Chlorsuccillin

Package leaflet: Information for the patient

CHLORSUCCILLIN
200 mg, powder for solution for injection
(Suxamethonium chloride)
Please read all of this leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• Consult your doctor, pharmacist, or nurse if you have any doubts.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If any side effects occur which are not listed in this leaflet, inform your doctor, pharmacist, or nurse.

Table of contents of the leaflet:

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

1. What Chlorsuccillin is and what it is used for

Suxamethonium chloride is a depolarizing agent with a very short duration of action. It causes
skeletal muscle relaxation by depolarization of the neuromuscular junction. Immediately
after administration, brief muscle fasciculations occur, which subside after a few seconds, followed by
muscle relaxation.
After intravenous administration, the effect of suxamethonium chloride begins within 30 seconds
and lasts for approximately 5 minutes.
Indications
Short-term muscle relaxation required for tracheal intubation during short surgical procedures.
Adjunctive treatment of convulsions induced by electroshock or caused by overdose of certain drugs.

2. Important information before using Chlorsuccillin

When not to use Chlorsuccillin
Do not use the medicine if the patient has:

• hypersensitivity to suxamethonium chloride;
• myasthenia gravis;
• myopathies (with increased creatine kinase activity);
• a personal or family history of malignant hyperthermia (malignant fever);
• severe liver or kidney disease;
• increased intracranial pressure;
• open eye injuries;
• extensive tissue damage (in severe burns and major trauma);
• hyperkalemia (elevated blood potassium levels);
• genetically determined low plasma cholinesterase activity.

Warnings and precautions
The medicine is intended for hospital use only and may be administered solely by qualified medical personnel, provided that equipment for controlled ventilation is available.
Inform the doctor if the patient has:

• genetically determined cholinesterase activity disorders;

• severe generalized tetanus;

• tuberculosis and other severe chronic infections;

• severe burns;

• a disease associated with exhaustion;

• cancer;

• chronic anemia and malnutrition;

• end-stage liver failure;

• acute or chronic renal failure;

• autoimmune disease;

• myxedema (hypothyroidism);

• collagenosis. Inform the doctor also about:

• recent plasmapheresis, plasma exchange, or extracorporeal circulation;

• exposure to insecticides.

Other medicines and Chlorsuccillin
Tell the doctor about all medicines currently used or recently used, as well as any medicines the patient plans to take.
In particular, inform about the use of the following medicines:

• anesthetics and analgesics;
• eye drops used for elevated intraocular pressure;
• medicines used for cough, colds, and allergies;
• medicines used in the treatment of malaria;
• oral contraceptives;
• medicines used in the treatment of asthma and other respiratory disorders;
• medicines used in cancer treatment (cytotoxic drugs);
• medicines used in the treatment of psychiatric disorders;
• medicines containing magnesium salts;
• medicines containing steroids;
• medicines containing estrogens;
• antibiotics;
• medicines used in cardiac arrhythmias;
• medicines used in the treatment of myasthenia gravis;
• immunosuppressive medicines.
  Also inform about possible exposure to insecticides.

Pregnancy, breastfeeding, and effects on fertility
During pregnancy, while breastfeeding, or if pregnancy is suspected or planned, consult a doctor before using this medicine.
Use during pregnancy
The medicine may be used during pregnancy only if, in the opinion of the doctor, the benefit to the mother outweighs the potential risk to the fetus.
When considering the use of suxamethonium chloride for muscle relaxation during delivery, one must consider the possibility of the drug crossing the placenta and causing apnea in the newborn. This effect may occur after administering suxamethonium chloride to the mother in doses exceeding 1 mg/kg body weight.
Breastfeeding
Due to its short half-life and lack of effect on lactation, there are no contraindications to the use of suxamethonium chloride during breastfeeding.
Driving and operating machinery
Suxamethonium chloride severely impairs psycho-physical performance. Absolute prohibition of driving and operating machinery applies for 24 hours after administration of the medicine.

3. How to use Chlorsuccillin

The medicine may be given as an intravenous injection or infusion.
This medicine can only be administered by medical personnel.
During administration of the medicine, respiratory function must be monitored or controlled ventilation must be used.
The doctor will decide how and in what dose to administer this medicine. This depends on:

• the patient's body weight;
• the degree of muscle relaxation required in the individual case;
• the expected response to the medicine.

4. Possible adverse effects

Like all medicines, this medicinal product can cause adverse effects, although not everybody will experience them.

Cardiac disorders:
Large doses, especially when repeated, may cause dangerous bradycardia and sudden drop in blood pressure. Bradycardia can be prevented by prior administration of atropine.
The depolarizing mechanism of action of suxamethonium chloride causes a rapid and significant shift of potassium ions (K⁺) from muscle cells into blood serum. This is particularly dangerous in conditions with pre-existing hyperkalemia (e.g. burns, extensive muscle damage, severe infections).

