Drugs List

Therapeutic Indications

Uses

Acute exacerbation of chronic obstructive airways disease
Acute otitis media
Bacterial endocarditis
Bacterial meningitis
Bone and joint infection
Community acquired pneumonia
Complicated skin and soft tissue infections
Complicated urinary tract infections
Disseminated Lyme borreliosis
Gonorrhoea
Infections in neutropenic patients
Infections intra-abdominal
Nosocomial pneumonia
Prophylaxis against infection during surgical procedures
Syphilis

Unlicensed Uses

Congenital gonococcal conjunctivitis
Meningococcal meningitis - prophylaxis of
Pelvic inflammatory disease
Prophylaxis of Haemophilus influenzae

Administration

Following reconstitution, ceftriaxone may be administered by deep intramuscular injection, slow intravenous injection or as a slow intravenous infusion.

Intramuscular injection
Dosages greater than 1 g should be divided and injected at more than one site. Solutions prepared in lidocaine injection should not be administered intravenously. For doses greater than 2 g intravenous route should be used.

Intravenous injection
The injection should be administered by slow injection over 5 minutes, directly into the vein or via the tubing of an intravenous infusion. In children aged up to 12 years of age, doses of 50 mg/kg or more should be given by intravenous infusion.

Intravenous infusion
The infusion should be administered over at least 30 minutes (over 60 minutes in neonates to reduce potential risk of bilirubin encephalopathy). In children aged up to 12 years of age, doses of 50 mg/kg or more should be given by intravenous infusion.

Contraindications

Neonates requiring IV treatment with any calcium containing solution
Neonates with hypoalbuminaemia
Premature infants
Neonatal hyperbilirubinaemia
Neonates with acidosis

Precautions and Warnings

Allergic disposition
Immobilisation
Breastfeeding
Hepato-renal syndrome
History of colitis
History of gastrointestinal disorder
History of nephrolithiasis
Hypercalciuria
Hypoprothrombinaemia
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment

Jarisch-Herxheimer reaction possible in treatment of Spirochetes infection
Before initiating therapy enquire about previous hypersensitivity reactions
Consult national/regional policy on the use of anti-infectives
Restore electrolyte & fluid balance in case of dehydration
TPN increases the risk of ceftriaxone precipitation in the gall bladder
Do not give calcium containing solutions in the same line
Monitor closely patient with pre-existing renal impairment
Monitor fluid and electrolyte status
Perform blood counts on prolonged use of this treatment
Consider discontinuation if biliary precipitates are symptomatic
Consider discontinuation if encephalopathy is suspected
Consider discontinuation of treatment if haemolytic anaemia occurs
Consider pseudomembranous colitis if patient presents with diarrhoea
Drug precipitates in gallbladder more likely with treatment > 14 days
Prolonged use may result in superinfection with non-susceptible organisms
May cause false positive Coomb's test and glycosuria test
May cause false positive test for galactosaemia
Discontinue if severe and persistent diarrhoea develops
Discontinue if severe hypersensitivity reactions occur
Consider dose adjustment in hepato-renal syndrome
Female:Non-hormonal contraception advised until 1 month after treatment

Ceftriaxone is contraindicated in patients who have had a previous hypersensitivity reaction to any cephalosporin. It is also contraindicated in patients who have had a previous immediate and/or any severe hypersensitivity reaction to any penicillin or to any other beta-lactam drug. Ceftriaxone should be given with caution to patients who have had any other type of hypersensitivity reaction to a penicillin or any other beta-lactam drug. Anaphylactic shock cannot be ruled out even if patient history is taken.

Because of precipitation of a ceftriaxone-calcium salt, ceftriaxone and calcium containing solutions (e.g. Ringer's, Hartmann's and some total parenteral nutrition solutions) must not be administered simultaneously at the same infusion site. Infusion of calcium and ceftriaxone may be infused sequentially in patients aged 28 days or older provided that the infusion line is rinsed or flushed thoroughly between solutions or the infusions are given via different infusion lines at different sites. In patients requiring continuous parenteral nutrition with calcium-containing solutions, an alternative antibacterial treatment which does not carry a similar risk of precipitation may be appropriate. If there is no alternative to giving ceftriaxone with a calcium-containing solution, then administration can be simultaneous provided they are given via different infusions lines at different sites. Alternatively, infusion of TPN solution could be stopped for the period of ceftriaxone infusion, considering the advice to flush infusion lines between solutions.

