Adco-Ceftriaxone Injection

ADCO-CEFTRIAXONE is indicated for the treatment of the following infections:

• BACTERIAL SEPTICAEMIA caused by: Methicilin-sensitive Staphylococcus aureus (MSSA), Streptococcus pneumonia, Haemophilus influenzae, Escherichia coli, or Klebsiella pneumoniae.
• MENINGITIS caused by: Haemophilus influenzae, Neisseria meningitides or Streptococcus pneumonia.
• INTRA-ABDOMINAL INFECTIONS caused by: Escherichia coli, Klebsiella pneumoniae or Peptostreptococcus species.
• SKIN AND SKIN STRUCTURE INFECTIONS caused by: Methicilin-sensitive Staphylococcus aureus (MSSA), Streptococcus pyogenes, Streptococcus viridans group, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus miribalis, Morganella morganii, Serratia marcescans or Peptostreptococcus species.
• BONE AND JOINT INFECTIONS caused by: Methicilin-sensitive Staphylococcus aureus (MSSA), Streptococcus pneumonia, Escherichia coli, Proteus miribalis, Klebsiella pneumoniae or Enterobacter species.
• RENAL AND URINARY TRACT INFECTIONS (complicated and uncomplicated) caused by: Escherichia coli, Proteus miribalis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae.
• RESPIRATORY TRACT INFECTIONS caused by: Streptococcus pneumonia, Methicilin-sensitive Staphylococcus aureus (MSSA), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus miribalis or Serratia marcescens.
• EAR NOSE AND THROAT INFECTIONS (Acute Bacterial Otitis Media) caused by: Streptococcus pneumonia, Haemophilus influenzae (including beta-lactamase-producing strains), or Moraxella catarrhalis (including beta-lactamase-producing strains).
• UNCOMPLICATED GONORRHOEA (cervical/ urethral and rectal) caused by: Neisseria gonorrhoeae, including both beta-lactamase-, and non-beta-lactamase-producing strains, and pharyngeal gonorrhoea caused by non-beta-lactamase-producing strains of Neisseria gonorrhoeae.
• PERIOPERATIVE INFECTION PROPHYLAXIS

Posology

Standard dosage

Adults and children over 12 years: The usual dosage is 1 u2013 2 g ADCO-CEFTRIAXONE once daily. In severe cases or in infections caused by moderately sensitive organisms, the dosage may be raised to 4 g, once daily.

Neonates, infants and children up to 12 years: The following dosage schedules are recommended for once daily administration:

• Neonates (up to 14 days): 20 u2013 50 mg/ kg bodyweight once daily. The daily dose should not exceed 50 mg/ kg. It is not necessary to differentiate between premature and term infants.
• Infants and children (15 days to 12 years): 20 u2013 80 mg/ kg once daily. For children with bodyweights of 50 kg or more, the usual adult dose should be used. Intravenous doses of > 50 mg/ kg bodyweight should be given by infusion over at least 30 minutes.

Elderly patients: No dose modification is needed in the elderly.

Duration of therapy

The duration of therapy varies according to the course of the disease. Administration of ADCO-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.

Special dosage Instructions

Meningitis: In bacterial meningitis in neonates, infants and children, treatment begins with doses of 100 mg/ kg (not to exceed 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dose can be adapted accordingly.

For bacterial meningitis in adults, the recommended dose is 4 g once daily.

Gonorrhoea: For the treatment of uncomplicated gonorrhoea (both beta-lactamase-producing and non-beta-lactamase-producing strains), a single intramuscular (i.m.) dose of 125 mg ADCO-CEFTRIAXONE is recommended.

Peri-operative Infection Prophylaxis: A single dose of 1 u2013 2 g ADCO-CEFTRIAXONE administered 30 u2013 90 minutes prior to surgery. In colorectal surgery, administration of ADCO-CEFTRIAXONE with or without a 5-nitroimidozole, e.g. metronidazole, has been proven effective, (separate administration: see u2018Method of administrationu2019)

Impaired renal and hepatic function: In patients with impaired renal function, there is no need to reduce the dosage of ADCO-CEFTRIAXONE provided that hepatic function is intact. In cases of severe renal failure (creatinine clearance < 10 ml/ min) the ADCO-CEFTRIAXONE dosage should not exceed 2 g daily. In patients with liver damage, there is no need for the dosage to be reduced, provided that renal function is intact.

Method of administration

Ceftriaxone must be reconstituted prior to use. Reconstituted solutions retain their physical and chemical stability for 6 hours at room temperature or 24 hours in the refrigerator at +5 u00b0C. As a general rule, however, the solutions should be used immediately after preparation. The solutions range in colour from pale yellow to amber, depending on the concentration and length of storage. The colouration of the solutions is of no significance for the efficacy or tolerance of the drug.

