ROCEPHIN FOR INJECTION 1 G/VIAL (INTRAVENOUS) [SIN00566P]

Product Info

ROCEPHIN FOR INJECTION 1 G/VIAL (INTRAVENOUS)

[SIN00566P]

2.1. THERAPEUTIC INDICATION(S)
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.

2.2. DOSAGE AND ADMINISTRATION
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 treatment 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 micro-organisms 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 IV 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.

Weight-dependent dosing
The displacement volume of ceftriaxone sodium powder in water for injections, and in 1% lidocaine hydrochloride solution is approximately 0.71 ml per labelled gram of ceftriaxone powder. This requires the offset of solvent volume to facilitate weight-dependent dosing (primarily in children up to 12 years) if only part of the total solution is measured and administered. To prepare a final solution of a specified concentration please refer to Table 1 below.

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 is injected at one site. The lidocaine solution should never be administered intravenously (see section 2.3 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, of 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 above, 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 IV administration because a precipitate can form.

Precipitation of ceftriaxone-calcium can also occur when Rocephin is mixed with calcium-containing solutions in the same IV administration line. Rocephin must not be administered simultaneously with calcium-containing IV 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 sections 2.3 Contraindications, 2.4.1 Warnings and Precautions General and 2.8 Interactions with other Medicinal Products and other Forms of Interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

2.2.1. 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 41weeks (gestational age + chronological age) (see section 2.3 Contraindications).
Rocephin is contraindicated in neonates (≤28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see 2.3 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:

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 of 30–90 minutes prior to surgery. In colorectal surgery, administration of Rocephin with or without a 5-nitroimidazole, e.g. ornidazole (separate administration, see 2.2 Dosage and Administration) has been proven effective.

2.3. 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 a greater risk of hypersensitivity to ceftriaxone (see section 2.4.1 Warnings and Precautions General – Hypersensitivity – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Lidocaine
Contraindications to lidocaine must be excluded before intramuscular injection of ceftriaxone when lidocaine solution is used as a solvent (see section 2.2 Dosage and Administration). See contraindications section 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
Hyperbilirubinaemic 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 can possibly develop in these patients.

Neonates and Calcium Containing IV Solutions
Rocephin is contraindicated in neonates (≤28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see 2.2 Dosage and Administration and 2.8 Interactions with other Medicinal Products and other Forms of Interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
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 2.6.2 Post marketing Experience – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).