Consumer medicine information

Ceftriaxone-AFT

Ceftriaxone

BRAND INFORMATION

Brand name

Ceftriaxone-AFT

Active ingredient

Ceftriaxone

Schedule

SUMMARY CMI

Ceftriaxone-AFT

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given Ceftriaxone-AFT?

Ceftriaxone-AFT contains the active ingredient ceftriaxone sodium. Ceftriaxone-AFT is an antibiotic used to treat infections in different parts of the body caused by bacteria. For more information, see Section 1. Why am I given Ceftriaxone-AFT? in the full CMI.

2. What should I know before I am given Ceftriaxone-AFT?

You should not be given Ceftriaxone-AFT if you have ever had an allergic reaction to ceftriaxone sodium or penicillin.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given Ceftriaxone-AFT? in the full CMI.

3. What if I am taking other medicines?

Some medicines and Ceftriaxone-AFT may interfere with each other.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How Ceftriaxone-AFT is Given?

Ceftriaxone-AFT will be given by either a doctor or nurse. It can be given either as a slow injection into a vein or as an injection into a large muscle. More instructions can be found in Section 4. How Ceftriaxone-AFT is given? in the full CMI.

5. What should I know while I am given Ceftriaxone-AFT?

Things you should 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 diarrhea tell your doctor, nurse or pharmacist immediately even if occurs several weeks after Ceftriaxone-AFT has stopped. Tell your doctor if you get a sore or white furry mouth or tongue or if you get vaginal itching or discharge. You may have a fungal infection called thrush.
Things you should not do	If you have diarrhea, do not take any medicine to stop the diarrhea without first checking with your doctor. Diarrhea may mean you have a serious condition affecting your bowel.
Driving or using machines	Be careful before you drive or use any machines or tools until you know how Ceftriaxone-AFT affects you. Ceftriaxone-AFT generally does not cause any problems with your ability to drive or operate machinery. However, Ceftriaxone-AFT may cause dizziness in some people.

For more information, see Section 5. What should I know while using Ceftriaxone-AFT? in the full CMI.

6. Are there any side effects?

Like all medicines, Ceftriaxone-AFT can cause 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. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Ceftriaxone-AFT

Active ingredient(s): Ceftriaxone sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using Ceftriaxone-AFT. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Ceftriaxone-AFT.

Where to find information in this leaflet:

1. Why am I given Ceftriaxone-AFT?
2. What should I know before I am given Ceftriaxone-AFT?
3. What if I am taking other medicines?
4. How Ceftriaxone-AFT is Given?
5. What should I know while I am given Ceftriaxone-AFT?
6. Are there any side effects?
7. Product details

1. Why am I given Ceftriaxone-AFT?

Ceftriaxone-AFT contains the active ingredient ceftriaxone sodium. Ceftriaxone-AFT is an antibiotic used to treat infections in different parts of the body caused by bacteria. Ceftriaxone-AFT is also used to prevent infections before, during and after surgery. It will not work against infections caused by viruses such as colds and flus.

Ceftriaxone-AFT belongs to a group of antibiotics called cephalosporins. They work by killing the bacteria that are causing your infection or by stopping the bacteria from growing.

If you are not sure why Ceftriaxone-AFT has been prescribed for you, talk to your doctor. They may have prescribed it for another reason.

2. What should I know before I am given Ceftriaxone-AFT?

Warnings

You should not be given Ceftriaxone-AFT if:

you are allergic to ceftriaxone sodium, or any of the ingredients listed at the end of this leaflet.
have had an allergic reaction to any penicillin.

Symptoms of allergic reactions include severe skin rash, itching, hives, dry skin, swelling of the face, lips, mouth, throat which may cause difficulty in swallowing or breathing, swelling of the hands, feet or ankles.

You may have an increased risk of being allergic to Ceftriaxone-AFT if you are allergic to penicillin.

Always check the ingredients to make sure you can use this medicine.

Ceftriaxone-AFT should not be given to newborn infants if they need or are expected to need treatment with calcium containing intravenous solutions including intravenous nutrition.

Ceftriaxone-AFT should not be given to preterm newborns or newborns with certain liver disorders.

If you are uncertain if Ceftriaxone-AFT should be given to you, talk to your doctor.

