Ceftriaxone Ratiopharm

PATIENT INFORMATION LEAFLET

Patient information leaflet: information for the patient

Ceftriaxone ratiopharm 500 mg/2 ml

powder and solvent for injectable solution for intramuscular use
Ceftriaxone (as ceftriaxone sodium)
Lidocaine (as lidocaine hydrochloride)
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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Ceftriaxone ratiopharm is and what it is used for

Ceftriaxone ratiopharm 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.
Ceftriaxone ratiopharm 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.

2. What you should know before being given Ceftriaxone ratiopharm

Do not use Ceftriaxone ratiopharm if:

• you are allergic to ceftriaxone or to any of the other ingredients of this medicine (listed in section 6);
• you have previously experienced 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 (or other amide-type local anesthetics) and Ceftriaxone ratiopharm is to be administered by intramuscular injection;
• you have a heart conduction disorder causing low blood pressure and slowed heart rate (complete atrioventricular block);
• you have a condition characterized by reduced blood volume (hypovolemia).

Ceftriaxone ratiopharm must not be given to children in the following cases:

• the child is premature;
• the child is a newborn (up to 28 days of life) 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 Ceftriaxone ratiopharm if:

• you have recently received or are about to receive calcium-containing products;
• you have recently had diarrhea after taking an antibiotic; you have intestinal problems, particularly colitis (inflammation of the intestine);
• you have liver or kidney problems (see section 4);
• you have gallstones or kidney stones;
• you have other diseases, such as hemolytic anemia (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 loss of muscle function and weakness (myasthenia gravis);
• you have seizures (epilepsy);
• you have any heart condition, especially if it affects your heart rate (cardiac conduction impairment, congestive heart failure, bradycardia);
• you have respiratory problems (respiratory depression);
• you have porphyria (a rare inherited disease affecting the skin and nervous system);
• you are experiencing or have previously experienced any combination of the following symptoms: rash, skin redness, blistering on lips, eyes, and mouth, skin peeling, high fever, flu-like symptoms, increased liver enzyme levels detectable in blood tests, increased levels of a type of white blood cell (eosinophilia), and swollen lymph nodes (signs of serious skin reactions; see also section 4 “Possible side effects”).

If you need blood or urine tests
If you are given Ceftriaxone ratiopharm for a prolonged period, you may need regular blood tests. Ceftriaxone ratiopharm may affect the results of urine and blood 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 Ceftriaxone ratiopharm.

Children
Talk to your doctor, pharmacist, or nurse before administering Ceftriaxone ratiopharm to a child if the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and Ceftriaxone ratiopharm
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).
  Several drugs may interact with lidocaine, leading to altered effects. These include:
• medicines used to treat infections (antibiotics such as clarithromycin, erythromycin, or rifampicin);
• medicines used to treat stomach ulcers (e.g., cimetidine);
• sedatives, anxiolytics (barbiturates);
• medicines used to treat epilepsy (e.g., carbamazepine, phenytoin, or primidone);
• medicines used to treat irregular heart rate (e.g., mexiletine, tocainide).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will evaluate the benefits of treatment with Ceftriaxone ratiopharm against the potential risks to the unborn child, especially during the first months of pregnancy.

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

Ceftriaxone ratiopharm contains sodium
Ceftriaxone ratiopharm contains approximately 41 mg of sodium (a main component of table salt) per vial (each gram of Ceftriaxone ratiopharm contains 3.6 mmol of sodium). This corresponds to 2.05% of the maximum daily dietary intake recommended for an adult.

3. How Ceftriaxone ratiopharm is administered

Ceftriaxone ratiopharm is generally administered by a doctor or nurse via an injection given directly into a muscle. Ceftriaxone ratiopharm will be prepared by a doctor, pharmacist, or nurse and will not be mixed with, nor administered simultaneously with, calcium-containing injections.

Standard dose
Your doctor will determine the appropriate dose of Ceftriaxone ratiopharm for you. The dose will depend on the severity and type of infection, whether you are receiving concomitant treatment with other antibiotics, your body weight and age, and the functioning of your kidneys and liver. The number of days or weeks during which you will receive Ceftriaxone ratiopharm 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 may 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 Ceftriaxone ratiopharm once daily per kg of the child’s body weight, depending on the severity and type of infection. If you have a severe infection, your 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 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 standard adult dose.

