Neorelium

Package leaflet: Information for the patient

NEORELIUM, 5 mg/ml, solution for injection
Diazepamum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor or nurse immediately. See section 4.

Table of contents:

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

1. What Neorelium is and what it is used for

Neorelium contains diazepam as the active substance, which belongs to a group of medicines called benzodiazepines. Diazepam has anxiolytic, sedative, anticonvulsant properties. It also has hypnotic effects and reduces skeletal muscle tension.
Neorelium is used:

• in states of severe nervous agitation and anxiety;
• in the treatment of severe symptoms of alcohol withdrawal ( delirium tremens );
• in treating conditions with increased skeletal muscle tension (tetanus, spastic states of various etiologies);
• in epileptic seizures, convulsive states due to poisoning, and febrile convulsions;
• as a sedative in preparation for surgical procedures and uncomfortable diagnostic examinations (e.g. endoscopy).

2. Important information before using Neorelium

When Neorelium must not be used
Do not use Neorelium if the patient has:

• hypersensitivity (allergy) to diazepam or other medicines in the benzodiazepine group, or to any of the excipients listed in section 6;
• severe respiratory insufficiency, regardless of cause;
• sleep apnoea syndrome (frequent, brief breathing interruptions during sleep);
• severe hepatic insufficiency;
• myasthenia gravis (a disease causing muscle weakness and excessive fatigue);
• phobias and obsessive-compulsive disorders;
• chronic psychoses.

Warnings and precautions
General information regarding effects observed during benzodiazepine treatment, which should be considered when using Neorelium.

• Tolerance
  After several weeks of Neorelium use, its effectiveness may decrease.

• Dependence
  Prolonged use of Neorelium may lead to psychological and physical dependence. The risk of dependence increases with higher doses and longer treatment duration, and is greater in patients with alcohol or drug dependence, as well as in patients with personality disorders.

• Withdrawal symptoms
  If Neorelium is stopped abruptly, withdrawal symptoms may occur, such as: headache, muscle pain, increased anxiety, tension, agitation, restlessness, disorientation, sleep disturbances, irritability. In more severe cases, symptoms may include: loss of reality perception, personality disturbances, hypersensitivity to sound, touch, light, noise, tingling and numbness in limbs, hallucinations and delusions, epileptic seizures.

• Rebound phenomenon and anxiety
  During discontinuation of Neorelium, a temporary recurrence of intensified symptoms that were the reason for treatment may occur (so-called "rebound" phenomenon). These symptoms are often accompanied by mood changes, anxiety, sleep disturbances, and insomnia. To minimize the risk of these effects, gradual dose reduction is recommended.

• Anterograde amnesia (inability to remember events after drug administration)
  Neorelium may cause anterograde amnesia (difficulty learning and remembering new information – new data are not permanently stored). This usually occurs within a few hours after drug administration, especially at higher doses. If the physician has recommended taking Neorelium once daily, to reduce the risk of anterograde amnesia, it is advised to take the medicine half an hour before going to bed and ensure appropriate conditions for continuous, uninterrupted sleep lasting 7–8 hours.

• Psychiatric and paradoxical reactions
  In children and elderly patients, the risk of abnormal and paradoxical (opposite to expected) reactions is increased, such as: anxiety, excitement, irritability, aggression, anger, rage, delusions, nightmares, hallucinations, psychoses, behavioural disturbances. If such symptoms occur, contact the physician immediately.

Specific patient groups

• Elderly and debilitated patients should receive lower doses of Neorelium due to the risk of increased adverse effects, mainly disturbances in orientation and motor coordination (falls, injuries).
• Patients with hepatic or renal insufficiency or chronic respiratory insufficiency should inform the physician about these conditions before taking Neorelium.
• Use in depression
  Before using Neorelium, inform the physician about any psychiatric disorders. Patients with symptoms of depression or anxiety associated with depression should receive combination therapy. Administering Neorelium alone to patients with depression may worsen depressive symptoms, including suicidal thoughts.
• Patients with porphyria (a blood disorder), myasthenia gravis, or atherosclerosis should inform the physician about these conditions before using Neorelium.
• In patients where a drop in blood pressure may lead to cardiovascular disturbances, Neorelium should be administered very slowly and with great caution.
• Patients dependent on alcohol, narcotics, or drugs should inform the physician about their addiction before taking Neorelium. These patients have a high risk of developing psychological and physical dependence. Therefore, this group of patients should use Neorelium only under strict medical supervision.

