ATRACURIUM BESILATE HAMELN 10 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before you use Atracurium Hameln Besylate

Do not use Atracurium Hameln Besylate

• If you are allergicto atracurium besylateor to any of the other ingredientsof this medicine (listed in section 6). An allergic reaction may cause a skin rash, itching, difficulty breathing, or swelling of the face, lips, or tongue. You may already know this from past experiences.

Warnings and precautions

Before using Atracurium Hameln Besylate, tell your doctor if you have the following conditions:

• A disease that affects the muscles or the nervous control of the muscles (due to a neuromuscular disease such as myasthenia gravis or Eaton-Lambert syndrome).
• A severe electrolyte disorder.
• Widespread cancer spread from a primary cancer site (carcinomatosis).
• Hypersensitivity to histamine.
• Asthma-like symptoms (history of allergy, asthma, or bronchospasm).
• Burns.
• Insufficient circulating blood volume (hypovolemia).

Children:

Atracurium Hameln Besylate should not be used in neonates (children under one month of age). If it is necessary to treat neonates or premature neonates with this medicine, the dose should be significantly reduced. If you have any doubts, consult your doctor.

Using Atracurium Hameln Besylate with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. It is especially important with the following medicines, as they may interact with Atracurium Hameln Besylate:

• Antibiotics (e.g., aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin, clindamycin, and vancomycin).
• Anti-arrhythmic drugs (used to control heart rhythm, such as lidocaine, procainamide, or quinidine).
• Diuretics (drugs that promote urination), such as furosemide, acetazolamide, and mannitol.
• Medicines to control blood pressure, angina, or other heart problems (e.g., propranolol, oxprenolol, diltiazem, nicardipine, nifedipine, and verapamil).
• Antiepileptic drugs (e.g., carbamazepine or phenytoin).
• Drugs used to treat rheumatism (e.g., chloroquine or D-penicillamine).
• Corticosteroids (for the treatment of inflammation).
• Trimetaphan, hexamethonium (used to reduce blood pressure during surgery).
• Dantrolene (a muscle relaxant).
• Magnesium sulfate.
• Ketamine (an anesthetic drug).
• Lithium, chlorpromazine (treatment of mental illnesses).
• Quinine (treatment of malaria or leg cramps).

It may still be possible to receive Atracurium Hameln Besylate, and your doctor will decide what is best for you.

Pregnancy and breastfeeding

Atracurium Hameln Besylate should not be administered to pregnant women unless it is medically justified. Mothers should stop breastfeeding for 24 hours after receiving Atracurium Hameln Besylate. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

After receiving Atracurium Hameln Besylate, you should not drive, use machinery, or work in hazardous situations. You should not go home alone or drink alcohol until you feel recovered.

3. How to use Atracurium Hameln Besylate

Atracurium Hameln Besylate can only be administered by doctors with experience in carefully controlled conditions.

Atracurium Hameln Besylate is used during procedures for which the patient needs to be fully anesthetized (unconscious) or under deep sedation.

The dose will be determined by your doctor. Atracurium Hameln Besylate should only be administered by injection into a vein (intravenous use). Atracurium Hameln Besylate should not be injected into a muscle.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

At the end of this leaflet, information intended for doctors or healthcare professionals is presented.

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:

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

• Tachycardia (rapid heartbeats).
• Transient hypotension (low blood pressure).
• Wheezing.
• Bronchospasm (asthma-like symptoms).
• Redness of the skin.
• Urticaria.

Very rare (may affect up to 1 in 10,000 people):

• Myasthenia or myopathy (weak or inactive muscles).
• Severe allergic reactions such as anaphylactic shock, circulatory failure, and myocardial infarction in patients receiving atracurium along with one or more anesthetics.
• Seizures when administered with other drugs in patients at risk.
• Laryngospasm (spasms in the vocal cords).