Neonates (0–14 days of life):

• 20–50 mg of Ceftriaxone ratiopharm once daily per kg of the neonate’s body weight, depending on the severity and type of infection;
• the maximum daily dose must not exceed 50 mg per kg of the neonate’s body weight.

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

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

If you miss a dose of Ceftriaxone ratiopharm
If you miss an injection, it should be administered 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 the missed dose.

If you stop treatment with Ceftriaxone ratiopharm
Do not stop taking Ceftriaxone ratiopharm unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You may experience the following side effects with this medicine:

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:

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

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 a serious rash that develops rapidly, with blistering or peeling of the skin and possibly blisters 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 usually resolves spontaneously. These symptoms typically occur shortly after starting ceftriaxone 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);
• loose 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., oral 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 Ceftriaxone ratiopharm 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);
• rash with raised itchy areas (urticaria), possibly affecting large areas of the body, associated with itching and swelling;
• blood or sugar in the urine;
• oedema (fluid accumulation);
• chills.

Frequency not known (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 reduction in the number of white blood cells (agranulocytosis);
• seizures;
• vertigo;
• 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, 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 galactosemia (an abnormal accumulation of the sugar galactose);
• Ceftriaxone ratiopharm may interfere with certain types of blood glucose tests; please consult your doctor.

Treatment with ceftriaxone, particularly in elderly patients with severe renal impairment or neurological disorders, may rarely cause reduced consciousness, abnormal movements, agitation, and seizures.
Following accidental intravascular injection of lidocaine during intramuscular administration, additional side effects may occur, which may include:
Rare (may affect up to 1 in 1,000 people)

• allergic reaction, even severe (anaphylactoid reaction and anaphylactic shock);

Frequency not known (cannot be estimated from available data)

• nervousness;
• dizziness;
• tremors;
• numbness around the mouth (circumoral paresthesia) and numbness of the tongue (oral hypoaesthesia);
• drowsiness;
• convulsions;
• coma;
• blurred vision, double vision (diplopia), or temporary loss of vision (amaurosis fugax);
• ringing in the ears (tinnitus), difficulty tolerating everyday sounds (hyperacusis);
• excessive slowing of heart rate (bradycardia), changes in heart rhythm (arrhythmias), cardiac depression or arrest;
• excessive drop in blood pressure (hypotension), which may lead to fainting (circulatory collapse);
• breathing difficulties (dyspnoea, bronchospasm) or possible cessation of breathing (respiratory depression);
• feeling unwell (nausea or vomiting);
• skin eruptions, urticaria;
• oedema (fluid accumulation, including of the face).

Reporting of side effects
If you experience any side effect, 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.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Ceftriaxone ratiopharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial or bottle, after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C. Store the vial in the original packaging.
Chemical and physical stability during use of the reconstituted product has been demonstrated for at least 6 hours at a temperature not exceeding 25°C, or up to 24 hours at 2-8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the period and conditions of storage prior to use are the responsibility of the user and must not exceed the time limits indicated above for chemical and physical stability during use.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ceftriaxone ratiopharm contains
Ceftriaxone ratiopharm 500 mg/2 ml powder and solvent for injectable solution for intramuscular use
Each vial of powder contains 500 mg of ceftriaxone as ceftriaxone sodium.
Each solvent ampoule contains an aqueous solution of 1% lidocaine (20 mg in 2 ml).
Description of the appearance of Ceftriaxone ratiopharm and contents of the pack
Ceftriaxone ratiopharm 500 mg/2 ml powder and solvent for injectable solution for intramuscular use: 1
vial of powder + 1 ampoule of solvent of 2 ml.
Marketing Authorization Holder and Manufacturer
ratiopharm GmbH, Graf-Arco Strasse 3, Ulm (Germany)
Manufacturer
MITIM S.r.l.
Via Cacciamali, 34-36-38
25125 Brescia

The following information is intended for healthcare professionals only:

Ceftriaxone ratiopharm may be administered by deep intramuscular injection. Intramuscular injections must be administered deeply into a sufficiently large muscle, and no more than 1 g should be injected at a single site (doses exceeding 1 g must be divided and administered at more than one site). For intramuscular injection, 500 mg of Ceftriaxone ratiopharm should be dissolved in 2 ml of the provided solution, which contains 10 mg of lidocaine hydrochloride per ml of water for injections.
Ceftriaxone must not be mixed with other medicinal products in the same syringe, except with 1% lidocaine hydrochloride solution (for intramuscular injection only). Since lidocaine is used as the solvent, the resulting solution must never be administered intravenously (see section 2). Accidental intravenous administration must be prevented by aspirating with the syringe before injection to exclude inadvertent intravascular puncture.
Ceftriaxone is contraindicated in neonates (≤ 28 days) who require (or are likely to require) treatment with intravenous calcium-containing solutions, including continuous infusions containing calcium, e.g., for parenteral nutrition, due to the risk of formation of calcium-ceftriaxone precipitate (see section 2).
For pre-operative prophylaxis of surgical site infections, ceftriaxone should be administered 30–90 minutes before surgery.
For each single administration, the maximum dose of lidocaine must not exceed 5 mg per kg of body weight. In obese children, the maximum dose should be calculated based on ideal body weight according to age and sex.
In neonates, the optimal serum concentration of lidocaine required to avoid toxicity, such as seizures and cardiac arrhythmias, in this age group is unknown.

INSTRUCTIONS FOR USE

Patient information leaflet

Ceftriaxone ratiopharm 1 g/10 ml

powder and solvent for injectable solution for intravenous use
Ceftriaxone (as ceftriaxone sodium)
Equivalent medicine
Please read this leaflet carefully before you are given this medicine as 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. Do not 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 Ceftriaxone ratiopharm is and what it is used for
2. What you need to know before being given Ceftriaxone ratiopharm
3. How Ceftriaxone ratiopharm is administered
4. Possible side effects
5. How to store Ceftriaxone ratiopharm
6. Contents of the pack and other information

1. What Ceftriaxone ratiopharm is and what it is used for

Ceftriaxone ratiopharm 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.
Ceftriaxone ratiopharm 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.

2. What you need to know before you are given Ceftriaxone ratiopharm

Do not use Ceftriaxone ratiopharm 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 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 Ceftriaxone ratiopharm needs to be administered by intramuscular injection.

Ceftriaxone ratiopharm 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 Ceftriaxone ratiopharm if:

• you have recently received or are about to receive products containing calcium;
• you have recently had diarrhoea after taking an antibiotic; you have intestinal problems, particularly colitis (inflammation of the intestine);
• you have liver or kidney problems (see section 4);
• you have gallstones or kidney stones;
• you have other diseases, for example haemolytic anaemia (a reduction in red blood cells which may cause pale yellow skin and lead to weakness or shortness of breath);
• you are on a low-sodium diet;
• you are experiencing or have previously experienced any combination of the following symptoms: skin rash, skin redness, blistering on 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”).

If you are undergoing blood or urine tests
If you are given Ceftriaxone ratiopharm for a prolonged period, you may need to have regular blood tests. Ceftriaxone ratiopharm may affect the results of urine and blood 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 Ceftriaxone ratiopharm.

Children
Talk to your doctor, pharmacist or nurse before giving Ceftriaxone ratiopharm to a child if the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and Ceftriaxone ratiopharm
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 to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will assess the benefits that treatment with Ceftriaxone ratiopharm would provide you and the potential risks for the baby.

Driving and using machines
Ceftriaxone ratiopharm 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.

Ceftriaxone ratiopharm contains sodium
Ceftriaxone ratiopharm contains approximately 83 mg of sodium (the main component of table salt) per vial (each gram of Ceftriaxone ratiopharm contains 3.6 mmol of sodium). This corresponds to 4.15% of the maximum daily recommended dietary intake for an adult.

3. How Ceftriaxone ratiopharm is administered

Ceftriaxone ratiopharm is generally administered by a doctor or nurse via intravenous infusion (IV infusion) or by direct injection into a vein.
Ceftriaxone ratiopharm will be prepared by a doctor, pharmacist, or nurse and will not be mixed with, nor administered simultaneously with, calcium-containing injections.

Standard dose
Your doctor will determine the appropriate dose of Ceftriaxone ratiopharm 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 functioning of your kidneys and liver. The number of days or weeks during which you will receive Ceftriaxone ratiopharm 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 may 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.

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

• 50–80 mg of Ceftriaxone ratiopharm 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 administered 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 standard adult dose.

