Rocefin

Package leaflet: Information for the patient

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

ceftriaxone (as ceftriaxone sodium)
Please read all of 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 may 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:

1. What Rocefin for injectable solution for intravenous use is and what it is used for
2. What you must know before you are administered Rocefin for injectable solution for intravenous use
3. How Rocefin for injectable solution for intravenous use is administered
4. Possible side effects
5. How to store Rocefin for injectable solution for intravenous use
6. Contents of the pack and other information

1. What Rocefin is and what it is used for

Rocefin for injectable solution for intravenous use 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.
Rocefin for injectable solution for intravenous use 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 also be administered:

• to treat specific sexually transmitted infections (gonorrhoea and syphilis).
• to treat patients with a low white blood cell count (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 Rocefin for injectable solution for intravenous use

Do not be given Rocefin 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 Rocefin for injectable solution for intravenous use is to be administered by intramuscular injection.

Rocefin for injectable solution for intravenous use 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 is to receive a product containing calcium through a vein.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before being given Rocefin for injectable solution for intravenous use if:

• 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 (see section 4).
• you have gallstones or kidney stones.
• you have other diseases, for example 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 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, 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 to undergo blood or urine tests
If you are given Rocefin for injectable solution for intravenous use for a prolonged period, you may need to have regular blood tests. Rocefin may affect the results of urine sugar tests and a blood test known as the Coombs test. If you are to undergo testing:

• inform the person taking your sample that you have been given Rocefin for injectable solution for intravenous use.

If you are diabetic or require monitoring of blood glucose levels, do not use certain blood glucose monitoring systems that may inaccurately measure blood glucose during treatment with ceftriaxone. If such systems are used, check the instructions for use and inform your doctor, pharmacist or nurse. Alternative testing methods should be used if necessary.

Children
Talk to your doctor, pharmacist or nurse before administering Rocefin for injectable solution for intravenous use to a child if:

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

Other medicines and Rocefin for injectable solution for intravenous use
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 one 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, ask your doctor for advice before taking this medicine.
Your doctor will assess the benefits that treatment with Rocefin for injectable solution for intravenous use would provide you and the potential risks to the baby.

Driving and using machines
Rocefin for injectable solution for intravenous use 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.

Rocefin for injectable solution for intravenous use contains sodium
This medicine contains 85.4 mg of sodium (the main component of table salt) per 1 g vial. This is equivalent to 4.3% of the maximum daily dietary intake recommended for an adult.

3. How Rocefin for injectable solution for intravenous use is administered

Rocefin is generally administered by a doctor or nurse through an intravenous infusion (intravenous drip) or via an injection directly into a vein. Rocefin will be prepared by a doctor, pharmacist, or nurse and will not be mixed with, nor administered simultaneously with, injections containing calcium.

Usual dose
Your doctor will determine the correct dose of Rocefin for injectable solution for intravenous use 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 extent of kidney and liver function. The number of days or weeks during which you will receive Rocefin for injectable solution for intravenous use 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 divided into 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 Rocefin for injectable solution for intravenous use 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.

Neonates (0–14 days of life):

• 20–50 mg of Rocefin for injectable solution for intravenous use 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 usual one. Your doctor will decide the amount of Rocefin for injectable solution for intravenous use you need and will monitor you closely, depending on the severity of your liver or kidney disease.

If you are given more Rocefin for injectable solution for intravenous use than you should
If you are accidentally given more Rocefin than prescribed, contact your doctor or the nearest hospital immediately.

If you miss a dose of Rocefin for injectable solution for intravenous use
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 missed dose.

If you stop treatment with Rocefin for injectable solution for intravenous use
Do not stop taking Rocefin for injectable solution for intravenous use unless your doctor tells you to. 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.
With this medicine, you may experience the following side effects:
Treatment with ceftriaxone, especially in elderly patients with severe renal insufficiency or neurological disorders, may rarely cause reduced consciousness, abnormal movements, agitation, and seizures.

Severe allergic reactions (frequency not known, cannot be estimated 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 occurring in the context of allergic reactions, which may be a symptom of an allergy-induced heart attack (Kounis syndrome).

Serious skin reactions (frequency not known, cannot be estimated from available data)
If you develop a serious skin reaction, inform a doctor 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 (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 treatment with Rocefin for injectable solution for intravenous use to treat 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., oral thrush or genital fungal infections).
• 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 at the site where Rocefin was administered. Blisters, bruising, deep redness or rash, irritation, itching, skin hardening, or swelling 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.
• Difficulty breathing (bronchospasm).
• Rash with wheals (urticaria), possibly affecting large areas of the body, associated with itching and swelling.
• Blood or sugar in the urine.
• Oedema (fluid accumulation).
• Chills.
• Infection at the injection site.

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.
• Vertigo.
• Inflammation of the pancreas (pancreatitis). Signs include severe stomach pain spreading to the back.
• Inflammation of the oral mucosa (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.
• False positive Coombs test result (a test to detect blood-related problems).
• False positive test result for galactosaemia (an abnormal accumulation of the sugar galactose).
• Rocefin for injectable solution for intravenous use may interfere with certain types of blood glucose tests; please check with your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://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 Rocefin for injectable solution for intravenous use

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 vial label, following “Exp.”. The expiry date refers to the last day of that month.
Do not store above 30 °C. Keep the vial in the outer packaging to protect it from light.
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 duration 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.
For single use only.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Rocefin for injectable solution for intravenous use contains
The active substance is ceftriaxone.
Each vial contains 1 g (gram) of ceftriaxone as ceftriaxone sodium.
Each ampoule contains 10 ml of water for injections.
The displacement volume of 1 g of Rocefin for injectable solution for intravenous use is 0.71 ml in
water for injections.
This requires compensation of the solvent volume when only a portion of the total solution is to be
dosed and administered (e.g. in neonates, infants and children from 15 days of age up to 12 years of
age with body weight below 50 kg). To obtain a final solution with a concentration of 100 mg/ml,
reconstitute 1 g of Rocefin with 9.4 ml of water for injections.
Rocefin for injectable solution for intravenous use must not be mixed with other medicinal products in
the same syringe.

