Consumer medicine information

Hospira Ceftriaxone Sodium Powder for Injection

Ceftriaxone

BRAND INFORMATION

Brand name

Hospira Ceftriaxone Sodium Powder for Injection

Active ingredient

Ceftriaxone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Hospira Ceftriaxone Sodium Powder for Injection.

What is in this leaflet

This leaflet answers some common questions about Hospira™ Ceftriaxone Sodium Powder for Injection. It does not contain all the available information. It does not take the place of talking to your doctor and pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given ceftriaxone against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet.

You may need to read it again.

What Hospira™Ceftriaxone Sodium Powder for Injection is used for

Ceftriaxone is an antibiotic used to treat infections in different parts of the body caused by bacteria.

It is also used to prevent infections following surgery.

Ceftriaxone will not work against infections caused by viruses such as colds or the flu.

Ceftriaxone belongs to a group of antibiotics called cephalosporins (kef-a-low-SPOR-ins). These antibiotics work by killing the bacteria that are causing your infection.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

Before you are given Hospira™Ceftriaxone Sodium Powder for Injection

When you must not be given it

Hospira™ Ceftriaxone Sodium Powder for Injection should not be given to you if you have an allergy to:

  • any medicine containing ceftriaxone
  • other cephalosporin antibiotics
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Hospira™ Ceftriaxone Sodium Powder for Injection should not be given to you if you have had a serious allergic reaction to penicillins.

Hospira™ Ceftriaxone Sodium Powder for Injection should not be mixed with lignocaine and given to you if you have had an allergic reaction to lignocaine.

Sometimes this medicine is mixed with lignocaine hydrochloride so that the injection into the muscle is less painful.

Hospira™ Ceftriaxone Sodium Powder for Injection should not be given to neonates (especially premature neonates) who may be at risk of developing, or have abnormally high amounts of bile pigment (bilirubin) in the blood.

Safety and effectiveness in children and infants have not been established.

If you are not sure whether you should be given Hospira™ Ceftriaxone Sodium Powder for Injection, talk to your doctor.

Before you are given it

Tell your doctor if you have had any type of allergic reaction to penicillin antibiotics.

You may have an increased chance of being allergic to ceftriaxone if you are allergic to penicillins.

Tell you doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney or liver disease
  • stomach or intestine diseases, such as inflammation of the large intestine (bowel).

Tell your doctor if you are pregnant or intend to become pregnant or are breast-feeding.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you are given Hospira™ Ceftriaxone Sodium Powder for Injection.

Taking other medicines

Tell your doctor or pharmacist if you are taking or using any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and ceftriaxone may interfere with each other. These include:

  • chloramphenicol, another medicine used to treat infections.

This medicine may be affected by ceftriaxone or may affect how well it works. You may need different amounts of your medicine, or you may need to use a different medicine.

Talk to your doctor or pharmacist about the need for an additional method of contraception while you are being treated with ceftriaxone.

Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with ceftriaxone.

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while being given this medicine.

How Hospira™ Ceftriaxone Sodium Powder for Injection is given

How much is given

Your doctor will decide what dose you will receive. This depends on your infection and other factors, such as your weight. For most infections, Hospira™ Ceftriaxone Sodium Powder for Injection is usually given once or twice a day.

How it is given

Hospira™ Ceftriaxone Sodium Powder for Injection can be given in the following ways:

  • as a deep injection into a large muscle
  • as a slow injection or infusion (drip) into a vein.

This medicine must only be given by a doctor or nurse.

How long it is given for

Your doctor will decide how long you will receive this medicine for.

The length of treatment is usually 4 to 14 days, although some infections may require longer treatment. Sometimes only a single dose is required for the treatment or prevention of certain infections.

If you are given too much (overdose)

As Hospira™ Ceftriaxone Sodium Powder for Injection is given under medical supervision, it is very unlikely that you will receive too much.

However, if you experience severe side effects after being given this medicine, tell your doctor immediately.