Neonates (0–14 days of life):

• 20–50 mg of Ceftriaxone ratiopharm once daily per kg of the neonate’s body weight, depending on the severity and type of infection;
• the maximum daily dose must not exceed 50 mg per kg of the neonate’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 Ceftriaxone ratiopharm you will need and will monitor you closely, depending on the severity of your liver or kidney disease.

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

If you miss a dose of Ceftriaxone ratiopharm
If you miss an injection, it should be given 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 missed dose.

If you stop treatment with Ceftriaxone ratiopharm
Do not stop taking Ceftriaxone ratiopharm unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

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

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

Severe skin reactions (frequency not known, cannot be estimated from the available data)
If you develop a severe skin reaction, seek medical advice immediately.

• Signs may include a severe rash that develops rapidly, with blistering or peeling of the skin and possibly 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 usually resolves spontaneously. These symptoms occur shortly after starting ceftriaxone 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);
• loose 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. 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 Ceftriaxone ratiopharm 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);
• 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 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 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, which may cause pain, nausea, vomiting, yellowing of the skin, itching, unusually dark urine and clay-coloured 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;
• a false positive Coombs test (a blood test to detect blood problems);
• a false positive test for galactosaemia (an abnormal accumulation of the sugar galactose);
• Ceftriaxone ratiopharm may interfere with certain types of blood glucose tests; please consult your doctor.

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.

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.

5. How to store Ceftriaxone ratiopharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial or bottle, after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C. Store the vial in the original packaging.
Chemical and physical in-use stability has been demonstrated for at least 6 hours at a temperature not exceeding 25°C, or up to 24 hours at 2-8°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and must not exceed the times indicated above for chemical and physical in-use stability.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ceftriaxone ratiopharm contains
Ceftriaxone ratiopharm 1 g/10 ml powder and solvent for injectable solution for intravenous use
Each vial of powder contains 1 g of ceftriaxone as ceftriaxone sodium.
The solvent vial contains water for injection.

Description of the appearance of Ceftriaxone ratiopharm and package contents
Ceftriaxone ratiopharm 1 g/10 ml powder and solvent for injectable solution for intravenous use: 1 vial of powder + 1 vial of 10 ml solvent.

Marketing Authorization Holder and Manufacturer
ratiopharm GmbH, Graf-Arco Strasse 3, Ulm (Germany)

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

The following information is intended for healthcare professionals only:

Ceftriaxone ratiopharm may be administered by intravenous infusion over at least 30 minutes (the preferred route of administration) or by intravenous injection over 5 minutes. Intermittent intravenous injection should be given over 5 minutes, preferably into large veins. Intravenous doses of 50 mg/kg or higher in children up to 12 years of age must be administered by infusion. In neonates, to reduce the potential risk of bilirubin encephalopathy, intravenous doses should be administered over 60 minutes (see section 2). Intramuscular injections should be used only when intravenous administration is not feasible or is otherwise inappropriate for the patient. For doses exceeding 2 g, the intravenous route must be used.

Ceftriaxone must not be mixed with other medicinal products in the same syringe.

For intravenous injection, 1 g of Ceftriaxone ratiopharm should be dissolved in 10 ml of water for injections provided.

Ceftriaxone is contraindicated in neonates (≤ 28 days) who require (or are likely to require) treatment with intravenous solutions containing calcium, including continuous infusions containing calcium (e.g., for parenteral nutrition), due to the risk of calcium-ceftriaxone precipitate formation (see section 2).

Diluents containing calcium (such as Ringer's solution or Hartmann's solution) must not be used to reconstitute ceftriaxone vials or for further dilution of reconstituted vials for intravenous administration, as precipitate may form. Precipitation of calcium-ceftriaxone may also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, ceftriaxone must not be mixed or co-administered with calcium-containing solutions (see section 2).

For preoperative prophylaxis of surgical site infections, ceftriaxone should be administered 30–90 minutes before surgery.