Description of the appearance of Rocefin for injectable solution for intravenous use and contents of the
package
Rocefin for injectable solution for intravenous use consists of powder and solvent for injectable solution.
The powder is white to yellowish-orange in colour. The solvent is clear and colourless.
Rocefin for injectable solution for intravenous use is available in packages containing 1 vial of powder and 1 ampoule of solvent.

Marketing Authorization Holder
Roche S.p.A. - Viale G.B. Stucchi 110, 20900 Monza (MB)

Manufacturer
Roche S.p.A.
Viale G.B. Stucchi, 110
20900 Monza (MB)
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the
following names:
Rocefin 1 g powder and solvent for solution for injection
Belgium, Luxembourg: Rocephine IV
Italy: Rocefin
France: Rocephine

Advice/health education
Antibiotics are used to treat bacterial infections. They are not effective against viral infections.
If your doctor has prescribed antibiotics for you, you specifically need them for your current illness.
Some bacteria may survive or multiply despite antibiotic treatment. This phenomenon is known as
resistance: some antibiotic treatments become ineffective.
Improper use of antibiotics increases resistance. You may even promote the development of resistance in bacteria and thereby delay recovery or reduce the effectiveness of antibiotics if you do not adhere to:

• dosage,
• frequency of administration,
• and duration of treatment.

Therefore, to preserve the effectiveness of this medicine:

1. Use antibiotics only when prescribed.
2. Follow the prescription exactly.
3. Do not reuse an antibiotic without medical prescription, even if you wish to treat a similar illness.
4. Never give the antibiotic prescribed for you to another person, as it may not be suitable for their illness.
5. After completion of treatment, return all unused medicines to a pharmacy to ensure they are properly disposed of.

---

The following information is intended for healthcare professionals only:

For complete prescribing information, refer to the product characteristics summary.
Solutions containing Rocefin must not be mixed with, or added to, solutions containing other agents. In particular, Rocefin is not compatible with solutions containing calcium. Diluents containing calcium (such as Ringer's or Hartmann's solution) must not be used to reconstitute vials of ceftriaxone or to further dilute 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 solutions containing calcium.
Based on reports published in the literature, ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole, and aminoglycosides.
Dosage
The dose varies according to the severity, sensitivity level, site and type of infection, and the patient's age and hepatic-renal function.
The recommended doses in the following tables are the generally recommended doses for these indications. In particularly severe cases, doses at the upper end of the recommended range should be considered.
Adults and children above 12 years of age (≥ 50 kg)

* In documented bacteraemia, the highest values within the recommended dose range should be considered.
** In the case of administration at doses higher than 2 g per day, administration twice daily (every 12 hours) may be considered.
Dosage recommendations for adults and children above 12 years of age (≥ 50 kg) requiring specific dosing regimens:

Acute otitis media
A single intramuscular dose of Rocefin 1–2 g may be administered.
Limited data suggest that in severely ill patients or in case of prior treatment failure, Rocefin may be effective when administered intramuscularly at a daily dose of 1–2 g for 3 days.

Preoperative prophylaxis of surgical site infections
2 g as a single preoperative dose.

Gonorrhoea
500 mg administered as a single intramuscular dose.

Syphilis
The generally recommended doses are 500 mg–1 g once daily, increased to 2 g once daily for neurosyphilis, for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on limited data. Refer to national or local guidelines.

Disseminated Lyme borreliosis (early [stage II] and late [stage III])
2 g once daily for 14–21 days. The recommended duration of treatment is variable; refer to national or local guidelines.

Paediatric population
Neonates, infants and children from 15 days of life to 12 years of age (< 50 kg)
Children with a body weight equal to or greater than 50 kg should receive the standard adult dosage.

* In documented bacteremia, the highest values within the recommended dose range should be considered.
** In case of administration at doses higher than 2 g per day, administration twice daily (every 12 hours) may be considered.
Indications for neonates, infants, and children from 15 days of life to 12 years (< 50 kg) requiring specific dosage regimens:
Acute otitis media
For initial treatment of acute otitis media, a single intramuscular dose of Rocefin 50 mg/kg may be administered. Limited data suggest that in severely ill children or in case of failure of initial therapy, Rocefin may be effective when administered intramuscularly at a daily dose of 50 mg/kg for 3 days.
Preoperative prophylaxis of surgical site infections
50–80 mg/kg as a single preoperative dose.
Syphilis
The generally recommended doses are 75–100 mg/kg (max 4 g) once daily for 10–14 days.
Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Disseminated Lyme borreliosis (early [stage II] and late [stage III])
50–80 mg/kg once daily for 14–21 days. The recommended duration of treatment is variable; refer to national or local guidelines.
Neonates from 0 to 14 days of life
Rocefin is contraindicated in premature neonates until a postmenstrual age of 41 weeks (gestational age + chronological age).

