 32.3mg Dopamine Base),
Sodium metabisulfite                         9mg
Citric acid                                        10mg
Sodium Citrate                                   5mg
Water for Injection                            q.s

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Concentrate for solution for infusion

Clear, colourless or pale yellow solution

  1. Clinical particulars

4.1 Therapeutic indications

For the correction of haemodynamic imbalances in low-perfusion circulatory insufficiency associated with myocardial infarction, trauma, septicaemia, cardiac failure and open heart surgery.

4.2 Posology and method of administration

Posology

Adults: Use as large a vein as possible for infusion. The initial rate of infusion is 2 to 5 micrograms per kilogram bodyweight per minute and this may be increased gradually by increments of 5 to 10 micrograms/kg/minute until the optimum dose for the individual is achieved. Up to 50 micrograms/kg/minute may be required, and even higher doses have been used.

Paediatric population

The safety and efficacy of dopamine hydrochloride therapy in children have not been established.

Method of administration:

For intravenous use

The solution must be diluted before administration.

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 should not be used in patients with –

  • Hypersensitivity to dopamine or any of the excipients listed in section 6.1.
  • Phaeochromocytoma or hyperthyroidism

Dopamine should not be used in the presence of uncorrected atrial or ventricular tachyarrhythmias or ventricular fibrillation.

Cyclopropane and halogenated hydrocarbon anaesthetics should be avoided.

4.4 Special warnings and precautions for use

Warnings:

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% Glucose 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 of dopamine hydrochloride during infusion may cause ischaemic necrosis and sloughing of 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.

Administration of dopamine hydrochloride should always be under the direct supervision of a physician to whom facilities are available for monitoring cardiovascular and renal indices, including blood volume, cardiac output, blood pressure, electrocardiography and urine flow.

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

When dopamine is used in patients with a history of occlusive vascular disease, particular attention should be paid to the status of blood circulation in the extremities.

The occurrence of undesirable increases in blood pressure or vasoconstriction or decrease in urinary output requires a reduction in dosage of dopamine hydrochloride.

The routine use of low-dose dopamine hydrochloride in critically ill patients to prevent or treat acute renal failure is not recommended because this may cause adverse effects which could further compromise such patients.

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.

Dopamine Hydrochloride 40mg/ml Concentrate for Solution for Infusion contains an antioxidant, sodium metabisulfite, a sulphite that may cause allergic-type reactions including bronchospasm, anaphylaxis and life- threatening episodes in certain susceptible individuals. The prevalence of sulphite-sensitivity in the general population is unknown and is probably low.

Sulphite-sensitivity is seen more frequently in persons with a history of asthma or atopic allergy.

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

  1. i) 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.

  1. ii) Alpha and Beta Blockers:

The cardiac effects of dopamine are antagonised by β -adrenergic blocking agents such as propanolol 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.

iii) 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).

  1. iv) 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.

Lactation

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

Fertility

No data available.

4.7 Effects on ability to drive and use machines

Not applicable in view of the indications for use and the short half-life of the drug.

4.8 Undesirable effects

Adverse reactions to dopamine are related to its pharmacological action.

The following adverse reactions are classified by system organ class and ranked under heading of frequency: Common (>1/100 to <1/10; Uncommon (≥1/1,000 to <1/100).

System Organ Class Frequency Adverse reactions
Nervous system disorders Common Headache
Uncommon Piloerection
Eye disorders Uncommon Mydriasis
Cardiac disorders Common Ectopic heart beats, tachycardia, anginal pain, palpitation, hypotension, vasoconstriction.
Uncommon Aberrant conduction, bradycardia, widened QRS complex, hypertension, gangrene, fatal ventricular arrhythmias have been reported on rare occasions.
Respiratory, thoracic and mediastinal disorders Common Dyspnoea
Gastrointestinal disorders Common Nausea, vomiting
Renal and urinary disorders Uncommon Azotaemia

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.

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.

Accidental Overdosage:

Accidental overdosage as evidenced by excessive blood pressure elevation can be controlled by dose reduction or discontinuing the dopamine infusion for a short period, since the duration of action of dopamine is short.

Should these measures fail, an infusion of phentolamine mesylate should be considered.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: adrenergic and dopaminergic agents

Dopamine (3,4-dihydroxyphenylethylamine) is the third naturally occurring catecholamine and is a metabolic precursor of noradrenaline and adrenaline. Dopamine is used therapeutically as the hydrochloride and its main effects are seen in the cardiovascular system and the kidneys.

Mechanism of action

Heart

Dopamine exerts positive inotropic and chronotropic effects on the myocardium, acting as an agonist at beta-adrenergic receptors. In addition to its direct action on beta-adrenergic receptors, dopamine acts indirectly by releasing noradrenaline from sympathetic storage sites.

Blood Vessels

Depending on the vascular bed being studied and the dose administered, Dopamine can cause relaxation or contraction of vascular smooth muscle.

