Aciclovir polpharma

Package leaflet: Information for the patient

Warning! Keep the leaflet, information on the immediate packaging in a foreign language.
Aciclovir Polpharma (Aciclovir Rompharm)
250 mg, powder for solution for infusion
Aciclovirum
Aciclovir Polpharma and Aciclovir Rompharm are different trade names for the same medicine.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

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

Aciclovir Polpharma contains the active substance aciclovir. This medicine has a direct antiviral effect (destroys or inhibits the growth of the virus causing shingles or herpes). It is used in the treatment of certain infections caused by the herpes virus and certain forms of chickenpox and shingles (a viral disease characterized by a painful rash, for example affecting the eye).

2. Important information before using Aciclovir Polpharma

When not to use Aciclovir Polpharma

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

Warnings and precautions
Before starting treatment with Aciclovir Polpharma, please 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 aciclovir intravenously or taking high oral doses of aciclovir, adequate hydration should be maintained.

Aciclovir Polpharma and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

• If Aciclovir Polpharma is used concomitantly with other medicines that have nephrotoxic effects, the risk of impaired renal function may increase. Caution is advised when administering aciclovir intravenously in combination with other nephrotoxic drugs.
• Concomitant intravenous administration (administering several medicines simultaneously through the same infusion set, or mixing them in the same 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) together 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 together 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 is planning to have a child, 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 finds out she is pregnant while undergoing treatment, she should inform her doctor, as only the doctor can decide whether treatment should continue.
Breastfeeding should not be continued during aciclovir treatment, 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 their health status and certain possible adverse effects, particularly those affecting the nervous system, which may occur during treatment (see section 4: Possible side effects).

Aciclovir Polpharma contains sodium
This medicine contains 26 mg of sodium (the main component of table salt) per vial. This corresponds to 1.3% of the maximum recommended daily dietary intake of sodium for adults.

3. How to use Aciclovir Polpharma

The patient will never self-administer this medicine. 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 body weight every 8 hours.
• Children over 3 months of age: the dose will be calculated based on body weight, 10 to 20 mg/kg body weight every 8 hours, with a maximum dose ranging from 400 mg to 800 mg every 8 hours.
• Newborns: 20 mg/kg body weight 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 doctor will adjust the dose of this medicine.
• If the patient is elderly, the doctor will adjust the dose, as renal function may be reduced in older individuals.
• In obese patients, particularly those with impaired renal function and elderly patients, the dose should be adjusted.
• In infants and children with impaired renal function, the dose should be appropriately adjusted depending on the severity of the 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 qualified medical personnel (intravenous administration only).
Duration of treatment
Treatment usually lasts from 5 to 10 days. This duration should be adjusted according to the patient's
clinical condition and response to treatment. In the case of neonatal herpes simplex infection and depending on the indication, treatment may last 14 or 21 days.
Use of a higher than recommended dose of Aciclovir Polpharma
Consult a doctor immediately.
In certain situations (e.g. if the patient has kidney disease), neurological disorders may occur (see section 4 "Possible side effects").
If you have any further doubts regarding the use of this medicine, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody experiences them.
Adverse reactions are listed in order from most frequent to least frequent.
Common (may affect up to 1 in 10 patients):

• Gastrointestinal disorders:
• nausea,
• vomiting,
• diarrhoea,
• abdominal pain.
• Hepatic function disorders: increased bilirubin concentration 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 (blood clot formation in a vein) 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 (cell death). Such inflammatory changes are related to the alkaline pH of this medicine.

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

• Blood disorders:
• thrombocytopenia (reduced number of platelets – cells that enable blood clotting),
• leukopenia (reduced number of white blood cells).
• Nervous system disorders:
• headache, dizziness,
• ataxia (problems with walking and lack of motor coordination) and dysarthria (slurred speech and speech difficulties), which may occur together or separately and 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. Such 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 (generalised 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, 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 medicines that have nephrotoxic effects. Investigations for the above-mentioned predisposing factors should be performed regardless of patient's 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 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 Adverse Drug Reactions of the 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
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Aciclovir Polpharma

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
After reconstitution
Chemical and physical stability has been demonstrated for 12 hours at a temperature of 15°C to 25°C after dissolution in 10 ml of water for injections or in sodium chloride 9 mg/ml (0.9%) solution for injections.
After dilution
Chemical and physical stability has been demonstrated for 12 hours at a temperature of 15°C to 25°C after dilution with compatible solutions listed in the Information for Healthcare Professionals only section entitled “Preparation and Handling”.
From a microbiological standpoint, 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 typically should not exceed 12 hours at a temperature of 15°C to 25°C.
Solutions after reconstitution or after reconstitution and dilution must not be refrigerated.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Aciclovir Polpharma contains

• The active substance is acyclovir. Each vial contains 250 mg of acyclovir (as sodium acyclovir).
• The other component is: sodium hydroxide (for pH adjustment).

