Cefrag

Package leaflet: Information for the patient

CEFRAG 1 g / 10 ml powder and solvent for injectable solution for intravenous use

Ceftriaxone (as ceftriaxone sodium)
Generic medicine
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What CEFRAG is and what it is used for
2. What you must know before being administered CEFRAG
3. How CEFRAG is administered
4. Possible side effects
5. How to store CEFRAG
6. Contents of the pack and other information

1. What CEFRAG is and what it is used for

CEFRAG contains the active substance ceftriaxone, an antibiotic administered to adults and children (including newborns). It works by killing bacteria that cause infections. It belongs to a group of medicines called cephalosporins.
CEFRAG is used to treat infections:

• of the brain (meningitis).
• of the lungs.
• of the middle ear.
• of the abdomen and abdominal wall (peritonitis).
• of the urinary tract and kidneys.
• of bones and joints.
• of the skin or soft tissues.
• of the blood.
• of the heart. It may be administered:
• to treat specific sexually transmitted infections (gonorrhoea and syphilis).
• to treat patients with a low number of white blood cells in the blood (neutropenia) who have fever due to bacterial infection.
• to treat chest infections in adults with chronic bronchitis.
• to treat Lyme disease (caused by tick bites) in adults and children, including newborns from 15 days of age.
• to prevent infections during surgery.

2. What you need to know before you are given CEFRAG

Do not receive CEFRAG if:

• you are allergic to ceftriaxone or to any of the other ingredients of this medicine (listed in section 6).
• you have previously had a sudden or severe allergic reaction to penicillin or to similar antibiotics (such as cephalosporins, penicillins, monobactams, and carbapenems). Possible signs include sudden swelling of the throat or face, which may make it difficult to breathe or swallow, sudden swelling of hands, feet and ankles, chest pain, and a severe rash that develops rapidly.
• you are allergic to lidocaine and CEFRAG is to be administered by intramuscular injection.

CEFRAG must not be given to children in the following cases:

• the child is premature.
• the child is a newborn (up to 28 days of age) and has certain blood disorders or jaundice (yellowing of the skin or whites of the eyes), or requires intravenous administration of a product containing calcium.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given CEFRAG if:

• you are experiencing or have previously experienced any combination of the following symptoms: rash, skin redness, blistering of the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, increased levels of liver enzymes detectable in blood tests, elevated levels of a type of white blood cells (eosinophilia), and swollen lymph nodes (signs of serious skin reactions; see also section 4 “Possible side effects”).
• you have recently received or are about to receive products containing calcium.
• you have recently experienced diarrhoea after taking an antibiotic, or have intestinal problems, particularly colitis (inflammation of the intestine).
• you have liver or kidney problems.
• you have gallstones or kidney stones.
• you have other diseases, such as haemolytic anaemia (a reduction in red blood cells that may cause pale yellow skin, weakness, or shortness of breath).
• you are on a low-sodium diet.
• you have liver or kidney problems (see section 4).

If you are due to have a blood or urine test
If you are receiving CEFRAG for a prolonged period, you may need regular blood tests. CEFRAG may affect urine sugar tests and a blood test known as the Coombs test. If you are due to have tests:

• inform the person taking your sample that you have been given CEFRAG.

Children
Talk to your doctor, pharmacist, or nurse before giving CEFRAG to a child if:

• the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and CEFRAG
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• an antibiotic called an aminoglycoside.
• an antibiotic called chloramphenicol (used to treat infections, particularly eye infections).

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will assess the benefits of treatment with CEFRAG for you and the possible risks for the unborn or breastfed child.

Driving and using machines
CEFRAG may cause dizziness. If you feel dizzy, do not drive or operate tools or machinery. Contact your doctor if you experience these symptoms.

CEFRAG contains sodium
Each gram of CEFRAG contains 3.6 mmol (82.8 mg) of sodium. This should be taken into account in patients with impaired renal function or those on a low-sodium diet.