* In documented bacteremia, the highest values within the recommended dose range should be considered.
The maximum daily dose of 50 mg/kg must not be exceeded.
Dosing recommendations for neonates aged 0–14 days requiring specific dosing regimens:
Acute otitis media
For initial treatment of acute otitis media, a single intramuscular dose of Rocefin 50 mg/kg may be administered.
Surgical prophylaxis of surgical site infections
20–50 mg/kg as a single preoperative dose.
Syphilis
The generally recommended dose is 50 mg/kg once daily for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Duration of therapy
The duration of therapy varies depending on the course of the disease. As with other antibiotic therapies, treatment with ceftriaxone should be continued for 48–72 hours after the patient has defervesced or until bacterial eradication has been demonstrated.
Elderly patients
The recommended adult dosages do not require adjustment in elderly patients, provided that renal and hepatic function are satisfactory.
Patients with impaired hepatic function
According to available data, dose adjustment is not necessary in cases of mild to moderate hepatic impairment, provided that renal function is not compromised.
There are no data from studies conducted in patients with severe hepatic impairment.
Patients with impaired renal function
In patients with impaired renal function, dose reduction of ceftriaxone is not required, provided that hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance < 10 mL/min) should the ceftriaxone dose not exceed 2 g per day.
In dialysis patients, no supplemental dose is required after dialysis. Ceftriaxone is not eliminated during peritoneal dialysis or hemodialysis. Clinical monitoring of safety and efficacy is recommended.
Patients with severe hepatic and renal impairment
In patients with severe renal and hepatic dysfunction, careful clinical monitoring of safety and efficacy is recommended.
Instructions for use
For single use only. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
It is recommended to use freshly prepared solutions.
For storage conditions of the reconstituted medicine, see section “How to store Rocefin”.
Rocefin is reconstituted in its respective solvent within 150 seconds. The reconstituted solution is a clear solution with a yellow to brown-yellow color.
Rocefin must not be mixed with other drugs in the same syringe. The infusion line must be flushed after each administration.
Intravenous injection:
Use in adults and children above 12 years of age (≥ 50 kg)
1 g of Rocefin must be dissolved in 10 mL of water for injections. The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter. The injection should be administered over 5 minutes, directly into the vein or via the intravenous infusion line.
Neonates, infants, and children from 15 days of age to 12 years of age (< 50 kg)
The displacement volume of 1 g of Rocefin is 0.71 mL in water for injections. This requires offsetting the solvent volume to facilitate weight-dependent dosing (primarily in children up to 12 years), when only a portion of the total solution is dosed and administered. To obtain a final solution concentration of 100 mg/mL, reconstitute 1 g of Rocefin in 9.4 mL of water for injections.
Package leaflet: information for the patient
Rocefin 2 g powder for solution for infusion
Rocefin 1 g powder for solution for injection/for infusion
ceftriaxone (as ceftriaxone sodium)
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 others, 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, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Rocefin is and what it is used for
2. What you need to know before Rocefin is administered to you
3. How Rocefin is administered
4. Possible side effects
5. How to store Rocefin
6. Package contents and other information

1. What Rocefin is and what it is used for

Rocefin 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.
Rocefin 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 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 Rocefin

Do not be given Rocefin 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 Rocefin is to be administered by intramuscular injection.

Rocefin 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 Rocefin if:

• 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 (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: rash, skin redness, blistering on lips, eyes, and mouth, skin peeling, high fever, flu-like symptoms, increased liver enzyme levels 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”).

If you need to have blood or urine tests
If you are given Rocefin for a prolonged period, you may need to have regular blood tests. Rocefin 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 taking your sample that you have been given Rocefin.

If you are diabetic or require monitoring of blood glucose levels, do not use certain blood glucose monitoring systems that may inaccurately measure blood glucose during treatment with ceftriaxone. If such systems are used, check the instructions for use and inform your doctor, pharmacist, or nurse. Alternative analytical methods should be used if necessary.

Children
Talk to your doctor, pharmacist, or nurse before Rocefin is given to a child if:

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

Other medicines and Rocefin
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, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Your doctor will evaluate the benefits of treatment with Rocefin for you and the potential risks for the unborn or breastfed child.

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

Rocefin contains sodium
Rocefin 2 g powder for solution for infusion contains 169.1 mg of sodium (the main component of table salt) per 2 g vial. This corresponds to 8.5% of the maximum daily recommended dietary sodium intake for an adult.
Rocefin 1 g powder for injectable solution/infusion contains 85.4 mg of sodium (the main component of table salt) per 1 g vial, equivalent to 4.3% of the maximum daily recommended dietary sodium intake for an adult.

3. How Rocefin is administered

Rocefin is generally administered by a doctor or nurse via

• intravenous infusion (IV infusion) or by injection directly into a vein. Rocefin will be prepared by a doctor, pharmacist, or nurse and must not be mixed or administered simultaneously with injections containing calcium.

Usual dose
Your doctor will determine the correct dose of Rocefin 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 function of your kidneys and liver. The number of days or weeks during which you will receive Rocefin 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 dose once daily 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 Rocefin 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 age):

• 20–50 mg of Rocefin 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 Rocefin you need and will monitor you closely, depending on the severity of your liver or kidney disease.

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

If you miss a dose of Rocefin
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 Rocefin
Do not stop taking Rocefin unless your doctor tells you to. 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 will experience them.
With this medicine, you may experience the following side effects:
Treatment with ceftriaxone, especially in elderly patients with severe renal insufficiency or disorders of the nervous system, may rarely cause reduced consciousness, abnormal movements, agitation, and seizures.

Severe allergic reactions (not known, frequency cannot be estimated from the available data)
If you experience 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 during allergic reactions, which may be a symptom of an allergy-induced heart attack (Kounis syndrome).

Severe skin reactions (not known, frequency cannot be estimated from the available data)
If you develop a severe skin reaction, inform a doctor immediately.
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, elevated liver enzymes, blood test abnormalities (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 skin rash, which usually resolves spontaneously. These symptoms may occur shortly after starting Rocefin 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 for liver function.
• Rash.

Uncommon (may affect up to 1 in 100 people)

• Fungal infections (e.g., oral thrush or genital fungal infections).
• 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 at the site where Rocefin was administered. Blisters, bruising, deep redness or rash, irritation, itching, skin hardening, or swelling 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 wheals (urticaria), which may cover a large area of the body, associated with itching and swelling.
• Blood or sugar in the urine.
• Edema (fluid accumulation).
• Chills.
• Infection at the injection site.