Check with your doctor if you:

have had any type of allergic reaction to any cephalosporin or penicillin medicines.
have had an allergy or over-reaction to lignocaine or other anesthetic medicines (these substances may be used to dissolve Ceftriaxone-AFT before administration).
have any allergies to any other medicines or other substances e.g., foods, preservatives, dyes.
have any other medical conditions including kidney disease, bowel problems (e.g., inflammation of the large bowel), diarrhea associated with previous use of antibiotics or a previous intestinal infection with a bacteria called Clostridium difficile.

If you have not told your doctor about any of the above, you must tell them before you are given Ceftriaxone-AFT.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

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

Some medicines and Ceftriaxone-AFT may interfere with each other. These include:

chloramphenicol, vancomycin, aminoglycosides (medicines to treat infections),
fluconazole (a medicine used to treat fungal infections)
amsacrine (a medicine used to treat cancer).

These medicines may be affected by Ceftriaxone-AFT or may affect how well it works. You may need to take different amounts of your medicines. Your doctor will advise you.

Some antibiotics decrease the effectiveness of some contraceptive pills. Talk to your doctor about the need for additional contraception while using Ceftriaxone-AFT.

Your doctor or pharmacist will have more information on medicines to be careful with or avoid while being given Ceftriaxone-AFT.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affects Ceftriaxone-AFT.

4. How Ceftriaxone-AFT is Given?

Ceftriaxone-AFT will be given by either a doctor or nurse.

Ceftriaxone-AFT can be given as either:

As a slow injection into a vein
As an injection into a large muscle

Ceftriaxone-AFT should not be mixed or administered with calcium-containing solutions even via different infusion lines.

Your doctor will decide what dose and for how long you will receive Ceftriaxone-AFT. It will depend on your infection and other factors such as your weight. For most infections Ceftriaxone-AFT is usually given once a day. The length of treatments is usually 4-14 days.

Sometimes only a single dose of Ceftriaxone-AFT is required for the treatment and prevention of certain infections.

If you are given too much Ceftriaxone-AFT

If too much Ceftriaxone-AFT is given to you, you may experience symptoms such as tingling or skin reactions, chills, diarrhea, stomach upsets, headache or dizziness.

If you think that you have been given too much Ceftriaxone-AFT, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while I am given Ceftriaxone-AFT?

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 diarrhea, tell your doctor, nurse or pharmacist immediately even if occurs several weeks after Ceftriaxone-AFT has been stopped. Diarrhea may mean you have a serious condition affecting your bowel. You may need urgent medical attention. Do not take any medicine to stop the diarrhea without first checking with your doctor.

Tell your doctor if you get a sore or white furry mouth or tongue or if you get vaginal itching or discharge. You may have a fungal infection called thrush. Sometimes the use of Ceftriaxone-AFT may allow fungi to grow and the above symptoms to occur. Ceftriaxone-AFT will not work against fungi.

Tell your doctor if you become pregnant while using Ceftriaxone-AFT.

If you test your urine for sugar, make sure your doctor knows which type of test you use as Ceftriaxone-AFT may affect the test results.

If you are having any blood tests tell whoever is doing the tests that you are taking Ceftriaxone-AFT as Ceftriaxone-AFT may affect the results of some blood tests.

Complete blood counts should be done at regular intervals as Ceftriaxone-AFT may affect the results of some blood tests.

Tell all doctors, dentists and pharmacists who are treating you that you are using Ceftriaxone-AFT.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Ceftriaxone-AFT affects you.

Ceftriaxone-AFT generally does not cause any problems with your ability to drive or operate machinery. However, Ceftriaxone-AFT may cause dizziness in some people.

Looking after your medicine

Ceftriaxone-AFT will be stored in the pharmacy or on the hospital ward. It should be kept in a cool, dry place, protected from light and moisture at a temperature below 25°C.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions.

Less serious/common side effects

Less serious side effects	What to do
Oral thrush – white, furry, sore tongue and mouth Vaginal thrush – sore and itchy vagina and/or discharge A hard lump, swelling, pain or tenderness at the injection site Diarrhea, nausea or vomiting Altered sense of taste Headache, dizziness Fast or irregular heartbeat	Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Serious/rare side effects

Serious side effects

What to do

Allergic reaction

Severe skin rash, itching or hives.
Red, peeling, or dry skin.
Swelling of the face, lips or tongue which may cause difficulty swallowing or breathing, swelling of the hands, feet, or ankles.