3. How CEFRAG is administered

CEFRAG is generally administered by a doctor or nurse through a drip (intravenous infusion) or via an injection directly into a vein. CEFRAG will be prepared by a doctor, pharmacist, or nurse and will not be mixed with, nor administered simultaneously to, injections containing calcium.
Usual dose
Your doctor will determine the correct dose of CEFRAG for you. The dose will depend on the severity and type of infection, any concomitant treatment with other antibiotics, your body weight and age, and the extent of your kidney and liver function. The number of days or weeks during which you will receive CEFRAG will depend on the type of infection you have.
Adults, elderly patients, and children aged 12 years and older with a body weight equal to or greater than 50 kilograms (kg):

• 1 to 2 g once daily, depending on the severity and type of infection. If you have a severe infection, your doctor will administer a higher dose (up to 4 g per day). If your daily dose exceeds 2 g, it may be given as a single daily dose or as two separate doses.

Newborns, infants, and children from 15 days to 12 years of age with a body weight below 50 kg

• 50–80 mg of CEFRAG per kg of body weight once daily, depending on the severity and type of infection. If you have a severe infection, your doctor will prescribe a higher dose, starting from 100 mg per kg of body weight, up to a maximum of 4 g per day. If your daily dose exceeds 2 g, it may be given as a single daily dose or as two separate doses.
• children with a body weight equal to or greater than 50 kg should receive the usual adult dose.

Newborns (0–14 days of age)

• 20–50 mg of CEFRAG per kg of body weight once daily, depending on the severity and type of infection.
• the maximum daily dose must not exceed 50 mg per kg of body weight of the newborn.

Patients with liver or kidney problems
You may be given a different dose from the usual. Your doctor will decide how much CEFRAG you need and will monitor you closely, depending on the severity of your liver or kidney disease.
If you are given more CEFRAG than you should
If you are accidentally given more CEFRAG than prescribed, contact your doctor or the nearest hospital immediately.
If you miss a dose of CEFRAG
If you miss an injection, you should receive it as soon as possible. However, if it is almost time for your next scheduled injection, skip the missed dose. Do not take a double dose (two injections together) to make up for a forgotten dose.
If you stop treatment with CEFRAG
Do not stop taking CEFRAG unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Treatment with ceftriaxone, especially in elderly patients with severe renal impairment or neurological disorders, may rarely cause reduced level of consciousness, abnormal movements, agitation, and seizures.
Like all medicines, this medicine can cause side effects, although not everybody experiences them.
With this medicine, you may experience the following side effects:

Severe allergic reactions (frequency not known, cannot be estimated from available data)
If you have a severe allergic reaction, seek immediate medical attention.
Signs may include:

• Chest pain occurring during allergic reactions, which may be a symptom of an allergy-induced heart attack (Kounis syndrome).
• Sudden swelling of the face, throat, lips, or mouth. This may make breathing or swallowing difficult.
• Sudden swelling of the hands, feet, and ankles.

Severe skin reactions (frequency not known, cannot be estimated from available data)
If you develop a severe skin reaction, seek immediate medical attention.
Signs may include:

• Severe rash developing rapidly, with blistering or peeling of the skin and possible blistering in the mouth (Stevens-Johnson syndrome and toxic epidermal necrolysis, also known as SJS and TEN).
• Any combination of the following symptoms: widespread rash, high body temperature, elevated liver enzymes, abnormalities in blood tests (eosinophilia), swollen lymph nodes, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).
• Jarisch-Herxheimer reaction, which may cause fever, chills, headache, muscle pain, and rash, usually resolving spontaneously. These symptoms may occur shortly after starting Cefrag treatment for spirochete infections such as Lyme disease.

Other possible side effects:
Common (may affect up to 1 in 10 people)

• Abnormalities in white blood cells (such as reduced leukocytes and increased eosinophils) and platelets (reduced thrombocytes).
• Soft stools or diarrhoea.
• Changes in blood test results indicating liver function abnormalities.
• Rash.

Uncommon (may affect up to 1 in 100 people)

• Fungal infections (e.g., thrush).
• Decreased number of white blood cells (granulocytopenia).
• Reduced number of red blood cells (anaemia).
• Blood clotting problems. Signs include easy bruising, joint pain, and swelling.
• Headache.
• Dizziness.
• Nausea or vomiting.
• Itching.
• Pain or burning sensation along the vein where CEFRAG was administered. Pain at the injection site.
• Fever.
• Abnormal kidney function test results (increased blood creatinine).

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

• Inflammation of the large intestine (colon). Signs include diarrhoea, often with blood and mucus, stomach pain, and fever.
• Breathing difficulties (bronchospasm).
• Rash with hives (urticaria), which may cover large areas of the body, associated with itching and swelling.
• Blood or sugar in the urine.
• Oedema (fluid accumulation).
• Chills.