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.
• 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.
• False positive Coombs test (a blood test to detect blood-related problems).
• False positive test for galactosemia (an abnormal accumulation of the sugar galactose).
• Rocefin may interfere with certain types of blood glucose tests; please consult your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website: https://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 Rocefin

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. Keep the vial or bottle in the outer packaging to protect it from light.
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.
For single use only.
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 Rocefin contains
Rocefin 2 g powder for solution for infusion
The active substance is ceftriaxone.
Each vial contains 2 g (grams) of ceftriaxone as ceftriaxone sodium.
There are no other excipients.
The displacement volume of 2 g of Rocefin is 1.37 ml in water for injections.
This requires adjustment of the solvent volume if only a portion of the total solution is to be dosed and administered (e.g. in neonates, infants and children from 15 days of age to 12 years of age with a body weight below 50 kg). To obtain a final solution with a concentration of 50 mg/ml, reconstitute 2 g of Rocefin in 39 ml of calcium-free infusion fluids.

Rocefin 1 g powder for injectable solution/for infusion
The active substance is ceftriaxone.
Each vial contains 1 g (gram) of ceftriaxone as ceftriaxone sodium.
There are no other excipients.
The displacement volume of 1 g of Rocefin is 0.71 ml in water for injections and in a 1% lidocaine hydrochloride solution. This requires adjustment of the solvent volume if only a portion of the total solution is to be dosed and administered (e.g. in neonates, infants and children from 15 days of age to 12 years of age with a body weight below 50 kg):

• To obtain a final intravenous solution with a concentration of 100 mg/ml, reconstitute 1 g of Rocefin in 9.4 ml of water for injections.
• To obtain a final intramuscular solution with a concentration of 285 mg/ml, reconstitute 1 g of Rocefin in 2.9 ml of 1% lidocaine hydrochloride solution.

Description of the appearance of Rocefin and contents of the pack
Rocefin 2 g powder for solution for infusion
Rocefin consists of a powder for solution for infusion.
Rocefin 1 g powder for injectable solution/for infusion
Rocefin consists of a powder for injectable solution or for infusion.
The powder is white to yellowish-orange in colour.
Rocefin is available in packs containing 1 vial.

Marketing Authorization Holder
Roche S.p.A. - Viale G.B. Stucchi 110, 20900 Monza (MB).

Manufacturer
Rocefin 2 g powder for solution for infusion
Roche S.p.A.
Viale G.B. Stucchi, 110
20900 Monza (MB)

Rocefin 1 g powder for injectable solution/for infusion
Roche S.p.A.
Viale G.B. Stucchi, 110
20900 Monza (MB)
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Rocefin 2 g powder for solution for infusion
Belgium, Luxembourg: Rocephine
Italy: Rocefin

Rocefin 1 g powder for injectable solution/for infusion
Ireland: Rocephin
Italy: Rocefin

Advice/health education
Antibiotics are used to treat bacterial infections. They are not effective against viral infections.
If your doctor has prescribed antibiotics for you, you specifically need them for your current illness.
Some bacteria may survive or multiply despite antibiotic treatment. This phenomenon is known as resistance: some antibiotic treatments become ineffective.
Improper use of antibiotics increases resistance. You may even promote the development of resistance in bacteria and thus delay recovery or reduce the effectiveness of antibiotics if you do not adhere to:

• dosage,
• frequency of administration,
• and duration of treatment.

Therefore, to preserve the effectiveness of this medicine:

6. Use antibiotics only when prescribed.
7. Strictly follow the prescription.
8. Do not reuse an antibiotic without a medical prescription, even if you wish to treat a similar illness.
9. Never give an antibiotic prescribed for you to another person, as it may not be suitable for their condition.
10. At the end of treatment, return all unused medicines to a pharmacy to ensure they are properly disposed of.

---

The following information is intended for healthcare professionals only:

Please refer to the Summary of Product Characteristics for complete prescribing information.
Solutions containing Rocefin must not be mixed or added to solutions containing other agents. In particular, Rocefin is not compatible with solutions containing calcium. Diluents containing calcium (e.g., Ringer's solution or Hartmann's solution) must not be used to reconstitute vials of ceftriaxone or to further dilute a reconstituted vial for intravenous administration, as a precipitate may form. Precipitation of ceftriaxone-calcium may also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, solutions containing ceftriaxone and calcium must not be mixed or administered simultaneously.
Based on reports published in the literature, ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole, and aminoglycosides.
Dosage
The dose varies according to the severity, sensitivity level, site and type of infection, and the patient's age and hepatic-renal function.
The recommended doses in the following tables are the generally recommended doses for these indications. In particularly severe cases, doses at the upper end of the recommended range should be considered.
Adults and children above 12 years of age (≥ 50 kg)

* In documented bacteremia, the maximum values within the recommended dose range should be considered.
** In the case of administration at doses exceeding 2 g per day, administration twice daily (every 12 hours) may be considered.

Indications for adults and children above 12 years of age (≥ 50 kg) requiring specific dosing regimens:

Acute otitis media
A single intramuscular dose of Rocefin 1–2 g may be administered. Limited data suggest that in severely ill patients or in cases of prior treatment failure, Rocefin may be effective when administered intramuscularly at a daily dose of 1–2 g for 3 days.

Preoperative prophylaxis of surgical site infections
2 g as a single preoperative dose.

Gonorrhoea
500 mg administered as a single intramuscular dose.

Syphilis
The generally recommended doses are 500 mg–1 g once daily, increased to 2 g once daily for neurosyphilis, for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on limited data. Refer to national or local guidelines.

Disseminated Lyme borreliosis (early [Stage II] and late [Stage III])
2 g once daily for 14–21 days. The recommended duration of treatment is variable and reference should be made to national or local guidelines.

Paediatric population
Infants and children from 15 days of age to 12 years of age (< 50 kg)
Children with a body weight equal to or greater than 50 kg should receive the standard adult dosage.

