Package leaflet: Information for the patient

ACIX 500, 500 mg, powder for solution for infusion
Aciclovirum
Please read the entire leaflet carefully before using this medicine, as 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 consult your doctor, nurse, or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm other people, even if their symptoms are the same.
If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor, nurse, or pharmacist. See section 4.

Table of contents

What ACIX is and what it is used for
Important information before using ACIX
How to use ACIX
Possible side effects
How to store ACIX
Contents of the pack and other information

1. What ACIX is and what it is used for

ACIX powder for solution for infusion contains the active substance aciclovir – a synthetic antiviral agent that inhibits the replication of herpes-type viruses, including Herpes simplex (HSV) types 1 and 2, Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV).

Indications for ACIX
Herpes simplex encephalitis.
Severe primary genital herpes infections caused by Herpes simplex virus.
Chickenpox, shingles (infections caused by Varicella-zoster virus).
Skin and mucous membrane infections caused by herpes simplex virus in patients with congenital immunodeficiency or secondary immunodeficiency during immunosuppressive or cytotoxic therapy.
Prophylaxis of herpes simplex virus infections in immunocompromised individuals, e.g. during intensive immunosuppressive treatment.
Herpes simplex virus infection in newborns.

2. Important information before using ACIX

When not to use ACIX
Do not use ACIX if the patient is allergic to aciclovir, valaciclovir, or to any of the other ingredients
of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with ACIX, discuss this with your doctor.
The patient should drink plenty of fluids to maintain adequate hydration.
Dosage adjustment may be necessary in patients with impaired renal function and in elderly patients due to the potential for aciclovir accumulation in the body.
For patients receiving high intravenous doses of aciclovir, the doctor will recommend monitoring tests of kidney function, especially in dehydrated patients or those with impaired renal function.
Long-term or repeated use of aciclovir in patients with significantly reduced immunity may lead to the selection of viral strains resistant to the drug.
The prepared solution must not be taken orally due to its highly alkaline reaction (pH approximately 11.0).

ACIX with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to use.
Aciclovir is eliminated via the kidneys. If the patient receives intravenous aciclovir together with other drugs that are also eliminated this way, serum concentrations of one or both drugs may increase. The doctor will closely monitor the patient's condition.
Probenecid and cimetidine reduce the renal excretion of aciclovir, but dosage adjustment of aciclovir is not required.
Concomitant administration of aciclovir and mycophenolate mofetil (a medicine used to prevent organ transplant rejection) increases the overall effect of these drugs on the patient's body.
High-dose intravenous aciclovir may increase the toxicity of lithium when administered simultaneously.
Caution is required when administering intravenous aciclovir together with medicines affecting kidney function (such as cyclosporine and tacrolimus).
The doctor will recommend monitoring tests of kidney function in the patient.
When aciclovir is used concomitantly with theophylline, the doctor will monitor theophylline blood levels in the patient.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she might be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
This medicine may be administered during pregnancy only if, in the opinion of the doctor, the expected benefits of using aciclovir outweigh the potential risks to the fetus.
Aciclovir passes into breast milk.
Caution is advised when administering aciclovir to breastfeeding women.

Driving and operating machinery
Aciclovir, when administered as intravenous infusion, is generally given to hospitalized patients; therefore, information regarding the effect of the product on the ability to drive or operate machinery is usually not applicable. Furthermore, there are no studies evaluating the effect of aciclovir on performing these activities.

ACIX contains sodium
This medicine contains 48.8 mg of sodium (the main component of table salt) per vial. This corresponds to 2.4% of the maximum recommended daily dietary sodium intake for adults.
The medicine may be diluted with 0.9% sodium chloride solution. The sodium content originating from the diluent should be considered when calculating the total sodium content in the prepared diluted solution. For precise information on the sodium content in the diluent solution used to dilute the medicine, refer to the patient leaflet of the diluent used.