Immediately telephone your doctor or the Poisons Information Centre (call 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Hospira™ Ceftriaxone Sodium Powder for Injection. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of a ceftriaxone overdose may include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

Ask your doctor if you have any concerns.

While you are being given Hospira™ Ceftriaxone Sodium Powder for Injection

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you get severe diarrhoea tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after ceftriaxone has been stopped. Do not take any diarrhoea medicine without first checking with your doctor.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.

If you get a sore white mouth or tongue while being given, or soon after stopping ceftriaxone, tell your doctor or pharmacist. Also tell your doctor or pharmacist if you get vaginal itching or discharge.

This may mean you have a fungal infection called thrush. Sometimes the use of ceftriaxone allows fungi to grow and the above symptoms to occur. Ceftriaxone does not work against fungi.

If you become pregnant while you are being treated with this medicine, tell your doctor immediately.

If you are about to start taking any new medicine, remind your doctor and pharmacist that you are being given ceftriaxone.

If you have to test your urine for sugar while you are being given this medicine, make sure your doctor knows which type of test you use.

Ceftriaxone may affect the results of some of these tests.

If you have to have any blood tests, tell your doctor you are being given this medicine.

Ceftriaxone may affect the results of some blood tests.

Tell any other doctors, dentists or pharmacists who treat you that you are being given this medicine.

Things to be careful of

Be careful driving or operating machinery until you know how ceftriaxone affects you.

Ceftriaxone generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, ceftriaxone may cause dizziness in some people. If this occurs, do not drive. If you drink alcohol, dizziness may be worse.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given ceftriaxone.

Ceftriaxone helps most people with infections, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by following lists of side effects.

You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

While using it

Tell your doctor or nurse if you notice any of the following and they worry you:

  • nausea, vomiting or mild diarrhoea
  • swelling, pain or tenderness at or near the injection site
  • headache or dizziness
  • oral thrush – white, furry, sore tongue and mouth
  • vaginal thrush – sore and itchy vagina and/or discharge.

These side effects are usually mild.

Tell your doctor as soon as possible if you notice the following:

  • sharp pain or a severe steady ache in the upper abdomen.

This side effect may require medical attention. This side effect is rare.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital (if you are not already in hospital) if you notice any of the following:

  • severe persistent diarrhoea
  • allergic reaction (for example, rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing)
  • excessive peeling of the skin.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

After finishing it

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with Hospira™ Ceftriaxone Sodium Powder for Injection:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea which may also be bloody
  • fever, in combination with one or both of the above.

These are serious side effects. You may have a serious condition affecting your bowel. Therefore, you may need urgent medical attention. However, these side effects are rare.

Do not take any diarrhoea medicine without first checking with your doctor.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After being given Hospira™ Ceftriaxone Sodium Powder for Injection

Storage

Hospira™ Ceftriaxone Sodium Powder for Injection will generally be stored in the pharmacy or on the ward.

The medicine is kept in a cool dry place, protected from light, where the temperature stays below 25°C. Once the powder for injection has been diluted to form a solution, it will be used as soon as possible. If storage is necessary, the solution will be kept in the fridge (at 2 to 8°C) for not more than 24 hours, and used as soon as practicable after removal from refrigeration. This medicine should not be frozen.

Product description

What it looks like

A white or yellowish crystalline powder in a glass vial. When Hospira™ Ceftriaxone Sodium Powder for Injection is made into a solution before injection, the solution ranges in colour from light yellow to amber.

Ingredients

Hospira™ Ceftriaxone Sodium Powder for Injection contains the active ingredient ceftriaxone sodium, equivalent to 1 g or 2 g of ceftriaxone.

Hospira™ Ceftriaxone Sodium Powder for Injection does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Sponsor

Hospira™ Ceftriaxone Sodium Powder for Injection is supplied by:
Hospira Pty Ltd
ABN 13 107 058 328
Level 3
500 Collins Street
Melbourne VIC 3000
Australia

Hospira™ Ceftriaxone Sodium Powder for Injection is available in the following presentations:
1 g /vial - AUST R 167648
2 g /vial - AUST R 167651

This leaflet was prepared in June 2011

BRAND INFORMATION

Brand name

Hospira Ceftriaxone Sodium Powder for Injection

Active ingredient

Ceftriaxone

Schedule

S4

 

Name of the medicine

Ceftriaxone sodium.