* In documented bacteremia, the highest values within the recommended dose range should be considered.
** In case of administration at doses higher than 2 g per day, administration twice daily (every 12 hours) may be considered.
Indications for neonates, infants, and children from 15 days of life to 12 years (<50 kg) requiring specific dosage regimens:
Acute otitis media
For initial treatment of acute otitis media, a single intramuscular dose of Rocefin 50 mg/kg may be administered. Limited data suggest that in severely ill children or in case of failure of initial therapy, Rocefin may be effective when administered intramuscularly at a daily dose of 50 mg/kg for 3 days.
Preoperative prophylaxis of surgical site infections
50–80 mg/kg as a single preoperative dose.
Syphilis
The generally recommended doses are 75–100 mg/kg (max 4 g) once daily for 10–14 days.
Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Disseminated Lyme borreliosis (early [stage II] and late [stage III])
50–80 mg/kg once daily for 14–21 days. The recommended duration of treatment is variable; refer to national or local guidelines.
Neonates from 0 to 14 days of life
Rocefin is contraindicated in premature neonates until a postmenstrual age of 41 weeks (gestational age + chronological age).

* In documented bacteremia, the highest values within the recommended dose range should be considered.
The maximum daily dose of 50 mg/kg must not be exceeded.
Dosage recommendations for neonates aged 0–14 days requiring specific dosing regimens:
Acute otitis media
For initial treatment of acute otitis media, a single intramuscular dose of Rocefin 50 mg/kg may be administered.
Surgical prophylaxis of surgical site infections
20–50 mg/kg as a single preoperative dose.
Syphilis
The generally recommended dose is 50 mg/kg once daily for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Duration of therapy
The duration of therapy varies depending on the course of the disease. As with other antibiotic therapies, treatment with ceftriaxone should be continued for 48–72 hours after the patient has defervesced or until bacterial eradication has been demonstrated.
Elderly patients
The recommended adult dosages do not require adjustment in elderly patients, provided that renal and hepatic function are satisfactory.
Patients with hepatic impairment
According to available data, dosage adjustment is not necessary in patients with mild to moderate hepatic impairment, provided that renal function is not impaired.
There are no data from studies conducted in patients with severe hepatic dysfunction.
Patients with renal impairment
In patients with renal impairment, dose reduction of ceftriaxone is not required if hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance < 10 ml/min) should the ceftriaxone dose not exceed 2 g per day.
In dialysis patients, no supplemental dose is required after dialysis. Ceftriaxone is not removed during peritoneal dialysis or hemodialysis. Close clinical monitoring of safety and efficacy is recommended.
Patients with severe hepatic and renal impairment
In patients with both impaired renal and hepatic function, close clinical monitoring of safety and efficacy is recommended.
Instructions for use
For single use only. Unused medicine and waste material arising from this medicine must be disposed of in accordance with local regulations.
Use of freshly prepared solutions is recommended.
For storage conditions of the reconstituted medicine, refer to the section "How to store Rocefin".
Rocefin is completely reconstituted in its respective solvent within 150 seconds. The reconstituted solution is a clear solution ranging in color from yellow to yellow-brown.
Rocefin must not be mixed in the same syringe with any other drug. The infusion line must be flushed after each administration.
Infusion 2 g intravenous solution:
Use in adults and children above 12 years of age (≥ 50 kg)
Dissolve 2 g of Rocefin in 40 ml of one of the following calcium-free infusion fluids: 0.9% sodium chloride, 0.45% sodium chloride + 2.5% dextrose, 5% dextrose, 10% dextrose, 6% dextran in 5% dextrose, water for injections. The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter. The infusion must be administered over at least 30 minutes.
Use in the pediatric population
Neonates, infants, and children from 15 days of age to 12 years of age (< 50 kg)
The displacement volume of 2 g of Rocefin is 1.37 ml in water for injections. This requires solvent volume offset to facilitate weight-dependent dosing (mainly in children up to 12 years of age), in case only a portion of the total solution is dosed and administered. To obtain a final solution concentration of 50 mg/ml, reconstitute 2 g of Rocefin in 39 ml of calcium-free infusion fluid.
Administration 1 g intravenous solution (for injection and infusion):
Use in adults and children above 12 years of age (≥ 50 kg)
Dissolve 1 g of Rocefin in 10 ml of water for injections.
The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter.
Intravenous injection must be administered over 5 minutes, directly into the vein or via an intravenous infusion line.
Alternatively, for intravenous infusion, the reconstituted solution should be transferred into 10 ml of one of the following calcium-free infusion fluids: 0.9% sodium chloride, 0.45% sodium chloride + 2.5% dextrose, 5% dextrose, 10% dextrose, 6% dextran in 5% dextrose, water for injections.
The infusion must be administered over at least 30 minutes.
Use in the pediatric population
Neonates, infants, and children from 15 days of age to 12 years of age (< 50 kg)
The displacement volume of 1 g of Rocefin is 0.71 ml in water for injections. This requires solvent volume offset to facilitate weight-dependent dosing (mainly in children up to 12 years of age), in case only a portion of the total solution is dosed and administered. To obtain a final solution concentration of 100 mg/ml, reconstitute 1 g of Rocefin in 9.4 ml of water for injections.
1 g intramuscular injection:
Use in adults and children above 12 years of age (≥ 50 kg)
Dissolve 1 g of Rocefin in 3.5 ml of 1% lidocaine hydrochloride solution.
The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter. The solution should be administered by deep intramuscular injection. Doses exceeding 1 g should be divided and injected at more than one site.
Use in the pediatric population
Neonates, infants, and children from 15 days of age to 12 years of age (< 50 kg)
The displacement volume of 1 g of Rocefin is 0.71 ml in 1% lidocaine hydrochloride solution.
This requires solvent volume offset to facilitate weight-dependent dosing (mainly in children up to 12 years of age), in case only a portion of the total solution is dosed and administered. To obtain a final solution concentration of 285 mg/ml, reconstitute 1 g of Rocefin in 2.9 ml of 1% lidocaine hydrochloride solution.
The solution containing lidocaine must never be administered intravenously.

