ACICLOVIR 250 mg Powder

Contents of the leaflet

1. Package Leaflet: Information for the User
   1. Read all of this leaflet carefully before you start using this medicine because it contains important information for you.
   2. Contents of the pack
2. What Aciclovir Jelfa is and what it is used for
   1. Indications for use of Aciclovir Jelfa
3. Before you use Aciclovir Jelfa
   1. When not to use Aciclovir Jelfa
   2. Warnings and precautions
   3. Use of Aciclovir Jelfa in patients with kidney function disorders
   4. Aciclovir Jelfa and other medicines
   5. Pregnancy, breastfeeding, and fertility
   6. Driving and using machines
4. How to use Aciclovir Jelfa
   1. Special patient groups
   2. Patients with kidney failure:
   3. Patients undergoing hemodialysis:
   4. Patients undergoing peritoneal dialysis:
   5. Elderly patients:
   6. Patients with significant overweight:
   7. Note: the dose should never exceed 500 mg/m2 body surface area every 8 hours.
   8. Use of a higher than recommended dose of Aciclovir Jelfa
5. Possible side effects
   1. Reporting of side effects
6. How to store Aciclovir Jelfa
7. Contents of the pack and other information
   1. What Aciclovir Jelfa contains:
   2. What Aciclovir Jelfa looks like and contents of the pack
   3. Marketing Authorization Holder
   4. Manufacturer
   5. Date of last revision of the leaflet:
   6. Information intended for healthcare professionals only
   7. Preparation of Aciclovir Jelfa solution
   8. Warning!
   9. Incompatibilities

Package Leaflet: Information for the User

ACICLOVIR JELFA 250 mg, powder for solution for infusion
Aciclovir

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What Aciclovir Jelfa is and what it is used for
• 2. Before you use Aciclovir Jelfa
• 3. How to use Aciclovir Jelfa
• 4. Possible side effects
• 5. How to store Aciclovir Jelfa
• 6. Contents of the pack and other information

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

Aciclovir Jelfa is an antiviral medicine. It is used to treat infections caused by viruses of the Herpesviridaefamily (herpes viruses).
The most common causes of infections in humans are the following herpes viruses: herpes simplex virus types I and II (Herpes simplex, HSV), varicella-zoster virus (Varicella zoster, VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV).
Aciclovir is most effective in the treatment of herpes simplex virus type I (Herpes simplex, HSV-I) infections, slightly less effective in the treatment of herpes simplex virus type II (Herpes simplex, HSV-II) infections, and even less effective in the treatment of varicella-zoster virus (Varicella zoster, VZV) infections.
Aciclovir has minimal antiviral activity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV), which is usually of no clinical significance.

Indications for use of Aciclovir Jelfa

Herpes simplex virus infections of the skin and mucous membranes (types I and II) and their recurrences in patients with immunodeficiency.
Varicella-zoster virus infections in patients with immunodeficiency.
Herpes simplex encephalitis in patients over 6 months of age.
Treatment of the initial phase of severe genital herpes (Herpes genitalis) in patients with immunodeficiency.

2. Before you use Aciclovir Jelfa

When not to use Aciclovir Jelfa

If you are allergic to aciclovir or valaciclovir.

Warnings and precautions

Before starting treatment with Aciclovir Jelfa, you should discuss it with your doctor, pharmacist, or nurse.
Particular caution should be exercised when using Aciclovir Jelfa in dehydrated patients, those receiving high doses of aciclovir, patients with a history of kidney disease, or those receiving other nephrotoxic drugs (toxic to the kidneys) at the same time. These conditions increase the risk of kidney damage from aciclovir.
The drug should not be administered by rapid intravenous injection, as this may cause kidney damage due to the increased risk of aciclovir crystallization in the renal tubules. This may lead to acute kidney failure.
Aciclovir solutions should only be administered by slow intravenous infusion at the appropriate concentration (see: Preparation of Aciclovir Jelfa solution).
Solutions with higher concentrations may cause phlebitis and kidney damage.
Aciclovir solutions should not be used topically, intramuscularly, subcutaneously, orally, or in the eyes (these are highly alkaline solutions, pH 10.5 - 12).
If the solution comes into contact with the skin or mucous membranes, it should be washed off thoroughly with soap and water.
If the solution gets into the eye, it should be rinsed immediately with a large amount of water, preferably running water.
Intravenous administration of aciclovir requires maintaining adequate hydration of the patient. Adequate hydration to prevent the precipitation of drug crystals in the urine is indicated by a daily urine output (diuresis) of not less than 500 ml/1g of administered drug. It is recommended to administer fluids in a volume of not less than 1 liter/1g of administered aciclovir per day.
Aciclovir administered by intravenous infusion may cause central nervous system disorders (see Possible side effects), including seizures, agitation, and disturbances of consciousness. Caution should be exercised when administering aciclovir to patients who have previously experienced neurological disorders.
The risk of such disorders is also increased in patients with kidney or liver failure, significant electrolyte disturbances, and those who are severely hypoxic or being treated concurrently with intravenous methotrexate or interferon.
It should be taken into account that reduced activity of the viral enzyme - thymidine kinase - leads to lower efficacy of aciclovir. Such cases have been observed in the intravenous administration of aciclovir to patients with severe immunodeficiency and after bone marrow transplants.
No correlation has been established between the antiviral activity of the drug in vitroand its clinical efficacy.