INSTRUCTIONS FOR USE

Package leaflet: Information for the patient

Ceftriaxone ratiopharm 250 mg/2 ml

powder and solvent for injectable solution for intramuscular use
Ceftriaxone ratiopharm 1 g/3.5 ml
powder and solvent for injectable solution for intramuscular use
Ceftriaxone (as ceftriaxone sodium)
Lidocaine (as lidocaine hydrochloride)
Equivalent medicine
Please read this leaflet carefully before you are given this medicine as 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. Do not 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, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Ceftriaxone ratiopharm is and what it is used for
2. What you need to know before you are given Ceftriaxone ratiopharm
3. How Ceftriaxone ratiopharm is administered
4. Possible side effects
5. How to store Ceftriaxone ratiopharm
6. Contents of the pack and other information

1. What Ceftriaxone ratiopharm is and what it is used for

Ceftriaxone ratiopharm contains the active substance ceftriaxone, which is 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.
Ceftriaxone ratiopharm 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 surgical procedures.

2. What you need to know before you are given Ceftriaxone ratiopharm

Do not be given Ceftriaxone ratiopharm 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 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 (or to other amide-type local anaesthetics) and Ceftriaxone ratiopharm is to be administered by intramuscular injection;
• you have a heart conduction disorder causing low blood pressure and slowed heart rate (complete atrioventricular block);
• you have a condition of reduced blood volume (hypovolemia).

Ceftriaxone ratiopharm 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 Ceftriaxone ratiopharm if:

• you have recently received or are about to receive products containing calcium;
• you have recently had diarrhoea after taking an antibiotic; you have intestinal problems, particularly colitis (inflammation of the intestine);
• you have liver or kidney problems (see section 4);
• 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 muscle function loss and weakness (myasthenia gravis);
• you have seizures (epilepsy);
• you have any heart condition, especially if it affects your heart rate (cardiac conduction disorders, congestive heart failure, bradycardia);
• you have respiratory problems (respiratory depression);
• you have porphyria (a rare inherited disease affecting the skin and nervous system);
• you are experiencing or have previously experienced any combination of the following symptoms: rash, skin redness, blistering on 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 cell (eosinophilia), and swollen lymph nodes
  (signs of serious skin reactions, see also section 4 “Possible side effects”).

Blood or urine tests
If you are given Ceftriaxone ratiopharm for a prolonged period, you may need to have regular blood tests. Ceftriaxone ratiopharm may affect the results of urine and blood 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 Ceftriaxone ratiopharm.

Children
Talk to your doctor, pharmacist, or nurse before giving Ceftriaxone ratiopharm to a child if the child has recently received or is about to receive intravenously a product containing calcium.

Other medicines and Ceftriaxone ratiopharm
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).
  Several medicines can interact with lidocaine, resulting in altered effects. These include:
• medicines used to treat infections (antibiotics such as clarithromycin, erythromycin, or rifampicin);
• medicines used to treat stomach ulcers (e.g. cimetidine);
• sedative medicines, anxiolytics (barbiturates);
• medicines used to treat epilepsy (e.g. carbamazepine, phenytoin, or primidone);
• medicines used to treat irregular heart rate (e.g. mexiletine, tocainide).

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 Ceftriaxone ratiopharm for you and the potential risks for the unborn child, especially during the first months of pregnancy.

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

Ceftriaxone ratiopharm contains sodium
Ceftriaxone ratiopharm 250 mg/2 ml powder and solvent for injectable solution for intramuscular use:
Ceftriaxone ratiopharm contains approximately 21 mg of sodium (the main component of table salt) per vial (each gram of Ceftriaxone ratiopharm contains 3.6 mmol of sodium). This corresponds to 1.05% of the maximum daily dietary intake recommended for an adult.

Ceftriaxone ratiopharm 1 g/3.5 ml powder and solvent for injectable solution for intramuscular use:
Ceftriaxone ratiopharm contains approximately 83 mg of sodium (the main component of table salt) per vial (each gram of Ceftriaxone ratiopharm contains 3.6 mmol of sodium). This corresponds to 4.15% of the maximum daily dietary intake recommended for an adult.

3. How Ceftriaxone ratiopharm is administered

Ceftriaxone ratiopharm is generally administered by a doctor or nurse via an injection given directly into a muscle. Ceftriaxone ratiopharm 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 correct dose of Ceftriaxone ratiopharm 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 Ceftriaxone ratiopharm 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 may 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 Ceftriaxone ratiopharm 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 administered 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 life):

• 20–50 mg of Ceftriaxone ratiopharm 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 usual one. Your doctor will decide the amount of Ceftriaxone ratiopharm you need and will monitor you closely, depending on the severity of your liver or kidney disease.
If you are given more Ceftriaxone ratiopharm than you should be
If you are accidentally given more Ceftriaxone ratiopharm than prescribed, contact your doctor or go to the nearest hospital immediately.
If you miss a dose of Ceftriaxone ratiopharm
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 the missed dose.
If you stop treatment with Ceftriaxone ratiopharm
Do not stop taking Ceftriaxone ratiopharm unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
You may experience the following side effects with this medicine:

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

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

Severe skin reactions (not known, frequency cannot be determined from available data)
If you experience a severe skin reaction, seek medical advice immediately.