Excipients

Contains approximately sodium 83 mg (3.6 mEq)/g of ceftriaxone activity.

Description

Chemical name: disodium (6R,7R)-7-[[(2Z)- (2-aminothiazol-4-yl)(methoxyimino)acetyl]amino]- 3-[[(2-methyl-6-oxido-5-oxo-2,5- dihydro-1,2,4-triazin-3-yl)sulphanyl]methyl]- 8-oxo-5-thia-1-azabicyclo[4.2.0]oct- 2-ene-2-carboxylate 3.5 hydrate. Molecular formula: C18H16N8Na2O7S3 3.½H2O. MW: 661.59. CAS: 104376-79-6. Ceftriaxone sodium is a white or yellowish crystalline powder which is very soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 5% aqueous solution is approximately 6 to 8. Ceftriaxone sodium solutions may be light yellow to amber coloured in colour.
Hospira Ceftriaxone Sodium Powder for Injection is a sterile, semisynthetic, broad spectrum cephalosporin antibiotic for intravenous or intramuscular administration.

Pharmacology

Pharmacokinetics.

Ceftriaxone is absorbed poorly from the gastrointestinal tract. Average plasma concentrations of ceftriaxone following a single 30 minute intravenous (IV) infusion of a 0.5, 1 or 2 g dose and intramuscular (IM) administration of a single 0.5 or 1 g dose in healthy subjects are presented in Table 1.
Mean maximum plasma concentrations following I.M. injection occurred between two and three hours postdosing. Multiple I.V. or I.M. doses ranging from 0.5 to 2 g at 12 to 24 hour intervals resulted in 15 to 36% accumulation of ceftriaxone above single dose values. Accumulation was more with the I.M. doses. Ceftriaxone concentrations in urine are high, as shown in Table 2.
Thirty three to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug. Substantial amounts are secreted in the bile and ultimately found in the faeces as microbiologically inactive compounds. A small fraction appears in the urine as an unidentified metabolite. Renal excretion of ceftriaxone is not affected by prior administration of probenecid. After a 1 g I.V. dose, average concentrations of ceftriaxone, determined from one to three hours after dosing, were 581 microgram/mL in the gall bladder bile, 788 microgram/mL in the common duct bile, 898 microgram/mL in the cystic duct bile, 78.2 microgram/g in the gall bladder wall and 62.1 microgram/mL in the concurrent plasma. There were, however, wide individual variations in levels.
Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours, apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of 25 microgram/mL to a value of 85% bound at 300 microgram/mL. Protein binding is reduced in children and in uraemic patients. The in vitro activity of ceftriaxone is decreased two to eightfold by the presence of human serum.
The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after 50 mg/kg I.V. doses in paediatric patients suffering from bacterial meningitis are shown in Table 3.
The half-life of ceftriaxone in neonates ranges from 7.2 to 19 hours and in infants over six weeks of age from 4.0 to 6.6 hours.
Ceftriaxone crosses the placenta and appears in the milk in low concentrations.
Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with hepatic dysfunction (see Table 4); therefore, dosage adjustments are not necessary for these patients with ceftriaxone doses up to 2 g/day. However in some patients with severely impaired renal function the t½ of ceftriaxone may be prolonged (37 to 52 hours) and dosage adjustment should be considered. Peak serum levels should be held below 280 microgram/mL.
Ceftriaxone was not removed to any significant extent from the plasma by haemodialysis. Plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary.

Microbiology.

The bactericidal activity of ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone has a high degree of stability in the presence of β-lactamases, types I, II & III, both penicillinases and cephalosporinases, of Gram negative and Gram positive bacteria. It is susceptible to type IV β-lactamases at approximately 18% of the rate of cephaloridine. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Indications).

