PENICRYL

Package leaflet: Information for the user

Penicryl, 5,000,000 IU, powder for solution for injection / infusion
benzylpenicillin (as benzylpenicillin potassium)
Read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

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

1. What Penicryl is and what it is used for

Penicryl is an antibacterial medicine effective against bacterial infections caused by bacteria sensitive to penicillin (it is an antibiotic).
Penicryl is indicated for the treatment of the following infections in adults, adolescents, and children:

• Community-acquired pneumonia;
• Skin and soft tissue infections (including gas gangrene and infections following animal bites);
• Acute bacterial meningitis;
• Severe infections caused by pneumococci, streptococci, meningococci, or gonococci, including sepsis, abscess, brain abscess, bone and joint infections;
• Endocarditis;
• Neuroborreliosis;
• Syphilis.

Official guidelines on appropriate use of antibacterial agents should be followed.

2. Important information before using Penicryl

When not to use Penicryl:

• if the patient is allergic to potassium benzylpenicillin or to other penicillins.
• if the patient has previously experienced a severe allergic reaction to penicillin or to other beta-lactam antibiotics (e.g. cephalosporins, carbapenems or monobactams).

Warnings and precautions
If any of the situations listed below apply to the patient, discuss them with a doctor, nurse or pharmacist before using Penicryl:

• if the patient has impaired kidney function
• if the patient has heart failure
• if the patient has diarrhoea
• if the patient is monitoring potassium intake in their diet
• if the patient has experienced severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or acute generalized exanthematous pustulosis (AGEP), which have been reported in association with beta-lactam antibiotic therapy, including penicillins (see section "Possible side effects")
• if the patient is over 60 years of age
• if the medicine is to be administered to newborns and preterm infants.

Prolonged use of Penicryl may lead to overgrowth of resistant microorganisms and consequently to superinfection.
High doses of potassium benzylpenicillin 5,000,000 IU (equivalent to 2.8 g of benzylpenicillin), powder for solution for injection/infusion, may cause serious, even fatal, electrolyte disturbances such as hyperkalaemia and hyponatraemia when administered intravenously in high doses (over 10 million IU). The physician always takes into account the potassium content. In patients treated with high doses for longer than 5 days, the physician recommends monitoring of electrolyte balance, blood morphology and kidney function (see section "Penicryl contains potassium").
High intravenous doses should be administered slowly due to potential adverse effects related to electrolyte imbalances resulting from the potassium content in penicillin.
Impaired kidney function may lead to a significant increase in serum potassium concentration, which may cause serious cardiac problems. Cases of flaccid paralysis, abnormalities in electrocardiogram (shortened QT interval and peaked T waves) and circulatory arrest have been reported after rapid intravenous administration of potassium benzylpenicillin (10-18 million IU/day). However, hyperkalaemia does not typically occur unless very high doses of potassium benzylpenicillin are administered over a prolonged period, particularly in patients with renal impairment.
If any of the above situations apply to the patient (or if the patient is uncertain), inform the doctor, pharmacist or nurse before using Penicryl.

Penicryl with other medicines
Tell your doctor or pharmacist about all medicines currently used, recently used, or which the patient plans to use.
It is especially important that the doctor knows if the patient is taking any of the following medicines:

• methotrexate (a cytostatic agent). Concomitant use of methotrexate with benzylpenicillin may increase its efficacy and toxicity.
• probenecid (a medication for gout that inhibits the excretion of Penicryl).

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
There are no known risks associated with using Penicryl during pregnancy.

Breastfeeding
Benzylpenicillin passes into human milk; however, the risk of effects on the infant with therapeutic doses is unlikely.

Driving and operating machinery
Penicryl has no or negligible effect on the ability to drive and operate machinery.

Penicryl contains potassium
Penicryl contains 8.42 mmol (329.07 mg) of potassium per vial. One million IU contains 1.68 mmol (or 65.81 mg) of potassium.
This should be taken into account in patients with reduced kidney function and in patients monitoring potassium intake in their diet (see "Warnings and precautions" in section 2).

3. How to use Penicryl

Information on dosage and method of administration is provided in the section "Information intended exclusively for healthcare professionals".
This medicine will be administered as an injection given by a doctor or nurse.
The doctor should adjust the appropriate dose according to kidney function, age, and body weight of the patient. Furthermore, the doctor will decide how and when the injection should be administered, as well as the duration of treatment.
Penicryl is supplied as a dry powder, which is dissolved by the doctor or nurse in a suitable diluent. The solution is administered either intravenously or intramuscularly as an injection, or intravenously as an infusion.

