Aciclovir noridem

Package leaflet: Information for the patient

Aciclovir Noridem, 250 mg, powder for solution for infusion
Aciclovir Noridem, 500 mg, powder for solution for infusion
Aciclovir

Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again later.
• If you have any further questions, please ask your doctor or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of the leaflet

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

1. What Aciclovir Noridem is and what it is used for

Aciclovir Noridem contains the active substance aciclovir. This medicine has a direct antiviral action (destroys or stops the growth of the virus causing shingles or herpes). It is used to treat certain infections caused by herpes viruses and certain forms of chickenpox and shingles (a viral disease characterized by a painful rash, for example on the eye).

2. Important information before taking Aciclovir Noridem

When not to take Aciclovir Noridem

• If the patient is allergic to aciclovir or to any of the other components of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Aciclovir Noridem, discuss this with your doctor, pharmacist,
or nurse.

• If the patient has kidney disease (impaired renal function).
• If the patient experiences back pain in the kidney area, which may be a symptom of kidney disease (impaired renal function); discontinuation of treatment may be recommended.
• If the patient is receiving intravenous aciclovir or taking high oral doses of aciclovir, adequate hydration should be maintained.

Aciclovir Noridem and other medicines
Inform your doctor or pharmacist about all medicines currently used or recently used,
as well as any medicines the patient plans to take.

• If Aciclovir Noridem is used concomitantly with other medicines that have nephrotoxic effects, this may increase the risk of impaired renal function. Caution is required when administering aciclovir intravenously in combination with other nephrotoxic drugs.
• Concomitant intravenous administration (administering several medicines simultaneously through the same infusion set and mixing them in one infusion) should not be used. This medicine may crystallize when mixed with certain other medicines.
• If the patient is taking lithium (a medicine used for mood disorders) concomitantly with high intravenous doses of aciclovir, serum lithium levels should be closely monitored due to the risk of lithium toxicity.
• If the patient is taking aciclovir concomitantly with theophylline (a medicine used in the treatment of asthma and certain respiratory diseases), the doctor may order blood tests to monitor theophylline levels.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant,
she should consult her doctor or pharmacist before using this medicine.
This medicine should not be used during pregnancy unless clearly recommended by a doctor.
If the patient becomes pregnant during treatment, she must inform her doctor, as only a doctor can decide whether treatment should continue.
Breastfeeding should not be performed during treatment with aciclovir, as it may pass into human milk.

Driving and operating machinery
The doctor will assess the patient's ability to drive and operate machinery based on the patient's health status and certain adverse effects, particularly those affecting the nervous system, which may occur during treatment (see section 4: Possible side effects).

Aciclovir Noridem contains sodium
250 mg vial
This medicine contains 26.1 mg of sodium (the main component of table salt) in each vial. This corresponds to 1.3% of the maximum recommended daily dietary sodium intake for adults.
500 mg vial
This medicine contains 52.2 mg of sodium (the main component of table salt) in each vial. This corresponds to 2.6% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Aciclovir Noridem

The patient will never self-administer this medication. The medicine will always be administered
to the patient by a person appropriately trained for this purpose.
Dosage
The dose is determined based on the patient's health status, age, and body weight.

• Adults: 5 to 10 mg/kg every 8 hours.
• Children over 3 months of age: the dose will be calculated based on body weight, 10 to 20 mg/kg every 8 hours, with a maximum dose of 400 mg to 800 mg every 8 hours, respectively.
• Neonates: 20 mg/kg every 8 hours.

Patients with impaired renal function
Caution should be exercised when administering acyclovir by infusion in patients with impaired renal function.

