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Package leaflet: Information for the Patient

Ceftriaxone 1 g

Powder for solution for injection or infusion

Ceftriaxone (as ceftriaxone sodium)

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor, pharmacist or nurse.

-    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-    If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

is in this leaflet

What Ceftriaxone 1 g Powder for solution for injection or infusion is and what it is used for What you need to know before you are

given Ceftriaxone 1 g Powder for solution for injection or infusion.

How Ceftriaxone 1 g Powder for solution for injection or infusion is given Possible side effects

How to store Ceftriaxone 1 g Powder for solution for injection or infusion Contents of the pack and other information

1.    What Ceftriaxone 1 g Powder for solution for injection or infusion is and what it is used for

Ceftriaxone 1 g Powder for solution for injection or infusion is an antibiotic given to adults and children (including newborn babies). It works by killing bacteria that cause infections. It belongs to a group of medicines called cephalosporins.

Ceftriaxone 1 g Powder for solution for injection or infusion 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.

•    bones and joints.

•    the skin or soft tissues.

• the blood.

• the heart.

It can be given:

•    to treat specific sexually transmitted infections (gonorrhoea and syphilis).

•    to treat patients with low white blood cell counts (neutropenia) who have fever due to bacterial infection.

•    to treat infections of the chest in adults with chronic bronchitis.

•    to treat Lyme disease (caused by tick bites) in adults and children including newborn babies from 15 days of age.

•    to prevent infections during surgery.

2.    What you need to know before you are given Ceftriaxone 1 g Powder for solution for injection or infusion

You must not be given Ceftriaxone 1 g Powder for solution for injection or infusion if • You are allergic to ceftriaxone sodium.

•    You have had a sudden or severe allergic reaction to penicillin or similar antibiotics (such as cephalosporins, carbapenems or monobactams). The signs include sudden swelling of the throat or face which might make it difficult to breathe or swallow, sudden swelling of the hands, feet and ankles, and a severe rash that develops quickly.

•    You are allergic to lidocaine and you are to be given Ceftriaxone 1 g Powder for solution for injection or infusion as an injection into a muscle.

Ceftriaxone 1 g Powder for solution for injection or infusion must not be given to babies if:

•    The baby is premature

•    The baby is newborn (up to 28 days of age) and has certain blood problems or jaundice (yellowing of the skin or the whites of the eyes) or is about to be given a product that contains calcium into their vein.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Ceftriaxone 1 g Powder for solution for injection or infusion if:

•    You have recently received or are about to receive products that contain calcium.

•    You have recently had diarrhoea after having an antibiotic medicine. You have ever had problems with your gut, in particular colitis (inflammation of the bowel).

•    You have liver or kidney problems.

•    You have gall stones or kidney stones.

•    You have other illnesses, such as haemolytic anaemia (a reduction in your red blood cells that may make your skin pale yellow and cause weakness or breathlessness).

•    You are on a low sodium diet.

If you need a blood or urine test

If you are given Ceftriaxone 1 g Powder for solution for injection or infusion for a long time, you may need to have regular blood tests. Ceftriaxone 1 g Powder for solution for injection or infusion can affect the results of urine tests for sugar and a blood test known as the Coombs test. If you are having tests:

•    Tell the person taking the sample that you have been given Ceftriaxone 1 g Powder for solution for injection or infusion.

Children

Talk to your doctor or pharmacist or nurse before your child is administered Ceftriaxone 1 g Powder for solution for injection or infusion if:

•    He/She has recently been given or is to be given a product that contains calcium into their vein.

Other medicines and Ceftriaxone 1 g Powder for solution for injection or infusion

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

•    A type of antibiotic called an aminoglycoside.

•    An antibiotic called chloramphenicol (used to treat infections, particularly of the eyes).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. The doctor will consider the benefit of treating you with Ceftriaxone 1 g Powder for solution for injection or infusion against the risk to your baby.

Driving and using machines

Ceftriaxone 1 g Powder for solution for injection or infusion can cause dizziness. If you feel dizzy, do not drive or use any tools or machines. Talk to your doctor if you experience these symptoms.

Ceftriaxone 1 g Powder for solution for injection or infusion contains sodium.

