Rocephin

Rocephin

ceftriaxone

Manufacturer:

Roche

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Ceftriaxone.
Description
Active ingredient: ceftriaxone in the form of the disodium salt.
Vials containing dry substance equivalent to 0.25 g, 0.5 g, or 1 g ceftriaxone.
Rocephin contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone.
Solvent for parenteral use (when it is supplied with Rocephin): The solvent ampoule for i.v. injection contains sterile water for injections and for i.m. injection contains 1% lidocaine hydrochloride solution. 1 ml solvent for i.m. injection contains 10.66 mg lidocaine hydrochloride monohydrate equivalent to 10 mg anhydrous lidocaine hydrochloride (see Contraindications).
Action
Pharmacotherapeutic group: Antibacterials for systemic use, Third-generation cephalosporins. ATC code: J01DD04.
Pharmacology: Pharmacodynamics:
Mechanism of action: The bactericidal activity of ceftriaxone results from inhibition of bacterial cell wall synthesis. Ceftriaxone exerts in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Ceftriaxone is highly stable to most β-lactamases, both penicillinases and cephalosporinases, of gram-positive and gram-negative bacteria. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Indications/Uses): Gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive), Staphylococci coagulase-negative, Streptococcus pyogenes (β-hemolytic, group A), Streptococcus agalactiae (β-hemolytic, group B), β-hemolytic Streptococci (non-group A or B), Streptococcus viridans, Streptococcus pneumoniae.
Note: methicillin-resistant Staphylococcus spp. is resistant to cephalosporins, including ceftriaxone. In general, Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are resistant.
Gram-negative aerobes: Acinetobacter lwoffi, Acinetobacter anitratus (mostly A. baumanii)*, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Alcaligenes-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including C. amalonaticus), Citrobacter freundii*, Escherichia coli, Enterobacter aerogenes*, Enterobacter cloacae*, Enterobacter spp. (other)*, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae**, Moraxella catarrhalis (former Branhamella catarrhalis), Moraxella osloensis, Moraxella spp. (other), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri*, Proteus vulgaris*, Pseudomonas fluorescens*, Pseudomonas spp. (other)*, Providentia rettgeri*, Providentia spp. (other), Salmonella typhi, Salmonella spp. (non-typhoid), Serratia marcescens*, Serratia spp. (other)*, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (other).
* Some isolates of these species are resistant to ceftriaxone, mainly due to the production of the chromosomally encoded β-lactamase.
** Some isolates of these species are resistant due to production of extended spectrum, plasmid-mediated β-lactamase.
Note: Many strains of the previously mentioned microorganisms that are multiple resistant to other antibiotics, e.g. amino-penicillins and ureido-penicillins, older cephalosporins and aminoglycosides, are susceptible to ceftriaxone. Treponema pallidum is sensitive in vitro and in animal experiments. Clinical investigations indicate that primary and secondary syphilis respond well to ceftriaxone therapy. With a few exceptions clinical P. aeruginosa isolates are resistant to ceftriaxone.
Anaerobic organisms: Bacteroides spp. (bile-sensitive)*, Clostridium spp. (excluding C. difficile), Fusobacterium nucleatum, Fusobacterium spp. (other), Gaffkia anaerobica (formerly Peptococcus), Peptostreptococcus spp.
* Some isolates of these species are resistant to ceftriaxone due to β-lactamase-production.
Note: Many strains of β-lactamase-producing Bacteroides spp. (notably B. fragilis) are resistant.
Clostridium difficile is resistant.
Susceptibility to ceftriaxone can be determined by the disk diffusion test or by the agar or broth dilution test using standardized techniques for susceptibility testing such as those recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCCLS issued the following interpretative breakpoints for ceftriaxone: (See Table 1.)

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Microorganisms should be tested with the ceftriaxone disk since it has been shown by in vitro tests to be active against certain strains resistant to cephalosporin class disks.
Where NCCLS recommendations are not in daily use, alternative, well-standardized, susceptibility-interpretative guidelines such as those issued by DIN, ICS and others may be substituted.
Pharmacokinetics: The pharmacokinetics of ceftriaxone are nonlinear and all basic pharmacokinetic parameters, except the elimination half-life, are dose dependent if based on total drug concentrations, increasing less than proportionally with dose. Nonlinearity is due to saturation of plasma protein binding and is therefore observed for total plasma ceftriaxone but not for free (unbound) ceftriaxone.