Patient information leaflet

Rocefin 1 g/3.5 ml powder and solvent for injectable solution for intramuscular use, 250 mg/2 ml powder and solvent for injectable solution for intramuscular use

ceftriaxone (as ceftriaxone sodium)
lidocaine (as lidocaine hydrochloride)
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. Never give it to other people, even if they have the same symptoms as yours, because it could be dangerous.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Rocefin Injectable Solution for Intramuscular Use Is and What It Is Used For

Rocefin 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. Rocefin is administered by injection into a muscle in a solution containing lidocaine, which reduces the pain associated with the injection.
Rocefin 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 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 Rocefin injectable solution for

intramuscular use
Do not be given Rocefin 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 Rocefin injectable solution for intramuscular use is to be administered by injection into a muscle.
• you have a heart condition causing low blood pressure and slowed heart rate (complete atrioventricular block).
• you have a reduced blood volume (hypovolemia).

Rocefin injectable solution for intramuscular use 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 is to receive a product containing calcium intravenously.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given Rocefin injectable solution for
intramuscular use if:

• 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 (see section 4).
• you have gallstones or kidney stones.
• you have other diseases, for example haemolytic anaemia (a reduction in red blood cells that may cause pale yellow skin, weakness or breathlessness).
• you are on a low-sodium diet.
• you suffer from loss of muscle function and weakness (myasthenia gravis).
• you have seizures (epilepsy).
• you have any heart problems, especially if they affect your heart rate.
• you have breathing problems.
• you suffer from 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 cells (eosinophilia), and swollen lymph nodes (signs of serious skin reactions, see also section 4 “Possible side effects”).

If you need to have a blood or urine test
If you are given Rocefin injectable solution for intramuscular use for a prolonged period,
you may need to have regular blood tests. Rocefin injectable solution for intramuscular use
can affect the results of urine sugar tests and a blood test known as the Coombs test. If you are about to have tests:

• inform the person taking your sample that you have been given Rocefin injectable solution for intramuscular use.

If you are diabetic or require monitoring of blood glucose levels, you should not use certain blood glucose monitoring systems that may inaccurately measure blood glucose during treatment with ceftriaxone. If such systems are used, check the instructions for use and inform your doctor, pharmacist or nurse. Alternative testing methods should be used if necessary.
Children
Talk to your doctor, pharmacist or nurse before Rocefin injectable solution for
intramuscular use is given to a child if:

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

Other medicines and Rocefin injectable solution for intramuscular use
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, as
they may interact with ceftriaxone:

• an antibiotic called an aminoglycoside.
• an antibiotic called chloramphenicol (used to treat infections, particularly eye infections). Several drugs may interact with lidocaine, resulting in altered effects. These include:
• medicines used to treat infections (clarithromycin, erythromycin).
• medicines used to treat stomach ulcers (e.g. cimetidine).
• strong painkillers such as codeine and pethidine (narcotic or opioid drugs).
• 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,
ask your doctor for advice before taking this medicine.
Your doctor will evaluate the benefits that treatment with Rocefin injectable solution for intramuscular use
would provide you and the potential risks for your baby.
Driving and using machines
Rocefin injectable solution for intramuscular use 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.
Rocefin contains sodium
Rocefin 1 g/3.5 ml injectable solution for intramuscular use contains 85.4 mg of sodium (the main
component of table salt) per 1 g vial. This is equivalent to 4.3% of the recommended maximum daily
dietary intake for an adult.
Rocefin 250 mg/2 ml injectable solution for intramuscular use contains less than 1 mmol (23 mg) of
sodium per 250 mg vial, i.e. essentially ‘sodium-free’.

3. How Rocefin injectable solution for intramuscular use is administered

Rocefin is generally administered by a doctor or nurse via an injection given directly into a muscle. Rocefin will be prepared by a doctor, pharmacist, or nurse and will not be mixed or co-administered with calcium-containing injections.
Usual dose
Your doctor will determine the correct dose of Rocefin injectable solution for intramuscular use 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 Rocefin 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. Neonates, infants, and children from 15 days to 12 years of age with a body weight below 50 kg:
• 50–80 mg of Rocefin injectable solution for intramuscular use 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 will 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. Neonates (0–14 days of age)
• 20–50 mg of Rocefin injectable solution for intramuscular use 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 usual one. Your doctor will decide the amount of Rocefin injectable solution for intramuscular use you need and will monitor you closely, depending on the severity of your liver or kidney disease.
If you are given more Rocefin injectable solution for intramuscular use than you should
If you are accidentally given more Rocefin than prescribed, contact your doctor or go immediately to the nearest hospital.
If you miss a dose of Rocefin injectable solution for intramuscular use
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 take a double dose (two injections together) to make up for a missed dose.
If you stop treatment with Rocefin injectable solution for intramuscular use
Do not stop taking Rocefin unless your doctor tells you to. 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.
With this medicine, you may experience the following side effects:
Treatment with ceftriaxone, especially in elderly patients with severe renal insufficiency or neurological disorders, may rarely cause reduced consciousness, abnormal movements, agitation, and seizures.

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:

• 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).

Serious skin reactions (not known, frequency cannot be estimated from the available data)
If you develop a serious skin reaction, inform a doctor immediately.
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, 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 occur shortly after starting treatment with Rocefin injectable solution for intramuscular use 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., oral thrush or genital fungal infections).
• 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 at the site where Rocefin injectable solution for intramuscular use was administered. Blisters, bruising, deep redness or rash, irritation, itching, hardening of the skin, or swelling 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 wheals (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.
• Infection at the injection site.

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.
• 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.
• 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 the amount of urine produced may decrease.
• False positive Coombs test (a test to detect blood problems).
• False positive test for galactosaemia (an abnormal accumulation of the sugar galactose).
• Rocefin injectable solution for intramuscular use may interfere with certain types of blood glucose tests; please consult your doctor.