This medicinal product contains 3.6 mmol (or 83 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

3. How Ceftriaxone 1 g Powder for solution for injection or infusion is given

Ceftriaxone 1 g Powder for solution for injection or infusion is usually given by a doctor or nurse. It will be given as a drip (intravenous infusion) or as an injection directly into a vein or into a muscle. Ceftriaxone 1 g Powder for solution for injection or infusion is made up by the doctor, pharmacist or nurse and will not be mixed with or given to you at the same time as calcium-containing injections.

The usual dose

Your doctor will decide the correct dose of Ceftriaxone 1 g Powder for solution for injection or infusion for you. The dose will depend on the severity and type of infection; whether you are on any other antibiotics; your weight and age; how well your kidneys and liver are working. The number of days or weeks that you are given Ceftriaxone 1 g Powder for solution for injection or infusion depends on what sort of infection you have.

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

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

Newborn babies, infants and children aged 15 days to 12 years with a body weight of less than 50 kg:

•    50-80 mg Ceftriaxone 1 g Powder for solution for injection or infusion for each kg of the child’s body weight once a day depending on the severity and type of infection. If you have a severe infection, your doctor will give you a higher dose up to 100 mg for each kg of body weight to a maximum of 4 g once a day. If your daily dose is higher than 2 g, you may receive it as a single dose once a day or as two separate doses.

•    Children with a body weight of 50 kg or more should be given the usual adult dose.

Newborn babies (0-14 days)

•    20 - 50 mg Ceftriaxone 1 g Powder for solution for injection or infusion for each kg of the child’s body weight once a day depending on the severity and type of infection.

•    The maximum daily dose is not to be more than 50 mg for each kg of the baby’s weight.

People with liver and kidney problems

You may be given a different dose to the usual dose. Your doctor will decide how much Ceftriaxone 1 g Powder for solution for injection or infusion you will need and will check you closely depending on the severity of the liver and kidney disease.

If you are given more Ceftriaxone 1 g Powder for solution for injection or infusion than you should

If you accidentally receive more than your prescribed dose, contact your doctor or nearest hospital straight away.

If you forget to use Ceftriaxone 1 g Powder for solution for injection or infusion

If you miss an injection, you should have it as soon as possible. However, if it is almost time for your next injection, skip the missed injection. Do not take a double dose (two injections at the same time) to make up for a missed dose.

If you stop using Ceftriaxone 1 g Powder for solution for injection or infusion

Do not stop taking Ceftriaxone 1 g Powder for solution for injection or infusion unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

The following side effects may happen with this medicine:

Severe allergic reaction (not known, frequency cannot be estimated from the available data) If you have a severe allergic reaction, tell a doctor straight away.

The signs may include:

•    Sudden swelling of the face, throat, lips or mouth. This can make it difficult to breathe or swallow.

•    Sudden swelling of the hands, feet and ankles.

Severe skin rashes (not known, frequency cannot be estimated from the available data)

If you get a severe skin rash, tell adoctor straight away

•    The signs may include a severe rash that develops quickly, with blisters or peeling of the skin and possibly blisters in the mouth.

Other possible side effects:

Common (may affect up to 1 in 10 people)

•    Abnormalities with your white blood cells (such as decrease of leucocytes and an increase of eosinophils) and platelets (decrease of thrombocytes).

•    Loose stools or diarrhoea.

•    Changes in the results of blood tests for liver functions.

•    Rash.

Uncommon (may affect up to 1 in 100 people)

•    Fungal infections (for example, thrush).

•    A decrease in the number of white blood cells (granulocytopenia).

•    Reduction in number of red blood cells (anaemia).

•    Problems with the way your blood clots. The signs may include bruising easily and pain and swelling of your joints.

•    Headache.

•    Dizziness.

•    Feeling sick or being sick.

•    Pruritis (itching).

•    Pain or a burning feeling along the vein where Ceftriaxone has been given. Pain where the injection was given.

•    A high temperature (fever).

•    Abnormal kidney function test (blood creatinine increased).

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

•    Inflammation of the large bowel (colon). The signs include diarrhoea, usually with blood and mucus, stomach pain and fever.

•    Difficulty in breathing (bronchospasm).

•    A lumpy rash (hives) that may cover a lot of your body, feeling itchy and swelling.

•    Blood or sugar in your urine.

•    Oedema (fluid build-up)

•    Shivering.