Pharmacodynamic effects

Dopamine Receptors

Unlike other endogenous catecholamines or sympathomimetic amines, Dopamine caused vasodilation in renal, coronary, mesenteric and intracerebral arterial vascular beds in anaesthetised dogs. This vasodilator effect is not antagonised by beta-adrenergic blockers, atropine or antihistamines. However, butyrophenones, phenothiazines, apomorphine and bulbocapnine selectively attenuate dopamine-induced vasodilatation, thus suggesting the existence of specific dopamine vascular receptors similar to those in the basal ganglia and other areas in the central nervous system.

Alpha-adrenergic Receptors

Dose response studies indicate that with a sufficiently large dose, the vasoconstrictor effect of dopamine predominates over its vasodilator effect. This dopamine-induced vasoconstrictor effect is antagonised by alpha-adrenoreceptor blocking agents such as phentolamine and phenoxybenzamine, indicating that vasoconstriction results from the action of dopamine on alpha-adrenergic receptors.

Kidney

Intravenous infusions of dopamine (2.6 to 7.1μg/kg/min) to seven normal subjects increased estimated average renal plasma flow from 507 to 798ml/min, inulin clearance from 109 to 136ml/min and average sodium excretion from 171 to 571μEq./min. Although the diuretic and natriuretic effects of dopamine may result from vasodilatation in renal vascular bed (vide supra), disassociation between natriuresis and increments in renal blood flow has been observed, suggesting that other mechanisms such as redistribution of intrarenal blood flow may be involved.

5.2 Pharmacokinetic properties

Dopamine is inactive when taken orally and its vasoconstrictor properties preclude its administration by subcutaneous or intramuscular injection. Dopamine hydrochloride is administered by intravenous infusion

Biotransformation and Elimination

Dopamine is a metabolic precursor of noradrenaline and, whereas a proportion is excreted as the metabolic products of noradrenaline.

The plasma half-life of dopamine is approximately two 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 which are rapidly excreted in the urine. 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

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

  1. Pharmaceutical particulars

6.1 List of excipients

Sodium Metabisulfite

Water for Injections

6.2 Incompatibilities

Iron salts, alkalis or oxidising agents.

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

6.3 Shelf life

36 months

For single use only If only part of an ampoule is used, discard the remaining solution.

Diluted solutions should be used immediately. Discard any remaining solution

6.4 Special precautions for storage

Do not store above 25°C.

Keep the container in the outer carton in order to protect from light.

6.5 Nature and contents of container

5 ml clear glass one point-cut (OPC) ampoules, glass Type I Ph Eur. borosilicate glass ampoules packed in cardboard cartons to contain 10 x 5ml ampoules.

6.6 Special precautions for disposal and other handling

This solution must be diluted before use.

Do not dilute with alkaline solution.

Inspect the solution before use. Do not use the injection if it is darker than slightly yellow or discoloured in any other way or if it contains particulate matter.

Alkaline solutions such as 5% sodium bicarbonate should NOT be added to dopamine hydrochloride because the drug will be inactivated. The usual dilution is 1,600 micrograms per ml and this may be achieved by transfer, aseptically of 800mg of dopamine hydrochloride (20 ml of the Dopamine Hydrochloride 40mg/ml Concentrate for Solution for Infusion) to 480 ml one of the following sterile I.V. solutions to achieve 1,600 microgram per ml concentration:

Sodium Chloride Injection

5% Glucose Injection

5% Glucose and 0.9% Sodium Chloride Injection

5% Glucose and 0.45% Sodium Chloride Solution

5% Glucose in Ringer Lactate Solution

Sodium Lactate 1/6 Molar Injection

Lactated Ringer’s 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

Dopamine Hydrochloride injection USP 200mg/5ml Taj pharma.
Dopamine Hydrochloride injection USP 400mg/10ml Taj pharma.

Package Leaflet: Information for the user

Read all of this leaflet carefully before you start using this medicine.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or nurse.

If any of the side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Dopamine Hydrochloride 40mg/ml Concentrate for Solution for Infusion. It will be referred to as “Dopamine Concentrate” for ease of use hereafter.

What is in this leaflet:

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

  1. What Dopamine Hydrochloride Injection is and what it is used for

Dopamine Hydrochloride 40mg/ml Concentrate For Solution For Infusion contains 200mg of Dopamine Hydrochloride which helps to increase the strength of muscle contraction in the heart.

It is used to correct poor circulation to the tissues

  • when there is a low output of blood from the heart and shock associated with damage to the heart muscle due to obstruction of its blood supply.
  • also after an injury, blood infection, heart failure and open heart surgery.
  1. What you need to know before you are given dopamine concentrate

You should not be given this medicine if:

  • you are allergic to Dopamine hydrochloride or any other ingredients of this medicine (listed in section 6).
  • you have been told by your doctor that you have a tumour of the adrenal gland (phaeochromocytoma).
  • you have abnormal heartbeats and uncoordinated contraction of the heart muscles.
  • you have an overactive thyroid gland.