Ceftriaxone may precipitate in the gallbladder and consequently be detectable as shadows on a sonogram and can be mistaken for gallstones. Such precipitates disappear after discontinuation of ceftriaxone. They are more likely to develop in patients receiving doses of greater than 1 g per day and in infants and children who are given larger doses on a body weight basis. Doses greater than 80 mg/kg should be avoided in children because of the increased risk of biliary precipitates. Precipitates have rarely been associated with symptoms but in these cases conservative nonsurgical management is suggested and discontinuation of ceftriaxone should be considered.

Pancreatitis, possibly caused by biliary obstruction has been rarely reported with ceftriaxone therapy. Most patients had risk factors for biliary stasis and biliary sludge but it cannot be ruled out that ceftriaxone is a trigger or cofactor.

In symptomatic cases of renal lithiasis sonography should be performed. Patients with a history of renal lithiasis or with hypercalciuria should be treated with caution.

Cephalosporins may cause bleeding due to hypoprothrombinaemia and should be used with caution in patients with renal/hepatic impairment, malnourished patients with low vitamin K levels and also in patients receiving prolonged cephalosporin therapy who are at increased risk of developing hypoprothrombinaemia.

Encephalopathy has been observed with the use of ceftriaxone, particularly in elderly patients with severe renal impairment or CNS disorders. If encephalopathy is suspected (decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of ceftriaxone treatment should be considered.

Pregnancy and Lactation

Pregnancy

Use ceftriaxone with caution in pregnancy.

Schaefer suggests cephalosporins are safe for use during pregnancy if needed. Older cephalosporins are prefered. Manufacturers suggest ceftriaxone should only be used during pregnancy if the benefit outweighs the risk.

Ceftriaxone crosses the placental barrier and can reach therapeutic levels in amniotic fluid and foetal tissues.

Reproduction studies in rats have found no evidence on impaired fertility or foetal harm at doses up to 20 times the human dose. No evidence of embryotoxicity, foetotoxicity or teratogenicity was found in mice, rats and non-human primates at doses approximately 20, 20 and 3 times respectively, the human dose.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use ceftriaxone with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) considers ceftriaxone acceptable for using in breastfeeding. One manufacturer suggests a decision whether to discontinue ceftriaxone therapy or discontinue breastfeeding should be considered taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Concentrations of ceftriaxone in breast milk are too low to have bactericidal or systemic side effects on the infant. However alterations to oral and gastrointestinal flora resulting in diarrhoea and thrush have been reported with ceftriaxone, but these effects have not been adequately evaluated. Possibility of sensitisation should be taken into account.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Abnormal liver function tests
Acute tubular necrosis
Agranulocytosis
Allergic dermatitis
Allergic skin reactions
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anaphylaxis
Antibiotic-associated colitis
Anuria
Bronchospasm
Cholestatic jaundice
Coagulation disorders
Convulsions
Diarrhoea
Dizziness
Drug fever
Drug precipitate in gall bladder
Drug rash with eosinophilia and systemic symptoms (DRESS)
Encephalopathy
Eosinophilia
Erythema multiforme
Exanthema
False positive Coombs test
False positive test for galactosaemia
Fever
Genital mycosis
Glossitis
Glycosuria
Granulocytopenia
Haematuria
Haemolysis
Haemolytic anaemia
Headache
Hepatitis (transient)
Hypersensitivity reactions
Hypoprothrombinaemia
Increases in hepatic enzymes
Jarisch-Herxheimer reaction
Leucopenia
Local pain (injection site)
Lyell's syndrome
Maculopapular rash
Nausea
Neutropenia
Oedema
Oliguria
Pancreatitis
Phlebitis (injection site)
Prothrombin time increased
Pruritus
Pseudomembranous colitis
Pyrexia
Renal impairment
Rigors
Secondary infections
Serum creatinine increased
Shivering
Stevens-Johnson syndrome
Stomatitis
Superinfections
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vertigo
Vomiting

Presentation

Parenteral formulations of ceftriaxone.

Drugs List

Therapeutic Indications

Uses

Acute exacerbation of chronic obstructive airways disease
Acute otitis media
Bacterial endocarditis
Bacterial meningitis
Bone and joint infection
Community acquired pneumonia
Complicated skin and soft tissue infections
Complicated urinary tract infections
Disseminated Lyme borreliosis
Gonorrhoea
Infections in neutropenic patients
Infections intra-abdominal
Nosocomial pneumonia
Prophylaxis against infection during surgical procedures
Syphilis

Unlicensed Uses

Congenital gonococcal conjunctivitis
Meningococcal meningitis - prophylaxis of
Pelvic inflammatory disease
Prophylaxis of Haemophilus influenzae

Dosage

Official guidance on the appropriate use of antibacterial agents should be considered. Treatment may be started before the results of susceptibility tests are known.