Use of Aciclovir Jelfa in patients with kidney function disorders

Due to the risk of drug accumulation, in patients with kidney failure, the dose should be modified depending on the creatinine clearance rate (see: Special patient groups).

Note: During aciclovir treatment, creatinine clearance or its serum concentration should be constantly monitored.

Aciclovir Jelfa and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.
No clinically significant interactions have been found.
Aciclovir is excreted mainly in unchanged form in the urine through active secretion in the renal tubules. Any drugs administered concurrently that compete for this mechanism may increase the concentration of aciclovir in the blood.
Probenecid and cimetidine increase the area under the aciclovir concentration-time curve (AUC) and decrease renal clearance. However, there is no need to change the dosage due to the wide therapeutic index of aciclovir.
Caution should be exercised when administering Aciclovir Jelfa in infusion with drugs that compete with aciclovir for excretion, due to the possibility of increased concentration in the blood of one or both drugs, or their metabolites. During concurrent administration, it has been shown that the amount of aciclovir and mycophenolate mofetil, one of the inactive metabolites of the immunosuppressive drug administered to patients after transplants, that enters the systemic circulation in unchanged form increases (increase in the area under the concentration-time curve (AUC)).
Caution should also be exercised (with monitoring of changes in kidney function) when administering Aciclovir Jelfa intravenously with drugs that affect kidney function (cyclosporine, tacrolimus).

Pregnancy, breastfeeding, and 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 using this medicine.
There is limited data on the use of aciclovir in pregnant women.
Aciclovir can be used during pregnancy only if, in the doctor's opinion, the expected benefit to the mother outweighs the potential risk to the fetus.
Before using any medicine, you should consult your doctor.
After oral administration of aciclovir, its presence has been detected in breast milk at concentrations sometimes exceeding those in serum. The potential risks to the breastfed child have not been assessed.
If treatment with aciclovir is necessary, breastfeeding should be discontinued.

Driving and using machines

In patients treated with aciclovir infusions, numerous central nervous system disorders have been reported (see Possible side effects), including seizures, agitation, and disturbances of consciousness. Such symptoms impair psychomotor performance and make it impossible to drive vehicles and operate machinery.

3. How to use Aciclovir Jelfa

This medicine is for use in hospitals only.
Always use this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.
Treatment should be started as soon as possible after the appearance of symptoms and diagnosis.
The dosing below applies to adults and children with normal kidney function (see also Special patient groups).
Herpes simplex virus infections of the skin and mucous membranes in patients with immunodeficiency.
The drug is administered by continuous intravenous infusion lasting at least 1 hour.
Treatment lasts 7 days.
Adults:15 mg/kg body weight/day in divided doses (5 mg/kg body weight every 8 hours).
Children over 6 months to 12 years:750 mg/m2 body surface area/day in divided doses (250 mg/m2 body surface area every 8 hours).
Severe clinical forms of genital herpes (Herpes genitalis)
Adults and children over 6 months:Treatment lasts 5 days.
Doses, method, and frequency of administration are the same as for skin and mucous membrane infections with herpes simplex virus in patients with immunodeficiency (see above).
Varicella-zoster virus infections in patients with immunodeficiency
The drug is administered by continuous intravenous infusion, lasting at least 1 hour.
Treatment lasts 7 days.
Adults:10 mg/kg body weight every 8 hours.
Children over 6 months to 12 years:500 mg/m2 body surface area every 8 hours.
Herpes simplex encephalitis
The drug is administered by continuous intravenous infusion lasting at least 1 hour. Treatment lasts 10 days.
Adults:10 mg/kg body weight every 8 hours.
Children over 6 months to 12 years:500 mg/m2 body surface area every 8 hours.

Special patient groups

Patients with kidney failure:

Doses or dosing intervals should be changed depending on creatinine clearance according to the recommendations in the table below.

Note: During aciclovir treatment, creatinine clearance or its serum concentration should be constantly monitored.

Patients undergoing hemodialysis:

During dialysis, the concentration of aciclovir decreases. After each dialysis, the dose of the drug should be adjusted accordingly.

Patients undergoing peritoneal dialysis:

No dose adjustment is necessary if the dosing intervals are properly maintained

Elderly patients:

In elderly patients, kidney function may be reduced to varying degrees. The drug should be used after assessing the patient's kidney function. Dosing should be modified according to the recommendations for patients with kidney failure (see table above).

Patients with significant overweight:

The average dose is 10 mg/kg of idealbody weight.

Note: the dose should never exceed 500 mg/m2 body surface area every 8 hours.

If you feel that the effect of the drug is too strong or too weak, you should consult your doctor.

