ACICLOVIR NORIDEM 250 mg POWDER FOR SOLUTION FOR INFUSION

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

Do not takeAciclovir Noridem

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start taking this medicine.

• if you have kidney problems (renal insufficiency)
• if you experience back pain in the kidney area, this could be a sign of kidney problems (renal insufficiency); treatment may need to be discontinued
• if you are given intravenous aciclovir or taking high doses of oral aciclovir, you should also stay hydrated regularly.

Other medicines andAciclovir Noridem

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

• the use of this medicine at the same time as other medicines that are toxic to the kidneys may increase the risk of kidney problems. Caution should be exercised when administering aciclovir intravenously with nephrotoxic medicines.
• avoid combined intravenous treatment (injection of several medicines at the same time in the same set of tubes and, similarly, mixing them in the same infusion). This medicine may crystallize when combined with certain medicines.
• if you are given lithium (a medicine used to regulate mood) at the same time as high doses of intravenous aciclovir, your lithium blood levels should be closely monitored due to the risk of lithium toxicity.
• if you are given theophylline (a medicine used to treat asthma and some respiratory diseases) at the same time as aciclovir, your doctor may ask you to have tests to measure theophylline levels in your blood.

Pregnancy, breastfeedingand 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.

You should not take this medicine during pregnancy unless your doctor advises you to.

If you become pregnant during treatment, tell your doctor as soon as possible. Only your doctor can decide whether you need to 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 use machines, based on your health and certain side effects, especially in the nervous system, that may occur during treatment (see Section 4: Possible side effects).

Aciclovir Noridemcontains sodium

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

3. How to take Aciclovir Noridem

This medicine should never be administered by yourself. It will always be administered by a person who is properly qualified to do so.

Posology

The dosage is determined based on the condition being treated and the patient's age and weight.

• in adults:5-10 mg/kg every 8 hours,
• in childrenover 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 newborns:20 mg/kg every 8 hours.

Use in patients with kidney problems

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

• 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 patients who are overweight and particularly in those with kidney problems and elderly people, the dose should be adjusted.
• In infants and children with kidney problems, the dose should be adjusted according to the extent of the kidney problems.
• In any case, it is important that you stay hydrated during treatment to reduce the risk of kidney function deterioration.

Method of administration

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

Duration of treatment

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

If you are given moreAciclovir Noridemthan you should

Talk to your doctor immediately.

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

In case of overdose or accidental ingestion, talk to your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

These side effects are classified from the most frequent to the least frequent.

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

• Gastrointestinal problems:

• nausea,
• vomiting,
• diarrhea,
• abdominal pain.

• Liver problems:increased bilirubin and liver enzymes (substances produced by the liver) in the blood.

These effects usually disappear when treatment is discontinued.

• Skin reactions:
• • pruritus (itching)
  • rash
  • urticaria (rash identical to that caused by nettle stings).
• Kidney problems:increased urea and creatinine in the blood (sign of kidney function problems).
• General problems:inflammatory skin lesions or phlebitis (formation of a blood clot in a vein) at the injection site, which can cause necrosis (cell destruction) in exceptional cases of extravasation (when the medicine leaks out of the vein it was injected into) or insufficient dilution of the solution. These inflammatory lesions are related to the alkaline pH of this medicine.

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

• Blood problems:

• thrombocytopenia (decreased platelets, which are the cells that allow blood to clot)
• leukopenia (decreased white blood cells).

• Neuropsychiatric problems:

• headache, dizziness.
• balance problems, ataxia (problems walking and lack of coordination) and dysarthria (slowness of speech and articulation problems), which can occur together or separately and are evidence of a cerebellar syndrome (set of signs and symptoms characteristic of fairly severe damage to the cerebellum, a part of the brain used to maintain balance).
• neurological problems, sometimes severe, which can indicate encephalopathy (brain disease) and include confusion, agitation, tremors, myoclonus (involuntary muscle contractions), convulsions, hallucinations, psychosis (personality problems), somnolence, and coma. These neurological signs usually occur in patients with kidney problems who have received higher doses than recommended or in elderly patients (see "Warnings and precautions"). These effects usually disappear when treatment is discontinued. The presence of these symptoms may be due to an overdose; talk to your doctor as soon as possible.

