ERYTHROMYCIN Powder for solution for infusion Ref.[6823] Active ingredients: Erythromycin

Intravenous therapy must be replaced by oral administration at the appropriate time.

Posology

Adults and children over 12 years old or weighing >40 kg

The usual dose is 1 to 2 g per day equivalent to 25 mg/kg/day in divided doses (generally 3-4 single doses).

Severe infections

Dosage can be increased up to 4 g per day equivalent to 50 mg/kg/day in severe infections.

The maximum daily dose is 4 g.

Children up to 12 years old or weighing ≤ 40 kg

1 months to up to 12 years old: The daily dose for infants and children up to 12 years old for most infections is 15-20 mg of erythromycin/kg of body weight divided over 3-4 single doses. This dose may be doubled depending on the indication.

Term newborn infants (birth to 1 month)

10-15mg/kg/day divided over 3 singles doses

Renal/hepatic impairment

Patients with impaired hepatic function

In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in the bile. Although the effect of hepatic dysfunction on the excretion of erythromycin and its half-life in such patients is not known, caution should be exercised in administering the antibiotic in such cases particularly if patients with acute hepatic insufficiency receive high doses of erythromycin. In that case, monitoring of serum levels and dosage reduction will be required.

Patients with impaired renal function

The low proportion of renal excretion would suggest that dosage modification in patients with impaired renal function (slightly or moderately impaired renal function with creatinine clearance levels higher than 10ml/min) may not be necessary.

For patients with moderate to severely impaired renal function, however, toxicity has been reported and dosage adjustment in these cases may be warranted:

• Administration of doses of ≥4 g/day may increase the risk for the development of erythromycin-induced hearing loss in elderly patients, particularly those with reduced renal or hepatic function.
• In moderate to severely impaired renal function (with a level of serum creatinine of 2.0 mg/dl, kidney failure with anuria), the maximum daily dose for adolescents over 14 years old and adults (with a body weight over 50 kg) is 2 g erythromycin per day.
• In patients with severe renal insufficiency (creatinine clearance levels lower than 10ml/min), the erythromycin dose must be reduced to 50% to 75% of the normal dose, to be administered in accordance with the usual treatment regimen. The maximum daily dose must not exceed 2g.

Erythromycin is not removed by haemodialysis or peritoneal dialysis. For patients who have regular dialysis, an additional dose is therefore not recommended.

Elderly

Use adult dosage with care. Elderly patients, particularly those with reduced renal or hepatic function may be at increased risk for developing erythromycin-induced hearing loss, when erythromycin doses of 4 g/day or higher are given.

Method of administration

Precautions to be taken before handling or administering the medicinal product

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

Erythromycin can be administered in continuous or intermittent infusion.

The infusion should be administered over 60 minutes as a rapid infusion is more likely to be associated with local irritative effects as well as QT interval prolongation, arrhythmias or hypotension. A longer period of infusion should be used in patients with risk factors or previous evidence of arrhythmias. Not less than 100 ml of diluent should be used for preparing intermittent I.V. solutions so as to minimise venous irritation. For 100 ml of infused solution, this corresponds to about 35 drops/minute, for 250 ml of infused solution 85-90 drops/minute and for 500 ml of infused solution 170-180 drops/minute.

The erythromycin concentration should not exceed 5mg per ml and an erythromycin concentration of 1mg/ml (0.1% solution) is recommended.

Erythromycin should only be administered intravenously. Intra-arterial injection is strictly contraindicated. It can lead to angiospasm with ischaemia. Intramuscular administration and IV bolus injection are also contraindicated.

Intravenous therapy should be replaced by oral administration after 2-7 days. In the interest of sustaining successful treatment, erythromycin should be continued for a further 2-3 days after symptoms have disappeared.

The toxicity is low. Overdosage may be associated with ototoxicity, hearing loss, cholestasis, ventricular arrhythmias, severe nausea, vomiting and diarrhoea. The symptoms are typically reversible and will disappear when treatment with erythromycin is discontinued. No specific treatment has been proposed other than general supportive measures. In the event of an overdose, treatment with erythromycin should be paused or terminated depending on the symptoms. Erythromycin cannot be removed with peritoneal or haemodialysis.

Shelf life: 36 months.

For the reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 h in the refrigerator (2 to 8°C).

For the diluted solution: Chemical and physical in-use stability has been demonstrated for 24 h in the refrigerator (2 to 8°C).

From a 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 24 hours in the refrigerator, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

No special storage condition.

For storage conditions after reconstitution of the medicinal product, see section 6.3 and section 6.6.

Colourless type III vials clear glass vial. Pack size of 1, 10 or 25 glass vials.

Not all pack sizes may be marketed.

Each vial is for single use only.

Erythromycin is reconstituted and then further diluted prior to infusion.

Preparation of the solution for administration

A double dilution is required. An initial solution corresponding to 50 mg/ml of erythromycin base is prepared by adding 20 ml of water for injections to the content of the vial of Erythromycin Panpharma 1 g (shake abundantly until complete dissolution). For this step, a 0.9% sodium chloride solution should not be used.

The reconstituted solution can be kept in the refrigerator for 24 hours.

The diluted solution for administration: only a 0.9% sodium chloride solution or water for injection or a 5% glucose solution are to be used. It is prepared under the same conditions by mixing the content of the vial of Erythromycin Panpharma 1 g (20 ml) to 500 ml of 0.9% sodium chloride solution or water for injection or 5% glucose solution. The diluted solution can be kept in the refrigerator for 24 hours. The diluted solution is administered without addition any other substance whatsoever.

In children, adjust the quantity of initial solution for dilution and the volume of perfusion to the dosage chosen according to the child’s weight.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.