What Aciclovir Polpharma looks like and contents of the pack
Aciclovir Polpharma for powder for solution for infusion is supplied in vials made of colourless glass (type I), containing a white or almost white lyophilised powder, closed with a bromobutyl rubber stopper, sealed with an aluminium cap and a polypropylene flip-off cap, packed in a cardboard box.
Pack size: 5 vials.
For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.

Marketing Authorisation Holder in Romania, the country of export, and Manufacturer:
S.C. Rompharm Company S.R.L.
Str. Eroilor, nr. 1A, Otopeni 075100, Jud. Ilfov
Romania

Parallel Importer:
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański

Repackaged in:
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warszawa
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław

Marketing Authorisation Number in Romania, the country of export: 14775/2022/02
Parallel Import Licence Number: 362/25
(Parallel Importer's logo)

Information intended exclusively for medical professionals:

Preparation and handling
Prepare immediately before use. Any unused solutions must be discarded.
Reconstitution
Reconstitution of Aciclovir Polpharma should be performed using 10 ml of water for injections or sodium chloride 9 mg/ml (0.9%) for injection, to obtain a solution containing 25 mg of aciclovir per ml.
Based on the calculated dose, determine the appropriate number of vials required.
To reconstitute the contents of each vial, add the recommended volume of infusion solution to each vial and gently shake the vial until the contents are completely dissolved.

Route of administration
The required dose of Aciclovir Polpharma should be administered via slow intravenous infusion over at least one hour.
After reconstitution, Aciclovir Polpharma may be administered using an infusion pump with controlled infusion rate. Alternatively, the reconstituted solution may be further diluted to allow intravenous administration of aciclovir at a concentration not exceeding 5 mg/ml (0.5% w/v).
The required volume of reconstituted solution should be added to the chosen 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 aciclovir) is added to 20 ml of infusion solution.

In adults, infusion bags containing 100 ml of infusion solution are recommended, even if this results in aciclovir concentrations significantly below 5 mg/ml (0.5% w/v). Thus, a single 100 ml infusion bag may be used for any dose between 250 mg and 500 mg aciclovir (10 ml to 20 ml of reconstituted solution), whereas for doses between 500 mg and 1000 mg, a second bag should be used.

After dilution according to the recommended regimen, Aciclovir Polpharma is pharmaceutically compatible with the following infusion solutions:

• Sodium chloride 9 mg/ml (0.9%) solution for injection
• 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

After dilution according to the above regimen, Aciclovir Polpharma will provide an aciclovir concentration not exceeding 0.5% w/v.
Due to the absence of antimicrobial preservatives, reconstitution and dilution 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 refrigerated.
If any cloudiness or crystallization occurs in the solution before or during infusion, the solution must be discarded.
Any unused medicinal product or waste material 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
Dosing in patients with normal renal function is described 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 regarding duration of treatment, 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 (bw) every 8 hours; 10 to 15 mg/kg bw every 8 hours in pregnant women
• Herpes simplex virus (HSV) infections (excluding encephalitis and meningitis): 5 mg/kg bw every 8 hours
• Herpes simplex encephalitis and meningitis: 10 mg/kg bw 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 encephalitis and meningitis) or Varicella zoster virus infection: 10 mg/kg bw 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 bw every 8 hours, maximum dose 800 mg every 8 hours

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

• For confirmed or suspected herpes simplex infection in neonates, the recommended dose is 20 mg/kg bw intravenously every 8 hours for 21 days in cases of disseminated infection or central nervous system infection, or for 14 days in cases of skin and mucous membrane-limited 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 must be exercised when administering aciclovir to patients with renal impairment. In such patients, particular attention should be paid to adequate fluid intake.
The following dose adjustments are recommended.

Dose adjustment recommended for adults and adolescents over 12 years of age with renal impairment

Dose adjustment in children aged 12 years and younger, infants and neonates with impaired renal function

Elderly patients
Renal impairment in elderly patients should be taken into account; the dose should be adjusted based on creatinine clearance (see "Dosage in patients with impaired renal function").
Adequate fluid intake should be ensured in patients.

Duration of treatment
The usual duration of treatment is 5 days, but it may be adjusted depending on the patient's clinical condition and response to therapy. The duration is as follows:

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

The duration of prophylactic treatment with Aciclovir Polpharma depends on the length of the period of infection risk.

Administration
For intravenous use only.
Each dose should be administered slowly by intravenous infusion (using an infusion pump or gravity drip) 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 with intravenous acyclovir leads to increased serum creatinine and blood urea levels, resulting in renal dysfunction. Neurological symptoms observed after overdose include confusion, hallucinations, agitation, seizures, and coma.

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