Gram negative aerobes.

Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including ampicillin resistant strains), Klebsiella sp. (including K. pneumoniae); Neisseria gonorrhoeae (including penicillinase and nonpenicillinase producing strains), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Morganella morganii and Serratia marcescens.

Note.

Strains of the above organisms that are multiply resistant to other antibiotics, e.g. penicillins, cephalosporins and aminoglycosides, may be susceptible to ceftriaxone sodium. Ceftriaxone is also active against some strains of Pseudomonas aeruginosa. Other Pseudomonas species are usually resistant.

Gram positive aerobes.

Staphylococcus aureus (including penicillinase producing strains) and Staphylococcus epidermidis (note: methicillin resistant Staphylococci are resistant to cephalosporins, including ceftriaxone), Streptococcus pyogenes (group A β-haemolytic Streptococci), Streptococcus agalactiae (group B Streptococci) and Streptococcus pneumoniae, group G Streptococci, Streptococcus viridans and Streptococcus species. (Note: most species of group D Streptococci including Streptococcus faecalis and Streptococcus faecium are resistant.)

Susceptibility tests.

Standard susceptibility disk method. Quantitative methods that require measurement of zone diameters give the most precise estimate of antibiotic susceptibility. One such procedure (Bauer AW, Kirby WMM, Sherris JC, Turck M; Antibiotic Susceptibility testing by Standardized Single Disk Method, Am J Clin Pathol 45:493-496, 1966; Standardized Disk Susceptibility Test, Federal Register 39: 19182-19184, 1974: National Committee for Clinical Laboratory Standards Approved Standard: ASM-2, Performance Standards for Antimicrobial Disk Susceptibility Tests, July 1975) has been recommended for use with disks to test susceptibility to Ceftriaxone. Laboratory results of the standardised single disk susceptibility test using a 30 microgram Ceftriaxone disk should be interpreted according to the following three criteria:
1. Susceptible organisms produces zones of 21 mm or greater, indicating that the tested organism is likely to respond to therapy.
2. Organisms that produce zones of 14 to 22 mm are expected to be susceptible if a high dosage is used or if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic levels are attained.
3. Resistant organisms produce zones of 13 mm or less, indicating that other therapy should be selected.
Organism should be tested with the ceftriaxone disk, since ceftriaxone has been shown to by in vitro tests to be active against certain strains found resistant to cephalosporin class disks.
Standardised procedures require use of control organisms. The 30 microgram ceftriaxone disk should give zone diameters between 29 and 35 mm, 22 and 28 mm and 17 and 23 mm for the reference strains E. coli ATCC 25922, S. aureus ATCC 25923 and P. aeruginosa ATCC 27853, respectively.
Dilution techniques: A bacterial isolate may be considered susceptible if the MIC value for ceftriaxone is not more than 8 micrograms/mL. Organisms are considered resistant to ceftriaxone if the MIC is greater than 32 micrograms/mL. Organisms having a MIC value of equal to or less than 32 microgram/mL, but less than 8 micrograms/mL are expected to be susceptible if a high dosage is used or if the infection is confirmed to tissues and fluids (e.g. urine), in which high antibiotic levels are attained. E. coli ATCC 25922, S. auerus ATCC 25823 and P. aeruginosa ATCC 27853 are also the recommended reference strains for controlling ceftriaxone dilution tests. Greater than 95% of MICs for the E. coli strain should fall within the range of 0.016 at 0.5 microgram/mL. The range for the S. aureus strain should be 1 to 2 microgram/mL.
Dilution or diffusion techniques, either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.

Indications

Hospira Ceftriaxone Sodium Powder for Injection is indicated for the treatment of the following infections when caused by susceptible aerobic organisms.

Lower respiratory tract infections.

Caused by Streptococcus pneumoniae, Streptococcus sp. (excluding enterococci), methicillin sensitive Staphylococcus aureus, Haemophilus influenzae, H. parainfluenzae, Klebsiella sp. (including K. pneumoniae), E. coli, Enterobacter aerogenes, Proteus mirabilis and Serratia marcescens.

