ARDUAN 4 mg Powder

Contents of the leaflet

1. Package Leaflet: Information for the User
   1. Read all of this leaflet carefully before using this medicine because it contains important information for you.
   2. Contents of the pack and other information
2. What Arduan is and what it is used for
3. Important information before using Arduan
   1. Warnings and precautions
   2. Arduan and other medicines
   3. Pregnancy, breastfeeding, and fertility
   4. Driving and using machines
   5. Arduan contains sodium
4. How to use Arduan
   1. Overdose of Arduan
5. Possible side effects
   1. Reporting of side effects
6. How to store Arduan
7. Contents of the pack and other information
   1. What Arduan contains
   2. What Arduan looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Date of last revision of the leaflet:

Package Leaflet: Information for the User

ARDUAN 4 mg, powder and solvent for solution for injection
Pipecuronium bromide

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• You should keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Arduan is and what it is used for
• 2. Important information before using Arduan
• 3. How to use Arduan
• 4. Possible side effects
• 5. How to store Arduan
• 6. Contents of the pack and other information

1. What Arduan is and what it is used for

Arduan is a non-depolarizing muscle relaxant that blocks the transmission of nerve impulses from the motor nerve endings to the skeletal muscle by competitively binding to the nicotinic receptor located on the motor end plate of the skeletal muscle.
Unlike depolarizing muscle relaxants such as succinylcholine, Arduan does not cause muscle fasciculations and has no hormonal effect. The neuromuscular blocking effect is limited to skeletal muscles only.
It does not exhibit ganglionic blocking effect or vagolytic or sympathomimetic effects, even at doses much higher than the ED90 doses (dose required to achieve 90% receptor depression).
From dose-response studies, the ED50 and ED90 for Arduan in balanced anesthesia are 0.03 and 0.05 mg/kg body weight, respectively. A dose of 0.05 mg/kg body weight provides adequate muscle relaxation during numerous surgical procedures for an average of 40 to 50 minutes.
The time from injection to maximum neuromuscular blockade (onset time) depends on the dose administered and ranges from 1.5 to 5 minutes. The shortest onset times are seen with doses up to 0.07-0.08 mg/kg body weight. Further increases in dose result in minimal reduction in onset time but significantly prolong the effect.
Indications:

• Tracheal intubation and skeletal muscle relaxation during general anesthesia. It can be used during various operations that require prolonged muscle relaxation lasting more than 20-30 minutes.
• As part of artificial ventilation of the lungs.

2. Important information before using Arduan

When not to use Arduan:

Warnings and precautions

Before starting treatment with Arduan, discuss it with your doctor or pharmacist.

• Due to the effect of Arduan on respiratory muscles, it should only be administered in the presence of a person specialized in artificial respiration, in places where conditions for artificial respiration are available.
• In general, anaphylactic and anaphylactoid reactions to neuromuscular blocking agents have been described in the literature. Although only a few similar cases have been reported with Arduan, the product should only be administered under conditions where such reactions can be treated immediately.
• Arduan does not have significant cardiovascular effects within the dose range that causes muscle paralysis. Minor, clinically insignificant changes (usually a decrease) in heart rate, systolic and diastolic blood pressure, and cardiac output may occur. These changes are likely related to the effect of other drugs (fentanyl, thiopental, halothane) used concurrently during anesthesia induction.
• Considering the above facts, the administration of vagolytic drugs as premedication and their doses should be taken into account (of course, considering the stimulating effect of anesthetics used concurrently and the type of surgical intervention).
• In patients with conditions that may alter the effect of Arduan, the use of a peripheral nerve stimulator is recommended. It can help avoid overdosing and assess the recovery of neuromuscular transmission.