Use of more than the recommended dose of Penicryl
Since the injection is administered by a doctor or nurse, administration of a higher than recommended dose is unlikely. If the patient believes they have received too high a dose, they should inform the doctor or nurse who administered the injection. Symptoms of overdose may include nausea, vomiting, diarrhoea, electrolyte disturbances, muscle twitching, myoclonic seizures, loss of consciousness, epileptic seizures, coma, haemolytic reactions, kidney failure, or acidosis.
In exceptional cases, an anaphylactic reaction may occur.

Missed dose of Penicryl
If the patient believes a dose of Penicryl has been missed, they should inform the doctor or nurse immediately. A double dose must not be administered to make up for the missed dose.

Stopping Penicryl treatment prematurely
Stopping treatment too early may adversely affect treatment outcome or lead to recurrence of the disease, which may be more difficult to treat. Patients should follow the doctor's instructions.

Instructions for preparing the medicine for use are provided at the end of the patient leaflet, in the section "Information intended exclusively for healthcare professionals".
If there are any further questions regarding the use of this medicine, patients should consult their doctor, nurse, or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should immediately inform your doctor or seek medical help if the patient feels unwell or experiences any of the following symptoms:
Severe allergic reactions (anaphylactic reactions or angioedema), which may occur as:

• skin rash or itching
• difficulty breathing or chest tightness
• swelling of eyelids, face or lips; swelling or redness of the tongue
• fever
• joint pain
• swelling of lymph nodes.

Penicryl administered intravenously in high doses may cause serious, even fatal, electrolyte disturbances, namely hyperkalaemia.
Symptoms of high potassium levels, which may include:

• irregular heartbeat
• changes in clarity and logic of thinking
• weakness, feeling faint or dizzy
• feeling faint
• numbness or tingling
• shortness of breath.

Selected serious adverse reactions
Severe cutaneous adverse reactions (SCAR), including:

• SJS - Stevens-Johnson syndrome with flu-like symptoms followed by painful rash
• TEN - toxic epidermal necrolysis, characterized by blistering and skin peeling
• DRESS - drug reaction with eosinophilia (increased white blood cell count) and systemic symptoms
• AGEP - acute generalized exanthematous pustulosis with symptoms such as severe drug-induced skin reactions with or without skin redness, fever, and pustules (see also "Warnings and precautions" in section 2). Pseudomembranous colitis caused by Clostridioides difficile – symptoms: watery diarrhoea containing mucus, blood traces, with a characteristic odour, sometimes accompanied by fever and abdominal pain.

Other adverse reactions
Common (occurring in up to 1 in 10 people):

• rash
• inflammation of blood vessels (thrombophlebitis).

Uncommon (occurring in up to 1 in 100 people):

• increased white blood cell count
• rash (urticaria).

Rare (occurring in up to 1 in 1000 people):

• decreased white blood cell count
• haemolytic anaemia (reduced number of red blood cells in blood)
• diarrhoea
• itching.

Very rare (occurring in up to 1 in 10,000 people):

• severe skin reactions.

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

• decreased platelet count, which may increase the risk of bleeding (thrombocytopenia)
• decreased white blood cell count, which may increase the risk of infections (neutropenia)
• Jarisch-Herxheimer reaction may occur during treatment of Lyme disease (borreliosis) with Penicryl, causing fever, chills, headache, muscle pain and rash
• maculopapular rash (flat, red areas on the skin)
• morbilliform rash (rash resembling measles)
• itching
• erythema (inflammatory redness of the skin)
• angioedema (swelling of skin, mucous membranes and subcutaneous tissue, usually located on the face, lips or tongue)
• thrombocytopenia (low platelet count)
• metabolic encephalopathy (neurological disturbances with seizures and loss of consciousness)

Adverse effects on the kidneys may also occur, and excessive growth of fungi in the oral cavity and gastrointestinal tract may develop.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Penicryl

Keep this medicine out of sight and reach of children.
This medicine does not require any special storage conditions.
Information on storage conditions after reconstitution is provided in the section "Information intended solely for healthcare professionals".
Do not use this medicine after the expiry date stated on the label and the cardboard box 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 no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Penicryl contains
The active substance is benzylpenicillin (in the form of potassium benzylpenicillin).
Each vial contains 3.1 g of potassium benzylpenicillin (5 million IU of benzylpenicillin), corresponding to
2.8 g of benzylpenicillin.
Penicryl contains potassium (see section 2).
The medicine does not contain any other ingredients.