Boady as a whole

Tiredness, headaches, being short of breath when exercising, dizziness, looking pale, yellowing of the skin and/or eyes.
*Severe diarrhea that may contain blood or mucous, stomach pain and fever.
Problems with gallbladder and/or liver, which may cause pain, nausea, vomiting, yellowing of the skin, itching, unusually dark urine and clay-coloured stools.

Nervous system disorders

Reduced ability to think clearly or concentrate, memory loss, drowsiness, seizures, muscle twitches and personality change. These symptoms may be related to a condition called encephalopathy.

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

*Tell your doctor immediately even if these side effects occur even if it is several weeks after stopping treatment with Ceftriaxone-AFT. You may have a serious condition affecting your bowel. Do not take any medicine to stop the diarrhea without first checking with your doctor.

Treatment with ceftriaxone, particularly in elderly patients with serious kidney or nervous system problems may rarely cause decreased consciousness, abnormal movements, agitation, and convulsions.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

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

What Ceftriaxone-AFT contains

Active ingredient (main ingredient)	Ceftriaxone sodium
Other ingredients (inactive ingredients)	This product does not contain any other ingredients

Do not take this medicine if you are allergic to ceftriaxone sodium.

What Ceftriaxone-AFT looks like

Ceftriaxone-AFT is a white to yellowish powder. It is supplied in a glass vial containing 500 mg (AUST R 185099), 1 g (AUST R 185100) or 2 g (AUST R 185101) ceftriaxone sodium. The powder is dissolved before injection into a vein or muscle.

Who distributes Ceftriaxone-AFT

AFT Pharmaceuticals Pty Ltd
113 Wicks Road North Ryde
NSW 2113

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Ceftriaxone-AFT

Active ingredient

Ceftriaxone

Schedule

1 Name of Medicine

Ceftriaxone sodium, powder for injection.

2 Qualitative and Quantitative Composition

Ceftriaxone-AFT 500 mg: each vial contains ceftriaxone sodium equivalent to ceftriaxone 500 mg.
Ceftriaxone-AFT 1 g: each vial contains ceftriaxone sodium equivalent to ceftriaxone 1 g.
Ceftriaxone-AFT 2 g: each vial contains ceftriaxone sodium equivalent to ceftriaxone 2 g.
Ceftriaxone sodium is a white to yellowish orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 5% aqueous solution is approximately 6-8. The colour of ceftriaxone sodium solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.
Ceftriaxone-AFT contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Powder for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Ceftriaxone-AFT is indicated in the treatment of the following infections when caused by susceptible aerobic organisms:

Lower respiratory tract infections.

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

Skin and skin structure infections.

Caused by methicillin sensitive S. aureus and S. epidermidis, Streptococcus group B, Streptococcus group G, Streptococcus pyogenes, Streptococcus viridans, Streptococcus spp (excluding enterococci), Peptostreptococcus spp, E. coli, E. cloacae, Klebsiella spp (including K. pneumoniae, K. oxytoca), Proteus mirabilis, Morganella morganii, Serratia marcescens.

Urinary tract infections.

Complicated and uncomplicated caused by E. coli, Proteus mirabilis, Proteus vulgaris, M. morganii and Klebsiella spp (including K. pneumoniae).

Uncomplicated gonorrhoea.

Cervical, urethral and rectal caused by Neisseria gonorrhoea (both penicillinase and nonpenicillinase producing strains).

Bacterial septicaemia.

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

Bone infections.

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

Joint infections.

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

Meningitis.

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

Surgical prophylaxis.

The preoperative administration of a single 1 g dose of ceftriaxone 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 before obtaining the results of susceptibility testing.

4.2 Dose and Method of Administration

Dosage.

Ceftriaxone-AFT may be given either I.M. or I.V. The recommended adult daily dose is 1-2 g given once daily or in equally divided doses twice daily depending upon the type and severity of the infection. The lower dose is appropriate for less severe infections.

Uncomplicated gonococcal infections.

A single I.M. dose of 250 mg.

Surgical prophylaxis.

In cardiovascular surgery, biliary tract surgery in high risk patients and vaginal and abdominal hysterectomy a single dose of 1 g given 0.5-2 hours prior to surgery.

Children.

For treating serious miscellaneous infections in children the recommended total daily dose is 50-75 mg/kg (not more than 2 g), given once daily or in divided doses every 12 hours. In meningitis the dose should be divided and given 12 hourly.
Generally ceftriaxone therapy should be continued for at least 2 days after the signs and symptoms of the infection have disappeared. The usual duration of treatment is 4-14 days. In special conditions, e.g. endocarditis, osteomyelitis, infected joints etc, treatment may be continued for a longer duration. Prolonged therapy results in a higher incidence of adverse effects especially 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 10 days.