Musculoskeletal and connective tissue disorders:
Repeated administration of high doses of suxamethonium chloride may also lead to phase II block, usually accompanied by transient fascicular muscle twitching, especially in the face, neck, and limbs. Immediately after administration of the drug, generalized skeletal muscle rigidity may occur, which may trigger malignant hyperthermia. These effects can be prevented by administering, prior to suxamethonium chloride, a small dose of a non-depolarizing neuromuscular blocking agent, e.g. tubocurarine.

Eye disorders:
Transient increase in intraocular pressure.

Respiratory, thoracic and mediastinal disorders:
Bronchospasm.

Gastrointestinal disorders:
Excessive salivation.

Skin and subcutaneous tissue disorders:
Rash.

Immune system disorders:
Anaphylactic reactions.

Reporting of adverse effects
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Chlorsuccillin

Store below 25°C. Keep in the original packaging to protect from light.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Package Contents and Other Information

What Chlorsuccillin contains:
The active substance in Chlorsuccillin is suxamethonium chloride.
Each vial contains 200 mg of suxamethonium chloride.

What Chlorsuccillin looks like and contents of the package:
A white or almost white solidified or partially fragmented mass (lyophilisate). The product may appear as a more or less compacted mass adhering to the bottom and walls of the vial or as a so-called "cake" attached to the vial walls at various levels. The surface of the product may be matte or slightly glossy.
The package contains 10 vials made of colorless glass, closed with a rubber stopper and sealed with a red aluminum cap, placed in a cardboard box.

Marketing Authorisation Holder:
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus,
Dublin 24, D24PPT3
Ireland

Manufacturer:
Przedsiębiorstwo Farmaceutyczne Jelfa SA
58-500 Jelenia Góra, ul. Wincentego Pola 21

The following information is intended exclusively for medical personnel or healthcare professionals.

Warnings and Precautions
Chlorsuccillin must not be administered to patients in whom an increase in serum potassium ion (K⁺) concentration (normal range: 3.6–5.4 mmol/L in healthy individuals) may reach life-threatening levels, e.g., severely burned patients (especially within 2–6 weeks after the burn), patients with major trauma, paraplegia, spinal cord injury, or muscle damage.

In healthy individuals, administration of suxamethonium chloride rarely causes transient elevation of serum potassium levels. However, in certain pathological conditions, such an increase may be significant and may lead to severe cardiac arrhythmias, up to cardiac arrest.

Patients with neurological injury associated with flaccid paralysis of large muscle groups (upper and lower motor neuron disease) are at risk of increased potassium levels during the first 6 months following acute neurological injury. This risk correlates with the degree and extent of muscle paralysis. Patients requiring immobilization are particularly susceptible.

In healthy adults, suxamethonium chloride may cause transient bradycardia at the beginning of administration. Bradycardia is more frequently observed in children and with repeated dosing, in both children and adults. Preoperative intravenous administration of atropine significantly reduces the risk of severe bradycardia induced by suxamethonium chloride.

Repeated frequent administration of suxamethonium chloride may lead to tachyphylaxis.

Suxamethonium chloride may cause cardiac arrhythmias. The risk is increased when used concomitantly with cardiac glycosides (digitalis).

Extreme caution is required when used concomitantly with local anesthetics and in patients with elevated or reduced body temperature.

Prolonged and intensified neuromuscular blockade (when a dose of 1–1.5 mg/kg body weight lasts for 3–6 hours, due to very slow metabolism) may occur secondarily due to decreased plasma cholinesterase activity in the following pathological conditions: physiological changes during pregnancy and postpartum, genetically determined cholinesterase activity disorders, severe generalized tetanus, tuberculosis, other severe chronic infections, severe burns, cachexia, neoplastic disease, chronic anemia and malnutrition, end-stage liver failure, acute or chronic renal failure, autoimmune diseases, myxedema, collagenoses, iatrogenic conditions such as plasma exchange, plasmapheresis, extracorporeal circulation, and concomitant use of other drugs.

Prolonged depolarizing block and muscle relaxation may also occur in individuals occupationally exposed to esterase inhibitors (e.g., those in contact with organophosphate insecticides).

Controlled ventilation must be maintained in the patient until complete elimination of the drug.

Before administering neuromuscular blocking agents, plasma cholinesterase phenotype should be determined in the individual patient.

Suxamethonium chloride may act as a triggering agent causing prolonged skeletal muscle contraction in susceptible individuals and is contraindicated in patients with a family history of malignant hyperthermia. If such a condition unexpectedly develops, administration of all anesthetic agents (including suxamethonium chloride) potentially involved must be discontinued immediately, and all possible countermeasures should be initiated without delay. First-line treatment consists of rapid intravenous infusion of sodium dantrolene.