The following factors may affect the pharmacokinetics and/or muscle relaxant effect of Arduan:
Neuromuscular disorders
In patients with neuromuscular disorders - except for myasthenia (for which the use of Arduan is contraindicated), the doctor should administer Arduan with caution, as these disorders may cause both increased and decreased relaxation.
Before surgery, non-depolarizing muscle relaxants should not be used for tracheal intubation. It is not recommended to administer anesthetics and drugs affecting neuromuscular transmission (benzodiazepines) concurrently. Anticholinesterase should be administered at the end of the surgical procedure, 10 to 15 minutes before the required therapeutic effect. After the surgical procedure, the doctor should consider planned extension of artificial ventilation of the lungs. The transition to spontaneous breathing should be done under monitoring of neuromuscular blockade and respiratory parameters.
Cardiovascular failure
In such patients, the doctor should consider the possible delay in the onset of action of Arduan, and thus later intubation.
Malignant hyperthermia
Neither in experimental nor clinical conditions has malignant hyperthermia been associated with the administration of Arduan. Since muscle relaxants are never used in monotherapy, and malignant hyperthermia during anesthesia is possible even without known triggering factors, clinicians should be aware of the early symptoms, diagnostic methods, and treatment of malignant hyperthermia.
Others
Similar to other neuromuscular blocking agents, before anesthesia, acid-base balance and electrolyte homeostasis should be corrected.
Decreased body temperature may prolong the effect of the drug.
Hypokalemia (decreased potassium levels in the blood), digitalis glycosides, diuretics, hypermagnesemia (elevated magnesium levels in the blood), hypocalcemia (decreased calcium levels in the blood), dehydration, acidosis, hypoproteinemia (decreased serum protein levels in the blood), hypercapnia (respiratory acidosis due to excess carbon dioxide in the blood), and cachexia (wasting of the body due to nutritional deficiencies) may enhance or prolong the effect of Arduan.
Similar to other non-depolarizing muscle relaxants, Arduan may decrease partial thromboplastin time and prothrombin time (a test that evaluates the blood coagulation time in the presence of calcium ions after the administration of thromboplastin - a factor that causes the conversion of prothrombin to thrombin, which occurs in platelets, so-called thrombocytes).
You should consult a doctor, even if the above warnings refer to situations that have occurred in the past.
Use of Arduan in patients with renal and/or hepatic impairment:
Hepatic impairment
In liver cirrhosis, the onset of action of pipecuronium, which involves blocking neuromuscular transmission, may be prolonged, while the duration of clinical muscle relaxation remains unchanged. In extrahepatic cholestasis, the elimination half-life may be prolonged, mainly due to increased distribution volume.
Renal failure
In patients with renal failure, the duration of action is prolonged. The doctor should reduce the dose of Arduan accordingly.

Arduan and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.
Other medicines taken before or during surgery may affect the action of Arduan.
The following medicines may affect the action of Arduan:
Enhancement and/or prolongation of action.

• inhalation anesthetics (halothane, methoxyflurane, diethyl ether, enflurane, isoflurane, cyclopropane),
• intravenous anesthetics (ketamine, fentanyl, propanidid, barbiturates, etomidate, gamma-hydroxybutyrate)
• high doses of local anesthetics
• other non-depolarizing muscle relaxants administered before succinylcholine
• certain antibiotics and chemotherapeutic agents (aminoglycosides and polypeptide antibiotics, imidazole derivatives, metronidazole, and others)
• diuretics, beta blockers, thiamine, MAO inhibitors, guanidine, protamine, phenytoin, alpha blockers, calcium antagonists, magnesium salts
• most antiarrhythmic drugs, along with quinidine and intravenously administered lidocaine, increase the blockade caused by non-depolarizing muscle relaxants.

Reduction of action.
Prolonged administration of corticosteroids, neostigmine, edrophonium, pyridostigmine, noradrenaline, azathioprine, theophylline, KCl, NaCl, CaCl before administration of Arduan.
Enhancement or reduction of action.
Previous administration of depolarizing muscle relaxants (depending on the dose, time of administration, and individual sensitivity).
Others
Gentamicin, ampicillin administered during surgery do not affect the action of the drug and can be used concurrently without causing side effects. Like other muscle relaxants, Arduan may decrease prothrombin time and partial thromboplastin time.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
There are no sufficient data on the use of Arduan in pregnancy in humans to assess the potential risk to the fetus. Arduan should only be used during pregnancy if the benefits outweigh the risks.
Cesarean section
Clinical studies using Arduan as a supplement to general anesthesia for cesarean section have shown that Arduan does not affect Apgar scores, muscle tone, or cardiovascular adaptation of the fetus. No other side effects have been observed in newborns.
Pharmacokinetic studies have shown that very small amounts of pipecuronium bromide cross the placental barrier and enter the umbilical cord blood.
Breastfeeding
Before using the medicine, consult your doctor.
Due to the lack of information on the passage of the drug into breast milk, breastfeeding is not recommended after anesthesia until the attending physician's consent is obtained.

Driving and using machines

The patient should not drive vehicles or operate machines until the anesthesiologist or surgeon has given their consent.
Within 24 hours after the effect of Arduan has worn off, it is not recommended to drive vehicles or operate hazardous machines.

Arduan contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per ampoule, which means the medicine is considered "sodium-free".

