BIOPHIN Powder for solution for injection or infusion Ref.[115703] Active ingredients: Ceftriaxone

Posology

The dose depends on the severity, susceptibility, site and type of infection and on the age and hepato-renal function of the patient.

The doses recommended in the tables below are the generally recommended doses in these indications. In particularly severe cases, doses at the higher end of the recommended range should be considered.

Adults and children over 12 years of age (≥50 kg):

^* In documented bacteraemia, the higher end of the recommended dose range should be considered.
^** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.

Indications for adults and children over 12 years of age (≥50 kg) that require specific dosage schedules:

Acute otitis media:

A single intramuscular dose of Biophin 1-2 g can be given. Limited data suggest that in cases where the patient is severely ill or previous therapy has failed, Biophin may be effective when given as an intramuscular dose of 1-2 g daily for 3 days.

Pre-operative prophylaxis of surgical site infections:

2 g as a single pre-operative dose.

Gonorrhoea:

500 mg as a single intramuscular dose.

Syphilis:

The generally recommended doses are 500 mg-1 g once daily increased to 2 g once daily for neurosyphilis for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on limited data. National or local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early [Stage II] and late [Stage III]):

2 g once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Paediatric population

Neonates, infants and children 15 days to 12 years of age (<50 kg)

For children with bodyweight of 50 kg or more, the usual adult dosage should be given.

^* In documented bacteraemia, the higher end of the recommended dose range should be considered.
^** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.

Indications for neonates, infants and children 15 days to 12 years (<50 kg) that require specific dosage schedules:

Acute otitis media:

For initial treatment of acute otitis media, a single intramuscular dose of Biophin 50 mg/kg can be given. Limited data suggest that in cases where the child is severely ill or initial therapy has failed, Biophin may be effective when given as an intramuscular dose of 50 mg/kg daily for 3 days.

Pre-operative prophylaxis of surgical site infections:

50-80 mg/kg as a single pre-operative dose.

Syphilis:

The generally recommended doses are 75-100 mg/kg (max 4 g) once daily for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on very limited data. National or local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early [Stage II] and late [Stage III]):

50–80 mg/kg once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Neonates 0-14 days

Biophin is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age).

^* In documented bacteraemia, the higher end of the recommended dose range should be considered.

A maximum daily dose of 50 mg/kg should not be exceeded.

Indications for neonates 0-14 days that require specific dosage schedules:

Acute otitis media:

For initial treatment of acute otitis media, a single intramuscular dose of Biophin 50 mg/kg can be given.

Pre-operative prophylaxis of surgical site infections:

20-50 mg/kg as a single pre-operative dose.

Syphilis:

The generally recommended dose is 50 mg/kg once daily for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on very limited data. National or local guidance should be taken into consideration.

Duration of therapy

The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of Biophin should be continued for 48-72 hours after the patient has become afebrile or evidence of bacterial eradication has been achieved.

Older people

The dosages recommended for adults require no modification in older people provided that renal and hepatic function is satisfactory.

Patients with hepatic impairment

Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment provided renal function is not impaired.

There are no study data in patients with severe hepatic impairment (see section 5.2).

Patients with renal impairment

In patients with impaired renal function, there is no need to reduce the dosage of Biophin provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance <10 ml/min) should the Biophin dosage not exceed 2 g daily.

In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. Biophin is not removed by peritoneal- or haemodialysis. Close clinical monitoring for safety and efficacy is advised.

Patients with severe hepatic and renal impairment

In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.

Method of administration

Intramuscular administration

1g Biophin should be dissolved in 3.5ml of 1% Lidocaine Injection BP. The solution should be administered by deep intramuscular injection.

Intramuscular injections should be injected well within the bulk of a relatively large muscle and not more than 1 g should be injected at one site.

Dosages greater than 1g should be divided and injected at more than one site.