Use in renal and hepatic impairment.

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.

Ceftriaxone-AFT contains no microbial preservative. It is for single use in one patient only. Any unused product should be discarded. To reduce any microbial hazard, use as soon as practicable after reconstitution.
The use of freshly prepared solutions is recommended. Solutions retain their efficacy for 6 hours at room temperature or 24 hours when stored in the refrigerator (2-8°C). The solutions are yellowish in colour. This characteristic of the active ingredient is of no significance to the efficacy or tolerance of the medicine. A slight opalescence may be seen in the reconstituted solution.
Do not use diluents containing calcium such as Ringer's solution or Hartmann's solution to reconstitute Ceftriaxone-AFT vials or to further dilute a reconstituted vial for I.V. administration because a precipitate can form. Precipitation of ceftriaxone calcium can also occur when Ceftriaxone-AFT is mixed with calcium containing solutions in the same I.V. administration line. Ceftriaxone-AFT must not be administered simultaneously with calcium containing solutions such as parenteral nutrition via a Y-site. However in patients other than neonates Ceftriaxone-AFT and calcium containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see Section 4.3 Contraindications).
There have been no reports of an interaction between ceftriaxone and oral calcium containing products or interaction between intramuscular ceftriaxone and calcium containing products given either I.V. or orally.
Ceftriaxone-AFT should not be mixed with or piggybacked into solutions containing other antimicrobial medicines 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 administration. Dissolve 500 mg of Ceftriaxone-AFT in 2 mL or 1 g of Ceftriaxone-AFT in 3.5 mL lignocaine solution (1%). It should be 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 given intravenously. Ceftriaxone-AFT should be injected well into the body of a relatively large muscle mass. I.M. injection of Ceftriaxone-AFT is painful without lignocaine.
Intravenous administration. Ceftriaxone-AFT may be administered by intravenous injection or by continuous or intermittent infusion.

Intravenous injection.

Dissolve 500 mg in 5 mL or 1 g in 10 mL sterile water for injection and administer by direct I.V. injection given over a period of 2-4 minutes.

Intravenous infusion.

Dissolve 2 g Ceftriaxone-AFT in approximately 40 mL of one of the following infusion solutions: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5%; glucose 10%; levulose 5%; dextran 70 6% in glucose 5%.
The infusion should be given over a period of at least 30 minutes.

4.3 Contraindications

Ceftriaxone is contraindicated in patients with known allergy to the cephalosporin group of antibiotics or a major allergy to penicillin (anaphylaxis, angioneurotic oedema, urticaria).
Lignocaine should not be used as a diluent for I.M. administration in patients who are hypersensitive to lignocaine.
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.
Because of the risk of precipitation of ceftriaxone calcium, ceftriaxone is contraindicated in neonates requiring (or expected to require) treatment with calcium containing I.V. solutions including continuous calcium containing infusions such as parenteral nutrition (see Section 4.4 Special Warnings and Precautions for Use).
Interactions with other medicines and a small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium containing fluids. In some of these cases, the same I.V. line was used for both ceftriaxone and the calcium containing solution and in some a precipitate was noted in the I.V. infusion line. At least one fatality has been reported in a neonate who received ceftriaxone and calcium containing fluids at different time points via different I.V. lines - no crystalline material was observed at autopsy in this neonate. There have been no similar reports for patients other than neonates.

4.4 Special Warnings and Precautions for Use

Hypersensitivity.

Before therapy with Ceftriaxone-AFT therapy 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. Anaphylactic reactions with fatal outcome have been reported, even if a patient is not known to be allergic or previously exposed to ceftriaxone or other cephalosporins. 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 newborns, treated with ceftriaxone and calcium containing products. However ceftriaxone should not be mixed with or administered to any patient simultaneously with calcium containing solutions even via different infusion lines (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Clostridium difficile associated diarrhoea.

Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including ceftriaxone and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Toxin hyperproducing strains of C. difficile cause increased morbidity and mortality as these infections can be refractory to antibiotic therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary as CDAD has been reported to occur over 2 months after administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile and surgical intervention should be instituted as clinically indicated.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong 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 patients 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 including ceftriaxone. 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 cephalosporin associated anaemia should be considered and ceftriaxone discontinued until the etiology is determined.