Not known (frequency cannot be estimated from available data)

• Secondary infections that may not respond to the prescribed antibiotic.
• A form of anaemia characterised by destruction of red blood cells (haemolytic anaemia).
• Severe decrease in white blood cell count (agranulocytosis).
• Seizures.
• Dizziness.
• Inflammation of the pancreas (pancreatitis). Signs include severe stomach pain radiating to the back.
• Inflammation of the mouth lining (stomatitis).
• Inflammation of the tongue (glossitis). Signs include swelling, redness, and irritation of the tongue.
• Problems affecting the gallbladder and/or liver, which may cause pain, nausea, vomiting, yellowing of the skin, itching, abnormally dark urine, and pale stools.
• A neurological condition that may develop in newborns with severe jaundice (kernicterus).
• Kidney problems caused by calcium-ceftriaxone deposits. You may experience pain when urinating, or a reduced amount of urine produced.
• False positive Coombs test (a blood test to detect blood-related problems).
• False positive test for galactosaemia (an abnormal accumulation of the sugar galactose).
• CEFRAG may interfere with certain types of blood glucose tests; please consult your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at: www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store CEFRAG

Expiry: see the expiry date stated on the packaging
Warning: do not use the medicinal product after the expiry date stated on the packaging.
The stated expiry date refers to the product in its original, unopened packaging stored correctly.
This medicinal product does not require any special storage conditions.
From a microbiological standpoint, the product should be used immediately after reconstitution.
If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.
Chemical and physical stability of the medicinal product after reconstitution has been demonstrated for 24 hours between +2°C and +8°C, and for 6 hours when stored at a temperature below 25°C.
The solution may vary in colour from pale yellow to amber depending on concentration and storage duration; this characteristic does not affect the drug's efficacy or tolerability.
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. Package contents and other information

What CEFRAG contains
CEFRAG 1 g / 10 ml powder and solvent for injectable solution for intravenous use
one vial of powder contains:
active substance: ceftriaxone disodium 3,5 H₂O 1,193 g equivalent to ceftriaxone 1 g;
one ampoule of solvent contains: water for injection.
Description of the appearance of CEFRAG and package contents
CEFRAG 1 g / 10 ml powder and solvent for injectable solution for intravenous use: 1 vial of powder +
1 10 ml ampoule of solvent.
Marketing Authorization Holder
S.F. Group S.r.l. – Via Tiburtina, 1143 – 00156 Rome
Manufacturer
MITIM S.r.l. - Via Cacciamali, 34-36-38 - 25125 Brescia.

Patient Information Leaflet

CEFRAG 2 g powder for solution for infusion

Ceftriaxone (as ceftriaxone sodium)
Generic medicine
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

7. What CEFRAG is and what it is used for
8. What you need to know before you are given CEFRAG
9. How CEFRAG is administered
10. Possible side effects
11. How to store CEFRAG
12. Contents of the pack and other information

7. What CEFRAG is and what it is used for

CEFRAG contains the active substance ceftriaxone, which is an antibiotic administered to adults and children (including newborns). It works by killing the bacteria that cause infections. It belongs to a group of medicines called cephalosporins.
CEFRAG is used to treat infections:

• of the brain (meningitis).
• of the lungs.
• of the middle ear.
• of the abdomen and abdominal wall (peritonitis).
• of the urinary tract and kidneys.
• of the bones and joints.
• of the skin or soft tissues.
• of the blood.
• of the heart. It may be administered:
• to treat specific sexually transmitted infections (gonorrhoea and syphilis).
• to treat patients with a low number of white blood cells in the blood (neutropenia) who have fever due to a bacterial infection.
• to treat chest infections in adults with chronic bronchitis.
• to treat Lyme disease (caused by tick bites) in adults and children, including newborns from 15 days of age.
• to prevent infections during surgical procedures.

8. What you need to know before you are given CEFRAG

Do not be given CEFRAG if:

• you are allergic to ceftriaxone or to any of the other ingredients of this medicine (listed in section 6).
• you have had a sudden or severe allergic reaction to penicillin or to similar antibiotics (such as cephalosporins, penicillins, monobactams and carbapenems). Possible signs include sudden swelling of the throat or face, which may make breathing or swallowing difficult, sudden swelling of hands, feet and ankles, chest pain, and a severe rash that develops rapidly.
• you are allergic to lidocaine and CEFRAG is to be administered by intramuscular injection.