Absorption: Rocephin is administered as an intramuscular injection or as an IV injection or infusion. The maximum plasma concentration after a single i.m. dose of 1 g is about 81 mg/l and is reached in 2-3 hours after administration. The area under the plasma concentration-time curve after i.m. administration is equivalent to that after i.v. administration of an equivalent dose, indicating 100% bioavailability of intramuscularly administered ceftriaxone.
After intravenous bolus administration of ceftriaxone 500 mg and 1 g, mean peak plasma ceftriaxone levels are approximately 120 and 200 mg/l respectively. After intravenous infusion of ceftriaxone 500 mg, 1 g and 2 g, the plasma ceftriaxone levels are approximately 80, 150 and 250 mg/l respectively. Following intramuscular injection, mean peak plasma ceftriaxone levels are approximately half those observed after intravenous administration of an equivalent dose.
Distribution: The volume of distribution of ceftriaxone is 7-12 l.
Ceftriaxone has shown excellent tissue and body fluid penetration after a dose of 1-2 g; concentrations well above the minimal inhibitory concentrations of most pathogens responsible for infection are detectable for more than 24 hours in over 60 tissues or body fluids including lung, heart, biliary tract/liver, tonsil, middle ear and nasal mucosa, bone as well as cerebrospinal, pleural, prostatic and synovial fluids.
On intravenous administration, ceftriaxone diffuses rapidly into the interstitial fluid, where bactericidal concentrations against susceptible organisms are maintained for 24 hours (see figure).

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Protein binding: Ceftriaxone is reversibly bound to albumin. Plasma protein binding is about 95% at plasma concentrations below 100 mg/l. Binding is saturable and the bound portion decreases with rising concentration (up to 85% at a plasma concentration of 300 mg/l).
Penetration into particular tissues: Ceftriaxone penetrates the meninges. Penetration is greatest when the meninges are inflamed. Mean peak ceftriaxone concentrations in CSF in patients with bacterial meningitis are reported to be up to 25% of plasma levels compared to 2% of plasma levels in patients with uninflamed meninges. Peak ceftriaxone concentrations in CSF are reached approximately 4-6 hours after intravenous injection.
Ceftriaxone crosses the placental barrier and is excreted in the breast milk at low concentrations.
Metabolism: Ceftriaxone is not metabolised systemically; but is converted to inactive metabolites by the gut flora.
Elimination: Total plasma clearance is 10-22 ml/min. Renal clearance is 5-12 ml/min.
50-60% of ceftriaxone is excreted unchanged in the urine, while 40-50% is excreted unchanged in the bile. The elimination half-life in adults is about 8 hours.
Pharmacokinetics in Special Populations: Pediatric Population: The half-life of ceftriaxone is prolonged in neonates. From birth to 14 days of age, the levels of free ceftriaxone may be further increased by factors such as reduced glomerular filtration and altered protein binding. During childhood, the half-life is lower than in neonates or adults.
The plasma clearance and volume of distribution of total ceftriaxone are greater in neonates, infants and children than in adults.
Geriatric Population: In elderly persons aged over 75 years, the average elimination half-life is usually two to three times that of young adults.
Renal impairment: In patients with renal impairment, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased, (less than two-fold), even in patients with severely impaired renal function.
The modest increase in half-life in renal impairment is explained by a compensatory increase in non-renal clearance, resulting from a decrease in protein binding and corresponding increase in non-renal clearance of total ceftriaxone.
Hepatic Impairment: In patients with hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased, (less than two-fold), even in patients with severely impaired renal function.
In patient population, the elimination half-life of ceftriaxone is not increased, due to a compensatory increase in renal clearance. This is also due to an increase in plasma free fraction of ceftriaxone contributing to the observed paradoxical increase in total drug clearance, with an increase in volume of distribution paralleling that of total clearance.
Toxicology: Nonclinical Safety: Nonclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, acute and repeated dose toxicity, genotoxicity, or toxicity to reproduction.
Carcinogenicity: No carcinogenicity studies have been performed to establish the carcinogenic potential of Rocephin.
Genotoxicity: No evidence of mutagenicity has been found in vitro or in vivo.
Impairment of Fertility: No effect on male or female fertility has been detected.
Reproductive toxicity: Reproductive studies in animals have shown no evidence of embryotoxicity, fetotoxicity, teratogenicity, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed.
Indications/Uses
Rocephin is indicated for infections caused by pathogens sensitive to Rocephin, e.g.: sepsis; meningitis; disseminated Lyme borreliosis (early and late stages of the disease); abdominal infections (peritonitis, infections of the biliary and gastrointestinal tracts); infections of the bones, joints, soft tissue, skin and of wounds; infections in patients with impaired defense mechanisms; renal and urinary tract infections; respiratory tract infections, particularly pneumonia, and ear, nose and throat infections; genital infections, including gonorrhea.