Neorelium and other medicines
Inform the physician about all medicines currently or recently taken, as well as any medicines the patient plans to take.
This is particularly important if the patient is taking any of the following medicines or consuming alcohol:

• fluvoxamine, fluoxetine, and other medicines used to treat psychiatric disorders;
• medicines used for insomnia;
• medicines used for allergic conditions that may cause drowsiness;
• medicines used for epilepsy (e.g. carbamazepine, phenytoin, hydantoin);
• muscle relaxants (e.g. Baclofen);
• levodopa (a medicine used in Parkinson’s disease);
• medicines used for peptic ulcer disease (e.g. cimetidine, omeprazole, cisapride);
• ketoconazole (an antifungal medicine);
• strong opioid analgesics (e.g. morphine);
• alcohol: drinking alcohol while taking Neorelium may enhance its effects and lead to paradoxical reactions such as psychomotor excitation and aggressive behaviour (see section 2., Warnings and precautions).

Concomitant use of Neorelium and opioids (strong painkillers, medicines used in substitution therapy for addiction, some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may even be life-threatening.
Therefore, concomitant use of these medicines should only be considered when no other treatment options are available.
If the physician prescribes Neorelium together with opioids, the dose and duration of concurrent treatment should be minimized.
The patient should inform the physician about all opioid medicines being taken and strictly follow medical advice. Informing family members or close friends about the potential for these symptoms to occur may be helpful. If such symptoms occur, contact the physician immediately.

Pregnancy and breastfeeding
During pregnancy, breastfeeding, or if pregnancy is suspected, or when planning pregnancy, consult a physician or pharmacist before using this medicine.

If the patient is pregnant or suspects she may be pregnant
If the patient suspects she is pregnant or is planning pregnancy, she should inform her physician.
Neorelium should not be used during pregnancy.

If the patient is breastfeeding
Neorelium passes into breast milk. If treatment is necessary, breastfeeding should be discontinued.

Driving and operating machinery
During treatment with Neorelium, patients should not drive or operate machinery.
The ability to drive and operate mechanical equipment may be impaired due to possible drowsiness, concentration disturbances, or other adverse effects reducing alertness (see section 4., Possible side effects).

Neorelium contains benzyl alcohol (15.5 mg/ml).
Benzyl alcohol may cause allergic reactions.
Administration of benzyl alcohol to small children is associated with the risk of serious adverse effects, including breathing disorders (so-called "gasping syndrome").
Do not administer to neonates (up to 4 weeks of age) without medical advice.
Do not administer to small children (under 3 years of age) for longer than one week without medical advice or pharmacist’s recommendation.

Pregnant or breastfeeding women should consult a physician before using this medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).
Patients with liver or kidney disease should consult a physician before using this medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).

Neorelium contains ethanol 12.5% v/v, i.e. 100 mg/ml, equivalent to 2.5 ml of beer or 1 ml of wine.
This should be taken into account when administering to pregnant or breastfeeding women, children, and patients at high risk, such as those with liver disease or epilepsy.
Alcohol contained in the medicine may alter the effects of other medicines.
Harmful for patients with alcoholism.

Neorelium contains propylene glycol (E 1520) (455 mg/ml).
In the recommended daily dose range of diazepam from 0.1 to 10 mg/kg body weight, the amount of propylene glycol ranges from 54.6 mg to 910 mg/kg body weight per day, respectively.
Before administering the medicine to a child under 5 years of age, consult a physician or pharmacist, especially if the child is taking other medicines containing propylene glycol or alcohol.
Pregnant or breastfeeding women should not take this medicine without medical advice. The physician may decide to perform additional tests in such patients.
Patients with impaired liver or kidney function should not take this medicine without medical advice. The physician may decide to perform additional tests in such patients.
Propylene glycol contained in this medicine may cause symptoms similar to alcohol consumption and may increase the likelihood of adverse effects.
Neorelium should not be used in doses containing more than 500 mg/kg body weight per day of propylene glycol in children under 5 years of age.
This medicine should only be used on a physician’s prescription.
The physician may decide to perform additional tests in patients taking this medicine.

Neorelium contains sodium benzoate (E 211) (49 mg/ml) and benzoic acid (E 210) (1 mg/ml).
Benzoic acid/salts of benzoic acid may increase the risk of jaundice (yellowing of the skin and whites of the eyes) in neonates (up to 4 weeks of age).