Warnings and precautions

Talk to your doctor or nurse before using Dopamine Hydrochloride Injection if:

  • you have any heart related problems
  • you have recently used monoamine oxidase inhibitors (known as MAOIs which are used for the treatment of depression; see section “Taking other medicines” for further information)
  • you are sensitive to sulphite
  • you have a weaker pulse in your wrists than normal on examination
  • you have a blood disorder in which the volume of circulating blood is decreased (hypovolaemia)
  • you know that you are suffering or have suffered from problems related to circulation of blood in your hands and feet (peripheral vascular disease)
  • you have any kidney or liver diseases
  • you are pregnant or breast feeding
  • you have diabetes

Speak to your doctor before you are given this injection if this applies to you.

Your doctor will monitor you for any side-effects affecting the heart or kidneys while you are receiving dopamine.

Dopamine infusion should be withdrawn gradually, to avoid low blood pressure.

Other medicines and Dopamine Concentrate

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

Some medicines can interact with Dopamine Concentrate, which can significantly alter their effects. If you are already taking one of the following medicines, speak to your doctor before you receive this medicine:

  • Monoamine oxidase inhibitors (used for the treatment of depression) or if you have taken them in the last 14 days, e.g. phenelzine, moclobemide, rasagiline, selegiline, entacapone.
  • Water tablets (diuretics), e.g. furosemide, amiloride or triamterene.
  • Medicines which are often used for treating blood pressure and heart disorders (alpha and beta blockers e.g. propranolol, tolazoline).
  • Medicines used to treat epilepsy (phenytoin).
  • Medicines used to treat migraine (e.g. ergotamine derived from ergot alkaloids, methysergide).
  • Medicines used to treat depression such as Tricyclic antidepressants (e.g. amitriptyline).
  • Medicines used to reduce high blood pressure like guanethidine.
  • Medicine used to help your breathing (doxapram).
  • Medicines used to treat psychological problems like schizophrenia (e.g. haloperidol, clozapine).

Tell your doctor before you are given Dopamine Hydrochloride Injection if you have recently received any anaesthetic agent such as halothane, isoflurane or cyclopropane.

Pregnancy and 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 for advice before taking this medicine.

As with all drugs, this medicine should only be given in pregnancy and when breast feeding if absolutely necessary. Your doctor will be able to advise you.

Driving and using machines

Not applicable

Dopamine Hydrochloride Injection contains:

Sodium metabisulphite, which may rarely cause severe hypersensitivity (allergic) reactions and bronchospasm (breathing difficulties).

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

  1. How Dopamine Hydrochloride Injection is given to you

This injection will be administered under the supervision of a doctor. The solution is diluted before administration and will then be given by infusion (as a drip through a needle or tube) into a vein.

Your doctor will decide on the most suitable dose for you. This product is not recommended for use in children.

If you think you have been given more Dopamine Hydrochloride Injection than you should have

As the injection will be administered under the supervision of a doctor, it is unlikely that you will be given more than is necessary. However, if you have any concerns about the dose of your medicine discuss them with your doctor.

If you develop symptoms like narrowing of the blood vessels, tissue death around blood vessels, restriction in blood supply due to tissue damage due to over use of this product your doctor will stop giving you this medicine and give you other medications for treatment.

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

  1. Possible side effects

Like all medicines Dopamine Hydrochloride Injection can sometimes cause side effects, although not everybody gets them.

All medicines can cause allergic reactions although serious allergic reactions are rare. Any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face, lips, rash or itching (especially affecting your whole body), should be reported to a doctor immediately.

Other side effects:

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

  • headache
  • a rapid or slow heart beat, chest pain, irregular heart beat and awareness of a rapid or irregular pulse
  • difficulty in breathing
  • low blood pressure (which may cause symptoms such as faintness or dizziness)
  • narrowing of blood vessels (which may cause the skin to become cold and to turn pale or to have a bluish colour)
  • nausea and vomiting

Uncommon (may affect up to 1 in 100 people):

  • dilation of the pupil of the eye which may cause difficulty with bright lights
  • shortness of breath
  • goose pimples or hair ‘standing at ends’
  • pain in your fingers or toes (at higher doses, especially in people who have had problems with their circulation, gangrene can occur)
  • abnormalities in the ECG (a tracing of electrical currents in the heart)
  • high blood pressure.
  • an excess of urea or other waste products in the blood (which may make you feel generally unwell and is identified by blood tests)

If dopamine hydrochloride escapes from the vein into the surrounding tissues during administration, it may cause damage of the surrounding tissues; tell your doctor if you notice any pain or swelling at the injection site so that the appropriate treatment may be given.

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 dopamine concentrate

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

Do not use this medicine after the expiry date printed on the ampoule and carton. The expiry date refers to the last day of that month.

Do not store above 25°C.

Keep the container in the outer carton in order to protect from light.

If only part used, discard the remaining solution.

If the solution appears darker than slightly yellow or discoloured in any other way, it should be returned unused to the pharmacist.

  1. Contents of the pack and other information

The active substance is dopamine hydrochloride.

The other ingredients are sodium metabisulphite in water for injections.

What Dopamine Hydrochloride Injection looks like and contents of pack

Dopamine Hydrochloride Injection is a clear, colourless or pale yellow solution presented in 5ml clear glass ampoules (small glass bottles).

Each 5ml ampoule contains 200mg Dopamine Hydrochloride.

There are ten 5ml ampoules packed in to one cardboard box.

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