• If the patient has impaired renal function, the physician will adjust the dose of this medicine.
• If the patient is elderly, the physician will adjust the dose, as renal function may be reduced in older individuals.
• Dosage adjustment is required in obese patients, particularly those with impaired renal function and elderly patients.
• In infants and children with impaired renal function, the dose should be appropriately adjusted depending on the severity of renal impairment.
• In all cases, adequate hydration should be maintained
  during treatment to reduce the risk of renal function impairment.
  Method of administration
  This medicine is administered intravenously by trained medical personnel (intravenous administration only).
  Duration of treatment
  The treatment duration is usually 5 to 10 days. This period should be adjusted according to the patient's health status and response to treatment. In cases of neonatal herpes, and depending on the indication, the duration may be 14 or 21 days.
  Use of a higher than recommended dose of Aciclovir Noridem
  Consult a physician immediately.
  In certain situations (e.g., if the patient has kidney disease), neurological disorders may occur (see section 4: Possible side effects).
  If there are any further doubts regarding the use of this medicine, consult a physician, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Adverse reactions are listed below in order from most frequent to least frequent.

Common: (may occur in up to 1 in 10 patients)

• Gastrointestinal disorders:
  • nausea,
  • vomiting,
  • diarrhoea,
  • abdominal pain.
• Hepatic function disorders: increased bilirubin levels and increased liver enzyme activity (substances produced by the liver) in serum. These symptoms usually resolve after discontinuation of treatment.
• Skin reactions:
  • itching,
  • rash,
  • urticaria (rash resembling that caused by nettles).
• Renal function disorders: increased blood urea and creatinine levels (indicating impaired kidney function).
• General disorders: inflammatory skin changes or phlebitis (inflammation of a vein with blood clot formation) at the injection site of this medicine, which in rare cases of extravasation (when the medicine leaks out of the vein into which it was injected) or insufficient dilution of the solution may lead to necrosis (tissue death). Such inflammatory changes are related to the alkaline pH of this medicine.

Frequency not known: (cannot be estimated from the available data)

• Blood disorders:

  • thrombocytopenia (reduced platelet count – cells that enable blood clotting),
  • leukopenia (reduced white blood cell count).

• Nervous system disorders:

  • headache, dizziness.
  • Ataxia (problems with walking and lack of motor coordination), dysarthria (slurred speech and difficulty speaking), and balance disturbances, which may occur together or separately and may indicate cerebellar syndrome (a group of symptoms indicating significant cerebellar damage, the part of the brain responsible for balance).

• Neurological disorders, in some cases severe, which may indicate encephalopathy (brain disease) and include disorientation, agitation, tremors, myoclonus (involuntary muscle jerks), seizures, hallucinations, psychosis (personality disturbances), somnolence, and coma. These neurological symptoms are usually observed in patients with impaired kidney function who have received a higher than recommended dose, or in elderly patients (see "Warnings and precautions"). These symptoms usually resolve after discontinuation of treatment. The occurrence of these symptoms may be due to overdose; therefore, a doctor should be informed as soon as possible.

  • Hepatic function disorders: acute liver damage.
  • Respiratory system disorders: dyspnoea (difficulty breathing).
  • Immune system disorders: anaphylactic reaction (generalized allergic reaction).
  • Skin reactions: angioedema (sudden swelling of the face and neck).
  • Renal function disorders: acute renal failure, particularly in elderly patients or patients with impaired kidney function who have received a higher than recommended dose, and back pain in the kidney area which may indicate impaired kidney function (see also "Warnings and precautions"). The risk of acute renal failure is caused by overdose and (or) dehydration, or concomitant use of drugs that have nephrotoxic effects. Investigations for these predisposing factors should be performed regardless of patient age. The risk of renal function disorders can be avoided by using the correct dose, observing the warnings regarding use (especially maintaining adequate hydration), and administering the medicine by slow infusion.

Other adverse reactions
Frequency not known: (cannot be estimated from the available data)

• fatigue,
• fever.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Reactions of Medicinal Products, 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 reactions can also be reported to the responsible entity.
Reporting adverse reactions enables the collection of further information on the safety of the medicine.

5. How to store Aciclovir Noridem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and the outer carton after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
There are no special requirements for storage conditions regarding temperature.

After reconstitution 250 mg
Chemical and physical stability has been demonstrated for 24 hours at a temperature of 23°C to 27°C under artificial light, and at a temperature of 2°C to 8°C, after dissolution in 10 mL of water for injections or in sodium chloride solution 9 mg/mL (0.9%) for injection.