Overgrowth of nonsusceptible organisms.

Prolonged use of ceftriaxone may result in the overgrowth of nonsusceptible organisms. Careful clinical 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 reported in patients treated with ceftriaxone. 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 ceftriaxone related biliary precipitation can therefore not be ruled out.

Gallbladder concretions/precipitates.

Shadows which have been mistaken for gallstones have been detected on sonograms of the gall bladder usually following doses higher than the recommended standard dose. These shadows are however precipitates of calcium ceftriaxone which disappear on completion or discontinuation of ceftriaxone therapy. Rarely have these finding been associated with symptoms. In symptomatic cases, conservative nonsurgical management is recommended. Discontinuation of ceftriaxone therapy in symptomatic cases should be at the discretion of the physician.

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 required if prothrombin time is prolonged before or during therapy.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, Ceftriaxone-AFT should be discontinued immediately and an alternative treatment should be considered.

Encephalopathy.

Encephalopathy has been reported with the use of ceftriaxone (see Section 4.8), particularly in elderly patients with severe renal impairment or central nervous system disorders. If ceftriaxone-associated encephalopathy is suspected (e.g. decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of ceftriaxone should be considered.

Neurotoxicity.

There have been reports of neurotoxicity associated with cephalosporin treatment. Symptoms of neurotoxicity include seizures and/or myoclonus. Risk factors for developing neurotoxicity with cephalosporin treatment include being elderly, renal impairment, central nervous system disorders and intravenous administration. Withdrawal of the medicine should be considered if there are signs of neurotoxicity.

Special patient populations.

Use in hepatic impairment.

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).

Use in renal impairment.

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 by both biliary and renal excretion (see Section 5.2 Pharmacokinetic Properties). 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 periodically monitored. If evidence of accumulation exists the dosage should be reduced accordingly. Dosage adjustments should not be necessary in patients with hepatic dysfunction. In patients with both hepatic dysfunction and significant renal disease ceftriaxone dosage requires close monitoring of serum concentrations.

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of ceftriaxone in infants and children have been established for the doses described in Dose and Method of 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 Section 4.3 Contraindications). Because of the risk of precipitation of ceftriaxone calcium (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), ceftriaxone is contraindicated in neonates requiring or expected to require treatment with calcium containing I.V. solutions including continuous calcium containing infusions such as parenteral nutrition (see Section 4.3 Contraindications).

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 galactosemia.
Likewise nonenzymatic methods for glucose determination in urine may give false positive results. For this reason, urine glucose determination during therapy with ceftriaxone should be done enzymatically.
Haematological changes such as eosinophilia, leucopenia, granulocytopenia, haemolytic anemia, thrombocytopenia, isolated cases of agranulocytosis (< 500/mm³) have been reported mostly after 10 days of treatment and following doses of 20 g or more. During prolonged treatment the complete blood counts should be done at regular intervals.

4.5 Interactions with Other Medicines and Other Forms of 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 any clinically significant changes in the elimination of ceftriaxone. Concomitant use does not confer any therapeutic benefit.
In an in vitro study antagonists effects have been observed with the combination of chloramphenicol and ceftriaxone.
Do not use calcium containing diluents, e.g. Ringer's or Hartmann's solutions, to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for I.V. administration because a precipitate can form. Precipitation of ceftriaxone calcium can also occur when ceftriaxone is mixed with calcium containing solutions in the same I.V. administration line. Ceftriaxone must not be administered simultaneously with calcium containing I.V. solutions including continuous calcium containing infusions such as parenteral nutrition via a Y-site. However in patients other than neonates, ceftriaxone and calcium containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates are at an increased risk of precipitation of ceftriaxone calcium (see Section 4.3 Contraindications; Section 4.2 Dose and Method of Administration).
No impairment of renal function has so far been observed after concurrent administration of ceftriaxone and diuretics, e.g. frusemide. Healthy adults treated with 3 mg ceftriaxone and 3 mg/kg/day of tobramycin for 3 days did not show any enzymatic evidence of impaired renal function.
Based upon literature reports ceftriaxone is physically incompatible in admixtures with amsacrine, vancomycin, fluconazole and aminoglycosides.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Ceftriaxone produced no impairment of fertility when given intravenously to rats at daily doses up to 586 mg/kg/day.
(Category B1)

Teratogenic effects.