Intramuscular injection

For i.m. injection, ADCO-CEFTRIAXONE 250 mg or 500 mg is dissolved in 2 ml and ADCO-CEFTRIAXONE 1 g in 3,5 ml, of water for injection. ADCO-CEFTRIAXONE dissolved in a 1 % lignocaine solution instead of water for injection can reduce pain at the site of injection. It is recommended that not more than 1 g be injected at one site. Reconstitution with 1 % lignocaine (without adrenaline) has no effect on the absorption or the elimination of ADCO-CEFTRIAXONE.

Intravenous injection

The lignocaine solution must never be administered intravenously. For i.v. injection, ADCO-CEFTRIAXONE 250 mg or 500 mg is dissolved in 5 ml, and ADCO-CEFTRIAXONE 1 g in 10 ml sterile water for injection. The intravenous administration should be given over 2 to 4 minutes.

Intravenous infusion: The infusion should be given over a period of at least 30 minutes. For i.v. infusion, 2 g of ADCO-CEFTRIAXONE is dissolved in approximately 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 %; hydroxy ethyl starch 6 u2013 10 % infusions; sterile water for injection. ADCO-CEFTRIAXONE solutions should not be mixed with or piggybacked into solutions containing other antimicrobial medication or into diluent solutions other than those listed above, owing to possible incompatibility. For instructions on reconstitution of the medicine before administration, see section 6.6

Hypersensitivity to cephalosporins or any other ingredients. Hypersensitivity to penicillins, due to the possibility of cross-reactivity.

Pseudomembranous enterocolitis and coagulation disorders have been reported with ADCO-CEFTRIAXONE. It is important to consider pseudomembranous enterocolitis in patients who present with diarrhoea subsequent to administration of ADCO-CEFTRIAXONE. Superinfections with non-susceptible micro-organisms may occur. Shadows, which have been mistaken for gallstones have been detected in sonograms of the gallbladder, usually following doses higher than the standard recommended dose. These shadows are, however, precipitates of calcium ceftriaxone, which disappear on completion or discontinuation of ADCO-CEFTRIAXONE therapy. In symptomatic cases, conservative non-surgical management is recommended. Cases of pancreatitis, possibly of biliary obstruction aetiology, have been reported in patients treated with ADCO-CEFTRIAXONE. Most patients who developed pancreatitis have had risk factors associated with biliary stasis and biliary sludge, e.g. severe illness and total parenteral nutrition. Ceftriaxone displaces bilirubin from serum albumin. Caution should be exercised when considering ADCO-CEFTRIAXONE treatment in hyperbilirubinaemic neonates. ADCO-CEFTRIAXONE is not recommended for use in neonates (especially premature) at risk of developing bilirubin encephalopathy.

Renal function impairment has not been observed after concurrent administration of ADCO-CEFTRIAXONE and diuretics (e.g. furosemide). There is no evidence that ADCO-CEFTRIAXONE increases renal toxicity of aminoglycosides. The elimination of ADCO-CEFTRIAXONE is not altered by probenecid.

Interaction with Laboratory Tests: In patients treated with ADCO-CEFTRIAXONE the Coombsu2019 test and tests for galactosaemia may become false-positive. Non-enzymatic methods for glucose determination in urine may give false-positive results.

Pregnancy and lactation

Ceftriaxone crosses the placental barrier and is excreted in breast-milk. Safety in pregnancy and lactation has not been established.

N/A

a. Summary of the safety profile

Not Applicable

b. Tabulated summary of adverse reactions

Gastro-intestinal system: Loose stools/ diarrhoea, nausea, vomiting, stomatitis, glositis, precipitation of ceftriaxone salts in the gallbladder, increase in liver enzymes, pseudomembranous colitis.

Haematological system: Eosinophilia, haematoma or bleeding, thrombocytopenia, leukopenia, lymphopenia, granulocytopenia and haemolytic anaemia. Prolongation of prothrombin time. Isolated cases of agranulocytosis (< 500 mm 3 ) have been reported, most of them following total doses of 20 g or more.

Skin and appendages: Exanthema, allergic dermatitis, pruritis, urticaria, oedema. Isolated cases of severe cutaneous adverse reactions (erthema mutiforme, Stevens-Johnson syndrome or Lyellu2019s syndrome/ toxic epidermal necrolysis) have been reported.

Central Nervous system: Headache and dizziness.

Urogenital system: Oliguria, genital mycosis. Cases of drug precipitation in the kidneys have been reported, mostly in children older than 3 years and who have been treated with either high daily doses (e.g. > 80 mg/ kg/ day) or total doses exceeding 10 g and presenting with other risk factors (e.g. fluid restrictions, confinement to bed, etc.). This event may lead to renal insufficiency and is usually reversible upon discontinuation of ADCO-CEFTRIAXONE.

Hypersensitivity reactions: Anaphylactic shock and anaphylactoid reactions.

Local reactions: Phlebitic reactions may occur after i.v. administration. These may be minimized by slow (2 u2013 4 minutes) injection of the medicine. Intramuscular injection without lignocaine solution is painful, (see section 4.2)

Other: Increase in serum creatinine, fever, shivering.

c. Description of selected adverse reactions

N/A

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

In cases of over-dosage, plasma concentration would not be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic and supportive.