Posology : מינונים

4.2 Posology and method of administration

Posology
Dosage in patients with normal renal function

Adults and adolescents
Treatment of bacterial infections
The daily dose recommended in adolescents and adults with normal renal function, is 3 – 6 mg/kg body weight per day as 1 (preferred) up to 2 single doses.
A maximum daily dose of 6 mg/kg may be needed for the treatment of serious infections and when the susceptibility of the pathogen is relatively poor.
Gentamicin has a long-lasting post-antibiotic effect (see section 5.1). Recent in vitro and in vivo studies show, that the uptake of aminoglycosides in renal cortex is limited and hence, with higher peak serum gentamicin levels (after single daily dosing) less aminoglycoside is stored in the kidneys than with conventional multiple dosing.
In the case of combination treatment (e.g. with a beta-lactam antibiotic in the normal dosage) it is also possible to administer the total daily dose as a single dose once a day.
Due to the requirement for dose adjustments once daily dosing of gentamicin is not recommended for patients with weakened immunity (e.g. neutropenia), severe renal failure, ascites, bacterial endocarditis, patients with extensive burns (more than 20% of the skin), and in pregnancy.
The duration of treatment should be limited to 7 – 10 days. A longer duration of treatment may be necessary in difficult and complicated infections.

Paediatric population
The daily dose in newborns is 4 – 7 mg/kg body weight per day. Due to the longer half-life, newborns are given the required daily dose in 1 single dose.
The daily dose in infants after the first month of life is 4.5 – 7.5 mg/kg body weight per day as 1 (preferred) up to 2 single doses.
The daily dose recommended in older children with normal renal function is 3 – 6 mg/kg body weight per day as 1 (preferred) up to 2 single doses.
One 80 ml bottle of Gentamicin 1 mg/ml solution for infusion (Gentamicin 3 mg/ml solution for infusion) contains 80 mg gentamicin (240 mg gentamicin). To avoid overdosing especially in children, Gentamicin 1 mg/ml solution for infusion (Gentamicin 3 mg/ml solution for infusion) should not be administered to children who need less than 80 mg gentamicin (240 mg gentamicin) per dose.

Dosage in patients with renal impairment
In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function.
Patients with renal function impairment should be monitored in order to adjust the therapeutic concentrations in plasma, either by decreasing the dose or by increasing the dosage interval (see section 4.4).
Dose reduction and interval prolongation are equivalently suitable solutions. Nonetheless, it should be remembered that doses determined in the way described below are only approximate and that the same dose may lead to different concentrations in the organisms of different patients. Therefore gentamicin serum levels should be determined in the given patient, so that the dosage can then be adapted accordingly.

1) Extension of dosage interval at the normal dose:
Since the gentamicin clearance is directly proportional to the creatinine clearance, the following approximate equation may be used:
Normal dose interval × (normal creatinine clearance/creatinine clearance of the patient) = subsequent dose interval.
Based on a normal creatinine clearance of 100 ml/min and a creatinine clearance of 30 ml/min in the patient, the application interval with a constant dose would in this case be 26 hours (8 × 100/30 [h]).

Normal dose (80 mg) at extended dose interval:
Blood urea           Creatinine clearance          Dose and dosage interval (mmol/l)             (ml/min)
 6.7                > 72                          80* mg every 8 hours 6.7 – 16.7           30 – 72                       80* mg every 12 hours 16.7 – 33.3          12 – 30                       80* mg every 24 hours > 33.3               6 – 12                        80* mg every 48 hours *In case patient’s weight is < 60 kg the dose should be decreased to 60 mg 

2) Reduction of dose at the normal dose interval:
After the usual initial dose, dividing the normal recommended dose by the serum creatinine may be taken as a rough guide for the measurement of the reduced dose that should be administered every 8 hours.
30 mg may therefore be administered every 8 hours to a patient weighing 60 kg with a serum creatinine level of 2.0 mg/100 ml after an initial dose of 60 mg (1 mg/kg; 60:2).
Alternatively, after the usual initial dose, subsequent doses every 8 hours may be calculated to the formula: Normal dose × creatinine clearance of the patient/normal creatinine clearance (100 ml/min) = subsequent dose.


Reduced dose at normal dose interval (8-hourly):
Serum creatinine Approximate rate of        Percentage of
(mg/100 ml)       creatinine clearance    the normal dose
(ml/min)
 1.0                > 100                  100
1.1 – 1.3             70 – 100                 80
1.4 – 1.6             55 – 70                  65
1.7 – 1.9             45 – 55                  55
2.0 – 2.2             40 –  45                 50
2.3 – 2.5             35 – 40                  40
2.6 – 3.0             30 – 35                  35
3.1 – 3.5             25 – 30                  30
3.6 – 4.0             20 – 25                  25
4.1 – 5.1             15 – 20                  20
5.2 – 6.6             10 –  15                 15
6.7 – 8.0               < 10                   10

The creatinine clearance should be preferred as a parameter especially in the elderly and in patients with fluctuating serum-creatinine concentrations, as is observed in severe infections (e.g. sepsis).
It should be emphasized that renal function may change during therapy with gentamicin.

Dosage in patients undergoing haemodialysis
Gentamicin is dialysable. In the case of a 4 – 5-hour haemodialysis, a 50% – 60% reduction in concentration should be expected and in the case of an 8 – 12-hour haemodialysis, a 70% – 80% reduction in concentration.
The dosage must be individually adjusted after each dialysis, based on the gentamicin serum concentration at that time.
The normal recommended dose after dialysis is 1 – 1.7 mg/kg body weight.
Elderly patients may require lower maintenance doses than younger adults because of impaired renal function.

In obese patients the initial dose should be based on ideal body weight plus 40% of weight excess.

In patients with impaired hepatic function no dose adjustment is necessary.
Monitoring advice:
Serum concentration monitoring of gentamicin is recommended, especially in elderly, in newborns and in patients with impaired renal function. Blood samples are taken before the start of the next dosage interval (trough level). Trough levels should not exceed 2 μg/ml administering gentamicin twice daily and 1 μg/ml for a once daily dose. Please refer to section 4.4.


Method of administration
Gentamicin B. Braun 1 mg/ml solution for infusion and Gentamicin B. Braun 3 mg/ml solution for infusion is administered by intravenous infusion over a period of 30 – 60 minutes. Gentamicin B. Braun 1 mg/ml and Gentamicin B. Braun 3 mg/ml are not suitable for intramuscular or slow intravenous injection.
Only for intravenous use.