Reproduction studies (segment II) have been performed in rats and mice 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, foetotoxicity 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 medicine 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.
Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Ceftriaxone is generally well tolerated. In clinical trials the following adverse effects, 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 reactions.

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

Hypersensitivity.

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

Haematological.

Occasionally eosinophilia, thrombocytosis, leucopenia. Less frequently haemolytic anaemia, neutropenia, lymphopenia, granulocytopenia, thrombocytopenia and prolongation of the prothrombin time and bleeding. Very rare cases of agranulocytosis have been reported.

Gastrointestinal.

Occasional diarrhoea. Less frequently nausea, vomiting, stomatitis, glossitis and dysgeusia. The incidence of diarrhoea tends to be higher in women and children. Pseudomembranous colitis has been reported rarely.

Hepatic.

Occasional elevations of SGOT or SGPT. Less frequently elevations of alkaline phosphatase and bilirubin. Symptomatic precipitation of ceftriaxone calcium salt in the gallbladder.
Hepatitis and hepatic cholestatic (frequency unknown).

Renal.

Infrequent elevations of serum urea. Less frequently elevations of creatinine and the presence of casts in the urine. Rare cases of crystalluria and oliguria have been reported. Renal adverse effects are reported more frequently in the elderly.

Central nervous system.

Occasionally headache and dizziness.
Encephalopathy (rare).

Genitourinary.

Occasionally moniliasis, and vaginitis.

Miscellaneous.

Occasionally diaphoresis, flushing and fever.
Rarely observed adverse reactions include leukocytosis, lymphocytosis, monocytosis, basophilia, jaundice, glycosuria, haematuria, bronchospasm, oedema, shivering, serum sickness, abdominal pain, flatulence, dyspepsia, palpitations and epistaxis have been reported.
Isolated cases of Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) have been reported.

Postmarketing experience.

Nervous system disorders.

Seizures, myoclonus - frequency not known.
Cases of fatal reactions with calcium ceftriaxone precipitates in lungs and kidneys 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 (see Section 4.3 Contraindications).

Interaction with calcium.

Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood have been carried out to assess the interaction between ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 g of ceftriaxone infused over 30 minutes) were used on combination with calcium concentrations of up to 12 mM (48 mg/100 mL) in adult plasma. Recovery of ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/100 mL) or higher in adult plasma or 4 mM (16 mg/100 mL) or higher in neonatal plasma. This may be reflective of ceftriaxone calcium precipitation (see Section 4.3 Contraindications).

Skin and other subcutaneous tissue disorders.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

In the case of overdosage, drug concentration would not be reduced by haemodialysis or peritoneal dialysis.
There is no specific antidote. Treatment of overdosage should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Microbiology.

The bactericidal activity of ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone has a high degree of stability in the presence of beta-lactamases, types I, II and III, both penicillinases and cephalosporinases, of gram negative and gram positive bacteria. It is susceptible to type IV beta-lactamases at approximately 18% of the rate of cephaloridine. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Section 4.1 Therapeutic Indications).
Gram negative aerobes. Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including ampicillin resistant strains), Klebsiella species (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 multiple 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 beta-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 testing.

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 a 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 standardized single disk susceptibility test using a 30 microgram ceftriaxone disk should be interpreted according to the following three criteria:
1. Susceptible organisms produce 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 20 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.
Organisms should be tested with the ceftriaxone disk, since ceftriaxone has been shown by in vitro tests to be active against certain strains found resistant to cephalosporin class disks.
Standardized 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 microgram/mL. Organisms are considered resistant to ceftriaxone if the MIC is greater than 32 microgram/mL. Organisms having a MIC value of equal to or less than 32 microgram/mL, but greater than 8 microgram/mL, 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. E. coli ATCC 25922, S. aureus ATCC 25923 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 to 0.5 microgram/mL. The range for the S. aureus strain should be 1 to 2 microgram/mL.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Ceftriaxone is poorly absorbed from the gastrointestinal tract.

Distribution.

Average plasma concentrations in microgram/mL following a single 30 minute I.V. infusion of a 0.5, 1 or 2 g dose and I.M. administration of a single 0.5 or 1 g dose are presented in Table 1.

Mean maximum plasma concentrations following I.M. injection occurred 2-3 hours postdosing. Multiple I.M. and I.V. doses ranging between 500 mg-2 g at 12-24 hourly intervals resulted in 15-36% accumulation of ceftriaxone above single dose results. Accumulation was greater with I.M. doses.
Ceftriaxone concentrations in urine are high as shown in Table 2.