And perioperative prophylaxis of infections.
Dosage/Direction for Use
General: Standard dosage: Adults and children over 12 years: The usual dosage is 1-2 g of Rocephin once daily (every 24 hours). In severe cases or in infections caused by moderately sensitive organisms, the dosage may be raised to 4 g, once daily.
Duration of treatment: The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of Rocephin should be continued for a minimum of 48-72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.
Combination treatment: Synergy between Rocephin and aminoglycosides has been demonstrated with many gram-negative bacteria under experimental conditions. Although enhanced activity of such combinations is not always predictable, it should be considered in severe, life-threatening infections due to microorganisms such as Pseudomonas aeruginosa. Due to chemical incompatibility between Rocephin and aminoglycosides, the two drugs must be administered separately at the recommended dosages. Chemical incompatibility with Rocephin has also been observed with i.v. administration of amsacrine, vancomycin and fluconazole.
Method of administration: As a general rule, the solutions should be used immediately after preparation.
Reconstituted solutions retain their physical and chemical stability for 6 hours at room temperature (or 24 hours in the refrigerator at 2-8°C). The solutions range in colour from pale yellow to amber, depending on the concentration and length of storage. The coloration of the solutions is of no significance for the efficacy or tolerance of the drug.
Intramuscular injection: For i.m. injection, Rocephin 250 mg or 500 mg is dissolved in 2 ml, and Rocephin 1 g in 3.5 ml, of 1% lidocaine hydrochloride solution and injected well within the body of a relatively large muscle. It is recommended that not more than 1 g be injected at one site.
The lidocaine solution should never be administered intravenously (see Contraindications).
Intravenous injection: For i.v. injection, Rocephin 250 mg or 500 mg is dissolved in 5 ml, and Rocephin 1 g in 10 ml, sterile water for injections. The intravenous administration should be given over 2-4 minutes.
Intravenous infusion: The infusion should be given over at least 30 minutes. For i.v. infusion, 2 g Rocephin is dissolved in 40 ml of one of the following calcium-free infusion solutions: sodium chloride 0.9%, sodium chloride 0.45% + dextrose 2.5%, dextrose 5%, dextrose 10%, dextran 6% in dextrose 5%, water for injections. Rocephin solutions should not be mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed previously, owing to possible incompatibility.
Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute Rocephin 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 Rocephin is mixed with calcium-containing solutions in the same i.v. administration line. Rocephin 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, Rocephin 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 Contraindications, General under Precautions and Interactions).
There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (i.v. or oral).
Special Dosage Instructions: Pediatric use: Neonates, infants and children up to 12 years: The following dosage schedules are recommended for once daily administration: Neonates (up to 14 days): 20-50 mg/kg bodyweight once daily. The daily dose should not exceed 50 mg/kg. Rocephin is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age) (see Contraindications).
Rocephin is contraindicated in neonates (≤28 days) if they require (or are expected to require) treatment with calcium-containing i.v. solutions, including continuous calcium-containing infusions such as parenteral nutrition, because of the risk of precipitation of ceftriaxone-calcium (see Contraindications).
For neonates, infants, and children (15 days to 12 years): 20-80 mg/kg once daily.
For children with bodyweights of 50 kg or more, the usual adult dosage should be used.
Intravenous doses of ≥50 mg/kg bodyweight, in infants and children up to 12 years of age, should be given by infusion over at least 30 minutes. In neonates, intravenous doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy.
Meningitis: In bacterial meningitis in infants and children, treatment begins with doses of 100 mg/kg (up to a maximum of 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dosage can be reduced accordingly. The following duration of therapy has shown to be effective: Neisseria meningitidis: 4 days; Haemophilus influenzae: 6 days; Streptococcus pneumoniae: 7 days.
Geriatric use: No dose adjustment of Rocephin is required in patients ≥65 years of age provided there is no severe renal and hepatic impairment.
Renal impairment: No dose adjustment is required, provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance <10 ml/min) should the Rocephin dosage not exceed 2 g daily. Ceftriaxone is not removed by peritoneal- or hemodialysis. In patients undergoing dialysis, no additional supplementary dosing is required following the dialysis.
Hepatic impairment: No dose adjustment of Rocephin is required, provided renal function is not impaired.
Severe renal and hepatic impairment: In patients with both severe renal and hepatic dysfunction, clinical monitoring for safety and efficacy is advised.
Lyme borreliosis: 50 mg/kg to a maximum of 2 g in children and adults, once daily for 14 days.