• Signs may include a severe rash that develops rapidly, with blistering or peeling of the skin and possibly blisters 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, usually resolving spontaneously. These symptoms occur shortly after starting ceftriaxone 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);
• loose 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. candidiasis);
• 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 Ceftriaxone ratiopharm was administered. Pain at the injection site;
• fever;
• abnormal kidney function tests (increased creatinine in blood).

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);
• 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 determined 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 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 with the gallbladder and/or liver, which may cause pain, nausea, vomiting, yellowing of the skin, itching, unusually dark urine and clay-coloured 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);
• Ceftriaxone ratiopharm may interfere with certain types of tests to measure blood glucose; check with your doctor.

Treatment with ceftriaxone, especially in elderly patients with severe renal impairment or neurological disorders, may rarely cause reduced consciousness, abnormal movements, agitation and seizures.
Following accidental intravascular injection of lidocaine during intramuscular administration, additional side effects may occur, which may include:
Rare (may affect up to 1 in 1,000 people)

• allergic reaction, even severe (anaphylactoid reaction and anaphylactic shock);

Not known (frequency cannot be determined from available data)

• nervousness;
• dizziness;
• tremors;
• numbness around the mouth (circumoral paresthesia) and numbness of the tongue (oral hypoesthesia);
• drowsiness;
• seizures;
• coma;
• blurred vision, double vision (diplopia) or temporary loss of vision (amaurosis fugax);
• ringing in the ears (tinnitus), difficulty tolerating everyday sounds (hyperacusis);
• excessive slowing of heart rate (bradycardia), changes in heart rhythm (arrhythmias), cardiac depression or arrest;
• excessive reduction in blood pressure (hypotension) which may lead to fainting (circulatory collapse);
• breathing difficulties (dyspnoea, bronchospasm) or possible cessation of breathing (respiratory depression);
• feeling unwell (nausea or vomiting);
• skin rashes, urticaria;
• oedema (fluid accumulation, including of the face).

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.

5. How to store Ceftriaxone ratiopharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial or bottle, following "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C. Store the vial in the original packaging.
Chemical and physical in-use stability has been demonstrated for at least 6 hours at a temperature not exceeding 25°C, or up to 24 hours at 2-8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the period and conditions of storage prior to use are the responsibility of the user and must not exceed the times indicated above for chemical and physical in-use stability.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ceftriaxone ratiopharm contains
Ceftriaxone ratiopharm 250 mg/2 ml powder and solvent for injectable solution for intramuscular use
Each vial of powder contains 250 mg of ceftriaxone as ceftriaxone sodium.
Each solvent vial contains an aqueous solution of 1% lidocaine (20 mg in 2 ml).
Ceftriaxone ratiopharm 1 g/3.5 ml powder and solvent for injectable solution for intramuscular use
Each vial of powder contains 1 g of ceftriaxone as ceftriaxone sodium.
Each solvent vial contains an aqueous solution of 1% lidocaine (35 mg in 3.5 ml).

Description of the appearance of Ceftriaxone ratiopharm and contents of the pack
Ceftriaxone ratiopharm 250 mg/2 ml powder and solvent for injectable solution for intramuscular use: 1
powder vial + 1 solvent vial of 2 ml.
Ceftriaxone ratiopharm 1 g/3.5 ml powder and solvent for injectable solution for intramuscular use: 1
powder vial + 1 solvent vial of 3.5 ml.