3. How to use ACIX

This medicine should always be used according to the doctor's instructions. In case of doubt, consult
your doctor.
The acyclovir dose calculated per kilogram of body weight is the same for all patients.
For children aged 3 months to 12 years, the acyclovir dose is calculated based on body surface area
to avoid administering too low doses.
In patients with normal kidney function, the medicine is given three times daily, every 8 hours.
The recommended dosing is presented below.
Table 1. Adults, children over 12 years of age, infants under 3 months of age,
and newborns
a) Patients with normal immune function

Indications	Single dose of acyclovir (mg/kg b.w.)	Daily dose in patients with normal renal function (mg/kg b.w.)	Mean duration of treatment (days)
Primary genital herpes	5	15	5*
Herpes zoster	5	15	5*
Herpes simplex encephalitis	10	30	10
Neonatal herpes	10	30	10

b) Patients with reduced immunity

Indications	Single dose of acyclovir (mg/kg b.w.)	Daily dose in patients with normal renal function (mg/kg b.w.)	Mean duration of treatment (days)
Herpes simplex	5	15	5*
Varicella	10	30	5*
Herpes zoster	10	30	5*

In individual cases, depending on the type and duration of the disease, the medication may be
administered for a longer period.
Table 2. Children from 3 months to 12 years of age
a) Patients with normal immunity

Indications	Single dose of acyclovir (mg/m2 BSA)	Daily dose in patients with normal renal function (mg/m2 BSA)	Mean duration of treatment (days)
Initial genital herpes	250	750	5*
Herpes zoster	250	750	5*
Herpes simplex encephalitis	500	1500	10

b) Patients with reduced immunity

Indications	Single dose of acyclovir (mg/m2 BSA)	Daily dose in patients with normal renal function (mg/m2 BSA)	Mean duration of treatment (days)
Herpes simplex	250	750	5*
Varicella	500	1500	5*
Herpes zoster	500	1500	5*

* In individual cases, depending on the type and duration of the illness, the medication may be
administered for a longer period.
Dosing in patients with renal function impairment
Acyclovir dosage depends on the degree of renal function impairment. Adequate hydration of the
patient's body is important.
Table 3. Dosing in adults and adolescents with renal function impairment

Creatinine clearance	Dosing
25 to 50 ml/min	The recommended dose above (5 or 10 mg/kg b.w.) should be administered every 12 hours.
10 to 25 ml/min	The recommended dose above (5 or 10 mg/kg b.w.) should be administered every 24 hours.
0 (anuria) to 10 ml/min	In patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the recommended dose above (5 or 10 mg/kg b.w.) should be reduced by half and administered every 24 hours.
0 (anuria) to 10 ml/min	In patients undergoing hemodialysis, the recommended dose above (5 or 10 mg/kg b.w.) should be reduced by half and administered every 24 hours and after each dialysis session.

Table 4. Dosing in infants and children with renal function impairment

Creatinine clearance	Dosing
25 to 50 ml/min/1.73m²	The recommended dose above (250 or 500 mg/m² BSA or 20 mg/kg IBW) should be administered every 12 hours.
10 to 25 ml/min/1.73m²	The recommended dose above (250 or 500 mg/m² BSA or 20 mg/kg IBW) should be administered every 24 hours.
0 (anuria) to 10 ml/min/1.73m²	For patients undergoing continuous ambulatory peritoneal dialysis, the recommended dose above (250 or 500 mg/m² BSA or 20 mg/kg IBW) should be reduced by half and administered every 24 hours. For patients undergoing hemodialysis, the recommended dose above (250 or 500 mg/m² BSA or 20 mg/kg IBW) should be reduced by half and administered every 24 hours and after each dialysis session.