CEFRAG must not be given to children in the following cases:

• the child is premature.
• the child is a newborn (up to 28 days of age) and has certain blood disorders or jaundice (yellowing of the skin or whites of the eyes), or requires intravenous administration of a product containing calcium.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given CEFRAG if:

• you are experiencing or have previously experienced any combination of the following symptoms: rash, skin redness, blistering of lips, eyes and mouth, skin peeling, high fever, flu-like symptoms, increased levels of liver enzymes detectable in blood tests, increase in a type of white blood cells (eosinophilia), and swollen lymph nodes (signs of serious skin reactions; see also section 4 “Possible side effects”).
• you have recently received or are about to receive products containing calcium.
• you have recently had diarrhoea after taking an antibiotic. You have had intestinal problems, particularly colitis (inflammation of the intestine).
• you have liver or kidney problems.
• you have gallstones or kidney stones.
• you have other diseases, such as haemolytic anaemia (a reduction in red blood cells that may cause pale yellow skin and lead to weakness or shortness of breath).
• you are on a low-sodium diet.
• you have liver or kidney problems (see section 4).

If you are due to have blood or urine tests
If you are given CEFRAG for a prolonged period, you may need to have regular blood tests. CEFRAG may affect the results of urine sugar tests and a blood test known as the Coombs test. If you are about to undergo testing:

• inform the person collecting your sample that you have been given CEFRAG.

Children
Talk to your doctor, pharmacist or nurse before giving CEFRAG to a child if:

• the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and CEFRAG
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• an antibiotic called an aminoglycoside.
• an antibiotic called chloramphenicol (used in the treatment of infections, particularly eye infections).

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor for advice before taking this medicine.
Your doctor will assess the benefits that treatment with CEFRAG would provide you and the potential risks for your baby.

Driving and using machines
CEFRAG may cause dizziness. If you feel dizzy, do not drive and do not use tools or machinery. Contact your doctor if you experience these symptoms.

CEFRAG contains sodium
Each gram of CEFRAG contains 3.6 mmol (82.8 mg) of sodium. This should be taken into consideration in patients with impaired renal function or those on a low-sodium diet.

9. How CEFRAG is administered

CEFRAG is generally administered by a doctor or nurse through an intravenous infusion (intravenous drip) or by direct injection into a vein. CEFRAG will be prepared by a doctor, pharmacist, or nurse and will not be mixed or administered simultaneously with calcium-containing injections.

Standard dose
Your doctor will determine the correct dose of CEFRAG for you. The dose will depend on the severity and type of infection, any concomitant treatment with other antibiotics, your body weight and age, and the extent of kidney and liver function. The number of days or weeks during which you will receive CEFRAG will depend on the type of infection you have.

Adults, elderly patients, and children aged 12 years or older with a body weight equal to or greater than 50 kilograms (kg):

• 1 to 2 g once daily, depending on the severity and type of infection. If you have a severe infection, your doctor will administer a higher dose (up to 4 g per day). If your daily dose exceeds 2 g, it may be given as a single daily dose or divided into two separate doses.

Newborns, infants, and children from 15 days to 12 years of age with a body weight below 50 kg:

• 50–80 mg of CEFRAG once daily per kg of the child's body weight, depending on the severity and type of infection. If the child has a severe infection, the doctor may prescribe a higher dose, starting from 100 mg per kg of body weight, up to a maximum of 4 g per day. If the daily dose exceeds 2 g, it may be given as a single daily dose or divided into two separate doses.
• Children with a body weight equal to or greater than 50 kg should receive the standard adult dose.

Newborns (0–14 days of life):

• 20–50 mg of CEFRAG once daily per kg of the newborn's body weight, depending on the severity and type of infection.
• The maximum daily dose must not exceed 50 mg per kg of the newborn's body weight.

Patients with liver or kidney problems
You may be given a different dose than the standard one. Your doctor will decide the amount of CEFRAG you need and will closely monitor you, depending on the severity of your liver or kidney disease.

If you are given more CEFRAG than you should
If you are accidentally given more CEFRAG than prescribed, contact your doctor or the nearest hospital immediately.