After reconstitution 500 mg
Chemical and physical stability has been demonstrated for 24 hours at a temperature of 23°C to 27°C under artificial light, and at a temperature of 2°C to 8°C, after dissolution in 20 mL of water for injections or in sodium chloride solution 9 mg/mL (0.9%) for injection.

After dilution 250 mg
Chemical and physical stability has been demonstrated for 12 hours at a temperature of 23°C to 27°C, at an acyclovir concentration of 2.5 mg/mL, after dilution with compatible solutions listed in the Information for Healthcare Professionals Only, Preparation and Handling.

After dilution 500 mg
Chemical and physical stability has been demonstrated for 12 hours at a temperature of 23°C to 27°C, at an acyclovir concentration of 5.0 mg/mL, after dilution with compatible solutions listed in the Information for Healthcare Professionals Only, Preparation and Handling.

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user and should generally not exceed 24 hours at a temperature of 2°C to 8°C, or the times specified above for chemical and physical stability, whichever is shorter, unless the method of opening/reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Aciclovir Noridem contains

• The active substance is aciclovir. Each 250 mg of powder for solution for infusion contains 250 mg of aciclovir (as sodium aciclovir). Each 500 mg of powder for solution for infusion contains 500 mg of aciclovir (as sodium aciclovir).
• The other ingredient is sodium hydroxide.

What Aciclovir Noridem looks like and contents of the pack
Aciclovir Noridem powder for solution for infusion is supplied in colourless glass vials (type I), with a capacity of 10 mL (for 250 mg) or 20 mL (for 500 mg), containing a white or almost white powder, closed with a bromobutyl rubber stopper, sealed with an aluminium cap and a polypropylene flip-off seal (250 mg: dark blue, 500 mg: yellow), packed in a cardboard box.
Pack sizes: 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Noridem Enterprises Limited
Evagorou & Makariou
Mitsi Building 3, Office 115
Nicosia 1065
Cyprus

Manufacturer
Demo S.A. PHARMACEUTICAL INDUSTRY
21st km National Road Athens-Lamia
14568 Krioneri, Attiki, Greece,
T: +30 210 8161802, F: +30 2108161587.

This medicinal product is authorised in the European Economic Area countries under the following names:

Germany
Aciclovir Noridem 250 mg Powder for solution for infusion
Aciclovir Noridem 500 mg Powder for solution for infusion

Romania
Aciclovir Noridem 250 mg Pulbere pentru soluţie perfuzabilă
Aciclovir Noridem 500 mg Pulbere pentru soluţie perfuzabilă

Czech Republic
Aciclovir Noridem
Aciclovir Noridem

Croatia
Aciklovir Noridem 250 mg prašak za otopinu za infuziju
Aciklovir Noridem 500 mg prašak za otopinu za infuziju

Austria
Aciclovir Noridem 250 mg Pulver zur Herstellung einer Infusionslösung
Aciclovir Noridem 500 mg Pulver zur Herstellung einer Infusionslösung

Italy
Aciclovir Noridem
Aciclovir Noridem

Poland
Aciclovir Noridem
Aciclovir Noridem

Slovakia
Aciclovir Noridem 250 mg Prášok na infúzny roztok
Aciclovir Noridem 500 mg Prášok na infúzny roztok

France
Aciclovir Noridem 250 mg Poudre pour solution pour perfusion
Aciclovir Noridem 500 mg Poudre pour solution pour perfusion

Spain
Aciclovir Noridem 250 mg polvo para solución para perfusión
Aciclovir Noridem 500 mg polvo para solución para perfusión

Portugal
Aciclovir Noridem
Aciclovir Noridem

Netherlands
Aciclovir Noridem 250 mg Poeder voor oplossing voor infusie
Aciclovir Noridem 500 mg Poeder voor oplossing voor infusie

Hungary
Aciclovir Noridem 250 mg Por oldatos infúzióhoz
Aciclovir Noridem 500 mg Por oldatos infúzióhoz

Slovenia
Aciklovir Noridem 250 mg prašek za raztopino za infundiranje
Aciklovir Noridem 500 mg prašek za raztopino za infundiranje

Information intended exclusively for healthcare professionals:

Preparation and handling
Prepare immediately before use. Any unused solutions must be discarded.
Reconstitution
Reconstitution of the medicinal product Aciclovir Noridem should be carried out using the specified volumes of water for injections or sodium chloride 9 mg/mL (0.9%) solution for injections to obtain a solution containing 25 mg of acyclovir per mL:
Volume of solvent for reconstitution
Vial 250 mg 10 mL
Vial 500 mg 20 mL
Based on the calculated dose, determine the appropriate number and size of vials required.
To reconstitute the contents of each vial, add the recommended volume of infusion solution to each vial and gently shake until the contents are completely dissolved.