Skin and skin structure infections.

Caused by methicillin sensitive Staphylococcus aureus, methicillin sensitive Staphylococcus epidermidis, Streptococcus group B, Streptococcus group G, Strep. pyogenes, Strep. viridans, Streptococcus sp. (excluding enterococci), Peptostreptococcus sp., E. coli, Enterobacter cloacae, Klebsiella sp. (including K. pneumoniae, K. oxytoca), P. mirabilis, M. morganii, Serratia marcescens.

Urinary tract infections (complicated and uncomplicated).

Caused by E. coli, P. mirabilis, P. vulgaris, M. morganii and Klebsiella sp. (including K. pneumoniae).

Uncomplicated gonorrhoea (cervical/ urethral and rectal).

Caused by N. gonorrhoea, including both penicillinase and nonpenicillinase producing strains.

Bacterial septicemia.

Caused by Streptococcus pneumoniae, E. coli and H. influenzae.

Bone infections.

Caused by methicillin sensitive Staph. aureus, methicillin sensitive Staph. epidermidis, Streptococcus group B, Streptococcus pneumoniae, Streptococcus sp. (excluding enterococci), E. coli, Enterobacter sp., P. mirabilis and K. pneumoniae.

Joint infections.

Caused by methicillin sensitive Staph. aureus, Streptococcus pneumoniae, Streptococcus sp. (excluding enterococci), E. coli, P. mirabilis, K. pneumoniae and Enterobacter sp.

Meningitis.

The initial treatment, as a single agent, of meningitis in children and immunocompetent adults when presumed or proven to be caused by H. influenzae type b, N. meningitidis, Strep. pneumoniae or Enterobacteriaceae pending culture and sensitivity results.

Surgical prophylaxis.

The preoperative administration of a single dose of ceftriaxone 1 g may reduce the incidence of postoperative infections in patients undergoing vaginal or abdominal hysterectomy or cholecystectomy in high risk patients, surgical procedures which are classified as contaminated or potentially contaminated and patients undergoing coronary artery bypass surgery. Although ceftriaxone has been shown to have been as effective as cefazolin in the prevention of infection following coronary artery bypass surgery, no placebo controlled trials have been conducted.

Susceptibility testing.

Before instituting treatment with ceftriaxone, appropriate specimens should be obtained for isolation of the causative organism and for determination of its susceptibility to the drug. Therapy may be instituted prior to obtaining results of susceptibility testing.

Contraindications

Ceftriaxone is contraindicated in patients with known allergy to the cephalosporin class of antibiotics or a major allergy to penicillin (anaphylaxis, angioneurotic oedema, urticaria).
Lignocaine should not be used as a diluent for intramuscular injection in patients who are hypersensitive to lignocaine.
Hospira Ceftriaxone Sodium Powder for Injection must not be administered with calcium containing solutions in newborn infants because of the risk of precipitation of ceftriaxone calcium salt (see Precautions, Calcium containing solutions and Use in children and Adverse Effects). Cases of fatal reactions with calcium ceftriaxone precipitates in lung and kidney in newborn infants have been described. In some cases the infusion lines and times of administration of ceftriaxone and calcium containing solutions differed. Therefore, Hospira Ceftriaxone Sodium Powder for Injection and I.V. calcium containing solutions must not be administered within 48 hours of each other in newborns.
Hyperbilirubinaemic newborns and preterm newborns should not be treated with ceftriaxone. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a possible risk of bilirubin encephalopathy in these patients.

Precautions

Hypersensitivity to cephalosporins, penicillins or other drugs.

Before therapy with ceftriaxone is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs. This product should be given cautiously to penicillin sensitive patients. Antibiotics should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs. Serious acute hypersensitivity reactions may require the use of subcutaneous adrenaline and other emergency measures. If an allergic reaction occurs ceftriaxone should be discontinued.

Calcium containing solutions.