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse; even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

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

5. Storage of Atracurium Hameln Besylate

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging “Exp.:” The expiry date is the last day of the month indicated.
• Store in a refrigerator (between 2°C and 8°C). Do not freeze. Keep the ampoules in the outer packaging to protect them from light.
• The medicine should be used immediately after opening the packaging.
• Validity period of prepared infusion solutions: Physical and chemical stability has been demonstrated during the use of the medicine in intravenous infusion of sodium chloride BP for a maximum of 24 hours at 30°C and in other frequently used infusion solutions for a maximum of 4 to 8 hours, respectively. From a microbiological point of view, the preparation should be administered immediately. If not used immediately, the conditions prior to use of the medicine and the storage time during use of the medicine are the responsibility of the patient and normally should not exceed 24 hours at a temperature of 2 to 8°C, unless the reconstitution and dilution have been performed under controlled and validated aseptic conditions.
• Do not use Atracurium Hameln Besylate if you notice that the solution is not clear, colorless, or if there are particles in suspension or if the packaging is damaged.

6. Container Contents and Additional Information

Composition of Atracurium-hameln Besilate

The active ingredient is atracurium besilate.

1 ml of Atracurium-hameln Besilate contains 10 mg of atracurium besilate.

An ampoule with 2.5 ml contains 25 mg of atracurium besilate.

An ampoule with 5.0 ml contains 50 mg of atracurium besilate.

The other components are water for injectable preparations and benzenesulfonic acid.

Appearance of the Product and Container Contents

Atracurium-hameln Besilate is a clear, colorless solution.

3 or 5 ml glass ampoules.

Box of 5 ampoules with 2.5 or 5 ml.

Box of 10 ampoules with 2.5 or 5 ml.

Box of 5 x 10 ampoules with 2.5 or 5 ml.

Only some package sizes may be marketed.

Marketing Authorization Holder

hameln pharma gmbh

Inselstraße 1

31787 Hameln

Germany

Manufacturer

Siegfried Hameln GmbH

Langes Feld 13

31789 Hameln

Germany

This Medicinal Product is Authorized in the Member States of the European Economic Area under the following Names:

DE: Atracurium-hameln 10 mg/ml Injektions-/ Infusionslösung

IT: Atracurium-hameln 10 mg/ml soluzione iniettabile

NL: Atracurium-hameln 10 mg/ml oplossing voor injectie en infusie

ES: Besilato de Atracurio-hameln 10 mg/ml solución inyectable y para perfusión EFG

SE: Atracurium-hameln 10 mg/ml injektionsvätska, lösning

UK: Atracurium besilate 10 mg/ml solution for injection

Date of the Last Revision of this Leaflet: January 2015

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This Information is Intended Only for Healthcare Professionals:

Atracurium-hameln Besilate 10 mg/ml Solution for Injection and Perfusion EFG

It is essential to read the entire contents of this guide before preparing this medicinal product.

Incompatibilities

Atracurium besilate is inactivated at high pH and should therefore not be mixed in the same syringe with thiopental or any other alkaline agent.

Consequently, the intravenous cannula should be flushed well between the perfusion of atracurium besilate and thiopental to avoid the formation of aggregates, which could cause an anaphylactoid reaction.

Reconstitution Instructions

Atracurium besilate is compatible with the following solutions for IV perfusion:

Diluted in the mentioned solutions to provide atracurium besilate concentrations of 0.5 mg/ml or higher, the resulting solutions remain stable in daylight for the mentioned periods, at temperatures up to 30°C.

Posology and Method of Administration

Solution for injection and perfusion

For single doses only. Any opened and unused solution should be discarded.

As with all neuromuscular blocking agents, it is recommended to monitor neuromuscular function during the administration of atracurium besilate, in order to establish individual dosing requirements.

• Use as an injection, in adults

Atracurium-hameln Besilate is administered by intravenous injection and should not be administered intramuscularly.

Relaxation

The recommended dose range for adults is 0.3 to 0.6 mg/kg of atracurium besilate (depending on the required duration of total neuromuscular blockade). This dose will provide adequate muscle relaxation for approximately 15 to 35 minutes.

Intubation

Endotracheal intubation can usually be performed within 90 seconds after intravenous injection of 0.5 to 0.6 mg/kg of atracurium besilate.