If you forget to receive CEFRAG
If you miss an injection, it should be given as soon as possible. However, if it is almost time for the next scheduled injection, skip the missed dose. Do not administer a double dose (two injections together) to make up for the missed dose.

If you stop CEFRAG treatment
Do not stop taking CEFRAG unless your doctor tells you to. If you have any doubts about using this medicine, consult your doctor or nurse.

10. Possible side effects

Treatment with ceftriaxone, especially in elderly patients with severe renal impairment or disorders of the
nervous system, may rarely cause reduced level of consciousness, abnormal movements, agitation, and seizures.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
With this medicine, you may experience the following side effects:

Severe allergic reactions (not known, frequency cannot be estimated from the available data)
If you have a severe allergic reaction, seek immediate medical attention.
Signs may include:

• Chest pain occurring as part of an allergic reaction, which may be a symptom of an allergic-triggered heart attack (Kounis syndrome).
• Sudden swelling of the face, throat, lips, or mouth. This may make breathing or swallowing difficult.
• Sudden swelling of the hands, feet, and ankles.

Severe skin reactions (not known, frequency cannot be estimated from the available data)
If you develop a severe skin reaction, seek immediate medical attention.
Signs may include:

• Severe rash that develops rapidly, with blistering or peeling of the skin and possible blistering in the mouth (Stevens-Johnson syndrome and toxic epidermal necrolysis, also known as SJS and TEN).
• Any combination of the following symptoms: widespread rash, high body temperature, increased liver enzymes, abnormalities in blood tests (eosinophilia), swollen lymph nodes, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).
• Jarisch-Herxheimer reaction, which may cause fever, chills, headache, muscle pain, and rash, which generally resolves spontaneously. These symptoms may occur shortly after starting treatment with Cefrag for spirochete infections such as Lyme disease.

Other possible side effects:
Common (may affect up to 1 in 10 people)

• Abnormalities in white blood cells (such as reduced leukocytes and increased eosinophils) and platelets (decreased thrombocytes).
• Soft stools or diarrhoea.
• Changes in blood test results indicating liver function abnormalities.
• Rash.

Uncommon (may affect up to 1 in 100 people)

• Fungal infections (e.g., oral thrush).
• Decreased number of white blood cells (granulocytopenia).
• Reduced number of red blood cells (anaemia).
• Blood clotting problems. Signs include easy bruising, joint pain, and swelling.
• Headache.
• Dizziness.
• Nausea or vomiting.
• Itching.
• Pain or burning sensation along the vein where CEFRAG was administered. Pain at the injection site.
• Fever.
• Abnormal kidney function test results (increased blood creatinine).

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

• Inflammation of the large intestine (colon). Signs include diarrhoea, often with blood and mucus, stomach pain, and fever.
• Breathing difficulties (bronchospasm).
• Skin rash with hives (urticaria), which may cover a large area of the body, associated with itching and swelling.
• Blood or sugar in the urine.
• Oedema (fluid accumulation).
• Chills.

Not known (frequency cannot be estimated from the available data)

• Secondary infections that may not respond to the prescribed antibiotic.
• A type of anaemia characterised by destruction of red blood cells (haemolytic anaemia).
• Severe decrease in white blood cell count (agranulocytosis).
• Seizures.
• Vertigo.
• Inflammation of the pancreas (pancreatitis). Signs include severe stomach pain spreading to the back.
• Inflammation of the mouth lining (stomatitis).
• Inflammation of the tongue (glossitis). Signs include swelling, redness, and irritation of the tongue.
• Gallbladder and/or liver problems that may cause pain, nausea and vomiting, yellowing of the skin, itching, unusually dark urine, and pale stools.
• A neurological condition that may develop in newborns with severe jaundice (kernicterus).
• Kidney problems caused by calcium-ceftriaxone deposits. You may experience pain when urinating, or a reduced amount of urine produced.
• False positive Coombs test result (a blood test to detect blood-related problems).
• False positive test result for galactosaemia (an abnormal accumulation of the sugar galactose).
• CEFRAG may interfere with certain types of blood glucose tests; please consult your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at: www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

11. How to store CEFRAG

Expiry date: see expiry date stated on the packaging
Warning: do not use the medicinal product after the expiry date stated on the packaging.
The stated expiry date refers to the product in its original packaging, correctly stored.
This medicinal product does not require any special storage conditions.
From a microbiological point of view, the product should be used immediately after reconstitution.
If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.
Chemical and physical stability of the medicinal product after reconstitution has been demonstrated for 24 hours between +2°C and +8°C, and for 6 hours when stored at a temperature below 25°C.
The solution may vary in colour from pale yellow to amber depending on concentration and storage period; this characteristic does not affect the efficacy or tolerability of the medicine.
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.