Dosing in elderly patients
Since renal impairment is more likely in elderly patients, careful monitoring of kidney function is recommended. If necessary, the dose of ACIX should be adjusted according to Table 3.
When high doses of acyclovir are administered (e.g. during treatment of herpes encephalitis), renal function should be monitored, especially in patients with impaired kidney function and in patients receiving low fluid intake.
Preparation of infusion solution and method of administration – see section "Information intended exclusively for healthcare professionals".
Use of a higher than recommended dose of ACIX
Acyclovir overdose administered intravenously may lead to increased serum creatinine and blood urea nitrogen levels, followed by renal failure. Neurological symptoms have also been reported, such as confusion, hallucinations, agitation, seizures, and coma.
Haemodialysis significantly removes acyclovir from the blood and may be considered as a management approach in cases of overdose.
Missed dose of ACIX
Do not administer a double dose to make up for a missed dose.
If you have any further doubts regarding the use of this medicinal product, consult your doctor.

4. Possible adverse reactions

Like any medicine, this medicinal product may cause adverse reactions, although not everyone experiences them.
The frequency of the listed adverse reactions is only approximate, as in most cases precise data are not available.
Moreover, the frequency of adverse reactions may vary depending on the indication.

Common adverse reactions (may occur in less than 1 in 10 people):
phlebitis, nausea and vomiting, itching, rash, urticaria, photosensitivity, transient increase in liver enzyme activity in blood, increased serum urea and creatinine levels (a rapid increase in urea and creatinine levels in blood may be related to the peak plasma concentration of the drug and the patient's hydration status; therefore, the medicine must not be administered as an intravenous bolus injection, but only as a slow intravenous infusion over at least 60 minutes).

Uncommon adverse reactions (may occur in less than 1 in 100 people):
anaemia (reduced number of red blood cells), thrombocytopenia (reduced number of platelets), leukopenia (reduced number of white blood cells).

Very rare adverse reactions (may occur in less than 1 in 10,000 people):
anaphylactic reactions (severe hypersensitivity reactions), headache, dizziness, restlessness, confusion, tremor, motor incoordination, speech disorders, hallucinations, psychotic symptoms, seizures, somnolence, encephalopathy (non-inflammatory brain changes), coma, dyspnoea, diarrhoea, abdominal pain, transient increase in bilirubin concentration, jaundice, hepatitis, angioedema, renal function disorders [which resolve rapidly after fluid replacement and (or) dose reduction or after discontinuation of the drug], renal pain, in isolated cases acute renal failure, fatigue, fever, local inflammatory reactions.

Severe local inflammatory reactions, sometimes leading to tissue necrosis, may occur if the medicine is inadvertently administered extravascularly.

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 Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warszawa
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 marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store ACIX

Keep this medicine out of sight and reach of children.
Store below 25°C.
The prepared infusion solution should be stored for up to 48 hours at a temperature below 25°C.
Do not freeze.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ACIX contains
The active substance is acyclovir.
One vial of ACIX 500 contains 500 mg of acyclovir in the form of sodium acyclovir salt (548.8 mg).
What ACIX looks like and contents of the pack
The pack contains 10 vials placed on a polystyrene tray in a cardboard box.
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria
Manufacturer
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
For further information, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00

Information intended exclusively for healthcare professionals

The infusion solution must be prepared under aseptic conditions immediately before use.
To dissolve the product and withdraw the concentrated solution from the vial, needles with a diameter of up to 0.8 mm are recommended.
Dissolve the contents of the vial by adding 20 mL of Water for Injections or 0.9% sodium chloride solution. Dilute the resulting concentrated solution immediately (in a single step, at least 100 mL, up to a maximum of 500 mL). The diluent used should be 0.9% sodium chloride solution without any additional components.
The ACIX 500 solution prepared according to the recommendations remains stable for up to 48 hours at a temperature below 25°C.
Do not use the solution if cloudiness or crystallization occurs before or during infusion.
Any unused portion of the dry substance or solution must be discarded.
Administration method
The prepared infusion solution should be administered as a slow intravenous infusion over at least 60 minutes. Do not administer ACIX 500 as a rapid intravenous injection (bolus).
If ACIX 500 is administered using an infusion pump, the acyclovir concentration should be 2.5% (25 mg/mL).
Warning: The pH of the concentrated ACIX solution is approximately 11. Do not administer orally.

Acix 500