3. How to use Neorelium

Neorelium should always be used as directed by the physician.
In case of doubt, consult your doctor.
The medicine should be administered under medical supervision. It may be given intramuscularly or intravenously.
Except in emergencies, another person should always be present during intravenous administration; a resuscitation kit (for emergency treatment) should also always be available.
Patients should remain under medical supervision for at least one hour after administration of the drug. At home, the patient should always be accompanied by a responsible adult.

Adults

• In severe psychotic agitation and anxiety occurring in organic mental syndromes and psychoses: 5 to 10 mg intramuscularly or intravenously. The dose may be repeated after 4 hours.
• In acute alcohol withdrawal syndrome: initially 10 mg intramuscularly or intravenously, followed by 5 to 10 mg every 3 to 4 hours.
• In acute muscle spasms: 5 to 10 mg, intramuscularly or intravenously. The dose may be repeated after 4 hours.
• In tetanus: 0.1 to 0.3 mg/kg body weight every 4 hours via intravenous injection, or 3 to 10 mg/kg body weight via intravenous infusion every 24 hours. The number of doses depends on the patient's response to the drug.
• In epileptic seizures, seizures due to poisoning, and febrile convulsions: 0.15 to 0.25 mg/kg body weight (usually 10 to 20 mg) via intravenous injection or intramuscularly. If necessary, the dose may be repeated after 30–60 minutes. After seizure control is achieved, diazepam may be administered via intravenous infusion at a maximum dose of 3 mg/kg body weight per day to prevent recurrent seizures.
• In premedication (preparation for surgical procedures and uncomfortable diagnostic tests, e.g. endoscopy): 0.1 to 0.2 mg/kg body weight.

Children
In epileptic seizures, seizures due to poisoning, febrile convulsions:
0.2 to 0.3 mg/kg body weight intravenously or intramuscularly, or 1 mg per year of age. If there is no improvement after 5 minutes, the dose may be repeated.
Due to the presence of benzyl alcohol, the medicine should not be administered to premature infants and newborns (see section 2).

Duration of treatment
The duration of treatment is determined by the physician.

Use of a higher than recommended dose of Neorelium
The medicine is administered by a physician or nurse, so administration of a dose higher than recommended is unlikely. However, if the patient suspects having received an excessive dose, contact a physician immediately or go to the nearest hospital emergency department. The medicine should be brought along in its original packaging so that the medical staff can verify exactly which medicine was administered.
Symptoms of diazepam overdose include disturbances of consciousness, drowsiness, confusion, and slurred speech. In severe cases of poisoning, symptoms may include impaired motor coordination, hypotension, muscle weakness, respiratory depression, coma, and even death.

Missed dose of Neorelium
Do not use a double dose to make up for a missed dose.

Discontinuation of Neorelium
Do not stop using the medicine unless instructed by the physician. Symptoms of the illness may recur. If the physician decides to discontinue treatment, the dose should be gradually reduced over several days.
In case of any doubts regarding the use of the medicine, consult your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The frequency of adverse effects occurring after administration of the medicine has been defined as follows:
very common – occurs in more than 1 in 10 people;
common – occurs in less than 1 in 10 people;
uncommon – occurs in less than 1 in 100 people;
rare – occurs in less than 1 in 1,000 people;
very rare – occurs in less than 1 in 10,000 people;
frequency not known – cannot be estimated from the available data.

Serious adverse effects
If any of the following adverse effects occur, you should immediately
contact your doctor or go to the nearest hospital emergency department:

Occurring very rarely:

• severe allergic reaction manifesting as itching, swelling of lips or tongue, wheezing or difficulty breathing

Occurring with frequency not known:

• disorientation, excitement and agitation, depression with suicidal tendencies, anxiety, irritability, hallucinations, nightmares, illusions (seeing or hearing things that do not exist), psychoses (loss of contact with reality), unusual behaviour. These disorders most commonly occur in children and elderly patients. The frequency of occurrence of these symptoms cannot be determined from the available data.