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/hr and renal clearance from 0.32 to 0.73 L/hr. 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 uremic patients. The in vitro activity of ceftriaxone is decreased 2 to 8-fold by the presence of human serum.

Excretion.

33-67% of a ceftriaxone dose is excreted in the urine as the unchanged drug. Substantial amounts are secreted in the bile and eventually 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 ceftriaxone concentrations, determined from 1-3 hours after dosing were 581 microgram/mL in the gallbladder bile, 788 microgram/mL in the common duct bile, 898 microgram/mL in the cystic duct bile, 78.2 microgram/mL in the gallbladder wall and 62.1 microgram/mL in the concurrent plasma. There were however, wide individual variations in levels.

Pharmacokinetics in paediatric patients.

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 7.2-19 hours and in infants over six weeks of age from 4.0-6.6 hours.
Ceftriaxone crosses the placenta and appears in the milk in low concentrations.

Pharmacokinetics in the elderly or those with renal or hepatic impairment.

Compared to that in healthy adults, the pharmacokinetics of ceftriaxone are only minimally altered in the elderly or in patients with hepatic dysfunction (Table 4); therefore dosage adjustments are not necessary for these patients with doses of up to 2 g/day. However in some patients with severely impaired renal function the t_1/2 of ceftriaxone may be prolonged (37-52 hours) and dosage adjustment should be considered. Peak serum levels should held below 280 microgram/mL. Ceftriaxone is not removed from the plasma to any significant extent by haemodialysis. Plasma concentrations of ceftriaxone should be monitored to determine if dosage adjustments are necessary.

5.3 Preclinical Safety Data

Genotoxicity.

Genetic toxicity tests including 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.

Carcinogenicity.

Carcinogenicity studies with ceftriaxone in animals to determine the toxicity and carcinogenic potential of ceftriaxone have not been performed. The maximum duration of animal toxicity studies was 6 months.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 Incompatibilities

Ceftriaxone-AFT should not be mixed with or piggybacked into solutions containing other antimicrobial medicines or into diluent solutions other than those listed in Section 4.2. Ceftriaxone should not be added to solutions containing calcium such as Hartmann's solution and Ringer's solution. Based on literature reports ceftriaxone is incompatible with amsacrine, vancomycin and fluconazole and aminoglycosides.

6.3 Shelf Life

The reconstituted solutions of Ceftriaxone-AFT are physically and chemically stable for 6 hours at room temperature and for 24 hours if stored under refrigeration (2-8°C). Do not freeze reconstituted Ceftriaxone-AFT.
To reduce microbiological hazards, use as soon as practicable after reconstitution. If storage is necessary store under refrigeration (2-8°C) for not more than 24 hours.
Ceftriaxone-AFT does not contain any antimicrobial agents and is intended for single use in one patient only. Discard any residue. Prior to administration, parenteral medicine products should be inspected visually for particulate matter and discolouration whenever solution and container permit.
In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

For intramuscular and intravenous injection.

Ceftriaxone-AFT 500 mg.

Each glass vial contains ceftriaxone sodium equivalent to ceftriaxone 500 mg. Packs of 1, 5 and 10 vials: AUST R 185099.

Ceftriaxone-AFT 1 g.

Each glass vial contains ceftriaxone sodium equivalent to ceftriaxone 1 g. Packs of 1, 5 and 10 vials: AUST R 185100.

For intravenous infusion.

Ceftriaxone-AFT 2 g.

Each glass vial contains ceftriaxone sodium equivalent to ceftriaxone 2 g. Packs of 1, 5 and 10 vials: AUST R 185101.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Ceftriaxone sodium has the chemical name sodium (Z)-(6R,7R)-7-[2-(2-amino- 1,3-thiazol-4-yl)-2-(methoxy-imino) acetamido]-8-oxo-3-[(2,5-dihydro-2-methyl-6-oxido-5-oxo-1,2,4-triazin-3-yl) thiomethyl]-5-thia-1-azabicyclo{4.2.0}oct-2-ene-2- carboxylate,hydrate (2:7). The structural formula is:

It has the chemical formula C₁₈H₁₆N₈Na₂O₇S₃, 3.5 H₂O with a molecular weight of 661.6.

CAS number.

The CAS number is 104376-79-6.

7 Medicine Schedule (Poisons Standard)

S4-Prescription Only Medicine.

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