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© Admeda Arzneimittel GmbH 2002

Dopamin Solvay

SUMMARY OF PRODUCT CHARACTERISTICS
(INTERNATIONAL VERSION)

 

1. Name of the medicinal product
Dopamin Solvay 50
50 mg/5 ml

Dopamin Solvay 200
200 mg/10 ml

2. Qualitative and quantitative composition
1 ampoule Dopamin Solvay 50 contains 50 mg dopamine hydrochloride in 5ml concentrate for infusion.

1 ampoule Dopamin Solvay 200 contains 200 mg dopamine hydrochloride in 10ml concentrate for infusion.

For excipients, see 6.1

3. Pharmaceutical form
concentrate for intravenous infusion

4. Clinical particulars

4.1 Therapeutic indications
For the correction of poor haemodynamic perfusion present in shock associated with acute myocardial infarction (cardiogenic shock), heart failure, hypovolaemia, cardiac and other surgery, trauma, endotoxic septicaemia (septic shock) and anaphylaxis and for use in imminent shock (pre-shock), severe hypotension and impending renal failure.

4.2. Posology and method of administration

Dosing in Adults:
Dosage should be adjusted individually according to the severity of the condition and the response of the patient.

The following doses are a general guideline:

Low' (e.g. medical intensive care and renal indications):
1.5 - 3.5 m g/kg/min

'Medium' (e.g. surgical intensive care):
4 - 10 m g/kg/min

'High' (e.g. septic shock):
10.5 - 50 m g/kg/min.

The infusion rate should be titrated to achieve optimum patient response. The majority of patients can be maintained satisfactorily on doses of dopamine less than 20 m g/kg/min.

Dosing in Children:
Start with a low dose and increase slowly.
The usual maintenance dose is 4-6 m g/kg/min.

Duration of treatment in Adults and Children
The duration of infusion will depend on the circumstances of each individual case; positive results have been reported with an infusion treatment of 28 days. When treatment is completed the infusion should be terminated gradually and not abruptly.

Method of Administration
Where appropriate, blood volume should be restored before the start of treatment with dopamine.

Despite the use of dopamine, the additionally required measures such as adequate volume replacement and close monitoring of electrolyte metabolism etc. should not be neglected. Airway patency should be monitored in somnolent patients because of the risk of aspiration. Volume replacement should if possible be carried out before initiating treatment. For patients with elevated preload or afterload, combined administration with glyceryl trinitrate or sodium nitroprusside is recommended to reduce the load on the heart.

Dopamin Solvay 50/200 must be diluted before administration. Recommended diluents include:
0.9 % sodium chloride solution
5 % glucose solution
Ringer-lactate solution

Dopamine should not be added to 5% sodium bicarbonate or other alkaline solution since the drug is inactivated.

The infusion solution should be prepared immediately before use. Only clear infusion solutions that are not discoloured after adding Dopamin Solvay should be used.

Ready for use infusion solutions with Dopamin Solvay are stable for the usual infusion periods (at least 24 hours), with the exception of mixtures with Ringer's lactate solution (max. 6 hours).

4.3. Contraindications
Dopamine is contra-indicated in
•  hyperthyroidism,
•  phaeochromocytoma,
•  uncorrected tachyarrhythmias or ventricular fibrillation,
•  narrow-angle glaucoma
•  prostatic adenoma with urinary retention
• known hypersensitivity to any of the excipients

4.4. Special warnings and special precautions for use

Hypovolaemia should be corrected where necessary prior to treatment with dopamine.
Since dopamine facilitates AV-conduction, a digitalis preparation should be used prior to institution of dopamine therapy in patients who have atrial fibrillation with rapid ventricular response.
The infusion rate should be constantly evaluated in terms of the patient's changing condition and the following indices closely monitored: urine flow, cardiac output and blood pressure. Once cardiac function and blood pressure have been stabilized, it may be necessary to reduce the dose to achieve optimum urine flow.
In the event of an unwarranted increase in diastolic blood pressure, decrease in urine output or occurrence of arrhythmia, the dose of dopamine should be reduced.
Dopamine should be infused into a large vein whenever possible to reduce the risk of extravasation. Inadvertent paravenous infusion can lead to soft tissue necrosis.
In the event of extravasation, infiltration of the affected area with phentolamine may prevent tissue necrosis.
As a general precaution, special care should be taken to avoid intra-arterial infusion and bolus injection due to the pharmacological properties of the drug.
Severe vasoconstriction leading to skin necrosis and gangrene may occur, particularly in patients with a history of occlusive peripheral vascular disease and/or disseminated intravascular coagulation (DIC). These patients should be closely monitored; once peripheral ischaemia is detected, the dopamine infusion should be stopped immediately.
Since the effect of dopamine on impaired renal or hepatic function is not known, close monitoring is advisable.
An unrestricted airway should be ensured in comatosed patients.

4.5. Interaction with other medicinal products and other forms of interaction

Dopamine should be used with extreme caution in patients inhaling cyclopropane or halogenated hydrocarbon anaesthetics due to the arrhythmogenic potential.
The combination of dopamine and ergot alkaloids can lead to maximal peripheral vascular constriction with risk of gangrene.
Patients who are receiving, or who have received in the past 2 weeks, monoamine oxidase inhibitors (MAOI) require a considerably lower dose of dopamine. The starting dose should be one tenth (1/10) of the usual dose.
Hypotension and bradycardia can occur with tricyclic antidepressants and with phenytoin.
Simultaneous administration of dopamine and diuretics can have additive and potentiating effects.
The cardiac effects of dopamine are antagonised by beta-adrenergic blocking agents such as propranolol and metoprolol.
Simultaneous administration with guanethidine augments the sympathomimetic effect of dopamine.
When dobutamine is given with dopamine, a more marked increase in blood pressure can occur, but ventricular filling pressure decreases or remains the same.