In the available scientific data, there are no reports of intravascular precipitations in patients, other than newborn infants, treated with ceftriaxone and calcium containing solutions or any other calcium containing products. However, ceftriaxone should not be mixed or administered to any patient simultaneously with calcium containing solutions, even via different infusion lines (see Contraindications for information regarding newborn infants).

Antibiotic associated pseudomembranous colitis.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including ceftriaxone. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against Cl. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
Other causes of colitis should also be considered.

History of gastrointestinal disease.

Ceftriaxone should be prescribed with caution in individuals with a history of gastrointestinal disease, especially colitis.

Immune mediated haemolytic anaemia.

Immune mediated haemolytic anaemia has been observed in patients receiving cephalosporin class antibacterials. Severe cases of haemolytic anaemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anaemia while on ceftriaxone, the diagnosis of a cephalosporin associated anaemia should be considered and ceftriaxone discontinued until the etiology is determined.

Overgrowth of other nonsusceptible organisms.

Prolonged use of Hospira Ceftriaxone Sodium Powder for Injection may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Pancreatitis and biliary precipitation.

Cases of pancreatitis (possibly of biliary obstruction aetiology) have been rarely reported in patients treated with Hospira Ceftriaxone Sodium Powder for Injection. Most patients presented with risk factors for biliary stasis and biliary sludge, e.g. preceding major therapy, severe illness and total parenteral nutrition. A trigger or cofactor role of Hospira Ceftriaxone Sodium Powder for Injection related biliary precipitation can, therefore, not be ruled out.

Gall bladder concretions/ precipitates.

Ceftriaxone produces gall bladder concretions/ precipitates in dogs and baboons, and rarely in human being (see Adverse Effects).

Renal impairment and toxicity.

Ceftriaxone has shown some evidence of renal toxicity in animals. Clinical studies have shown only transient elevations of serum urea and serum creatinine at the recommended dosages.
Ceftriaxone is excreted via both biliary and renal excretion (see Pharmacology, Pharmacokinetics). The half-life of ceftriaxone may be prolonged in some patients with renal failure, adjustment in dosage may be required. Concentrations of drug in the serum should be monitored periodically. If evidence of accumulation exists, dosage should be decreased accordingly. Dosage adjustments should not be necessary in patients with hepatic dysfunction. In patients with both hepatic dysfunction and significant renal disease, Hospira Ceftriaxone Sodium Powder for Injection dosage requires close monitoring of serum concentrations.

Alterations in clotting time.

Alterations in prothrombin times have occurred rarely in patients treated with ceftriaxone. Patients with impaired vitamin K synthesis or low vitamin K stores (e.g. chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during ceftriaxone treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.

Use of lignocaine hydrochloride in patients with impaired hepatic function.

Repeated use of lignocaine hydrochloride should be avoided in patients with severe liver disease or decreased hepatic blood flow due to the possibility of lignocaine toxicity (resulting from decreased metabolism and accumulation).

Carcinogenesis, genotoxicity, effects of fertility

Carcinogenesis.

Carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum duration of animal toxicity studies was six months.

Genotoxicity.

Genetic toxicology tests included the Ames test, a micronucleus test and a test for chromosomal aberrations in human lymphocytes cultured in vitro with ceftriaxone. Ceftriaxone showed no potential for mutagenic activity in these studies.

Effects of fertility.

Ceftriaxone produced no impairment of fertility when given intravenously to rats at daily doses up to 586 mg/kg/day.

Use in pregnancy.

(Category B1)

Teratogenic effects.

Reproductive studies (segment II) have been performed in mice and rats at doses up to 586 mg/kg/day and no evidence of embryotoxicity, foetotoxicity or teratogenicity was seen. In primates, at doses up to 84 mg/kg/day no embryotoxicity or teratogenicity was demonstrated.
There are, however, no adequate and well controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic effects.

In rats, in the segment I (fertility and general reproduction) and segment III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behaviour and reproductive ability of the offspring, at doses of 586 mg/kg/day or less.

Use in lactation.

Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a breastfeeding woman.