12. Package contents and other information

What CEFRAG contains
CEFRAG 2 g powder for solution for infusion
one vial contains:
active substance: ceftriaxone disodium 3,5 H₂O 2,386 g equivalent to ceftriaxone 2 g.
Description of the appearance of CEFRAG and contents of the pack
CEFRAG 2 g powder for solution for infusion: 1 vial of powder.
Marketing Authorization Holder
S.F. Group S.r.l. – Via Tiburtina, 1143 – 00156 Rome
Manufacturer
MITIM S.r.l. - Via Cacciamali, 34-36-38 - 25125 Brescia.

Package leaflet: Information for the patient

CEFRAG 500 mg / 2 ml powder and solvent for injectable solution for intramuscular use, 1 g / 3.5 ml powder and solvent for injectable solution for intramuscular use

Ceftriaxone (as ceftriaxone sodium)
Generic medicinal product
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

13. What CEFRAG is and what it is used for
14. What you need to know before being administered CEFRAG
15. How CEFRAG is administered
16. Possible side effects
17. How to store CEFRAG
18. Contents of the pack and other information

13. What CEFRAG is and what it is used for

CEFRAG contains the active substance ceftriaxone, which is an antibiotic administered to adults and children (including newborns). It works by killing the bacteria that cause infections. It belongs to a group of medicines called cephalosporins.
CEFRAG is used to treat infections:

• of the brain (meningitis).
• of the lungs.
• of the middle ear.
• of the abdomen and abdominal wall (peritonitis).
• of the urinary tract and kidneys.
• of bones and joints.
• of the skin or soft tissues.
• of the blood.
• of the heart. It may be administered:
• to treat specific sexually transmitted infections (gonorrhoea and syphilis).
• to treat patients with a low number of white blood cells in the blood (neutropenia) who have fever due to a bacterial infection.
• to treat chest infections in adults with chronic bronchitis.
• to treat Lyme disease (caused by tick bites) in adults and children, including newborns from 15 days of age.
• to prevent infections during surgery.

14. What you need to know before you are given CEFRAG

Do not be given CEFRAG if:

• you are allergic to ceftriaxone or to any of the other ingredients of this medicine (listed in section 6).
• you have had a sudden or severe allergic reaction to penicillin or to similar antibiotics (such as cephalosporins, penicillins, monobactams, and carbapenems). Possible signs include sudden swelling of the throat or face, which may make it difficult to breathe or swallow, sudden swelling of hands, feet, and ankles, chest pain, and a severe rash that develops rapidly.
• you are allergic to lidocaine and CEFRAG is to be administered by intramuscular injection.

CEFRAG must not be given to children in the following cases:

• the child is premature.
• the child is a newborn (up to 28 days of age) and has certain blood disorders or jaundice (yellowing of the skin or whites of the eyes), or needs to receive a calcium-containing product intravenously.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given CEFRAG if:

• you are experiencing or have previously experienced any combination of the following symptoms: rash, skin redness, blistering on lips, eyes, or mouth, skin peeling, high fever, flu-like symptoms, increased levels of liver enzymes detectable in blood tests, increase in a type of white blood cells (eosinophilia), and swollen lymph nodes (signs of serious skin reactions; see also section 4 “Possible side effects”).
• you have recently received or are about to receive products containing calcium.
• you have recently had diarrhoea after taking an antibiotic. You have had intestinal problems, particularly colitis (inflammation of the intestine).
• you have liver or kidney problems.
• you have gallstones or kidney stones.
• you have other diseases, such as haemolytic anaemia (a reduction in red blood cells that may cause pale yellow skin and lead to weakness or shortness of breath).
• you are on a low-sodium diet.
• you have liver or kidney problems (see section 4).

If you are to undergo blood or urine tests
If you are given CEFRAG for a prolonged period, you may need to have regular blood tests. CEFRAG may affect the results of urine sugar tests and a blood test known as the Coombs test. If you are about to undergo testing:

• inform the person collecting your sample that you have been given CEFRAG.