Following accidental injection of lidocaine into a blood vessel during intramuscular administration of Rocefin injectable solution for intramuscular use, additional side effects may occur, which may include:
Not known (frequency cannot be estimated from the available data)

• Changes in heart rhythm and rate.
• Low blood pressure.
• Slowed heart rate (less than 60 beats/minute).
• Interruption of normal blood circulation due to cardiac arrest and reduced blood flow.
• Loss of balance, tingling around the mouth, numbness of the tongue, difficulty tolerating everyday sounds (hyperacusis), ringing in the ears (tinnitus), dizziness or lightheadedness, confusion, nervousness, involuntary rhythmic muscle contractions, seizures or epileptic fits, profound unconsciousness (coma).
• Blurred vision, double vision, or temporary loss of vision.
• Feeling unwell (nausea or vomiting).
• Breathing difficulties.
• Reduced respiratory rate or possible cessation of breathing.
• Unusual drowsiness or daytime fatigue, or fainting.

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 https://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 Rocefin injectable solution for intramuscular use

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, after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30 °C. Keep the vials in the outer packaging to protect them from light.
Chemical and physical in-use stability has been demonstrated for at least 6 hours at a temperature not exceeding 25 °C, or for 24 hours at 2-8 °C.
From a microbiological point of view, 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.
For single use only.
Do not dispose of medicines 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 Rocefin injectable solution for intramuscular use contains
Rocefin 1 g powder and solvent for injectable solution for intramuscular use
The active substances are ceftriaxone and lidocaine.
Each vial contains 1 g (gram) of ceftriaxone powder as ceftriaxone sodium.
Each ampoule contains 35 mg (milligrams) of lidocaine hydrochloride in 3.5 ml. The other excipient is water for
injections.
The displacement volume of 1 g of Rocefin is 0.71 ml in a 1% lidocaine hydrochloride solution. This requires adjustment of the solvent volume when only a portion of the total solution is dosed and administered (e.g. in neonates, infants and children from 15 days of age to 12 years of age with a body weight below 50 kg). To obtain a final solution with a concentration of 285 mg/ml, reconstitute 1 g of Rocefin in 2.9 ml of a 1% lidocaine hydrochloride solution.
Rocefin 250 mg powder and solvent for injectable solution for intramuscular use
The active substances are ceftriaxone and lidocaine.
Each powder vial contains 250 mg of ceftriaxone powder as ceftriaxone sodium.
Each ampoule contains 20 mg of lidocaine hydrochloride in 2 ml. The other excipient is water for injections.
The displacement volume of 250 mg of Rocefin is 0.18 ml in a 1% lidocaine hydrochloride solution. This requires adjustment of the solvent volume when only a portion of the total solution is dosed and administered (e.g. in neonates, infants and children from 15 days of age to 12 years of age with a body weight below 50 kg). To obtain a final solution with a concentration of 125 mg/ml, reconstitute 250 mg of Rocefin in 1.9 ml of a 1% lidocaine hydrochloride solution.
Rocefin must not be mixed with other medicines in the same syringe.

Description of the appearance of Rocefin injectable solution for intramuscular use and contents of the pack
Rocefin injectable solution for intramuscular use consists of powder and solvent for injectable solution.
The powder is white to yellowish-orange in colour. The solvent is clear and colourless.
Rocefin injectable solution for intramuscular use is available in packs containing 1 vial of powder and 1 ampoule of solvent.

Marketing Authorization Holder
Roche S.p.A. - Viale G.B. Stucchi 110, 20900 Monza (MB).

Manufacturer
Roche S.p.A.
Viale G.B. Stucchi, 110
20900 Monza (MB)
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Rocefin 1 g/3.5 ml powder and solvent for injectable solution for intramuscular use
Belgium, Luxembourg: Rocephine IM + Lidocaine
Finland, Sweden: Rocephalin
Italy: Rocefin
France: Rocephine
Ireland: Rocephin
Rocephin 250/2 ml mg powder and solvent for injectable solution for intramuscular use
Italy: Rocefin

Advice/health education
Antibiotics are used to treat bacterial infections. They are not effective against viral infections.
If your doctor has prescribed antibiotics for you, you specifically need them for your current illness.
Some bacteria may survive or multiply despite antibiotic treatment. This phenomenon is known as resistance: certain antibiotic treatments become ineffective.
Improper use of antibiotics increases resistance. You may even promote the development of bacterial resistance, thereby delaying recovery or reducing the effectiveness of antibiotics if you do not adhere to:

• dosage
• frequency of administration
• and duration of treatment.

Therefore, to preserve the effectiveness of this medicine:

1. Use antibiotics only when prescribed.
2. Strictly follow the prescription.
3. Do not reuse an antibiotic without a medical prescription, even if you are treating a similar illness.
4. Never give the antibiotic prescribed for you to another person, as it may not be suitable for their condition.
5. At the end of treatment, return all unused medicines to a pharmacy to ensure they are properly disposed of.

---

The following information is intended exclusively for healthcare professionals:

For complete prescribing information, refer to the product characteristics summary.
Solutions containing Rocefin must not be mixed with, or added to, solutions containing other agents. In particular, Rocefin is not compatible with calcium-containing solutions.
Based on reports published in the literature, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole, and aminoglycosides.
Dosage
The dose varies according to the severity, sensitivity level, site and type of infection, and the patient's age and hepatic and renal function.
The recommended doses in the following tables are the generally recommended doses for these indications.
In particularly severe cases, doses at the upper end of the recommended range should be considered.
Adults and children above 12 years of age (≥ 50 kg)

* In documented bacteremia, the highest values within the recommended dose range should be considered.
** In case of administration at doses higher than 2 g per day, administration twice daily (every 12 hours) may be considered.

Dosage recommendations for adults and children above 12 years of age (≥ 50 kg) requiring specific dosing regimens:

Acute otitis media
A single intramuscular dose of Rocefin 1–2 g may be administered.
Limited data suggest that in severely ill patients or in case of failure of prior therapy, Rocefin may be effective when administered intramuscularly at a daily dose of 1–2 g for 3 days.

Preoperative prophylaxis of surgical site infections
2 g as a single preoperative dose.

Gonorrhoea
500 mg administered as a single intramuscular dose.