Route of administration
The required dose of the medicinal product Aciclovir Noridem should be administered by slow intravenous infusion lasting at least one hour.
After reconstitution, the medicinal product Aciclovir Noridem may be administered using an infusion pump with controlled infusion rate. Alternatively, the reconstituted solution may be further diluted for intravenous infusion to achieve a concentration not exceeding 5 mg/mL (0.5% w/v).
The required volume of reconstituted solution should be added to the selected infusion solution according to the recommendations below, and the mixture should be shaken vigorously to ensure complete mixing.

In children and neonates, when the smallest possible volume of infusion solution is indicated, it is recommended to dilute the solution so that 4 mL of reconstituted solution (100 mg acyclovir) is added to 20 mL of infusion solution.

For adults, it is recommended to use infusion bags containing 100 mL of infusion solution, even if this results in an acyclovir concentration significantly below 5 mg/mL (0.5% w/v). Thus, one 100 mL infusion bag may be used for any dose between 250 mg and 500 mg acyclovir (10 mL to 20 mL of reconstituted solution), but for doses between 500 mg and 1000 mg, a second bag should be used.

After dilution according to the recommended scheme, the medicinal product Aciclovir Noridem is pharmaceutically compatible with the following infusion solutions:

• Sodium chloride 9 mg/mL (0.9%) solution for injections
• Sodium chloride 0.45% w/v solution for infusion
• Sodium chloride 0.18% w/v and glucose 4% w/v solution for infusion
• Sodium chloride 0.45% w/v and glucose 2.5% w/v solution for infusion
• Multicomponent sodium lactate solution (Hartmann's solution) for infusion

When diluted according to the above scheme, the medicinal product Aciclovir Noridem will result in an acyclovir concentration not exceeding 0.5% w/v.
Due to the absence of antimicrobial preservatives, reconstitution and dilution of the medicinal product must be performed under aseptic conditions immediately before use, and any unused portions of the solution must be discarded.
Reconstituted and diluted solutions must not be stored in a refrigerator.
If cloudiness or crystals appear in the solution before or during infusion, the solution must be discarded.
Any unused residues of the medicinal product or waste materials must be disposed of in accordance with local regulations.

Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products except those listed under "Route of administration".

Dosage and administration
Dosage
Dosage in patients with normal renal function is given below. In patients with impaired renal function, the dose must be adjusted according to the severity of renal impairment (see "Patients with renal impairment").
For recommendations on treatment duration, see "Duration of treatment".

Dosage in patients with normal renal function
Adults and adolescents (aged over 12 years)

• Varicella zoster virus (VZV) infections: 10 mg/kg body weight (b.w.) every 8 hours; 10–15 mg/kg b.w. every 8 hours in pregnant women
• Herpes simplex virus (HSV) infections (excluding meningitis and encephalitis): 5 mg/kg b.w. every 8 hours
• Herpes simplex encephalitis and meningitis: 10 mg/kg b.w. every 8 hours

Obese patients should receive the recommended adult dose based on ideal body weight, not actual body weight.

Children and adolescents
Children over 3 months of age
The dose for children aged between 3 months and 12 years must be calculated based on body weight.

• Herpes simplex virus infection (excluding meningitis and encephalitis) or Varicella zoster virus infection: 10 mg/kg b.w. every 8 hours, maximum dose 400 mg every 8 hours
• Herpes simplex encephalitis and meningitis or Varicella zoster virus infection in immunocompromised children: 20 mg/kg b.w. every 8 hours, maximum dose 800 mg every 8 hours

Neonates
For neonates and infants up to 3 months of age, the dose must be calculated based on body weight.