• Liver 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).
• Kidney problems:acute kidney failure, especially in elderly people or those with kidney problems if the dose is exceeded, back pain around the kidney area, which may be associated with kidney problems (see also "Warnings and precautions").

The risk of acute kidney failure is caused by an overdose and/or dehydration, or by combination with medicines that are 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 following the posology, precautions for use (especially maintaining adequate hydration) and a slow administration rate.

Other side effects

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

• fatigue,
• fever.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System, www.notificaRAM.es. By reporting side 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 which is stated on the vial and carton after EXP. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

After reconstitution:

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

After dilution:

Chemical and physical stability in use has been demonstrated for 12 hours at 23°C to 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 point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C or the times established above for chemical and physical stability in use, whichever is shorter, unless the opening/reconstitution/dilution has taken place in 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. Container Content and Additional Information

Composition ofAciclovir Noridem

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

Appearance ofAciclovir Noridemand container content

Aciclovir Noridem powder for solution for infusion is presented in colorless glass vials type I, with a capacity of 10 ml, which contain a white or off-white powder, closed with a 20 mm bromobutyl plug and sealed with 20 mm aluminum caps, with detachable blue plastic caps.

Container sizes: 1, 5 or 10 vials.

Only some container 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:

Date of last revision of this leaflet: November 2022

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Preparation and handling

It should be prepared immediately before use. Unused solution should be discarded.

Reconstitution:

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

Volume of liquid for reconstitution formulation

250 mg vial 10 ml

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

To reconstitute each vial, the recommended volume of infusion liquid should be added and shaken gently until the vial contents are completely dissolved.

Administration

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

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

The required volume of reconstituted solution should be added to the chosen infusion solution, as recommended below, and shaken well to ensure adequate mixing.

For children and neonates, in whom the volume of infusion liquid should be kept to a minimum, it is recommended that the dilution be based on 4 ml of reconstituted solution (100 mg of aciclovir) added to 20 ml of infusion liquid.

For adults, it is recommended to use infusion bags containing 100 ml of infusion liquid, even if this provides a substantially lower concentration of aciclovir than 0.5% w/v. Therefore, a 100 ml infusion bag can 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 infusion liquids:

• 9 mg/ml (0.9%) sodium chloride injection 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
• Composite sodium lactate intravenous infusion (Hartmann solution)

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

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

Reconstituted or diluted solutions should not be refrigerated.

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

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Incompatibilities

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

Posology and method of administration

Posology

The dose for patients with normal renal function is indicated below. In patients with abnormal renal function, the posology should be adjusted according to the level of renal insufficiency (see section Patients with renal insufficiency).

Regarding recommendations on treatment duration, see the section Treatment duration.

Posology 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.
• Herpetic meningoencephalitis: 10 mg/kg every 8 hours

Patients with obesity should be given the recommended dose for adults based on ideal body weight rather than actual body weight.

Pediatric population

Children over 3 months of age

In children between 3 months and 12 years of age, 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 of body weight intravenously every 8 hours for 21 days for disseminated or CNS disease, or for 14 days for disease confined to the skin and mucous membranes.

Posology in patients with renal insufficiency

The interval between doses and posology should 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. Caution is recommended when administering aciclovir by infusion to patients with renal insufficiency. In such patients, care should be taken to ensure adequate fluid intake.

The following dose adjustments are proposed.

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

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

Elderly

The possibility of renal insufficiency in elderly patients should be considered and the posology adjusted according to creatinine clearance (see section “Posology in patients with renal insufficiency”).

Adequate fluid intake should be ensured.

Treatment duration

The duration of treatment is generally 5 days, but may be adjusted according to the patient's condition and response to treatment. 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 for mucocutaneous (skin/eye/mouth) infections
• 21 days for the treatment of neonatal herpes for disseminated or CNS disease.

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

Method of administration

Intravenous use only:

Each dose should be injected slowly intravenously (by pump or infusion) for at least one hour.

For instructions on reconstituting the medicinal product before administration, see the section Preparation and handling.

Overdose

Symptoms and signs

Overdose of intravenous aciclovir has caused increased serum creatinine, blood urea, and consequent renal insufficiency. Neurological effects such as confusion, hallucinations, agitation, seizures, and coma have been described in association with overdose.

Treatment

Patients should be closely monitored for any signs of toxicity.

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