Gonorrhea (penicillinase-producing and nonpenicillinase-producing strains): A single i.m. dose of 250 mg.
Perioperative prophylaxis: A single dose of 1-2 g depending on the risk of infection 30-90 minutes prior to surgery. In colorectal surgery, administration of Rocephin with or without a 5-nitroimidazole, e.g. ornidazole (separate administration, see Dosage &Administration) has been proven effective.
Route of Administration: Powder for solution for injection: intramuscular injection, intravenous injection.
Powder for solution for infusion: intravenous infusion.
Overdosage
In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.
Contraindications
Hypersensitivity: Rocephin is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to penicillin and other beta-lactam agents may be at greater risk of hypersensitivity to ceftriaxone (see General: Hypersensitivity under Precautions).
Lidocaine: Contraindications to lidocaine must be excluded before intramuscular injection of ceftriaxone when lidocaine solution is used as a solvent (see Dosage & Administration). See Contraindications in the prescribing information of lidocaine. Ceftriaxone solutions containing lidocaine should never be administered intravenously.
Premature neonates: Rocephin is contraindicated in premature neonates up to postmenstrual age of 41 weeks (gestational age + chronological age).
Hyperbilirubinemic newborns: Hyperbilirubinemic 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.
Neonates and calcium-containing i.v. solutions: Rocephin is contraindicated in neonates (≤28 days) if they require (or are expected to require) treatment with calcium-containing i.v. solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see Dosage & Administration and Interactions).
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 Rocephin and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Rocephin and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom Rocephin and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates (see Postmarketing Experience under Adverse Reactions).
Special Precautions
General: Hypersensitivity: As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported (see Postmarketing Experience under Adverse Reactions). In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated. Before beginning treatment, it should be established whether the patient has a history of hypersensitivity reactions to ceftriaxone, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if ceftriaxone is given to patients with a history of hypersensitivity to other beta-lactam agents.
Hemolytic anemia: An immune-mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including Rocephin. Severe cases of hemolytic anemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anemia while on ceftriaxone, the diagnosis of a cephalosporin associated anemia should be considered and ceftriaxone discontinued until the etiology is determined.
Clostridium difficile associated diarrhea (CDAD): Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Rocephin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of 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 antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the 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 evaluation should be instituted as clinically indicated.
Superinfections: Superinfections with non-susceptible microorganisms may occur as with other antibacterial agents.
Calcium-ceftriaxone precipitates: Calcium-ceftriaxone precipitates in the gallbladder have been observed on ultrasound scan in patients receiving ceftriaxone, particularly at doses of 1 g per day and above. The probability of such precipitates appears to be greatest in pediatric patients. Precipitates disappear after discontinuation of ceftriaxone therapy and are rarely symptomatic. In symptomatic cases, conservative nonsurgical management is recommended, and discontinuation of ceftriaxone treatment should be considered by the physician based on an individual benefit-risk assessment.
In the available scientific data, there are no reports of intravascular precipitations in patients, other than newborns, 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 newborns, Interactions and Postmarketing Experience under Adverse Reactions).
Pancreatitis: Cases of pancreatitis, possibly of biliary obstruction aetiology, have been rarely reported in patients treated with Rocephin. 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 Rocephin-related biliary precipitation can not be ruled out.
Blood monitoring: During prolonged treatment, the complete blood count should be done at regular intervals.
Influence on diagnostic tests: In patients treated with Rocephin the Coombs' test may become falsely positive. Rocephin, like other antibiotics, may result in false-positive test results for galactosemia.
Likewise, non-enzymatic methods for the glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with Rocephin should be done enzymatically.
The presence of ceftriaxone may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Refer to instructions for use for each system. Alternative testing methods should be used if necessary.
Drug Abuse and Dependence: Not applicable.
Ability to Drive and Use Machines: During treatment with Rocephin, undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use machines (see Adverse Reactions). Patients should be cautious when driving or operating machinery.
Renal Impairment: See Special Dosage Instructions under Dosage & Administration.
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration.
Use in Children: Safety and effectiveness of Rocephin in neonates, infants and children have been established for the dosages described under Dosage & Administration. Studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin.
Rocephin should not be used in neonates (especially prematures) at risk of developing bilirubin encephalopathy (see Contraindications).
See Special Dosage Instructions under Dosage & Administration.
Use in the Elderly: See Special Dosage Instructions under Dosage & Administration.
Use In Pregnancy & Lactation
Females and Males of Reproductive Potential: Fertility: See Pharmacology: Toxicology: Nonclinical Safety: Impairment of Fertility under Actions.
