Aciclovir Noridem 250 mg powder for solution for infusion EFG

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Aciclovir Noridem 250 mg powder for solution for infusion EFG

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor or nurse.

• If you experience any adverse reactions, consult your doctor or nurse, even if they are not adverse reactions listed in this leaflet. See section 4.

Leaflet Contents

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

2. What you need to know before starting to take Aciclovir Noridem

3. How Aciclovir Noridem is administered

4. Possible adverse effects

   1. How to store Aciclovir Noridem

5. 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 is a direct-acting antiviral agent (destroys or stops the growth of viruses that cause herpes zoster or herpes).

It is used to treat certain infections caused by the herpes virus and certain forms of chickenpox and herpes zoster (a viral disease characterized by a painful rash, for example, in the eye).

2. What you need to know before starting to take Aciclovir Noridem

Do not take Aciclovir Noridem

• if you are allergic to aciclovir or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use this medicine.

• if you have kidney problems (renal failure)
• if you experience back pain in the kidney area, this could be a sign of kidney problems (renal failure); discontinuation of treatment may be considered
• if you are receiving intravenous aciclovir or taking high doses of oral aciclovir, you should also maintain regular hydration.

Other medicines and Aciclovir Noridem

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

• using this medicine at the same time as other medicines that are toxic to the kidneys may increase the risk of kidney problems. Caution is required when administering aciclovir intravenously together with nephrotoxic drugs.
• avoid combined intravenous treatment (injection of several medicines simultaneously into the same tubing set, or similarly, mixing them in the same infusion). This medicine may crystallize when combined with certain medicines.
• if you are receiving lithium (a medicine used to regulate mood) at the same time as high doses of intravenous aciclovir, blood levels of lithium should be closely monitored due to the risk of lithium toxicity.
• if aciclovir is administered at the same time as theophylline (a medicine used to treat asthma and certain respiratory diseases), your doctor may request tests to measure theophylline levels in your blood.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

You must not take this medicine during pregnancy unless specifically instructed by your doctor.

If you find out you are pregnant while undergoing treatment, inform your doctor, as only they can determine whether you should continue treatment.

Avoid breastfeeding during treatment with aciclovir, as it may be excreted in breast milk.

Driving and using machines

Your doctor will assess your ability to drive vehicles and operate machinery based on your 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

This medicine contains 26.1 mg of sodium (a main component of table/cooking salt) per vial. This corresponds to 1.3% of the maximum daily recommended sodium intake for an adult.

3. How Aciclovir Noridem is administered

You must never administer this medicine to yourself. It will always be administered by a suitably qualified person.

Dosage

The dosage is determined according to the condition being treated and the patient's age and body weight.

• in adults: 5–10 mg/kg every 8 hours,
• in children over 3 months of age: the dose should be calculated according to body weight, 10 to 20 mg/kg every 8 hours, with a maximum dose of 400 mg to 800 mg every 8 hours, respectively,
• in newborn children: 20 mg/kg every 8 hours.

Use in patients with renal problems

Caution is recommended when administering aciclovir by infusion to patients with renal impairment.

• If you have kidney problems, your doctor will need to adjust your dose of this medicine.
• If you are elderly, your doctor will adjust the dose, as kidney function in elderly people may be reduced.
• In overweight patients, and particularly in those with renal problems and elderly individuals, the dose should be adjusted.
• In infants and children with renal problems, the dose must be appropriately adjusted depending on the severity of the renal impairment.
• In any case, it is important to maintain adequate hydration during treatment to reduce the risk of deterioration in renal function.

Method of administration

This medicine will be administered by a healthcare professional, who will inject it into a vein (strictly intravenous (IV) use).

Duration of treatment

The usual duration of treatment is 5 to 10 days. This should be adjusted according to the patient's condition and response to treatment. In the case of neonatal herpes, and depending on the indication, the duration may be 14 or 21 days.

If you are given more Aciclovir Noridem than you should

Contact your doctor immediately.

In some situations (for example, if you have kidney problems), neurological disorders may occur (see section 4: Possible side effects).

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount ingested.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

These adverse effects are classified from the most frequent to those observed less frequently.

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

• Gastrointestinal problems:

• nausea,

• vomiting,

• diarrhea,

• abdominal pain.

• Hepatic problems: increases in serum bilirubin and liver enzymes (substances produced by the liver).

These effects usually disappear when treatment is discontinued.

• Skin reactions:
  • pruritus (itching)
  • rash
  • urticaria (rash similar to that caused by stinging nettle stings).
• Renal problems: increased blood urea and creatinine (signs of impaired kidney function).
• General problems: inflammatory skin lesions or phlebitis (formation of a blood clot in a vein) at the injection site, which may exceptionally lead to necrosis (cell destruction) in cases of extravasation (when the medicine leaks out of the vein into surrounding tissue) or insufficient dilution of the solution. These inflammatory lesions are related to the alkaline pH of this medicine.

Frequency unknown: (frequency cannot be estimated from available data)

• Blood-related problems:

• thrombocytopenia (reduction in platelets, the cells responsible for blood clotting)

• leucopenia (reduction in white blood cells).

• Neuropsychiatric problems:

• Headache, dizziness.

• Balance disorders, ataxia (difficulty walking and lack of coordination), and dysarthria (slurred speech and articulation problems), which may occur together or in isolation and are signs of cerebellar syndrome (a set of signs and symptoms characteristic of significant damage to the cerebellum, a part of the brain involved in maintaining balance).

• Neurological problems, sometimes serious, which may indicate encephalopathy (brain disease) and include confusion, agitation, tremors, myoclonus (involuntary muscle contractions), seizures, hallucinations, psychosis (personality disturbances), somnolence, and coma. These neurological signs are usually observed in patients with kidney problems who have received doses higher than recommended, or in elderly patients (see "Warnings and precautions"). These effects usually resolve when treatment is stopped. The presence of these symptoms may indicate an overdose; consult your doctor as soon as possible.

• Hepatic problems: acute liver injury.

• Respiratory problems: dyspnea (difficulty breathing).

• Immune system problems: anaphylactic reactions (generalized allergic reaction).

• Skin reactions: angioedema (sudden swelling of the face and neck).

• Renal problems: acute renal failure, especially in elderly patients or those with pre-existing kidney problems if the dose is exceeded, and back pain around the kidney area, which may be associated with kidney problems (see also "Warnings and precautions").

The risk of acute renal failure is caused by overdose and/or dehydration, or by concomitant use of medicines that are nephrotoxic (toxic to the kidneys).

These risk factors should be controlled regardless of the patient's age. The risk of kidney problems can be avoided by adhering to the recommended dosage, observing usage precautions (especially maintaining adequate hydration), and administering the medicine slowly.

Other adverse effects

Frequency unknown: (frequency cannot be estimated from available data)

• fatigue,
• fever.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines at www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 following EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require special storage temperature conditions.

After reconstitution:

Chemical and physical in-use stability has been demonstrated for 24 hours at between 23 °C and 27 °C under artificial light, and between 2 °C and 8 °C when dissolved in 10 ml of water for injections or in an injection solution of sodium chloride 9 mg/ml (0.9 %).

After dilution:

Chemical and physical in-use stability has been demonstrated for 12 hours at between 23 °C and 27 °C at an aciclovir concentration of 2.5 mg/ml after dilution with the compatible solutions mentioned in the section "Information for healthcare professionals, Preparation and handling."

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage and handling conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at between 2 °C and 8 °C, or the previously stated periods for chemical and physical in-use stability—whichever is shorter—unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Aciclovir Noridem

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

Appearance of Aciclovir Noridem and contents of the pack

Aciclovir Noridem powder for solution for infusion is presented in colorless type I glass vials with a capacity of 10 ml, containing a white or almost white powder, closed with a 20 mm bromobutyl stopper and sealed with a 20 mm aluminum cap, with removable plastic flip-off caps of colored plastic (dark blue).

Pack sizes: 1, 5 or 10 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Noridem Enterprises Ltd.

Evagorou & Makariou

Mitsi Building 3, Office 115

1065 Nicosia, Cyprus

Manufacturer

DEMO S.A. PHARMACEUTICAL INDUSTRY

21st Km National Road Athens-Lamia.

14568 Greece

T: +30 210 8161802, F: +30 2108161587.

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany	Aciclovir Noridem 250 mg Powder for the preparation of an infusion solution
Romania	Aciclovir Noridem 250 mg Powder for infusion solution
Czech Republic	Aciclovir Noridem
Croatia	Aciclovir Noridem 250 mg Powder for infusion solution
Austria	Aciclovir Noridem 250 mg Powder for the preparation of an infusion solution
Italy	Aciclovir Noridem
Poland	Aciclovir Noridem
Slovakia France Spain Portugal Netherlands Hungary Slovenia	Aciclovir Noridem 250 mg Powder for infusion solution Aciclovir Noridem 250 mg Powder for solution for infusion Aciclovir Noridem 250 mg Powder for solution for perfusion Aciclovir Noridem Aciclovir Noridem 250 mg Powder for solution for infusion Aciclovir Noridem 250 mg Powder for infusion solution Aciclovir Noridem 250 mg Powder for solution for infusion

Date of last review of this summary: November 2022

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The following information is intended for healthcare professionals only:

Preparation and handling

It must be prepared immediately before use. Any unused solution must be discarded.

Reconstitution:

Aciclovir Noridem should be reconstituted using the following volumes of water for injections or 9 mg/ml (0.9%) sodium chloride injectable solution to obtain a solution containing 25 mg of aciclovir per ml:

Volume of liquid formulation for reconstitution

250 mg vial: 10 ml

Based on the calculated dose, the appropriate number and concentration of vials to be used must be determined.

To reconstitute each vial, add the recommended volume of perfusion fluid and gently shake until the vial contents are completely dissolved.

Administration

The required dose of Aciclovir Noridem must be administered by intravenous infusion over a period of one hour.

After reconstitution, Aciclovir Noridem may be administered using a controlled-rate infusion pump. Alternatively, the reconstituted solution may be further diluted to give an aciclovir concentration of no more than 5 mg/ml (0.5% w/v) for infusion administration.

The required volume of reconstituted solution should be added to the chosen perfusion solution, as recommended below, and mixed thoroughly to ensure adequate mixing.

For children and neonates, where it is recommended to keep the perfusion fluid volume to a minimum, dilution should be based on 4 ml of reconstituted solution (100 mg aciclovir) added to 20 ml of perfusion fluid.

For adults, perfusion bags containing 100 ml of perfusion fluid are recommended, even when this results in an aciclovir concentration substantially lower than 0.5% w/v. Therefore, a 100 ml perfusion bag may be used for any dose between 250 mg and 500 mg of aciclovir (10 and 20 ml of reconstituted solution), but a second bag should be used for doses between 500 mg and 1000 mg.

When diluted according to the recommended schemes, Aciclovir Noridem is known to be compatible with the following perfusion fluids:

• Sodium chloride 9 mg/ml (0.9%) injectable solution
• 0.45% w/v sodium chloride intravenous infusion
• 0.18% w/v sodium chloride and 4% w/v glucose intravenous infusion
• 0.45% w/v sodium chloride and 2.5% w/v glucose intravenous infusion
• Compound sodium lactate intravenous infusion (Hartmann's solution)

When diluted according to the above scheme, Aciclovir Noridem provides an aciclovir concentration not exceeding 0.5% w/v.

As no antimicrobial preservative is included, reconstitution and dilution must be carried out under completely aseptic conditions, immediately before use, and any unused solution must be discarded.

Reconstituted or diluted solutions must not be refrigerated.

If visible turbidity or crystallization occurs in the solution before or during infusion, the preparation must be discarded.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in the Administration section.

Dosage and method of administration

Dosage

The dose for patients with normal renal function is indicated below. In patients with abnormal renal function, dosage must be adjusted according to the degree of renal impairment (see section Patients with Renal Impairment).

For recommendations on treatment duration, see section Duration of Treatment.

Dosage in patients with normal renal function

Adults and adolescents (>12 years)

• Varicella zoster virus (VZV) infections: 10 mg/kg every 8 hours; 10–15 mg/kg every 8 hours in pregnant women
• Herpes simplex virus (HSV) infections (except meningoencephalitis): 5 mg/kg every 8 hours
• Herpes meningoencephalitis: 10 mg/kg every 8 hours

Obese patients should receive the recommended adult dose based on ideal body weight rather than actual body weight.