3. How to use Arduan

Arduan is administered intravenously (into a vein). The dose will be determined by your doctor based on your body weight, health status, expected duration of surgery, and other medications used concurrently.
Only freshly prepared solution should be used.
Arduan must not be mixed with other solutions or medicines in the same syringe or bag.
Recommended dosage

During individual dose titration, the doctor should consider: the type of anesthesia, the expected duration of the surgical procedure, possible interactions with other medications administered before and during anesthesia, concomitant diseases, and the overall condition of the patient. The use of a peripheral nerve stimulator is recommended to monitor relaxation and the return of muscle strength. Arduan is intended for intravenous administration, both as a rapid bolus injection (in which case it is recommended to administer into venous cannulae with a constant flow of infusion fluid) for the maintenance of muscle relaxation and as a continuous infusion ensuring the desired period of relaxation.
Arduan, like other neuromuscular blocking agents, should only be administered by or under the supervision of an experienced clinician and with access to appropriate equipment to provide artificial ventilation of the lungs.
The dosing recommendations below should be treated as general guidelines for initial and maintenance doses to ensure adequate muscle relaxation during surgical procedures of medium and long duration, which are performed under general anesthesia with or without the administration of Arduan to facilitate tracheal intubation (balanced anesthesia).
Adults
The initial dose that allows intubation and the start of the surgical procedure is 0.06 mg/kg body weight to 0.10 mg/kg body weight. After administration of this dose, conditions suitable for intubation are observed after 150 seconds to 180 seconds, and muscle relaxation lasts for 60 to 90 minutes.
The initial dose that allows the start of the surgical procedure after intubation performed with succinylcholine is 0.05 mg/kg body weight. After administration of this dose, muscle relaxation lasts for 30 to 60 minutes.
The maintenance dose is 0.01 mg/kg body weight to 0.02 mg/kg body weight. Each subsequent dose prolongs the duration of muscle relaxation by approximately 30 to 60 minutes.
In order to achieve muscle relaxation in patients with renal impairment, it is not recommended to exceed a dose of 0.04 mg/kg body weight due to the prolonged effect of the muscle relaxant.
Reversal of relaxation
The neuromuscular blockade caused by Arduan usually subsides spontaneously. If necessary, the muscle relaxant effect can be reversed by administering anticholinesterase drugs intravenously, 0.5 mg to 2 mg of neostigmine methylsulfate and 0.6 mg to 1.20 mg of atropine sulfate (in separate syringes). The use of a peripheral nerve stimulator or observation of clinical signs of recovery from motor blockade allows assessment of the return of muscle strength. If necessary, reversal agents can be administered again.

Overdose of Arduan

In case of overdose and prolonged neuromuscular blockade, the patient should be artificially ventilated until spontaneous breathing is restored.
At the same time, the doctor will administer an antidote in the form of cholinesterase inhibitors in appropriate doses (e.g., neostigmine, pyridostigmine, edrophonium) until respiratory function is restored. Breathing will be constantly monitored by the doctor.
In case of any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Arduan can cause side effects, although not everybody gets them.
Although only a few cases of anaphylactic reactions have been reported with Arduan, appropriate equipment and medicines should always be available.
The following side effects have been reported rarely (may affect up to 1 in 1,000 people):

• Anaphylactic shock (anaphylactic reactions);
• Central nervous system disorders (CNS);
• Atrial fibrillation, myocardial ischemia, ventricular extrasystoles;
• Hypertension, thrombosis;
• Atelectasis, dyspnea, laryngospasm;
• Rash, urticaria;
• Muscle atrophy;
• Anuria.

The following side effects have been reported with an unknown frequency (frequency cannot be estimated from the available data):

• Decreased blood pressure (hypotension);
• Slight decrease in heart rate (bradycardia).

Reporting of side effects

If you experience any side effects, including any possible side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Arduan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Store in the original package to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Arduan contains

Each vial contains 4 mg of pipecuronium bromide.
The other ingredients are:
Vial: mannitol.
Ampoule (solvent): sodium chloride, water for injections.

What Arduan looks like and contents of the pack

Powder for solution for injection: white or almost white, sterile lyophilizate.
Solvent for solution for injection: clear, colorless, sterile solution.
25 vials with powder for 4 mg of active substance + 25 ampoules with solvent for 2 ml (0.9% sodium chloride solution) in a cardboard box.

Marketing authorization holder and manufacturer

Gedeon Richter Plc.
Gyömrői út 19-21
Budapest
Hungary
For more information about this medicine, please contact:
GEDEON RICHTER POLSKA Sp. z o.o.
Medical Department
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Phone: +48 (22)755 96 48
[email protected]
Fax: +48 (22) 755 96 24

Date of last revision of the leaflet: