PENICRYL 5,000,000 IU Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
2. What is Penicryl and what is it used for
3. Important information before using Penicryl
   1. When not to use Penicryl:
   2. Warnings and precautions
   3. Penicryl and other medicines
   4. Pregnancy and breastfeeding
   5. Driving and using machines
   6. Penicryl contains potassium
4. How to use Penicryl
   1. Using a higher dose of Penicryl than recommended
   2. Missing a dose of Penicryl
   3. Stopping use of Penicryl
5. Possible side effects
   1. The patient should immediately tell their doctor or seek medical attention if they think the medicine is causing them to feel unwell, or if they experience any of the following symptoms:
   2. Reporting side effects
6. How to store Penicryl
7. Contents of the pack and other information
   1. What Penicryl contains
   2. What Penicryl looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   5. Information intended for healthcare professionals only:
   6. To obtain additional information, refer to the Summary of Product Characteristics.
   7. Incompatibilities

Leaflet accompanying the packaging: information for the user

Penicryl, 5,000,000 IU, powder for solution for injection/infusion
benzylpenicillin (as benzylpenicillin potassium)

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Penicryl and what is it used for
• 2. Important information 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 is Penicryl and what is it used for

Penicryl is a medicine that acts 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 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 the proper use of antibacterial agents should be taken into account.

2. Important information before using Penicryl

When not to use Penicryl:

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

Warnings and precautions

If any of the following situations apply to the patient, they should discuss it with their doctor, nurse, or pharmacist before using Penicryl:

• if the patient has kidney function disorders
• if the patient has heart failure
• if the patient has diarrhea
• if the patient is controlling potassium intake in their diet
• if the patient has experienced severe skin reactions (SCAR - Severe Cutaneous Adverse Reactions), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which have been reported in association with beta-lactam antibiotic therapy, including penicillins (see "Possible side effects" in section 4)
• if the patient is over 60 years old
• if the medicine is to be administered to newborns and premature infants.

Prolonged use of Penicryl may cause an overgrowth of non-susceptible microorganisms, which may lead to superinfection.
High doses of benzylpenicillin potassium 5,000,000 IU (equivalent to 2.8 g of benzylpenicillin), powder for solution for injection/infusion, may cause serious, even fatal, electrolyte disturbances, i.e., hyperkalemia and hyponatremia, when administered intravenously in large doses (over 10 million units). The doctor will always consider the potassium content. In patients treated with high doses for more than 5 days, the doctor recommends monitoring electrolyte balance, blood morphology, and kidney function (see "Penicryl contains potassium").
Large intravenous doses should be administered slowly due to potential side effects related to electrolyte imbalance caused by the potassium content in penicillin.
Kidney function disorders may lead to a significant increase in potassium levels in the blood, which can cause serious cardiac problems. After rapid intravenous administration of benzylpenicillin potassium (10-18 million IU/day), cases of flaccid paralysis, echocardiogram abnormalities (shortened QT interval and spiked T waves), and cardiac arrest have been reported. However, hyperkalemia does not occur until very large doses of benzylpenicillin potassium are used for a long time, especially in patients with renal failure.
If any of the above situations apply to the patient (or the patient is unsure), they should inform their doctor, pharmacist, or nurse before using Penicryl.

Penicryl and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
It is especially important for the doctor to know if the patient is taking any of the following medicines:

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

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before using this medicine.
Pregnancy
There are no known risks associated with the use of Penicryl during pregnancy.
Breastfeeding
Benzylpenicillin passes into human milk, but the risk to the baby is unlikely when therapeutic doses are used.

Driving and using machines

Penicryl has no influence or negligible influence on the ability to drive and use machines.

Penicryl contains potassium

Penicryl contains 8.42 mmol (329.07 mg) of potassium per vial. 1 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 controlling potassium intake in their diet (see "Warnings and precautions" in section 2).

3. How to use Penicryl

Information on dosing and administration is presented in the section "Information intended for healthcare professionals only".
This medicine will be administered by injection by a doctor or nurse.
The doctor should adjust the appropriate dosebased on the patient's kidney function, age, and body weight.
Additionally, the doctor will decide how and whenthe injection should be administered, as well as the duration of treatment.
Penicryl is a dry powder that is dissolved by the doctor or nurse in an appropriate solvent. The solution is administered intravenously or intramuscularly by injection or intravenously by infusion.

Using a higher dose of Penicryl than recommended

Since the injection is administered by a doctor or nurse, administration of a higher dose than recommended is unlikely. If the patient thinks they have received too much medicine, they should tell their doctor or nurse who administered the injection. Symptoms of overdose may include nausea, vomiting, diarrhea, electrolyte disturbances, muscle twitching, myoclonic seizures, loss of consciousness, seizures, coma, hemolytic reactions, kidney failure, or acidosis.
In exceptional cases, an anaphylactic reaction may occur.

Missing a dose of Penicryl

If the patient thinks they have missed a dose of Penicryl, they should immediately tell their doctor or nurse. They should not take a double dose to make up for the missed dose.

Stopping use of Penicryl

Stopping treatment too early may have an unfavorable effect on the treatment outcome or lead to a relapse of the disease, which is more difficult to treat. The patient should follow their doctor's instructions.
Instructions for preparing the medicine for use are at the end of the patient leaflet, in the section "Information intended for healthcare professionals only".
If the patient has any further doubts about using this medicine, they should consult their doctor, nurse, or pharmacist.

4. Possible side effects

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

The patient should immediately tell their doctor or seek medical attention if they think the medicine is causing them to feel unwell, or if they experience 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 the eyelids, face, or lips; swelling or redness of the tongue
• fever
• joint pain
• swelling of the lymph nodes.

Penicryl administered intravenously in large doses may cause serious, even fatal, electrolyte disturbances, i.e., hyperkalemia.
Symptoms of high potassium levels, which may occur as:

• irregular heartbeat
• changes in brightness and logic of thinking
• weakness, feeling of dizziness or lightheadedness
• feeling of impending fainting
• numbness or tingling
• shortness of breath.

Selected severe side effects
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 and systemic symptoms
• AGEP - acute generalized exanthematous pustulosis, with symptoms such as severe drug reactions with redness of the skin or without redness of the skin, fever, pustules (see also "Warnings and precautions" in section 2)
• Pseudomembranous colitis caused by Clostridioides difficile - symptoms: watery diarrhea containing mucus, blood, with a characteristic odor, sometimes fever and abdominal pain.

Other side effects
Frequent (occurring in no more than 1 in 10 people):

• rash
• phlebitis (inflammation of the vein).

Uncommon (occurring in no more than 1 in 100 people):

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

Rare (occurring in no more than 1 in 1,000 people):

• decreased white blood cell count
• hemolytic anemia (decreased red blood cell count)
• diarrhea
• pruritus (itching).

Very rare (occurring in no more than 1 in 10,000 people):

• severe skin reactions.

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

• decreased platelet count, which may increase the risk of bleeding (thrombocytopenia)
• decreased white blood cell count, which may increase the risk of infection (neutropenia)
• Jarisch-Herxheimer reaction may occur during the 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)
• pruritus (itching)
• erythema (inflammatory redness of the skin)
• angioedema (swelling of the skin, mucous membranes, and subcutaneous tissue, usually located on the face, lips, or tongue)
• thrombocytopenia (low platelet count)
• metabolic encephalopathy (neurological disorders with seizures and loss of consciousness).

Other side effects may include kidney and liver disorders, and an overgrowth of fungi in the mouth and abdomen.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, 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. Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Penicryl

The medicine should be stored out of sight and reach of children.
This medicine does not require special storage conditions.
Information on storage conditions after reconstitution is in the section "Information intended for healthcare professionals only".
Do not use this medicine after the expiry date stated on the label and carton after EXP. The expiry date refers to the last day of the month stated.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Penicryl contains

The active substance of Penicryl is benzylpenicillin (as benzylpenicillin potassium).
Each vial contains 3.1 g of benzylpenicillin potassium (5 million IU of benzylpenicillin), equivalent to 2.8 g of benzylpenicillin.
Penicryl contains potassium (see section 2).
The medicine does not contain other ingredients.

What Penicryl looks like and contents of the pack

White or almost white crystalline powder in colorless, transparent vials.
The vials are made of soda-lime-silica glass (type III) with a nominal capacity of 20 mL.
The vials are closed with gray rubber stoppers (type I) and an aluminum cap.
1 or 10 vials in a carton.

Marketing authorization holder and manufacturer

Tarchomińskie Zakłady Farmaceutyczne "Polfa" Spółka Akcyjna, ul. A. Fleminga 2, 03-176 Warsaw, Phone: (22) 811 18 14. For more detailed information on this medicine, the patient should contact the marketing authorization holder.

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Poland
Penicryl
Sweden
Penicryl
Finland
Penicryl 5,000,000 IU injection/infusion powder

Norway
Penicryl
Denmark
Penicryl
Date of last revision of the leaflet:
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Information intended for healthcare professionals only:

To obtain additional information, refer to the Summary of Product Characteristics.

Dosage should be adjusted according to kidney 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 a day (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 can be increased 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.
Newborns and premature 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 can be administered by intramuscular injection or continuous intravenous infusion using an infusion pump. In premature infants and children 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 newborns, the dose and frequency of administration should be reduced, as the immature kidney function in newborns may delay the elimination of penicillin.
In case of endocarditis, benzylpenicillin should be used in combination with an aminoglycoside.
Elderly patients
Benzylpenicillin potassium should be administered with caution and frequent monitoring of serum potassium levels due to the increased risk of hyperkalemia.
Patients with kidney or liver disorders
Patients with uremia and CrCl above 10 mL/min/1.73 m: The full loading dose should be administered (see recommended dosing above), and then half of the loading dose every 4 to 5 hours.
CrCl below 10 mL/min/1.73 m: The full loading dose should be administered (see recommended dosing above), and then half of the loading dose every 8 to 10 hours.
In patients with kidney or liver disorders, the dose should be reduced.
The total dose should be considered for reduction in case of suspected or confirmed organ disorders (including electrolyte balance, liver and biliary tract, urinary tract, and hematopoietic system, as well as heart and blood vessel conditions).
Benzylpenicillin potassium should be administered with caution and frequent monitoring of serum potassium levels due to the increased risk of hyperkalemia.
After reconstitution
Do not store in a refrigerator or freeze.
Chemical and physical stability of the product after opening has been demonstrated for 4-12 hours 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 the storage time and conditions after opening lies with the user.
The reconstituted product should be protected from light.
Intramuscular injection
The medicine should be injected into large muscle groups.
Do not inject a dose greater than 1.67 million IU (equivalent to 0.9 g of benzylpenicillin) into one site.
In children and newborns, the preferred route of administration is intravenous. Intramuscular administration should only be used in emergency situations when intravenous access is not available.
Intravenous injection/infusion
The medicine can be administered intravenously (as an injection lasting from 3 to 5 minutes or as an intravenous infusion).
In case of daily doses of 10 million units or more, the medicine can be diluted with an infusion solution and administered over 24 hours.
In intermittent intravenous infusion, one-quarter or one-sixth of the daily dose can be administered over 1 to 2 hours and repeated every 6 to 4 hours.
Divided doses are usually administered by infusion lasting from 15 to 30 minutes in children and newborns.
A dose of 20,000,000 IU (20 million IU) can only be administered by intravenous infusion.
Information on preparation of the solution - see the table below.
Method of preparation, diluents, and stability of the solution after preparation, depending on the diluent used, are presented in the table below.

Before use, the solution should be visually inspected. The solution should be clear and practically free from particulate matter.

Incompatibilities

Do not mix this medicinal product with other medicinal products, as compatibility studies have not been performed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.