Marketing Authorization Holder and Manufacturer
ratiopharm GmbH, Graf-Arco Strasse 3, Ulm (Germany)

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

The following information is intended for healthcare professionals only:

Ceftriaxone ratiopharm may be administered via deep intramuscular injection. Intramuscular injections must be administered deeply into a sufficiently large muscle, and no more than 1 g should be injected at a single site (doses exceeding 1 g should be divided and administered at multiple sites). For intramuscular injection, the powder in the vial must be dissolved with the solvent provided, which contains 10 mg of lidocaine hydrochloride per ml of water for injections (i.e., dissolve 1 g of Ceftriaxone ratiopharm in 3.5 ml, or 250 mg of Ceftriaxone ratiopharm in 2 ml of the provided solution).
Ceftriaxone must not be mixed with other medicinal products in the same syringe, except for 1% lidocaine hydrochloride solution (for intramuscular injection only). Since lidocaine is used as the solvent, the resulting solution must under no circumstances be administered intravenously (see section 2). Accidental intravenous administration must be prevented by aspirating with the syringe before injection to exclude possible puncture of blood vessels.
Ceftriaxone is contraindicated in neonates (≤ 28 days) who require (or are likely to require) treatment with intravenous calcium-containing solutions, including continuous infusions containing calcium, e.g., for parenteral nutrition, due to the risk of precipitation of calcium-ceftriaxone (see section 2).
For preoperative prophylaxis of surgical site infections, ceftriaxone should be administered 30–90 minutes before surgery.
For each individual administration, the maximum dose of lidocaine must not exceed 5 mg per kg of body weight. In obese children, the maximum dose should be calculated based on ideal body weight according to sex and age.
In neonates, the optimal serum concentration of lidocaine required to avoid toxicity, such as seizures and cardiac arrhythmias, in this age group is unknown.

PACKAGE LEAFLET

Package leaflet: information for the patient

Ceftriaxone ratiopharm 2 g powder for solution for infusion

Ceftriaxone (as sodium ceftriaxone)
Generic medicine
Please read this leaflet carefully before you are given this medicine, as 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. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Ceftriaxone ratiopharm is and what it is used for

Ceftriaxone ratiopharm contains the active substance ceftriaxone, which is 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.

Ceftriaxone ratiopharm is used to treat infections of:

• the brain (meningitis);
• the lungs;
• the middle ear;
• the abdomen and abdominal wall (peritonitis);
• the urinary tract and kidneys;
• the bones and joints;
• the skin or soft tissues;
• the blood;
• the heart.

It may also 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 Ceftriaxone ratiopharm

Do not receive Ceftriaxone ratiopharm 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 breathing or swallowing difficult, sudden swelling of hands, feet and ankles, chest pain, or a severe rash that develops rapidly;
• you are allergic to lidocaine and Ceftriaxone ratiopharm needs to be administered by intramuscular injection.

Ceftriaxone ratiopharm 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 Ceftriaxone ratiopharm if:

• you have recently received or are about to receive products containing calcium;
• you have recently had diarrhoea after taking an antibiotic, or have had intestinal problems, particularly colitis (inflammation of the intestine);
• you have liver or kidney problems (see section 4);
• 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 are experiencing or have previously experienced any combination of the following symptoms: skin 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, increased levels of a type of white blood cell (eosinophilia), and swollen lymph nodes (signs of serious skin reactions; see also section 4 “Possible side effects”).

If you are undergoing blood or urine tests
If you are given Ceftriaxone ratiopharm for a prolonged period, you may need to have regular blood tests. Ceftriaxone ratiopharm may affect the results of urine and blood 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 Ceftriaxone ratiopharm.

Children
Talk to your doctor, pharmacist or nurse before giving Ceftriaxone ratiopharm to a child if the child has recently received or is about to receive a calcium-containing product intravenously.

Other medicines and Ceftriaxone ratiopharm
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 might be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will assess the benefits of treatment with Ceftriaxone ratiopharm for you and the possible risks for your baby.

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

Ceftriaxone ratiopharm contains sodium
Ceftriaxone ratiopharm contains approximately 166 mg of sodium (the main component of table salt) per vial (each gram of Ceftriaxone ratiopharm contains 3.6 mmol of sodium). This corresponds to 8.3% of the maximum daily recommended dietary intake of sodium for an adult.

3. How Ceftriaxone ratiopharm is administered

Ceftriaxone ratiopharm is generally administered by a doctor or nurse via intravenous infusion (IV infusion) or by injection directly into a vein.
Ceftriaxone ratiopharm will be prepared by a doctor, pharmacist, or nurse and will not be mixed with, nor administered simultaneously with, calcium-containing injections.
Usual dose
Your doctor will determine the appropriate dose of Ceftriaxone ratiopharm 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 functioning of your kidneys and liver. The number of days or weeks during which you will receive Ceftriaxone ratiopharm 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 may 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 Ceftriaxone ratiopharm 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 administered 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 usual adult dose.