• In confirmed or suspected neonatal herpes simplex virus infection, the recommended dose is 20 mg/kg b.w. intravenously every 8 hours for 21 days in cases of disseminated infection or central nervous system involvement, or for 14 days in cases of skin, eye, or mucous membrane disease.

Dosage in patients with renal impairment
The interval between doses and the dose itself should be adjusted based on creatinine clearance expressed in mL/min for adults and adolescents, and in mL/min/1.73 m² body surface area (BSA) for infants and children under 13 years of age. Caution should be exercised when administering acyclovir to patients with renal impairment. Special attention should be paid to adequate fluid intake in such patients. The following dose adjustments are recommended.

Dose adjustment recommended for adults and adolescents over 12 years of age with renal impairment
| Creatinine clearance | Recommended dose and frequency according to indication |
|--------------------------|-------------------------------------------------------------|
| | HSV or VZV infection | VZV infection in immunocompromised patients or herpes simplex encephalitis and meningitis |
| 25–50 mL/min | 5 mg/kg b.w. every 12 hours | 10 mg/kg b.w. every 12 hours |
| 10–25 mL/min | 5 mg/kg b.w. every 24 hours | 10 mg/kg b.w. every 24 hours |
| 0 (anuria) to 10 mL/min | 2.5 mg/kg b.w. every 24 hours | 5 mg/kg b.w. every 24 hours |
| Patients undergoing hemodialysis | 2.5 mg/kg b.w. every 24 hours and after hemodialysis | 5 mg/kg b.w. every 24 hours and after hemodialysis |

Dose adjustment in children aged 12 years and younger, infants, and neonates with renal impairment
| Creatinine clearance (mL/min/1.73 m² BSA) | Recommended dose and frequency according to indication |
|---------------------------------------------|-------------------------------------------------------------|
| | HSV or VZV infection (excluding encephalitis and meningitis) | VZV infection in immunocompromised patients or herpes simplex encephalitis and meningitis |
| 25–50 mL/min/1.73 m² BSA | 10 mg/kg b.w. twice daily | 20 mg/kg b.w. twice daily |
| 10–25 mL/min/1.73 m² BSA | 5 mg/kg b.w. twice daily | 10 mg/kg b.w. twice daily |
| 0 (anuria) to 10 mL/min/1.73 m² BSA | 2.5 mg/kg b.w. twice daily | 5 mg/kg b.w. twice daily |
| Patients undergoing hemodialysis | 2.5 mg/kg b.w. twice daily, after hemodialysis | 5 mg/kg b.w. twice daily, after hemodialysis |

Elderly patients
Renal impairment should be considered in elderly patients, and dosage should be adjusted based on creatinine clearance (see "Dosage in patients with renal impairment"). Adequate fluid intake should be ensured.

Duration of treatment
Treatment duration is usually 5 days but may be adjusted depending on the patient's clinical condition and response to therapy. Duration of treatment is:

• 8–10 days for Varicella zoster virus infection
• 10 days for herpes simplex encephalitis and meningitis; this duration should be adjusted according to the patient's clinical status and response to treatment
• 5–10 days for other Herpes simplex virus infections
• 14 days for neonatal herpes simplex virus infection involving skin and mucous membranes (skin/eye/mouth)
• 21 days for neonatal herpes simplex virus infection presenting as disseminated disease or central nervous system infection

The duration of prophylactic use of the medicinal product Aciclovir Noridem depends on the length of the period of infection risk.

Route of administration
Intravenous use only
Each dose must be administered slowly by intravenous infusion (via pump or infusion) over at least one hour.
For instructions on reconstitution of the medicinal product prior to administration, see "Preparation and handling".

Overdose
Subjective and objective symptoms
Overdose of intravenously administered acyclovir leads to increased serum creatinine and blood urea levels, resulting in renal dysfunction. Neurological symptoms such as confusion, hallucinations, agitation, seizures, and coma have been observed after overdose.

Management
Patients should be closely monitored for signs of toxicity.
Hemodialysis effectively removes acyclovir from the blood and may be considered as a management strategy in cases of overdose symptoms.