What Penicryl looks like and contents of the pack
White or almost white crystalline powder in colourless, transparent vials.
The vials are made of soda-lime-silicate glass (type III) with a nominal capacity of 20 mL.
The vials are closed with grey chlorobutyl rubber stoppers (type I) and aluminium caps.
Pack containing 1 or 10 vials in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga Street 2
03-176 Warsaw
Telephone: (22) 811 18 14
For further information on this medicinal product, please contact the Marketing Authorisation Holder.

This medicinal product is authorised in the European Economic Area countries under the following names:
Poland Penicryl
Sweden Penicryl
Finland Penicryl 5 000 000 IU injektio-/infuusiokuiva-aine liuosta varten
Norway Penicryl
Denmark Penicryl

Information intended exclusively for healthcare professionals:

For additional information, refer to the Summary of Product Characteristics.
Dosage should be adjusted according to renal function, age, and body weight of the patient.

Adults and adolescents over 12 years of age:
Intramuscularly: 1.67 million IU (equivalent to 0.9 g of benzylpenicillin) 4–6 times daily (every 6–4 hours)
Intravenously: 5–20 million IU (equivalent to 2.8–11.2 g of benzylpenicillin) per day
If necessary, the daily dose may be increased up to a maximum of 50 million IU (equivalent to 28.1 g of benzylpenicillin).

Children aged 1–12 years:
250,000 IU (equivalent to 140.5 mg of benzylpenicillin) per kg of body weight per day.

Children aged 1 month to 1 year:
167,000 IU (equivalent to 93.9 mg of benzylpenicillin) per kg of body weight per day.

In neonates, a reduced dose and frequency of administration is recommended because immature renal function in neonates may delay penicillin elimination.

Neonates and preterm infants:
50,000 IU (equivalent to 28.1 mg of benzylpenicillin) per kg of body weight per day. The daily dose should be divided into 3–4 intravenous injections (every 8–6 hours) or intermittent infusions. Alternatively, the medicinal product may be administered via intramuscular injection or continuous intravenous infusion using an infusion pump. In preterm infants and infants under one week of age, the daily dose should be divided into two injections (every 12 hours) due to the prolonged half-life in these patients. In neonates, a reduced dose and frequency of administration is recommended because immature renal function in neonates may delay penicillin elimination.

In cases of endocarditis, benzylpenicillin should be used in combination with an aminoglycoside.

Elderly patients
Potassium benzylpenicillin should be administered with caution and serum potassium levels should be frequently monitored due to the increased risk of hyperkalaemia.

Patients with renal or hepatic impairment
Patients with uraemia and CrCl above 10 mL/min/1.73 m²: Administer a full loading dose (see recommended dosing above), followed by half the loading dose every 4 to 5 hours.
CrCl below 10 mL/min/1.73 m²: Administer a full loading dose (see recommended dosing above), followed by half the loading dose every 8 to 10 hours.
Dose reduction is recommended in patients with impaired renal or hepatic function.
Dose reduction should be considered in case of occurrence or suspicion of organ dysfunction (including electrolyte imbalance, liver and biliary tract, urinary and haematopoietic systems, and cardiovascular status).
Potassium benzylpenicillin should be administered with caution and serum potassium levels should be frequently monitored due to the increased risk of hyperkalaemia.

After reconstitution
Do not store in refrigerator or freeze.
Chemical and physical stability of the product has been demonstrated for 4–12 hours after opening at 25°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution eliminates the risk of microbial contamination, the product should be used immediately.
If the solution is not used immediately, the responsibility for storage duration and conditions after opening lies with the user.
After reconstitution, protect the solution from light.

Intramuscular injection
The medicinal product should be injected into large muscle groups.
Do not inject more than 1.67 million IU (equivalent to 0.9 g of benzylpenicillin) at a single site.
In children and neonates, intravenous administration is preferred. Intramuscular administration should be used only in emergency situations when intravenous access is unavailable.

Intravenous injection / intravenous infusion
The medicinal product may be administered intravenously (as an injection lasting 3–5 minutes or as an intravenous infusion).
For daily doses of 10 million IU or more, the medicinal product may be diluted with an infusion solution and administered over 24 hours.
In intermittent intravenous infusion, one-quarter or one-sixth of the daily dose may be administered over 1 to 2 hours and repeated every 6 to 4 hours, respectively.
Divided doses are usually administered as infusions lasting 15 to 30 minutes in children and neonates.
A dose of 20,000,000 IU (20 million IU) must be administered exclusively via intravenous infusion.

Information on solution preparation – see table below.
Details on solution preparation, diluents, and stability of the prepared solution depending on the diluent used are presented in the table below.

The solution should be inspected visually before use. The solution should be clear and practically free of solid particles.
Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products, as compatibility studies have not been conducted.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.