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

•    A secondary infection that may not respond to the antibiotic previously prescribed

•    For of anaemia where red blood cells are destroyed (haemolytic anaemia).

•    Severe decrease in white blood cells (agranulocytosis).

•    Convulsions.

•    Vertigo (spinning sensation).

•    Inflammation of the pancreas (pancreatitis). The signs include sever pain in the stomach which spreads to your back

•    Inflammation of the mucus linging of the mouth (stomatitis).

•    Inflammation of the tongue (glossitis). The signs include swelling, redness and soreness of the tongue.

•    Problems with your gallbladder, which may cause pain, feeling sick and being sick.

•    A neurological condition that may occur in neonates with severe jaundice (kernicterus).

•    Kidney problems caused by deposits of calcium ceftriaxone. There may be pain when passing water (urine) or low output of urine.

•    A false positive result in a Coombstest (a test for some blood problems).

•    A false positive result for galactosaemia (an abnormal build up of the sugar galactose).

•    Ceftriaxone may interfere with some types of blood glucose tests- please check with your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help to provide more information on the safety of this medicine.

5. How to store Ceftriaxone 1 g Powder for solution for injection or infusion

•    Keep this medicine out of the sight and reach of children.

•    Do not use this medicine after the expiry date which is stated on the vial and the carton after EXP. The expiry date refers to the last day of that month.

•    Do not store Ceftriaxone 1 g Powder for solution for injection or infusion above 25°C.

•    Keep the vial in the outer carton in order to protect from light.

Stability of the reconstituted solutions:

Chemical and physical in-use stability has been demonstrated for 6 hours at 25°C and for 24 hours at 2-8°C. From a microbiological point of view, unless the method of opening/ reconstitution/ dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not be longer than the times stated above for the chemical and physical in-use stability.

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Ceftriaxone 1 g Powder for solution for injection or infusion contains

-    The active substance is ceftriaxone. Each vial contains 1.19 g ceftriaxone sodium equivalent to 1 g ceftriaxone.

-    There are no other ingredients.

What Ceftriaxone 1 g Powder for solution for injection or infusion looks like and contents of the pack

•    Ceftriaxone 1 g Powder for solution for injection or infusion is an almost white or slightly yellowish, crystalline powder for solution for injection/infusion. It is supplied in a glass vial.

•    Pack size: 10 vials.

Marketing Authorisation Holder and Manufacturer

Midas® Pharma GmbH Rheinstr. 49 55218 Ingelheim Germany

This medicinal product is authorised in the Member States of the EEA under the following names:

Germany    Ceftriaxon Midas 1 g Pulver zur Herstellung einer Injektions-/Infusionslosung

United Kingdom Ceftriaxone 1 g Powder for solution for injection or infusion France    CEFTRIAXON MIDAS 1 g

poudre pour solution injectable ou pour perfusion Italy    Ceftriaxone Midas

This leaflet was last revised in 06/2014.

The following information is intended for healthcare professionals only:

INFORMATION FOR HEALTHCARE PROFESSIONALS

Ceftriaxone 1 g Powder for solution for injection or infusion Ceftriaxone (as ceftriaxone sodium)

Please refer to the Summary of Product Characteristics for full prescribing information.

Posology

The dose depends on the severity, susceptibility, site and type of infection and on the age and hepato-renal function of the patient.

The doses recommended in the tables below are the generally recommended doses in these indications. In particularly severe cases, doses at the higher end of the recommended range should be considered.

Adults and children over 12 years of age (> 50 kg)

administered.

Indications for adults and children over 12 years of age (> 50 kg) that require specific dosage schedules: Acute otitis media

A single intramuscular dose of Ceftriaxone 1 g Powder for solution for injection or infusion 1-2 g can be given. Limited data suggest that in cases where the patient is severely ill or previous therapy has failed, Ceftriaxone 1 g Powder for solution for injection or infusion may be effective when given as an intramuscular dose of 1-2 g daily for 3 days.

Pre-operative prophylaxis of surgical site infections 2 g as a single pre-operative dose.

Gonorrhoea

500 mg 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. The dose recommendations in syphilis, including neurosyphilis, are based on limited data. National or local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early [Stage II] and late [Stage III])

2 g once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Paediatric population

Neonates, infants and children 15 days to 12 years of age (< 50 kg)

For children with bodyweight of 50 kg or more, the usual adult dosage should be given.