Paediatric use

Safety and effectiveness of ceftriaxone in infants and children have been established for the dosages described in Dosage and Administration. In vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone should not be given to neonates who may be at risk of developing bilirubin encephalopathy (especially premature infants). (See Contraindications.)

Interactions

Ceftriaxone does not contain an N-methylthiotetrazole moiety which has been associated with significant impairment of vitamin K dependent coagulation by some other cephalosporins.
Probenecid does not cause clinically significant changes in the elimination of ceftriaxone. Concomitant use does not confer a therapeutic benefit.
In an in vitro study, antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone.

Effects on laboratory tests

In patients treated with ceftriaxone the Coombs' test may become false positive. Ceftriaxone, like other antibiotics, may result in false positive tests for galactosaemia.
Likewise, nonenzymatic methods for the glucose determination in urine may give false positive results. For this reason, urine glucose determination during therapy with ceftriaxone should be done enzymatically.

Adverse Effects

Ceftriaxone is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone therapy or of uncertain aetiology, were observed. Their incidence was somewhat higher in children and with higher doses.

Local effects.

Infrequent pain, induration or tenderness at the site of injection. Less frequently reported was phlebitis after intravenous administration. Local reactions were increased if water was used as the diluent instead of lignocaine.

Hypersensitivity.

Infrequent rash. Less frequently reported were pruritus, fever or chills, severe dermatitis including exfoliative erythroderma, anaphylaxis, erythema multiforme, urticaria, exanthema and allergic dermatitis.

Haematological.

Occasional eosinophilia, thrombocytosis and leucopenia.
Less frequently reported were haemolytic anaemia, neutropenia, lymphopenia, granulocytopenia, thrombocytopenia and prolongation of the prothrombin time and bleeding. In very rare cases agranulocytosis has been reported.

Gastrointestinal.

Occasional diarrhoea. Less frequently reported were nausea or vomiting, stomatitis, glossitis and dysgeusia. Incidence of diarrhoea was higher in women and children. Pseudomembranous colitis has been reported rarely.

Hepatic.

Occasional elevations of SGOT or SGPT. Less frequently reported were elevations of alkaline phosphatase, bilirubin. Shadows, which have been mistaken for gallstones, have been detected on sonograms of the gall bladder, usually following doses higher than the standard recommended dose (see Precautions). These shadows are, however, precipitates of calcium ceftriaxone which disappear on completion or discontinuation of ceftriaxone therapy. Rarely have these findings been associated with symptoms. In symptomatic cases, conservative nonsurgical management is recommended. Discontinuation of ceftriaxone treatment in symptomatic cases should be at the discretion of the clinician.

Renal.

Infrequent elevations of the serum urea. Less frequently reported were elevations of creatinine and the presence of casts in the urine. Crystalluria and oliguria have been reported very rarely.
Renal adverse effects were somewhat more frequent in the elderly.

Central nervous system.

Headache or dizziness were reported occasionally.

Genitourinary.

Moniliasis or vaginitis were reported occasionally.

Miscellaneous.

Diaphoresis, flushing and fever were reported occasionally.
Other rarely observed adverse reactions include leucocytosis, lymphocytosis, monocytosis, basophilia, jaundice, glycosuria, haematuria, bronchospasm, oedema, shivering, serum sickness, abdominal pain, flatulence, dyspepsia, palpitations and epistaxis.
Isolated cases of severe cutaneous reactions (Stevens-Johnson syndrome or Lyell's syndrome/ toxic epidermal necrolysis) have been reported.
Cases of fatal reactions with calcium ceftriaxone precipitates in lung and kidney in neonates and premature infants have been described. In some cases the infusion lines and times of administration of ceftriaxone and calcium containing solutions differed. Ceftriaxone must not be mixed or administered simultaneously with calcium containing solutions or products, even via different infusion lines.

Dosage and Administration

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

Dosage.