Pregnancy: Ceftriaxone crosses the placental barrier. Safety in human pregnancy has not been established. Reproductive studies in animals have shown no evidence of embryotoxicity, fetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed.
Lactation: Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when Rocephin is administered to a nursing woman.
Adverse Reactions
Clinical Trials: Summary of the safety profile: The most frequently reported adverse reactions for ceftriaxone are eosinophilia, leucopenia, thrombocytopenia, diarrhea, rash, and hepatic enzymes increased.
Data to determine the frequency of ceftriaxone adverse drug reactions (ADRs) was derived from clinical trials.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical trials (Table 2) are listed by MedDRA system organ class. The corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1000). (See Table 2.)

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Postmarketing Experience: The following adverse drug reactions have been identified from postmarketing experience with Rocephin. These reactions are reported from a population of uncertain size, therefore, it is not always possible to reliably estimate their frequency and/or establish a causal relationship to drug exposure.
Systemic side effects: Gastrointestinal complaints: pancreatitis, stomatitis and glossitis.
Hematological changes: isolated cases of agranulocytosis (<500/mm3) have been reported, most of them after 10 days of treatment and following total doses of 20 g or more.
Skin reactions: acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) have been reported.
Nervous system disorders: convulsion, encephalopathy.
Reversible encephalopathy has been reported with the use of cephalosporins, including ceftriaxone, particularly when high doses are administered in patients with renal impairment and additional predisposing factors such as older age, pre-existing central nervous system disorders.
Infections and infestations: superinfection.
Other, rare side effects: symptomatic precipitation of ceftriaxone-calcium salt in the gallbladder, kernicterus, oliguria, and anaphylactic or anaphylactoid reactions.
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 interaction of ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 grams ceftriaxone infused over 30 minutes) were used in combination with calcium concentrations up to 12 mM (48 mg/dl). Recovery of ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dl) or higher in adult plasma or 4 mM (16 mg/dl) or higher in neonatal plasma. This may be reflective of ceftriaxone-calcium precipitation.
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 Rocephin and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Rocephin and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom Rocephin and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates (see General under Precautions).
Cases of ceftriaxone precipitation in the urinary tract have been reported, mostly in children treated with high doses (e.g. ≥80 mg/kg/day or total doses exceeding 10 grams) and who have other risk factors (e.g. dehydration, confinement to bed). This event may be asymptomatic or symptomatic, and may lead to ureteric obstruction and postrenal acute renal failure but is usually reversible upon discontinuation of Rocephin.
Local side effects: In rare cases, phlebitis reactions occurred after i.v. administration. These may be minimized by slow (2-4 minutes) injection.
Investigations: Coombs' test false-positive, galactosemia test false-positive, non-enzymatic methods for glucose determination false-positive.
Drug Interactions
No impairment of renal function has so far been observed after concurrent administration of large doses of Rocephin and potent diuretics (e.g. furosemide). There is conflicting evidence regarding a potential increase in renal toxicity of aminoglycosides when used with cephalosporins. The recommended monitoring of aminoglycoside levels and renal function in clinical practice should be closely adhered to in such cases. No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of Rocephin.
Ceftriaxone does not contain an N-methylthiotetrazole moiety associated with possible ethanol intolerance and bleeding problems of certain other cephalosporins. The elimination of Rocephin is not altered by probenecid.
In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone.
Concomitant use of ceftriaxone with Vitamin K antagonists may increase the risk of bleeding. Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted accordingly, both during and after treatment with ceftriaxone (see Adverse Reactions).
Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute Rocephin 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 Rocephin is mixed with calcium-containing solutions in the same i.v. administration line. Rocephin 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, Rocephin 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 have an increased risk of precipitation of ceftriaxone-calcium (see Dosage & Administration and Contraindications).
Caution For Usage
Special Instructions for Use, Handling and Disposal: Instructions for reconstitution: see Dosage & Administration.
Disposal of unused/expired medicines: The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater, and disposal through household waste should be avoided. Use established 'collection systems' if available in the location.
Disposal of syringes/sharps: The following points should be strictly adhered to regarding the use and disposal of syringes and other medicinal sharps: Needles and syringes should never be reused.
Place all used needles and syringes into a sharps container (puncture-proof disposable container).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Storage
Do not store above 30°C, keep vial in the outer container. Reconstituted solutions retain their physical and chemical stability for 6 hours at room temperature (or 24 hours in the refrigerator at 2-8°C).
MIMS Class
Cephalosporins
ATC Classification
J01DD04 - ceftriaxone ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
IM/IV inj (vial) 250 mg x 1's. 500 mg x 1's. 1 g x 1's.
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