Ceftriaxone dosage*	Treatment frequency**	Indications
50-80 mg/kg	Once daily	Intra-abdominal infections
		Complicated urinary tract infections (including pyleonephritis)
		Community acquired pneumonia
		Hospital acquired pneumonia
50-100 mg/kg (Max 4 g)	Once daily	Complicated skin and soft tissue infections
		Infections of bones and joints
		Management of neutropenic patients with fever that is suspected to be due to a bacterial infection
80-100 mg/kg (Max 4 g)	Once daily	Bacterial meningitis
100 mg/kg (Max 4 g)	Once daily	Bacterial endocarditis

* In documented bacteraemia, the higher end of the recommended dose range should be considered. ** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.

Indications for neonates, infants and children 15 days to 12 years (< 50 kg) that require specific dosage schedules:

Acute otitis media

For initial treatment of acute otitis media, a single intramuscular dose of Ceftriaxone 1 g Powder for solution for injection or infusion 50 mg/kg can be given. Limited data suggest that in cases where the child is severely ill or initial therapy has failed, Ceftriaxone 1 g Powder for solution for injection or infusion may be effective when given as an intramuscular dose of 50 mg/kg daily for 3 days.

Pre-operative prophylaxis of surgical site infections 50-80 mg/kg as a single pre-operative dose.

Syphilis

The generally recommended doses are 75-100 mg/kg (max 4 g) once daily for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on very limited data. National or local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early [Stage II] and late [Stage III])

50-80 mg/kg once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Neonates 0-14 days

Ceftriaxone 1 g Powder for solution for injection or infusion is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age).

Ceftriaxone dosage*	Treatment frequency	Indications
20-50 mg/kg	Once daily	Intra-abdominal infections
		Complicated skin and soft tissue infections
		Complicated urinary tract infections (including pyleonephritis)
		Community acquired pneumonia
		Hospital acquired pneumonia
		Infections of bones and joints
		Management of neutropenic patients with fever that is suspected to be due to a bacterial infection
50 mg/kg	Once daily	Bacterial meningitis
		Bacterial endocarditis

* In documented bacteraemia, the higher end of the recommended dose range should be considered.

A maximum daily dose of 50 mg/kg should not be exceeded.

Indications for neonates 0-14 days that require specific dosage schedules:

Acute otitis media

For initial treatment of acute otitis media, a single intramuscular dose of Ceftriaxone 1 g Powder for solution for injection or infusion 50 mg/kg can be given.

Pre-operative prophylaxis of surgical site infections 20-50 mg/kg as a single pre-operative dose.

Syphilis

The generally recommended dose is 50 mg/kg once daily for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on very limited data. National or local guidance should be taken into consideration.

Duration of therapy

The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of ceftriaxone should be continued for 48 - 72 hours after the patient has become afebrile or evidence of bacterial eradication has been achieved.

Older people

The dosages recommended for adults require no modification in older people provided that renal and hepatic function is satisfactory.

Patients with hepatic impairment

Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment provided renal function is not impaired.

There are no study data in patients with severe hepatic impairment.

Patients with renal impairment

In patients with impaired renal function, there is no need to reduce the dosage of ceftriaxone provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance < 10 ml/min) should the ceftriaxone dosage not exceed 2 g daily.

In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. Ceftriaxone is not removed by peritoneal- or haemodialysis. Close clinical monitoring for safety and efficacy is advised.

Patients with severe hepatic and renal impairment

In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.

Method of administration

Ceftriaxone 1 g Powder for solution for injection or infusion can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes, or by deep intramuscular injection. Intravenous intermittent injection should be given over 5 minutes preferably in larger veins. Intravenous doses of 50 mg/kg or more in infants and children up to 12 years of age should be given by infusion. In neonates, intravenous doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy. Intramuscular injections should be injected well within the bulk of a relatively large muscle and not more than 1 g should be injected at one site. Intramuscular administration should be considered when the intravenous route is not possible or less appropriate for the patient. For doses greater than 2 g intravenous administration should be used.

If lidocaine is used as a solvent, the resulting solution should never be administered intravenously. The information in the Summary of Product Characteristics of lidocaine should be considered.

