RAZOBIN Powder for solution for injection/infusion Ref.[115313] Active ingredients: Piperacillin Tazobactam

RAZOBIN may be given by slow intravenous infusion over a 30 minute period.

Adults and Children 12 years and older

The usual dosage for adults and juveniles with normal renal function is 4/0,5 g piperacillin/tazobactam given every eight hours.

The dosage in immunocompromised and neutropenic patients with infection is 4/0, 5 g piperacillin/tazobactam every 6 hours in combination with an aminoglycoside.

Children under the age of 12 Years

RAZOBIN is only recommended for the treatment of children with neutropenia. For children weighing over 50 kg, follow the adult dosing guidance, including the aminoglycoside. For children with normal renal function and weighing less than 50 kg, the dose should be adjusted to 90 mg/kg (80 mg piperacillin/10 mg tazobactam) administered every 6 hours, in combination with an aminoglycoside.

Renal Insufficiency

In patients with renal insufficiency, the intravenous dose should be adjusted to the degree of actual renal function impairment. The suggested daily doses are as follows:

For patients on haemodialysis, the maximum daily dose is 2 g/0,25 g every 8 hours piperacillin/tazobactam. In addition, because haemodialysis removes 30 % - 40 % of piperacillin in 4 hours, one additional dose of 0,75 g piperacillin/tazobactam should be administered following each dialysis period. For patients with renal.

failure and hepatic insufficiency, measurement of serum levels of piperacillin/tazobactam will provide additional guidance for adjusting dosage.

Neutropenic Patients

In treating neutropenic patients, full therapeutic doses of RAZOBIN and an aminoglycoside should be used. The possibility of hypokalaemia should be kept in mind in patients who have low potassium reserves, and periodic electrolyte determinations should be made in these patients.

Duration of Therapy

In acute infections, treatment with RAZOBIN should be for a minimum of five days and continued for forty-eight hours beyond resolution of clinical symptoms or the fever. The usual duration of treatment is 7 - 10 days.

Hospitalised Children with intra-abdominal infection

For children aged 2 to 12 years, weighing up to 40 kg, and with normal renal function, the recommended dosage is 112,5 mg/kg (100 mg piperacillin/12,5 mg tazobactam) every 8 hours.

For children aged 2 to 12 years, weighing over 40 kg, and with normal renal function, follow the adult dose guidance, i.e. 4,5 g (4 g piperacillin/0,5 g tazobactam) every 8 hours.

The duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress. Therapy is recommended to be a minimum of 5 days and a maximum of 14 days, considering the dose administration should continue at least 48 hours after the resolution of clinical signs and symptoms.

Children Aged 2–12 Years with Renal Insufficiency

The pharmacokinetics of RAZOBIN have not been studied in paediatric patients with renal impairment. The following dosage adjustment for paediatric patients aged 2 to 12 years with renal impairment is recommended.

The dosage modification is only an approximation. Each patient must be monitored closely for signs of medicine toxicity. Medicine dose and interval should be adjusted accordingly.

Reconstitution Directions

Diluents for Reconstitution: (See "INTERACTIONS: Pharmaceutical Incompatibilities")

Sterile Water for Injection.
Sodium Chloride Injection.

Each vial of 2 g/0, 25 g RAZOBIN should be reconstituted with at least 10 mL of one of the above diluents. Shake until dissolved.

Each vial of 3 g/0,375 g RAZOBIN should be reconstituted with at least 15 mL of one of the above diluents. Shake until dissolved.

Each vial of 4 g/0, 5 g RAZOBIN should be reconstituted with at least 20 mL of one of the above diluents.

Shake until dissolved.

For intravenous infusion:

The reconstituted solution may be further diluted to the desired volume (e.g. 50 mL - 150 mL) with one of the reconstitution diluents or with: Dextrose 5 % in water.

See "SIDE-EFFECTS". The majority of events experienced during overdosage including nausea, vomiting and diarrhoea have also been reported with the usual recommended dosages. If higher than recommended doses are given intravenously, particularly in the presence of renal failure, patients may experience neuromuscular excitability or convulsions.

Treatment should be supportive and symptomatic according to the patient's clinical presentation. There is no known specific antidote. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by haemodialysis. In the event or an emergency, all required intensive medical measures are indicated as in the case of piperacillin. In case of motor excitability or convulsions, anticonvulsive agents (e.g. diazepam or barbiturates) may be indicated. In case of severe, hyperallergic (anaphylactic) reactions, the usual countermeasures are to be initiated (antihistamines, corticosteroids, sympathicomimetic medicines and, if required, oxygen and airway management). The possibility of antibiotic-induced life-threatening pseudomembranous colitis must be taken into consideration in case of severe, persistent diarrhoea.

Therefore, RAZOBIN must be discontinued immediately in such cases and suitable therapy be initiated (e.g. oral teicoplanin or oral vancomycin). Preparations, which inhibit peristalsis, are contraindicated.

Dry Powder: Vials containing sterile RAZOBIN dry powder may be stored at controlled room temperature (at or below 25°C). Keep the vial in the outer carton until required for use.

Solutions: Vials containing reconstituted solutions for intravenous use should be used immediately. Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and 48 hours at 2–8°C. RAZOBIN contains no preservatives, therefore reconstitution/dilution should take place in controlled and validated aseptic conditions.

RAZOBIN is for single use only. Any unused portion of the reconstituted/diluted solution must be discarded.

KEEP OUT OF REACH OF CHILDREN.

RAZOBIN 2

30 mL clear, colourless, tubular glass vials fitted with 20 mm grey colour bromo butyl rubber stoppers and sealed with 20 mm aluminium seal with a violet coloured PP disc.

Pack size: Single vial packed in printed carton with a package insert. Each vial contains piperacillin sodium and tazobactam sodium cryodessicated powder for injection equivalent to piperacillin 2,0 g and tazobactam 0,25 g.

RAZOBIN 3

30 mL clear, colourless, tubular glass vials fitted with 20 mm grey colour bromo butyl rubber stoppers and sealed with 20 mm aluminium seal with a light blue coloured PP disc.

Pack size: Single vial packed in printed carton with a package insert. Each vial contains piperacillin sodium and tazobactam sodium cryodessicated powder for injection equivalent to piperacillin 3,0 g and tazobactam 0,375 g.

RAZOBIN 4

48 mL clear, colourless, tubular glass vials fitted with 20 mm grey colour bromo butyl rubber stoppers and sealed with 20 mm aluminium seal with a red coloured PP disc.

Pack size: Single vial packed in printed carton with a package insert. Each vial contains piperacillin sodium and tazobactam sodium cryodessicated powder for injection equivalent to piperacillin 4,0 g and tazobactam 0,5 g.