Drug Interactions
Some drugs or chemical compounds reduce plasma cholinesterase activity and may prolong neuromuscular blockade after suxamethonium chloride administration. These include: organophosphate insecticides; eye drops containing echothiophate iodide; trimethaphan; cholinesterase antagonists: neostigmine, pyridostigmine, physostigmine, edrophonium; cytotoxic drugs: cyclophosphamide, thiotepa; psychotropic drugs: phenelzine, promazine, chlorpromazine; anesthetic agents: ketamine, morphine and morphine antagonists, pethidine, pancuronium.

Drugs potentially reducing plasma cholinesterase activity include: aprotinin, diphenhydramine, promethazine, estrogens, oxytocin, high-dose steroids, and oral contraceptives.

Some drugs or substances may potentiate or prolong the neuromuscular effects of suxamethonium chloride via mechanisms unrelated to cholinesterase activity. These include: magnesium salts, lithium carbonate, azathioprine, quinine, and chloroquine; antibiotics such as aminoglycosides, clindamycin, and polymyxins; antiarrhythmic drugs such as quinidine, procainamide, verapamil, beta-adrenergic receptor blockers, lignocaine, and procaine; inhalational anesthetics: halothane, enflurane, isoflurane, and ether for anesthesia have minimal effect on the phase I block induced by suxamethonium but may accelerate or intensify the phase II block induced by suxamethonium.

In cases where the depolarizing block changes into a phase II (non-depolarizing) block, which may occur after repeated doses of suxamethonium chloride, cholinesterase inhibitors may partially reverse the block.

Solutions of suxamethonium chloride must not be mixed in the same syringe with thiopental.

How to use Chlorsuccillin
Preparation of the medicinal product before injection or intravenous infusion
Immediately before administration, a solution is prepared by dissolving the contents of the vial in water for injections or 0.9% sodium chloride solution for injections.

The prepared solution must not be mixed in the same syringe with other medicinal products, including thiopental.

For intravenous injection, solutions containing 2% suxamethonium chloride are prepared by dissolving the contents of one vial in 10 mL of water for injections or 10 mL of 0.9% sodium chloride solution for injections.

For intravenous infusion, solutions containing 0.1% or 0.2% suxamethonium chloride are prepared by dissolving and diluting the contents of one vial in 200 mL or 100 mL, respectively, of diluent: water for injections or 0.9% sodium chloride solution for injections.

Stability after reconstitution
From a microbiological standpoint, the solution should be used immediately after preparation. If not used immediately, the user is responsible for the storage conditions and duration prior to use. The solution should not be stored for longer than 24 hours at 2–8°C, unless reconstitution was performed under controlled and validated aseptic conditions.

Dosage
Dosage is determined individually by the physician according to the type of procedure, patient's body weight, and individual sensitivity to suxamethonium chloride. It is recommended to perform a test dose to determine individual sensitivity, onset, and duration of action. For this purpose, 10 mg of the drug is administered intravenously.

Adults
Depending on the desired degree of muscle relaxation and expected duration of the procedure:

• For short surgical procedures:
  Intravenously: The average dose for short-term muscle relaxation is 40 mg (2 mL of 2% solution). The optimal dose may range from 20 mg to 80 mg (1 mL to 4 mL of 2% solution) (0.5 mg to 1.5 mg/kg body weight). Muscle relaxation occurs within approximately 1 minute, with maximal effect lasting about 2 minutes. Recovery to the pre-drug state occurs within 8–10 minutes.

• For prolonged surgical procedures:
  Intravenously or by continuous infusion: 0.1 mg to 0.5 mg, or even up to 1 mg/kg body weight. The infusion dosage depends on the duration of the procedure and the required degree of muscle relaxation. Typically, the continuous intravenous infusion rate is 2.5 mg to 4 mg per minute. The total dose administered, whether by repeated injections or infusion, must not exceed 500 mg per hour.

Use in Pediatrics
The drug is administered intravenously at the following doses:
Children: 1 mg to 2 mg/kg body weight.
Lower doses are recommended for older children.
Newborns and infants: 2 mg to 3 mg/kg body weight.
The total dose used in pediatric patients must not exceed 150 mg.

Use of a higher than recommended dose of Chlorsuccillin
In cases of overdose (e.g., due to too frequent repeated doses of suxamethonium chloride during general anesthesia), a so-called "dual block" may occur, i.e., transformation of the depolarizing block into a non-depolarizing (competitive) block. Overdose leads to prolonged muscle relaxation, prolonged apnea, and cardiac arrhythmias.
Treatment primarily includes controlled ventilation, oxygen therapy, and blood or plasma transfusion.