Ceftriaxone has a limited spectrum of activity and may not be suitable for use as single agent unless susceptibility of pathogen has been confirmed.

Dosage and mode of administration should be determined by the severity of the infection, susceptibility of the causative organism and the patient's condition. The duration of therapy varies according to the course of the disease.

Administration of ceftriaxone should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.

Adults

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

Following reconstitution, ceftriaxone may be administered by deep intramuscular injection, slow intravenous injection or as a slow intravenous infusion.

Intramuscular injection
Dosages greater than 1 g should be divided and injected at more than one site. Solutions prepared in lidocaine injection should not be administered intravenously. For doses greater than 2 g intravenous route should be used.

Intravenous injection
The injection should be administered by slow injection over 5 minutes, directly into the vein or via the tubing of an intravenous infusion. In children aged up to 12 years of age, doses of 50 mg/kg or more should be given by intravenous infusion.

Intravenous infusion
The infusion should be administered over at least 30 minutes (over 60 minutes in neonates to reduce potential risk of bilirubin encephalopathy). In children aged up to 12 years of age, doses of 50 mg/kg or more should be given by intravenous infusion.

Contraindications

Neonates requiring IV treatment with any calcium containing solution
Neonates with hypoalbuminaemia
Premature infants
Neonatal hyperbilirubinaemia
Neonates with acidosis

Precautions and Warnings

Allergic disposition
Immobilisation
Breastfeeding
Hepato-renal syndrome
History of colitis
History of gastrointestinal disorder
History of nephrolithiasis
Hypercalciuria
Hypoprothrombinaemia
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment

Jarisch-Herxheimer reaction possible in treatment of Spirochetes infection
Before initiating therapy enquire about previous hypersensitivity reactions
Consult national/regional policy on the use of anti-infectives
Restore electrolyte & fluid balance in case of dehydration
TPN increases the risk of ceftriaxone precipitation in the gall bladder
Do not give calcium containing solutions in the same line
Monitor closely patient with pre-existing renal impairment
Monitor fluid and electrolyte status
Perform blood counts on prolonged use of this treatment
Consider discontinuation if biliary precipitates are symptomatic
Consider discontinuation if encephalopathy is suspected
Consider discontinuation of treatment if haemolytic anaemia occurs
Consider pseudomembranous colitis if patient presents with diarrhoea
Drug precipitates in gallbladder more likely with treatment > 14 days
Prolonged use may result in superinfection with non-susceptible organisms
May cause false positive Coomb's test and glycosuria test
May cause false positive test for galactosaemia
Discontinue if severe and persistent diarrhoea develops
Discontinue if severe hypersensitivity reactions occur
Consider dose adjustment in hepato-renal syndrome
Female:Non-hormonal contraception advised until 1 month after treatment

Ceftriaxone is contraindicated in patients who have had a previous hypersensitivity reaction to any cephalosporin. It is also contraindicated in patients who have had a previous immediate and/or any severe hypersensitivity reaction to any penicillin or to any other beta-lactam drug. Ceftriaxone should be given with caution to patients who have had any other type of hypersensitivity reaction to a penicillin or any other beta-lactam drug. Anaphylactic shock cannot be ruled out even if patient history is taken.

Because of precipitation of a ceftriaxone-calcium salt, ceftriaxone and calcium containing solutions (e.g. Ringer's, Hartmann's and some total parenteral nutrition solutions) must not be administered simultaneously at the same infusion site. Infusion of calcium and ceftriaxone may be infused sequentially in patients aged 28 days or older provided that the infusion line is rinsed or flushed thoroughly between solutions or the infusions are given via different infusion lines at different sites. In patients requiring continuous parenteral nutrition with calcium-containing solutions, an alternative antibacterial treatment which does not carry a similar risk of precipitation may be appropriate. If there is no alternative to giving ceftriaxone with a calcium-containing solution, then administration can be simultaneous provided they are given via different infusions lines at different sites. Alternatively, infusion of TPN solution could be stopped for the period of ceftriaxone infusion, considering the advice to flush infusion lines between solutions.

Ceftriaxone may precipitate in the gallbladder and consequently be detectable as shadows on a sonogram and can be mistaken for gallstones. Such precipitates disappear after discontinuation of ceftriaxone. They are more likely to develop in patients receiving doses of greater than 1 g per day and in infants and children who are given larger doses on a body weight basis. Doses greater than 80 mg/kg should be avoided in children because of the increased risk of biliary precipitates. Precipitates have rarely been associated with symptoms but in these cases conservative nonsurgical management is suggested and discontinuation of ceftriaxone should be considered.