Newborns (0–14 days of age)

• 20–50 mg of Ceftriaxone ratiopharm 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 usual one. Your doctor will decide how much Ceftriaxone ratiopharm you need and will monitor you closely, depending on the severity of your liver or kidney disease.
If you receive more Ceftriaxone ratiopharm than you should
If you are accidentally given more Ceftriaxone ratiopharm than prescribed, contact your doctor or the nearest hospital immediately.
If you miss a dose of Ceftriaxone ratiopharm
If you miss an injection, it should be given 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 the missed dose.
If you stop treatment with Ceftriaxone ratiopharm
Do not stop taking Ceftriaxone ratiopharm unless instructed by your doctor. If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
With this medicine, you may experience the following side effects:

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

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

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

• Signs may include a severe rash that develops rapidly, with blistering or skin peeling, and possibly blisters 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 ceftriaxone 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);
• loose stools or diarrhoea;
• changes in blood test results related to liver function;
• 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 Ceftriaxone ratiopharm 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);
• rash with raised itchy welts (urticaria), possibly affecting large areas of the body, associated with itching and swelling;
• blood or sugar in the urine;
• oedema (fluid accumulation);
• chills.

Frequency not known (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 white blood cell count (agranulocytosis);
• seizures;
• vertigo;
• inflammation of the pancreas (pancreatitis). Signs include severe stomach pain extending 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, which may cause pain, nausea, 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);
• Ceftriaxone ratiopharm may interfere with certain types of blood glucose tests; please consult your doctor.

Treatment with ceftriaxone, especially in elderly patients with severe renal impairment or neurological disorders, may rarely cause reduced consciousness, abnormal movements, agitation and seizures.

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.

5. How to store Ceftriaxone ratiopharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial or bottle, after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C. Store the vial in the original packaging.
Chemical and physical in-use stability has been demonstrated for at least 6 hours at a temperature not exceeding 25°C, or up to 24 hours at 2-8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the period and conditions of storage prior to use are the responsibility of the user and must not exceed the time limits indicated above for chemical and physical in-use stability.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Ceftriaxone ratiopharm contains
Ceftriaxone ratiopharm 2 g powder for solution for infusion
Each vial contains: 2 g of ceftriaxone as ceftriaxone sodium.
Description of the appearance of Ceftriaxone ratiopharm and contents of the pack
Ceftriaxone ratiopharm 2 g powder for solution for infusion: 1 vial.
Marketing Authorisation Holder and Manufacturer
ratiopharm GmbH, Graf-Arco Strasse 3, Ulm (Germany)
Manufacturer
MITIM S.r.l.
Via Cacciamali, 34-36-38
25125 Brescia

The following information is intended for healthcare professionals only:

Ceftriaxone ratiopharm may be administered by intravenous infusion lasting at least 30 minutes (the preferred route of administration) or by slow intravenous injection over 5 minutes. Intermittent intravenous injection should be given over 5 minutes, preferably into large veins. Intravenous doses of 50 mg/kg or higher in children up to 12 years of age must be administered by infusion. In neonates, to reduce the potential risk of bilirubin encephalopathy, intravenous doses should be administered over 60 minutes (see section 2). Intramuscular injections should be used only when intravenous administration is not feasible or is considered less appropriate for the patient. For doses exceeding 2 g, the intravenous route of administration must be used.

Ceftriaxone is contraindicated in neonates (≤ 28 days) who require (or are likely to require) treatment with intravenous calcium-containing solutions, including continuous infusions containing calcium, such as for parenteral nutrition, due to the risk of formation of calcium-ceftriaxone precipitate (see section 2).

Diluents containing calcium (such as Ringer's or Hartmann's solutions) must not be used to reconstitute ceftriaxone vials or for further dilution of reconstituted vials for intravenous administration, as precipitate may form. Calcium-ceftriaxone precipitation may also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, ceftriaxone must not be mixed or co-administered with calcium-containing solutions (see section 2).

For preoperative prophylaxis of surgical site infections, ceftriaxone should be administered 30–90 minutes before surgery.

Ceftriaxone must not be mixed with other medicinal products in the same syringe.