Children
Talk to your doctor, pharmacist, or nurse before CEFRAG is administered to a child if:

• the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and CEFRAG
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• an antibiotic called an aminoglycoside.
• an antibiotic called chloramphenicol (used to treat infections, particularly eye infections).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will evaluate the benefits that treatment with CEFRAG may provide you and the potential risks to the baby.

Driving and using machines
CEFRAG may cause dizziness. If you experience dizziness, do not drive or operate tools or machinery. Contact your doctor if you experience these symptoms.

CEFRAG contains sodium
Each gram of CEFRAG contains 3.6 mmol (82.8 mg) of sodium. This should be taken into consideration for patients with impaired renal function or those on a low-sodium diet.

15. How CEFRAG is administered

CEFRAG is generally administered by a doctor or nurse via an injection given directly into a muscle. CEFRAG will be prepared by a doctor, pharmacist, or nurse and will not be mixed or administered simultaneously with injections containing calcium.
Usual dose
Your doctor will determine the appropriate dose of CEFRAG for you. The dose will depend on the severity and type of infection, any concomitant treatment with other antibiotics, your body weight and age, and the degree of function of your kidneys and liver. The number of days or weeks during which you will receive CEFRAG will depend on the type of infection you have.
Adults, elderly patients, and children aged 12 years and older with a body weight equal to or greater than 50 kilograms (kg):

• 1 to 2 g once daily, depending on the severity and type of infection. If you have a severe infection, your doctor will administer a higher dose (up to 4 g per day). If your daily dose exceeds 2 g, it may be given either as a single daily dose or as two separate doses.

Neonates, infants, and children from 15 days to 12 years of age with a body weight below 50 kg

• 50–80 mg of CEFRAG once daily per kg of body weight, depending on the severity and type of infection. If you have a severe infection, your doctor will prescribe a higher dose, starting from 100 mg per kg of body weight, up to a maximum of 4 g per day. If your daily dose exceeds 2 g, it may be given either as a single daily dose or as two separate doses.
• Children with a body weight equal to or greater than 50 kg should receive the usual adult dose.

Neonates (0–14 days of life)

• 20–50 mg of CEFRAG once daily per kg of body weight, depending on the severity and type of infection.
• The maximum daily dose must not exceed 50 mg per kg of body weight of the neonate.

Patients with liver or kidney problems
You may be given a different dose than the usual one. Your doctor will decide the amount of CEFRAG you need and will closely monitor you, depending on the severity of your liver or kidney disease.
If you are given more CEFRAG than you should
If you are accidentally given more CEFRAG than prescribed, contact your doctor or go to the nearest hospital immediately.
If you forget to receive CEFRAG
If you miss an injection, you should receive it as soon as possible. However, if it is almost time for your next scheduled injection, skip the missed dose. Do not administer a double dose (two injections together) to make up for the missed dose.
If you stop treatment with CEFRAG
Do not stop receiving CEFRAG unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

16. Possible side effects

Treatment with ceftriaxone, especially in elderly patients with severe renal impairment or disorders of the
nervous system, may rarely cause reduced level of consciousness, abnormal movements, agitation, and seizures.
Like all medicines, this medicine can cause side effects, although not everyone gets them.
With this medicine, you may experience the following side effects:

Severe allergic reactions (not known, frequency cannot be estimated from the available data)
If you have a severe allergic reaction, seek medical attention immediately.
Signs may include:

• Chest pain occurring during allergic reactions, which may be a symptom of a heart attack triggered by an allergy (Kounis syndrome).
• Sudden swelling of the face, throat, lips, or mouth. This may make breathing or swallowing difficult.
• Sudden swelling of the hands, feet, and ankles.

Severe skin reactions (not known, frequency cannot be estimated from the available data)
If you experience a severe skin reaction, seek medical attention immediately.
Signs may include:

• Severe rash developing rapidly, with blistering or peeling of the skin and possible blistering in the mouth (Stevens-Johnson syndrome and toxic epidermal necrolysis, also known as SJS and TEN).
• Any combination of the following symptoms: widespread rash, high body temperature, elevated liver enzymes, abnormalities in blood tests (eosinophilia), swollen lymph nodes, and involvement of other organs in the body (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).
• Jarisch-Herxheimer reaction, which may cause fever, chills, headache, muscle pain, and rash, which usually resolves spontaneously. These symptoms may occur shortly after starting treatment with Cefrag for spirochete infections such as Lyme disease.