Syphilis
The generally recommended doses are 500 mg–1 g once daily, increased to 2 g once daily for neurosyphilis, for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on limited data. Refer to national or local guidelines.

Disseminated Lyme borreliosis (early [stage II] and late [stage III])
2 g once daily for 14–21 days. The recommended duration of treatment is variable; refer to national or local guidelines.

Paediatric population
Neonates, infants, and children from 15 days of age to 12 years of age (< 50 kg)
Children with a body weight equal to or above 50 kg should receive the standard adult dose. The maximum single dose of lidocaine in children must not exceed 5 mg/kg body weight.
In obese children, the maximum dose should be calculated based on ideal body weight for sex and age.

* In documented bacteremia, the highest values within the recommended dose range should be considered.
** In case of administration at doses higher than 2 g per day, administration twice daily (every 12 hours) may be considered.
Indications for neonates, infants, and children from 15 days of life to 12 years (< 50 kg) requiring specific dosage regimens:
Acute otitis media
For initial treatment, a single intramuscular dose of Rocefin 50 mg/kg may be administered. Limited data suggest that in severely ill children or in case of failure of initial therapy, Rocefin may be effective when administered intramuscularly at a daily dose of 50 mg/kg for 3 days.
Preoperative prophylaxis of surgical site infections
50–80 mg/kg as a single preoperative dose.
Syphilis
The generally recommended doses are 75–100 mg/kg (max 4 g) once daily for 10–14 days.
Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Disseminated Lyme disease (early [stage II] and late [stage III])
50–80 mg/kg once daily for 14–21 days. The recommended duration of treatment is variable; refer to national or local guidelines.
Neonates from 0 to 14 days of life
Rocefin is contraindicated in premature neonates until a postmenstrual age of 41 weeks (gestational age + chronological age).

* In documented bacteraemia, the highest values within the recommended dose range should be considered.
The maximum daily dose of 50 mg/kg must not be exceeded.
Dosing recommendations for neonates aged 0–14 days requiring specific dosing regimens:
Acute otitis media
For initial treatment of acute otitis media, a single intramuscular dose of Rocefin 50 mg/kg may be administered.
Surgical site infection prophylaxis
20–50 mg/kg as a single preoperative dose.
Syphilis
The generally recommended dose is 50 mg/kg once daily for 10–14 days. Dose recommendations for syphilis, including neurosyphilis, are based on very limited data. Refer to national or local guidelines.
Duration of therapy
The duration of therapy varies depending on the course of the disease. As with other antibiotic therapies, treatment with ceftriaxone should be continued for 48–72 hours after the patient has defervesced or until bacterial eradication has been demonstrated.
Elderly patients
The recommended adult dosages do not require adjustment in elderly patients, provided that renal and hepatic function are satisfactory.
Patients with impaired hepatic function
According to available data, dosage adjustment is not necessary in cases of mild to moderate hepatic impairment, provided that renal function is not compromised.
There are no data from studies conducted in patients with severe hepatic impairment.
Patients with impaired renal function
Dosage adjustment of ceftriaxone is not required in patients with impaired renal function, provided that hepatic function is not compromised. Only in cases of preterminal renal failure (creatinine clearance < 10 mL/min) should the ceftriaxone dosage not exceed 2 g per day.
In dialysis patients, no supplemental dose is required after dialysis. Ceftriaxone is not eliminated during peritoneal dialysis or haemodialysis. Close clinical monitoring of safety and efficacy is recommended.
Patients with severe hepatic and renal impairment
In patients with severe renal and hepatic dysfunction, close clinical monitoring of safety and efficacy is recommended.
Instructions for use
For single use only. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.
It is recommended to use freshly prepared solutions.
For storage conditions of the reconstituted medicine, see section “How to store Rocefin”.
Rocefin is completely reconstituted in its respective solvent within 150 seconds. The reconstituted solution is a clear solution ranging in colour from yellow to brownish-yellow.
Rocefin must not be mixed with other medicinal products in the same syringe, except with 1% lidocaine hydrochloride solution (for intramuscular injection only).
Rocefin i.m. and associated names (see Annex I) 1 g powder and solvent for injectable solution
Intramuscular injection:
Use in adults and children above 12 years of age (≥ 50 kg)
1 g of Rocefin must be dissolved in 3.5 mL of 1% lidocaine hydrochloride solution. The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter. The solution should be administered by deep intramuscular injection. Doses exceeding 1 g should be divided and administered at more than one injection site.
Use in neonates, infants, and children from 15 days of age up to 12 years of age (< 50 kg)
The displacement volume of 1 g of Rocefin is 0.71 mL in lidocaine hydrochloride solution. This requires adjustment of the solvent volume to facilitate weight-dependent dosing (primarily in children up to 12 years of age), in case only a portion of the total solution is dosed and administered.
To obtain a final solution with a concentration of 285 mg/mL, reconstitute 1 g of Rocefin in 2.9 mL of 1% lidocaine hydrochloride solution.
Rocefin i.m. and associated names (see Annex I) 250 mg powder and solvent for injectable solution
Intramuscular injection:
Use in adults and children above 12 years of age (≥ 50 kg)
250 mg of Rocefin must be dissolved in 2 mL of 1% lidocaine hydrochloride solution. The vial should be gently rolled between the palms and visually inspected to ensure complete reconstitution and absence of particulate matter. The solution should be administered by deep intramuscular injection. Doses exceeding 1 g should be divided and administered at more than one injection site.
Use in neonates, infants, and children from 15 days of age up to 12 years of age (< 50 kg)
The displacement volume of 250 mg of Rocefin is 0.18 mL in 1% lidocaine hydrochloride solution. This requires adjustment of the solvent volume to facilitate weight-dependent dosing (primarily in children up to 12 years of age), in case only a portion of the total solution is dosed and administered.
To obtain a final solution with a concentration of 125 mg/mL, reconstitute 250 mg of Rocefin in 1.9 mL of 1% lidocaine hydrochloride solution.
Solutions containing lidocaine must never be administered by intravenous route.