Use of a higher than recommended dose of Aciclovir Jelfa

Overdose symptoms have been reported in cases of rapid intravenous injection or excessive dose, as well as in patients with impaired water and electrolyte balance.
Increased blood urea and creatinine levels have been observed, as well as kidney function disorders. Severe disturbances of consciousness, seizures, and coma may occur. Crystallization of aciclovir in the renal tubules occurs when the concentration in the tubule exceeds 2.5 mg/ml.
It is recommended to administer fluids in a volume that ensures diuresis exceeding 500 ml/1g of administered drug in infusion.
A 6-hour hemodialysis session can reduce the concentration of aciclovir in the serum by 60%.
In the event of kidney failure and anuria, the patient requires hemodialysis until kidney function returns.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequencies of side effects are approximate. In most cases, there was no data available to estimate the frequency of side effects, which may also vary depending on the indication for treatment.
Uncommon(may affect up to 1 in 100 people):

• decreased hematological parameters (anemia, thrombocytopenia, decreased white blood cell count).

Rare(may affect up to 1 in 1,000 people):

• anaphylactic reactions (severe allergic reactions causing difficulty breathing or dizziness);
• headaches, dizziness, agitation, disorientation, tremors, ataxia, speech disorders, hallucinations, psychotic symptoms, seizures, somnolence, encephalopathy (brain damage), coma.

These events are usually transient and are most often observed in patients with impaired kidney function or other predisposing factors (see Warnings and precautions).
Common(may affect up to 1 in 10 people):

• phlebitis, nausea, vomiting, transient increase in liver enzyme activity in the blood, itching, urticaria, rash (including photosensitivity);
• increased urea and creatinine levels.

Sometimes, a sudden increase in urea and creatinine levels in the serum has been observed in patients receiving aciclovir intravenously. It is believed that this is due to the maximum concentration of the drug in the blood and the patient's hydration status. To avoid this, the drug should not be administered by rapid intravenous injection, but only by slow intravenous infusion lasting more than 1 hour.
Rare(may affect up to 1 in 1,000 people):

• shortness of breath, diarrhea, abdominal pain, transient increase in bilirubin levels, jaundice, hepatitis, angioedema;
• kidney function disorders, acute kidney failure. It is necessary to maintain proper hydration of the patient. Kidney function disorders usually resolve quickly after fluid supplementation in the patient and (or) after reducing the dose or discontinuing the drug. However, in exceptional cases, acute kidney failure may occur.
• fatigue, fever, local inflammatory reactions. After accidental administration of aciclovir solution for infusion outside the vessel, severe local inflammatory reactions have been observed, sometimes leading to skin damage.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, you should inform your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aciclovir Jelfa

Store below 25°C.
The prepared solution can be stored for 24 hours at a temperature below 25°C.
Medicines should be kept out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Aciclovir Jelfa contains:

The active substance is aciclovir in the form of aciclovir sodium.
1 vial contains 250 mg of aciclovir in the form of aciclovir sodium.

What Aciclovir Jelfa looks like and contents of the pack

Powder for solution for infusion (lyophilized).
Aciclovir Jelfa is a white or almost white solid (lyophilizate) in a solid or partially broken form.
Pack size: 5 glass vials in a cardboard box.

Marketing Authorization Holder

Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland

Manufacturer

Jelfa Pharmaceutical Company SA
Wincentego Pola 21, 58-500 Jelenia Góra

Date of last revision of the leaflet:

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Information intended for healthcare professionals only

Preparation of Aciclovir Jelfa solution

Add 10 ml of water for injections or 10 ml of sodium chloride 0.9% solution for injections to the vial with the lyophilizate.
The resulting solution contains 25 mg of aciclovir in 1 ml.
Do not use solvents containing benzyl alcohol or parahydroxybenzoates (may precipitate).

After dissolving the dry substance in the vial before mixing with the infusion fluid, the resulting solution should be carefully inspected for contaminants.
The prepared solution can be stored for 24 hours at a temperature below 25°C.
The solution of aciclovir sodium has a pH of 10.5 - 12, which may cause a reaction with metal (e.g., parts of the syringe).
The appropriate dose of aciclovir should be added to the infusion fluid so that the concentration of the drug does not exceed 7 mg/ml.
In adults with a body weight of 70 kg, it is recommended to administer a single dose in a volume of

• 60 - 150 ml. In children, the amount of infusion fluid should be adjusted according to age and body weight.

The primary solution of aciclovir can be added to the following infusion solutions:

• sodium chloride 0.45% or 0.9% solution;
• sodium chloride 0.45% solution with glucose 2.5% solution;
• complex solution of sodium lactate (Hartmann's solution). The solution should be prepared under sterile conditions directly before administration. If turbidity or crystallization occurs (before or during infusion), the solution should be discarded. The prepared solution is administered by slow intravenous infusion at a constant rate, over a period of not less than 1 hour.

Warning!

Do not administer the product by rapid intravenous injection, or in concentrations higher than recommended. Intramuscular or subcutaneous injection may cause local tissue irritation (the pH of the aciclovir sodium solution is approximately 11).

Incompatibilities

The lyophilizate should not be dissolved in solutions containing bacteriostatic parahydroxybenzoates or benzyl alcohol.