4.6. Pregnancy and lactation
There are no adequate data from the use of dopamine in pregnant women. Studies in animals have shown reproduction toxicity. The potential risk for humans is unknown.
Dopamine should not be used during pregnancy unless clearly necessary.

4.7. Effects on ability to drive and use machines
Not applicable.

4.8. Undesirable effects
Mild nausea, vomiting, headache, restlessness, anxiety, finger tremor, anginal pain, palpitations and a rise in blood pressure may occur infrequently.
Myocardial ischemia may occur rarely.
Infrequently reported reactions include aberrant conduction, bradycardia, widened QRS complex, hypertension, azotaemia and piloerection.
There is a risk of triggering cardiac arrhythmia (sinus tachycardia, supraventricular and ventricular arrhythmia) and of an adverse rise in left ventricular end diastolic pressure.
At low doses, dopamine may rarely cause hypotension which can normally be corrected by increasing the infusion rate.
Polyuria has been observed during dopamine infusion. Urinary output should be monitored.
Very rarely, dopamine infusion can cause skin necrosis or gangrene. Inadvertent paravenous infusion can lead to soft tissue necrosis.

4.9. Overdose
Symptoms of overdosage:
Excessive blood pressure elevation; more frequent rhythm disorders. See also 4.8 "Undesirable effects".

Treatment of overdosage:
Symptoms of overdosage can be controlled by dose reduction or discontinuation of the infusion for a short period since the duration of action of dopamine is short. The administration of alpha- or beta-blockers should be considered only in severe cases.

5. Pharmacological properties

5.1. Pharmacodynamic properties
Dopamine, a catecholamine, is a positive inotropic agent; its spectrum of action is dose-dependent. At low doses it dilates the renal and mesenteric vascular beds.

Dopamine causes:
- an increase in stroke volume and cardiac output due to an increase in myocardial contractility;
- increases in coronary, cerebral and mesenteric blood flow; increased renal perfusion with diuresis and increased sodium and potassium elimination through stimulation of specific dopaminergic receptors (urine osmolality is usually not decreased);
- reduction, or no change, in peripheral resistance - for low doses (1.5 - 3.5 m g/kg/min)
- increase in peripheral resistance - for high doses (over 10 m g/kg/min).

5.2. Pharmacokinetic properties
Following intravenous administration the elimination half-life of dopamine is less than 5 minutes. Dopamine is metabolised to inactive metabolites in the liver, kidney and plasma; 85 % is excreted in urine within 24 hours.

5.3. Preclinical safety data
Acute and subacute toxicity testing showed markedly lower toxicity for dopamine than for other catecholamines. The LD 50 after intravenous administration was: 106 mg/kg in rats and 79-100 mg/kg in dogs.
Subacute tests (over 6 weeks) showed lethal effects in rats with a daily dosage of 10 mg/kg i.v.; dogs tolerated 40.5 mg/kg with no deaths.
No specific foetal toxicity was found in teratogenicity studies in rats, as abnormalities in pre-natal development were observed only at dosages that were toxic to the mothers.
Chronic toxicity, carcinogenicity and mutagenicity tests were not performed as dopamine is a biogenic amine and it is used intravenously, generally for only short periods (several days).

6. Pharmaceutical particulars

6.1. List of excipients
•  L-cysteine hydrochloride monohydrate
•  sodium chloride
•  citric acid monohydrate
•  sodium hydroxide
•  water for injections

6.2. Incompatibilities
Dopamine is alkali sensitive. Therefore do not mix with alkaline solutions (above pH 7) such as sodium bicarbonate.
Alteplase and amphotericin B are unstable in the presence of dopamine.

Known physical incompatibilities are also known to exist with the following:
- aciclovir
- alteplase
- amicacin
- amphotericin B
- ampicillin
- cephalotin
- dacarbazine
- theophylline ethylenediamine (Euphyllin)
- theophylline-calcium solution (Euphyllin calcium solution)
- furosemide
- gentamicin
- heparin
- iron salts
- nitroprusside
- benzylpenicillin (penicillin G)
- tobramycin

For recommended infusion solutions see Section 4.2 "Posology and method of administration".

6.3. Shelf life
Dopamin Solvay 50, Dopamin Solvay 200 have a shelf-life of t hree years.

6.4. Special precautions for storage
Since Dopamin Solvay is not intended for multiple dosing from the same containers, it contains no preservatives. The temperature stability information given in the table below for Dopamin Solvay and Dopamin Solvay in solution relates only to physical-chemical properties and disregard the microbiological aspect. Dopamin Solvay should always be prepared for administration under optimal hygienic (aseptic) conditions.

Physical and chemical storage stability:
  Dopamin Solvay 50 Dopamin Solvay 200
Storage at 40°C min. 6 months min. 6 months
Storage at 30°C 9 months 9 months
Storage at 2-8°C with glucose * stable for up to 14 days stable for up to 14 days
Storage at RT with NaCl *

24 hours

24 hours
Storage at RT with glucose * 24 hours 24 hours
Storage at RT with Ringer's lactate * up to 6 hours up to 6 hours
*Mixing ratio: contents of 1 ampoule in 250 or 500 ml infusion solution

6.5. Nature and contents of container
Colourless OPC-glass ampoules of hydrolytic resistance glass type I (Ph. Eur.).
Dopamine is available in folding, hard cardboard boxes of 5 ampoules each.

6.6. Instructions for use and handling
See 4.2

7. Marketing authorization holder
Transfer process is running to
Admeda Arzneimittel GmbH
Trift
D-23863 Nienwohld

8. Numbers in the community register of medicinal products

9. Date of first authorization/Renewal of authorization

10. Date of (partial) revision of the text
July 2002