Paediatric population

In children over 3 months of age

In children aged between 3 months and 12 years, the dose should be calculated according to body weight.

• HSV infection (except meningoencephalitis) or VZV infections: 10 mg/kg every 8 hours, with a maximum dose of 400 mg every 8 hours
• HSV meningoencephalitis or VZV infection in immunocompromised children: 20 mg/kg every 8 hours, with a maximum dose of 800 mg every 8 hours

Neonates

In neonates and infants up to 3 months of age, the dose is calculated based on body weight.

• Known or suspected neonatal herpes: the recommended regimen is 20 mg/kg body weight intravenously every 8 hours for 21 days for disseminated disease and CNS involvement, or for 14 days for disease limited to skin and mucous membranes.

Dosage in patients with renal impairment

The dosing interval and dosage must be adjusted according to creatinine clearance in ml/min for adults and adolescents and in ml/min/1.73 m² for infants and children under 13 years of age. Caution is recommended when administering aciclovir by infusion to patients with renal impairment. In such patients, special care should be taken to ensure adequate fluid intake.

The following dosage adjustments are recommended.

Recommended dose adjustment in adults and adolescents > 12 years with renal impairment:

Creatinine clearance	Recommended dose unit and dosing frequency according to indication
VHS or VZV infections (except meningitis)	VZV infections in immunocompromised children or herpetic meningitis
25-50 ml/min	5 mg/kg body weight every 12 hours	10 mg/kg body weight every 12 hours
10-25 ml/min	5 mg/kg body weight every 24 hours	10 mg/kg body weight every 24 hours
0 (anuria) to 10 ml/min	2.5 mg/kg body weight every 24 hours	5 mg/kg body weight every 24 hours
Patients on hemodialysis	2.5 mg/kg body weight every 24 hours and after hemodialysis	5 mg/kg body weight every 24 hours and after hemodialysis

Dosage adjustment in children ≤ 12 years, infants and neonates with renal insufficiency:

Creatinine clearance (mL/min/1.73 m²)	Recommended dosage unit and dosing frequency by indication
In infants and children aged 3 months or older
Infection with HSV or VZV (except herpes encephalitis) VZV infection	VZV infections in immunocompromised patients or with herpes encephalitis
25–50 mL/min/1.73 m²	10 mg/kg body weight twice daily	20 mg/kg body weight twice daily
10–25 mL/min/1.73 m²	5 mg/kg body weight twice daily	10 mg/kg body weight twice daily
0 (anuria) to 10 mL/min/1.73 m²	2.5 mg/kg body weight twice daily	5 mg/kg body weight twice daily
Patients on hemodialysis	2.5 mg/kg body weight twice daily after hemodialysis	5 mg/kg body weight twice daily after hemodialysis

Advanced age

Renal impairment should be considered in elderly patients, and dosage should be adjusted according to creatinine clearance (see section “Dosage in patients with renal impairment”).

Adequate fluid intake should be ensured.

Duration of treatment

The usual duration of treatment is 5 days, but may be adjusted according to the patient's condition and response to therapy. The duration is:

• 8–10 days for varicella zoster virus infections
• 10 days for the treatment of herpetic meningoencephalitis; should be adjusted according to the patient's condition and response to treatment
• 5–10 days for other herpes simplex virus infections
• 14 days for the treatment of neonatal herpes due to mucocutaneous (skin/eye/mouth) infections
• 21 days for the treatment of neonatal herpes due to disseminated disease or central nervous system involvement.

The duration of prophylactic treatment with Aciclovir Noridem is determined by the length of the risk period.

Method of administration

Strictly intravenous route:

Each dose must be administered slowly by intravenous injection (via infusion pump or perfusion) over at least one hour.

For instructions on reconstitution of the medicinal product prior to administration, see the section Preparation and handling.

Overdose

Symptoms and signs

Intravenous aciclovir overdose has led to increased serum creatinine, elevated blood urea, and subsequent renal failure. Neurological effects such as confusion, hallucinations, agitation, seizures, and coma have been reported in association with overdose.

Treatment

Patients should be closely monitored for any signs of toxicity.

Haemodialysis significantly increases the removal of aciclovir from the bloodstream and may therefore be considered as a treatment option in cases of symptomatic overdose.