Other possible side effects:
Common (may affect up to 1 in 10 people)

• Abnormalities in white blood cells (such as reduced leukocytes and increased eosinophils) and platelets (reduced thrombocytes).
• Soft stools or diarrhoea.
• Changes in blood test results for liver function.
• Rash.

Uncommon (may affect up to 1 in 100 people)

• Fungal infections (e.g., thrush).
• Decreased number of white blood cells (granulocytopenia).
• Reduced number of red blood cells (anaemia).
• Problems with blood clotting. Signs include easy bruising, joint pain, and swelling.
• Headache.
• Dizziness.
• Nausea or vomiting.
• Itching.
• Pain or burning sensation along the vein where CEFRAG was administered. Pain at the injection site.
• Fever.
• Abnormal kidney function tests (increased blood creatinine).

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

• Inflammation of the large intestine (colon). Signs include diarrhoea, often with blood and mucus, stomach pain, and fever.
• Difficulty breathing (bronchospasm).
• Skin rash with raised red areas (urticaria), which may cover a large area of the body, associated with itching and swelling.
• Blood or sugar in the urine.
• Oedema (fluid accumulation).
• Chills.

Not known (frequency cannot be estimated from the available data)

• Secondary infections that may not respond to the prescribed antibiotic.
• A form of anaemia characterised by destruction of red blood cells (haemolytic anaemia).
• Severe decrease in the number of white blood cells (agranulocytosis).
• Seizures.
• Vertigo.
• Inflammation of the pancreas (pancreatitis). Signs include severe stomach pain spreading to the back.
• Inflammation of the mouth lining (stomatitis).
• Inflammation of the tongue (glossitis). Signs include swelling, redness, and irritation of the tongue.
• Problems affecting the gallbladder and/or liver that may cause pain, nausea and vomiting, yellowing of the skin, itching, unusually dark urine, and pale stools.
• A neurological condition that may develop in newborns with severe jaundice (kernicterus).
• Kidney problems caused by calcium-ceftriaxone deposits. You may experience pain when urinating, or a reduced amount of urine produced.
• False positive Coombs test (a blood test to detect blood-related problems).
• False positive test for galactosaemia (an abnormal accumulation of the sugar galactose).
• CEFRAG may interfere with certain types of tests used to measure blood glucose; please consult your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your
doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at: www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

17. How to store CEFRAG

Expiry date: see expiry date on the packaging
Warning: do not use the medicine after the expiry date stated on the packaging.
The expiry date stated refers to the product in its original, unopened packaging and correctly stored.
This medicine does not require any special storage conditions.
From a microbiological point of view, the product should be used immediately after reconstitution.
If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.
Chemical and physical stability of the medicine after reconstitution has been demonstrated for 24 hours between +2°C and +8°C, and for 6 hours when stored below 25°C.
The solution may vary in colour from pale yellow to amber depending on concentration and storage period; this characteristic does not affect the drug's efficacy or tolerability.
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.

18. Package contents and other information

What CEFRAG contains
CEFRAG 500 mg / 2 ml powder and solvent for injectable solution for intramuscular use
One vial of powder contains:
active substance: ceftriaxone disodium 3,5 H₂O 596.5 mg equivalent to ceftriaxone 500 mg;
one solvent ampoule contains: aqueous solution of 1% lidocaine.

CEFRAG 1 g / 3.5 ml powder and solvent for injectable solution for intramuscular use
One vial of powder contains:
active substance: ceftriaxone disodium 3,5 H₂O 1.193 g equivalent to ceftriaxone 1 g;
one solvent ampoule contains: aqueous solution of 1% lidocaine.

Description of the appearance of CEFRAG and contents of the pack
CEFRAG 500 mg / 2 ml powder and solvent for injectable solution for intramuscular use: 1 powder vial + 1 solvent ampoule of 2 ml.
CEFRAG 1 g / 3.5 ml powder and solvent for injectable solution for intramuscular use: 1 powder vial + 1 solvent ampoule of 3.5 ml.

Marketing Authorization Holder
S.F. Group S.r.l. – Via Tiburtina, 1143 – 00156 Rome, Italy

Manufacturer
MITIM S.r.l. - Via Cacciamali, 34-36-38 - 25125 Brescia, Italy