Ceftriaxone is contraindicated in neonates (< 28 days) if they require (or are expected to require) treatment with calcium-containing intravenous solutions, including continuous calcium-containing infusions such as parenteral nutrition, because of the risk of precipitation of ceftriaxone-calcium.

Diluents containing calcium, (e.g. Ringer’s solution or Hartmann’s solution), should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for intravenous administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, ceftriaxone and calcium-containing solutions must not be mixed or administered simultaneously.

For pre-operative prophylaxis of surgical site infections, ceftriaxone should be administered 30-90 minutes prior to surgery.

For instructions on reconstitution of the medicinal product before administration.

Incompatibilities

Based on literature reports, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

Solutions containing ceftriaxone should not be mixed with or added to other agents except those mentioned. In particular diluents containing calcium, (e.g. Ringer’s solution, Hartmann’s solution) should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for intravenous administration because a precipitate can form. Ceftriaxone must not be mixed or administered simultaneously with calcium containing solutions including total parenteral nutrition.

Special precautions for disposal and other handling

Concentrations for the intravenous injection: 100 mg/ml,

Concentrations for the intravenous infusion: 50 mg/ml

Ceftriaxone 1 g Powder for solution for injection or infusion may be administered by deep intramuscular injection, slow intravenous bolus injection or by intravenous infusion, after reconstitution according to the directions given below.

Intramuscular injection:

Ceftriaxone 1 g Powder for solution for injection or infusion should be dissolved in 3.5 ml of 1% Lidocaine Hydrochloride solution.

The solution should be administered by deep intramuscular injection. Dosages greater than 1 g should be divided and injected at more than one site.

For intramuscular injection Ceftriaxone 1 g Powder for solution for injection or infusion should not be mixed in the same syringe with any drug other than 1% Lidocaine Hydrochloride solution.

Solutions in Lidocaine must not be administered intravenously.

Intravenous injection:

Ceftriaxone 1 g Powder for solution for injection or infusion should be dissolved in 10 ml of Water for Injections. The injection should be administered over at least 2 - 4 minutes, directly into the vein or via the tubing of an intravenous infusion. For risks in regard to shortened duration of injection.

When reconstituted for intramuscular or intravenous injection, the white to yellowish crystalline powder gives a pale yellow to amber solution.

This pale yellow colouration does not impair the efficacy or tolerability of Ceftriaxone 1 g Powder for solution for injection or infusion.

Reconstituted solutions should be inspected visually. Only clear solutions free of visible particles should be used.

The reconstituted product is for single use only and any unused solution must be discarded.

Intravenous infusion:

Ceftriaxone 1 g Powder for solution for injection or infusion should be dissolved in 20 ml of one of the calcium-free infusion solutions.

Compatibility with the following solutions have been demonstrated:

•    0.9% (9 mg/ml) Sodium Chloride Injection

•    Sodium Chloride & Glucose Injection (0.45%(4.5 mg/ml) sodium chloride and 2.5%(25 mg/ml) glucose

•    Glucose Injection 5% (50 mg/ml)

•    Glucose Injection 10% (100 mg/ml)

•    Dextran 6% (60 mg/ml) in Glucose Injection 5% (50 mg/ml)

•    Sterile Hydroxyethyl-starch 6% (60 mg/ml)

•    Sterile Hydroxyethyl-starch 10% (100 mg/ml)

The reconstitution of the ready to use solution for infusion has to take place in two steps in order to allow the reconstitution of the necessary volume of solution for infusion

1.    Ceftriaxone 1 g Powder for solution for injection or infusion is reconstituted with 10 ml of one of the compatible intravenous fluids in its vial. This solution has to be transferred into a suitable infusion bag. Controlled and validated aseptic conditions have to be observed.

2.    This solution should be diluted with 9 ml more of diluent giving a final volume of 20 ml and a concentration of 50 mg/ml.

This volume of 20 ml reconstituted solution for infusion should be administered immediately as a short time infusion over 30 minutes.

Smaller amounts for lower doses calculated on an mg/kg/bodyweight basis have to be calculated proportionally.The solution of the reconstituted product should be inspected visually for particulate matter prior to administration. Only clear solutions free from visible particles should be administered.

The reconstituted product is for single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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