Pancreatitis, possibly caused by biliary obstruction has been rarely reported with ceftriaxone therapy. Most patients had risk factors for biliary stasis and biliary sludge but it cannot be ruled out that ceftriaxone is a trigger or cofactor.

In symptomatic cases of renal lithiasis sonography should be performed. Patients with a history of renal lithiasis or with hypercalciuria should be treated with caution.

Cephalosporins may cause bleeding due to hypoprothrombinaemia and should be used with caution in patients with renal/hepatic impairment, malnourished patients with low vitamin K levels and also in patients receiving prolonged cephalosporin therapy who are at increased risk of developing hypoprothrombinaemia.

Encephalopathy has been observed with the use of ceftriaxone, particularly in elderly patients with severe renal impairment or CNS disorders. If encephalopathy is suspected (decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of ceftriaxone treatment should be considered.

Pregnancy and Lactation

Pregnancy

Use ceftriaxone with caution in pregnancy.

Schaefer suggests cephalosporins are safe for use during pregnancy if needed. Older cephalosporins are prefered. Manufacturers suggest ceftriaxone should only be used during pregnancy if the benefit outweighs the risk.

Ceftriaxone crosses the placental barrier and can reach therapeutic levels in amniotic fluid and foetal tissues.

Reproduction studies in rats have found no evidence on impaired fertility or foetal harm at doses up to 20 times the human dose. No evidence of embryotoxicity, foetotoxicity or teratogenicity was found in mice, rats and non-human primates at doses approximately 20, 20 and 3 times respectively, the human dose.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use ceftriaxone with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) considers ceftriaxone acceptable for using in breastfeeding. One manufacturer suggests a decision whether to discontinue ceftriaxone therapy or discontinue breastfeeding should be considered taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Concentrations of ceftriaxone in breast milk are too low to have bactericidal or systemic side effects on the infant. However alterations to oral and gastrointestinal flora resulting in diarrhoea and thrush have been reported with ceftriaxone, but these effects have not been adequately evaluated. Possibility of sensitisation should be taken into account.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Abnormal liver function tests
Acute tubular necrosis
Agranulocytosis
Allergic dermatitis
Allergic skin reactions
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anaphylaxis
Antibiotic-associated colitis
Anuria
Bronchospasm
Cholestatic jaundice
Coagulation disorders
Convulsions
Diarrhoea
Dizziness
Drug fever
Drug precipitate in gall bladder
Drug rash with eosinophilia and systemic symptoms (DRESS)
Encephalopathy
Eosinophilia
Erythema multiforme
Exanthema
False positive Coombs test
False positive test for galactosaemia
Fever
Genital mycosis
Glossitis
Glycosuria
Granulocytopenia
Haematuria
Haemolysis
Haemolytic anaemia
Headache
Hepatitis (transient)
Hypersensitivity reactions
Hypoprothrombinaemia
Increases in hepatic enzymes
Jarisch-Herxheimer reaction
Leucopenia
Local pain (injection site)
Lyell's syndrome
Maculopapular rash
Nausea
Neutropenia
Oedema
Oliguria
Pancreatitis
Phlebitis (injection site)
Prothrombin time increased
Pruritus
Pseudomembranous colitis
Pyrexia
Renal impairment
Rigors
Secondary infections
Serum creatinine increased
Shivering
Stevens-Johnson syndrome
Stomatitis
Superinfections
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vertigo
Vomiting

Effects on Laboratory Tests

False positive Coombs' test may occur with ceftriaxone.

Ceftriaxone may also result in false-positive tests for galactosaemia. Non-enzymatic methods such as copper reduction methods (Benedict's, Fehling's or Clinitest) for glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with ceftriaxone should be done enzymatically.

Ceftriaxone may falsely lower estimated blood glucose values with some blood glucose monitoring systems. See individual systems for instructions. Consider alternative methods.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Ceftriaxone 1 g powder for solution for injection. Wockhardt UK Ltd. Revised July 2017.
Summary of Product Characteristics: Ceftriaxone 2 g powder for solution for injection/infusion. Wockhardt UK Ltd. Revised July 2017.
Summary of Product Characteristics: Ceftriaxone Sodium 1 g injection. Stravencon Limited. Revised October 2016.
Summary of Product Characteristics: Ceftriaxone Sodium 2 g injection. Stravencon Limited. Revised October 2016.
Summary of Product Characteristics: Rocephin 250 mg, 1 g, 2 g vials. Roche Products Limited. Revised January 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Ceftriaxone. Last revised: September 07 2013
Last accessed: 04 February 2016