Hospira Ceftriaxone Sodium Powder for Injection may be administered intravenously or intramuscularly. The recommended adult daily dose is 1 to 2 g given once a day or in equally divided doses twice a day depending on the type and severity of the infection. The lower dose would be appropriate for less severe infections.
For the treatment of uncomplicated gonococcal infections a single intramuscular dose of 250 mg is recommended.
For preoperative use (surgical prophylaxis) in cardiovascular surgery, biliary tract surgery in high risk patients and in vaginal and abdominal hysterectomy a single dose of 1 g administered 30 minutes to two hours before surgery is recommended.
For the treatment of serious miscellaneous infections in children, the recommended total daily dose is 50 to 75 mg/kg (not to exceed 2 g), given once per day or in divided doses every 12 hours. In meningitis the dose should be divided and administered every 12 hours.
Generally, ceftriaxone therapy should be continued for at least two days after the signs and symptoms of infection have disappeared. The usual duration is 4 to 14 days. In special conditions e.g. endocarditis, osteomyelitis, infected joints, treatment may be continued for a longer duration. Prolonged therapy results in a higher incidence of adverse effects particularly diarrhoea, rash, eosinophilia, elevated liver enzymes and to a lesser extent neutropenia.
When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least ten days.
No dosage adjustment is necessary for patients with impairment of hepatic function; however, blood levels should be monitored in patients with severe renal impairment (e.g. dialysis patients) and in patients with both renal and hepatic dysfunction. Serum levels should not exceed 280 microgram/mL.

Administration.

The use of freshly prepared solutions is recommended. These retain their efficacy for at least six hours at room temperature (or 24 hours at 2 to 8°C). The solutions are yellowish in colour. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2 to 8°C for not more than 24 hours.
Hospira Ceftriaxone Sodium Powder for Injection should not be added to solutions containing calcium such as Hartmann's solution and Ringer's solution (see Precautions, Calcium containing solutions). Hospira Ceftriaxone Sodium Powder for Injection should also not be mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed below, owing to possible incompatibility. Specifically, the literature reports that ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

Intramuscular injection.

Hospira Ceftriaxone Sodium Powder for Injection 1 g in 3.5 mL of lignocaine 1% solution, and administered by deep intragluteal injection. It is recommended that no more than 1 g be injected on either side. The lignocaine solution must never be administered intravenously. Hospira Ceftriaxone Sodium Powder for Injection should be injected well into the body of a relatively large muscle mass. Intramuscular injection of Hospira Ceftriaxone Sodium Powder for Injection without lignocaine solution is painful.

Intravenous injection.

Hospira Ceftriaxone Sodium Powder for Injection 1 g in 10 mL of water for injections, and then administered by direct intravenous injection lasting two to four minutes.

Intravenous infusion.

Hospira Ceftriaxone Sodium Powder for Injection 2 g is dissolved in approximately 40 mL of one of the following infusion solutions: sodium chloride 0.9%, sodium chloride 0.45% and glucose 2.5%, glucose 5%, glucose 10%, dextran 70.6% in glucose 5%.
The infusion should be given over a period of at least 30 minutes.

Stability.

At the concentrations indicated under Administration (above), solutions of Hospira Ceftriaxone Sodium Powder for Injection reconstituted in the injection or infusion media listed above are stable for six hours at room temperature (25°C) and for 24 hours if stored under refrigeration (2 to 8°C). As the reconstituted injection/ infusion solutions do not contain a preservative, they should be used as soon as practical after reconstitution.

Overdosage

Excessive serum concentrations of ceftriaxone cannot be reduced by haemodialysis or peritoneal dialysis. Treatment of overdosage should be symptomatic.
In case of overdose, immediately contact the Poisons Information Centre for advice (call 131 126).

Presentation

Powder for injection (white or yellowish crystalline), 1 g/20 mL (≡ ceftriaxone sodium 1.19 g, AUST R 167648), 2 g/20 mL (≡ ceftriaxone sodium 2.39 g, AUST R 167651): 1's (molded glass type I clear vial with bromo butyl rubber stopper).

Storage

Store below 25°C. Protect from light.

Poison Schedule

S4.