Other adverse effects that may occur during treatment with Neorelium
The following adverse effects occur rarely:

• nausea, gastrointestinal discomfort, dry mouth

The following adverse effects occur with frequency not known:

• changes in the count of certain blood cells;
• skin rash, itching, urticaria;
• loss of appetite;
• paradoxical reactions – psychomotor agitation, insomnia, increased excitability and aggressiveness, muscle tremor, seizures. Paradoxical reactions most commonly occur after alcohol consumption, in elderly patients, and in patients with psychiatric disorders.
• psychological and physical dependence may develop during diazepam treatment at therapeutic doses. Abrupt discontinuation of treatment may lead to withdrawal syndrome. Patients who abuse alcohol or drugs are more susceptible to developing dependence. During diazepam treatment, previously existing undiagnosed depression may become apparent.
• drowsiness, dizziness, slowed reactions may occur during the first few days of treatment;
• somnolence, memory disturbances, motor coordination disorders, speech disturbances, changes in sexual drive;
• visual disturbances (blurred or double vision);
• slowed heart rate, chest pain;
• low blood pressure;
• slight increase in liver enzyme activity, liver function disturbances with jaundice (yellowing of the skin and whites of the eyes);
• muscle tremor, muscle weakness;
• urinary retention, urinary incontinence;
• menstrual disorders;
• general weakness, fainting;
• circulatory and respiratory depression have been observed after rapid intravenous administration. Keeping the patient in a lying position throughout the duration of injection or intravenous infusion and adhering to the recommended rate of diazepam administration almost completely eliminates such complications.
• phlebitis may occasionally occur at the injection site;
• pain, and sometimes redness at the injection site may occur following intramuscular injections.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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
Adverse effects can also be reported to the marketing authorisation holder.
By reporting adverse effects, additional information on the safety of this medicine can be collected.

5. How to store Neorelium

Keep out of the sight and reach of children.
Store below 25°C. Keep in the original packaging to protect from light.
Do not use the 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. This will help protect the environment.

6. Contents of the pack and other information

What Neorelium contains
The active substance is diazepam. 1 ml of solution contains 5 mg of diazepam.
The other ingredients are: propylene glycol (E 1520), 96% ethanol, benzyl alcohol, sodium
benzoate (E 211), benzoic acid (E 210), water for injections.

What Neorelium looks like and contents of the pack
Clear, colourless to yellow solution.
Pack: 50 ampoules (made of amber glass) containing 10 mg diazepam in 2 ml solution (5 mg/ml) in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint-Stock Company
A. Fleminga Street 2
03-176 Warsaw
Telephone number: 22 811-18-14

For further information, please contact the representative of the Marketing Authorisation Holder.

Information intended exclusively for medical professionals

Except in emergencies, another person should always be present during intravenous administration of the drug; resuscitation equipment must always be readily available. It is recommended that patients remain under medical supervision for at least one hour after administration of the drug. At home, the patient should always be accompanied by a responsible adult. Patients must be informed not to drive or operate machinery for 24 hours after drug administration.

Route of administration and preparation of solutions

Intramuscular injections
The Neorelium solution should be injected slowly and deeply into large muscle groups (the drug is relatively slowly absorbed).

Intravenous injections
The Neorelium solution should be administered slowly.
The contents of the ampoule should be injected slowly at a rate of 0.5 to 1 ml (2.5 to 5 mg) per minute (maximum 1 ml per minute) into large antecubital veins.
Too rapid intravenous administration of the drug may cause respiratory depression and a drop in arterial blood pressure.

Intravenous infusion
The product usually should not be diluted. An exception is the administration of the product as a slow intravenous infusion in a large volume of 0.9% sodium chloride solution or glucose solution in the treatment of tetanus and status epilepticus.
The contents of one ampoule (10 mg/2 ml) should be diluted in at least 50 ml of 0.9% sodium chloride solution or 5% glucose solution. Do not dilute more than 40 mg (8 ml solution – 4 ampoules) in 500 ml of 0.9% sodium chloride solution or 5% glucose solution.
The solution should be prepared immediately before administration and used within 6 hours.
The prepared Neorelium solution should be administered slowly.
Too rapid intravenous administration of the drug may cause respiratory depression and a drop in arterial blood pressure.
Glass bottles should be used for the preparation of solutions.
Over 50% of diazepam may be adsorbed onto the walls of plastic infusion containers. Adsorption onto plastic infusion set tubing may cause an initial significant reduction in the concentration of administered diazepam, which then slowly increases over several hours. The infusion rate should be frequently adjusted according to the patient's current condition.
Turbidity may occasionally occur during dilution of the drug, but usually disappears within a few minutes.
If turbidity does not disappear, the drug must not be administered.

Pharmaceutical incompatibilities
Neorelium must not be mixed with other drugs in the same syringe or infusion bottle.