MEDAXONUM Powder for solution for injection/infusion Ref.[28308] 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 ceftriaxone 1-2 g can be given.
Limited data suggest that in cases where the patient is severely ill or previous therapy has failed, Medaxonum 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 Medaxonum 50 mg/kg can be given. Limited data suggest that in cases where the child is severely ill or initial therapy has failed, Medaxonum 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

Medaxonum 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 Medaxonum 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 ceftriaxone 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 ceftriaxone provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance <10 ml/min) should the ceftriaxone dosage not exceed 2 g daily.

In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. Ceftriaxone 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

Medaxonum can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes, or by deep intramuscular injection. 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 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. 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.

If lidocaine is used as a solvent, 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.

Ceftriaxone 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 ceftriaxone-calcium (see section 4.3).

Diluents containing calcium, (e.g. Ringer’s solution or Hartmann’s solution), should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for intravenous administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, ceftriaxone 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, ceftriaxone 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. Ceftriaxone concentrations cannot be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdose should be symptomatic.

36 months.

Reconstituted solution: The reconstituted solution is preferably to be used immediately.

Chemical and physical in-use stability has been demonstrated for 6 hours at 25°C and 24hours at 2°C – 8°C.

From microbiological point of view, 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 24hours at 2°C – 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Powder for injection: This medicinal product does not require any special temperature storage conditions. Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Medaxonum250 mg, Medaxonum 500 mg, and Medaxonum 1 g are supplied in clear type I glass vials, nominal capacity 10 ml, sealed with a 20 mm diameter grey bromobutyl rubber stopper and aluminium overcap, in a carton with a leaflet.

Medaxonum 2 g are clear type I glass vials having a nominal capacity of 20 ml sealed with a 20 mm rubber stoppers and an aluminium cap.

Cartons containing 1, 10, 50, or 100 vials are available for Medaxonum" 250 mg,
Medaxonum 500 mg, and Medaxonum 1 g.

Cartons containing 1, 10, 25, 50, or 100 vials are available for Medaxonum 2g.

Not all pack sizes may be marketed.

Concentrations for the intravenous injection: 100 mg/ml,
Concentrations for the intravenous infusion: 50 mg/ml.

Reconstitution for injection

Reconstitution should be carried out under suitable conditions and with appropriate precautions to prevent microbial contamination. It is recommended that freshly prepared solutions be used; the solutions retain satisfactory potency for six hours at a temperature not exceeding 25°C, and up to twenty four hours at 2 to 8°C. Following reconstitution, a pale yellow to amber solution is produced.

Intramuscular injection: Reconstitution uses Lignocaine hydrochloride 1.06% injection; 250 mg ceftriaxone should be reconstituted using 1 ml of Lignocain hydrochloride 1.06% injection, 500mg ceftriaxone should be reconstituted using 2ml of Lignocain hydrochloride 1.06% injection and 1 g should be reconstituted using 3.5 ml of Lignocain hydrochloride 1.06% injection. 2g ceftriaxone should be dissolved in 7.0ml of 1% Lidocaine Injection. Administration is by deep intramuscular injection. If the dosage exceeds 1 g, the dose should be divided equally and administered at more than one injection site. Solutions reconstituted in Lignocaine should not be administered intravenously.

Intravenous injection: Reconstitution uses Water for Injection; 250 mg and 500 mg ceftriaxone should be reconstituted by dissolving in 5 ml of water and 1 g should be dissolved in 10 ml of water. Administration is by slow intravenous injection over two to four minutes.

Intravenous infusion: 2g of ceftriaxone should be dissolved in 40ml of one of the following calcium-free solutions; Glucose Intravenous Infusion 5% or 10%, Sodium Chloride Intravenous Infusion, Sodium Chloride and Glucose Intravenous Infusion (0.45% sodium chloride and 2.5% Glucose), Dextran 6% in Glucose Injection 5%, isotonic hydroxyethylstarch 6-10% infusions. The infusion should be administered over at least 30 minutes.

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

Reconstitution should be carried out under suitable aseptic precautions. Following reconstitution the solution should be visually examined for any foreign particulate matter and discarded if any is observed. It is recommended that reconstituted solution is used immediately following preparation. The solutions retain satisfactory potency for six hours at a temperature not exceeding 25°C, and up to twenty four hours at 2 to 8°C. Medaxonum vials are for single use only, any remaining suspension/solution should be discarded.