Repeat Dose

Total neuromuscular blockade can be prolonged by administering supplemental doses of 0.1 to 0.2 mg/kg of atracurium besilate. The first maintenance dose is usually required 20 to 45 minutes after the initial bolus injection; subsequent maintenance doses are typically administered at intervals of 15 to 25 minutes. However, the need for maintenance doses should be determined according to individual patient requirements and responses.

Successive supplemental dosing does not produce neuromuscular blocking effect accumulation.

As measured by the restoration of tetanic response to 95% of its normal intensity, spontaneous recovery occurs approximately 35 minutes after total neuromuscular blockade.

Once evidence of spontaneous recovery is present, the neuromuscular blockade produced by atracurium besilate can be rapidly reversed by administering standard doses of cholinesterase inhibitors, such as neostigmine or edrophonium, accompanied or preceded by atropine or glycopyrrolate, without evidence of recurarization.

• Use as a perfusion, in adults

Atracurium-hameln Besilate is a hypotonic solution and should therefore not be administered through the same perfusion system as a blood transfusion. In this case, atracurium besilate must be administered through a separate intravenous perfusion access.

After an initial bolus dose of 0.3 to 0.6 mg/kg, atracurium besilate can be administered as a continuous intravenous perfusion at a dose of 0.3 to 0.6 mg/kg/hour to maintain neuromuscular blockade during prolonged surgical procedures.

Atracurium-hameln Besilate can be administered as a continuous perfusion during cardiopulmonary bypass surgery, at the recommended perfusion doses.

Induced hypothermia, with a body temperature of 25° to 26°C, decreases the degradation rate of atracurium besilate. Consequently, under hypothermic conditions, total neuromuscular blockade can be maintained by administering approximately half of the original perfusion dose.

Atracurium-hameln can be diluted with a perfusion of the mentioned solutions.

• Application in children, in elderly patients, in patients with renal and/or hepatic insufficiency, with cardiovascular disease, with burns, and in patients treated in intensive care units (ICU)

Application in Children:

Calculated with respect to body weight, the dose in children over one month of age is similar to that of adults.

Neonates

The use of atracurium besilate is not recommended in neonates (children under one month of age), as there are insufficient data (see section 5.1). If neuromuscular blockade is required, even in newborns or premature neonates, the dose should be significantly reduced.

Application in Elderly Patients:

Atracurium besilate can be used at the standard dosage. However, it is recommended that the initial dose be at the lower end of the recommended range and that the medication be injected slowly.

Application in Patients with Renal and/or Hepatic Insufficiency:

Atracurium besilate can be used at the standard dosage in all levels of renal or hepatic insufficiency, including terminal stages.

Application in Patients with Cardiovascular Disease:

Patients with severe cardiovascular diseases may react more sensitively to transient hypotensive states. In such patients, atracurium besilate should be administered slowly and/or in fractionated doses over a period of 1-2 minutes.

Application in Patients with Burns:

As with other non-depolarizing neuromuscular blocking agents, patients who have suffered burns may develop resistance to its action. Depending on the time elapsed since the burn and the extent of the injuries, these patients may require higher doses of atracurium besilate.

Application in Patients Treated in Intensive Care Units (ICU):

When atracurium besilate needs to be administered for prolonged mechanical ventilation, the benefit-to-risk ratio of prolonged neuromuscular blockade should be considered.

After an optional initial bolus dose of 0.3 to 0.6 mg/kg, atracurium besilate can be used to maintain neuromuscular blockade by administering a continuous perfusion at a dose of 11 to 13 micrograms/kg/min (0.66-0.78 mg/kg/h). However, there is a wide interindividual variability in the required dosage in these patients. Some patients may require perfusion rates as low as 4.5 micrograms/kg/min (0.27 mg/kg/h) or as high as 29.5 micrograms/kg/min (1.77 mg/kg/h). Dosage requirements may vary over time. Therefore, the perfusion rate should be adjusted according to monitoring by peripheral nerve stimulation.

The rate at which spontaneous recovery from neuromuscular blockade occurs after atracurium besilate perfusion in ICU patients is independent of the duration of administration. Spontaneous recovery to a train-of-four ratio greater than 0.75 can be expected within approximately 60 minutes, with a range of 32-108 minutes observed in clinical studies (n=6).