As the solvent used is lidocaine, the resulting solution should never be administered intravenously (see section 4.3). The information in the Summary of Product Characteristics of lidocaine should be considered.

Intravenous administration

For IV injection 1 g Biophin is dissolved in 10 ml of water for injections PhEur. The injection should be administered over 5 minutes, directly into the vein or via the tubing of an intravenous infusion.

Biophin can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes. Intravenous intermittent injection should be given over 5 minutes preferably in larger veins. Intravenous doses of 50 mg/kg or more in infants and children up to 12 years of age should be given by infusion. In neonates, intravenous doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy (see section 4.3 and 4.4). Intramuscular administration should be considered when the intravenous route is not possible or less appropriate for the patient. For doses greater than 2 g intravenous administration should be used.

Biophin is contraindicated in neonates (≤28 days) if they require (or are expected to require) treatment with calcium-containing intravenous solutions, including continuous calcium-containing infusions such as parenteral nutrition, because of the risk of precipitation of Biophin-calcium (see section 4.3).

Diluents containing calcium, (e.g. Ringer's solution or Hartmann's solution), should not be used to reconstitute Biophin vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of Biophin-calcium can also occur when Biophin is mixed with calcium-containing solutions in the same IV administration line. Therefore, Biophin and calcium-containing solutions must not be mixed or administered simultaneously (see sections 4.3, 4.4 and 6.2).

For pre-operative prophylaxis of surgical site infections, Biophin should be administered 30-90 minutes prior to surgery.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

In overdose, the symptoms of nausea, vomiting and diarrhoea can occur. Biophin concentrations cannot be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic.

Unopened - 3 years.

For reconstituted solution, chemical and physical in-use stability has been demonstrated for 24 hours at 25ºC and for four days at 2-8ºC. From a microbiological point of view, once opened, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8ºC, unless reconstitution has taken place in controlled and validated aseptic conditions.

Unopened: Do not store above 25ºC. Keep the vials in the outer carton.

After reconstitution: Store at 2-8ºC, see section 6.3 for complete storage instructions.

Biophin is supplied in Type II 15ml clear glass vials, closed with a Type I rubber stopper uncoated/coated in Omniflex and sealed with an aluminium/plastic cap.

The vials are packed in boxes of 1, 5, 10, 25 or 50 vials.

Not all pack sizes may be marketed.

1 g vial - Concentrations for the intravenous injection: 100 mg/ml,
1 g vial - Concentrations for the intravenous infusion: 50 mg/ml
2 g vial – Concentrations for the intravenous injection or intravenous infusion: approximately 50 mg/ml

(Please refer to section 4.2 for further information).

Reconstitution Table:

¹ For Intravenous injection, 1g Biophin is dissolved in 10ml of Water for Injections. The injection should be administered over 5 minutes, directly into the vein or via the tubing of an intravenous infusion.
² Dosages greater than 1g should be divided and injected at more than one site.
^# These approximate available volume and approximate displacement volume values are when reconstituted using Water for Injections.

The use of freshly prepared solutions is recommended. For storage conditions of the reconstituted medicinal product, see section 6.3.

Biophin should not be mixed in the same syringe with any drug other than 1% Lidocaine Injection BP (for intramuscular injection only).

^* Biophin is compatible with several commonly used intravenous infusion fluids e.g. Sodium Chloride Intravenous Infusion BP, 5% or 10% Glucose Intravenous Infusion BP, Sodium Chloride and Glucose Intravenous Infusion BP (0.45% sodium chloride and 2.5% glucose), Dextran 6% in Glucose Intravenous Infusion BP 5%, isotonic hydroxyethylstarch 6-10% infusions and Water for Injections.

The reconstituted solution should be clear. Do not use if particles are present.

Biophin sodium when dissolved in Water for Injections Ph Eur forms a pale yellow to amber solution. Variations in the intensity of colour of the freshly prepared solutions do not indicate a change in potency or safety.

For single use only. Discard any unused contents.