STERISOL FERMENTMYCIN INFUSION

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

STERISOL FERMENTMYCIN INFUSION

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

STERISOL FERMENTMYCIN INFUSION

COMPOSITION:
Gentamicin sulphate equivalent to 80 mg base per 100 mL

PHARMACOLOGICAL CLASSIFICATION:
A20.1.1 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Gentamicin is a bactericidal aminoglycoside antibiotic with a wide range of activity against both Gram-positive and Gram-negative organisms including strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, Klebsiella species and Proteus species.

INDICATIONS:
Sterisol Fermentmycin Infusion is indicated for the following conditions, when caused by susceptible organisms:

1.	Acute and chronic urinary tract infections.
2.	Severe systemic infections, e.g. sepsis, peritonitis.
3.	Bone and soft-tissue infections, e.g. acute osteomyelitis, wound and soft tissue infections.
4.	Infected burns.
5.	Respiratory tract infections.
6.	Eye infections.

CONTRA-INDICATIONS:
Established intolerance to Gentamicin.

DOSAGE AND DIRECTIONS FOR USE:
Sterisol Fermentmycin Infusion for intravenous administration should be utilised in special cases (refer intravenous Administration).

Adult Patients with normal renal functions:

1.	Urinary tract infections: In infections of moderate severity: 2 mg/kg/day in 3 equal doses (8 hourly), In patients with severe infections: 3 mg/kg/day in 3 equal doses (8 hourly). In the treatment of urinary tract infections with gentamicin, alkalis should be given concomitantly to raise the urinary pH above 7.
2.	Systemic infections: In infections of moderate severity: 2 mg/kg/day in 3 equal doses (8 hourly). In patients with severe infections: 3 mg/kg/day in 3 equal doses (8 hourly).
3.	Life-threatening infections (e.g. sepsis)
	(a)	ADULTS: For patients with life-threatening infections up to 5 mg/kg/day in 3 equal doses (8 hourly). This dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.
	(b)	CHILDREN, INFANTS AND NEONATES: Children: A dose of 3 to 6 mg/kg/day is administered in three equally divided doses every 8 hours. Infants older than 1 week: Administer 3 to 6 mg/kg/day as for 'Children' above, or in two equal doses every 12 hours. Neonates and infants less than 1 week: 6 mg/kg/day is administered in two equally divided doses every 12 hours.

Duration of Treatment:
In all cases, the general duration of treatment is 7 to 10 days. When treatment exceeds this period, and in the administration of high dosage levels, it is advisable to monitor renal, auditory and vestibular functions (see Side-effects and special precautions).

INTRAVENOUS ADMINISTRATION:
This form of administration is only recommended when circumstances do not permit the intramuscular route. The recommended dose and precautions for intravenous administration are identical to those stipulated for the intramuscular route. Intravenous administration is to be carried out slowly or may be infused over a period up to 2 hours.
At room temperature Dextrose 5%, Dextrose-saline and normal saline infusion can be used as diluent. Adding carbenicillin or ampicillin causes significant potency losses, while cephalothin and cloxacillin addition causes visible precipitation. Chloramphenicol sodium succinate and Vit. B-complex are also incompatible with gentamicin.

Patients with impaired renal function:
Dosage must be adjusted in patients with impaired renal function. To minimise risk of toxicity in these patients, the first dose should be that normally recommended. Subsequent doses should be administered less frequently depending on the degree of renal impairment. Since the serum half-life of gentamicin has a close correlation with creatinine clearance and serum creatinine, the serum half-life (in hours) of gentamicin may be estimated by multiplying the serum creatinine (expressed in mg %), by four. The Interval between doses, in hours, may be approximated by doubling the serum half-life.

Table 1 provides the guidance for adjustment of the interval between doses of Gentamicin injection based on the aforementioned renal function tests.

In those instances when only a blood serum urea concentration is available this value may be utilised initially; however, it should be supplemented with a serum creatinine level or creatinine clearance rate whenever possible.
This dosage schedule is not intended as a rigid recommendation. It is provided as a guide to dosage when the measurement of gentamicin serum levels is not feasible. It should be used in conjunction with close clinical and laboratory observation of the patient, and modified as deemed necessary by the treating physician.

TABLE 1
Approximate dosage guidelines for Sterisol Fermentmycin Infusion in adult patients based on renal function.

Renal Function Test
Body Mass of Adult Patient (kg)	Dose (mg)	Creatinine Clearance Rate (mL/min)	Serum Creatinine (mg %)	Blood Urea (mg %)	Frequency of Administration
Over 60	80	Over 70	less than 1,4	less than 38	every 8 hours
		35-70	1,4-1,9	36-63	every 12 hours
		24-34	2,0-2,8	64-84	every 18 hours
		16-23	2,9-3,7	85-105	every 24 hours
		10-15	3,8-5,3	106-159	every 36 hours
		* 5-9	5,4-7,2	160-214	every 48 hours
60 or less	60	(same as above)	.	.	.

* When the creatinine clearance level is less than 5 mL/min, then haemodialysis is indicated. Gentamicin is dialysable and the dose should be individually adapted to the patient after each period of dialysis.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Hypersensitivity reactions have occured and cross-sensitivity with neomycin and kanamycin may occur. Less frequent effects include anaemia, purpura, convulsions, increased serum aminotransferase values and increased serumbilirubin concentrations. Reversible nephrotoxicity may occur and acute renal failure has been reported often in association with the concurrent administration of cephalosporin antibiotics.
Ototoxicity may occur. Patients with impaired renal function or those patients treated with gentamicin infusion for longer periods or at higher dosage than recommended, are especially susceptible to ototoxicity (Both vestibular and auditory).
In such patients, the frequency of gentamicin administration should be reduced as indicated under dosage and directions for use, by assessing blood urea, creatinine or creatinine clearance rates. It is considered advisable to check auditory and vestibular function and to monitor peak (one hour) gentamicin serum levels, as plasma concentrations above 10 to 12 µg/mL are associated with a high risk of toxicity. If symptoms of ototoxicity occur, gentamicin should be withdrawn immediately.
The concurrent use of gentamicin with diuretics such as ethacrynic acid and furosemide, should be avoided, as these two diuretics may individually result in ototoxicity. Similarly gentamicin should not be administered concurrently with other potentially ototoxic drugs (e.g. kanamycin, neomycin, streptomycin). Anti-emetics may mask symptoms of ototoxicity. Gentamicin and carbenicillin sodium should be administered separately when both are required. Caution should be exercised in the simultaneous administration of potentially nephrotoxic substance with gentamicin.
Gentamicin should not be administered concurrantly with neuromuscular blocking agents. Administer with caution to patients with myasthenia gravis.

PREGNANCY:
Safety in pregnancy has not been established.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See "Side-effects and special precautions".
Treatment is symptomatic and supportive.

IDENTIFICATION:
A clear solution.

PRESENTATION:
100 mL P.V.C. bags for I.V. infusion containing 80 mg Gentamicin base.

STORAGE INSTRUCTIONS:
Store below 25°C
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
U/20.1.1/155

NAME AND BUSINESS ADDRESS OF APPLICANT:
INTRAMED (Pty.) Ltd.
6 Gibaud Road
Port Elizabeth 6001

DATE OF PUBLICATION OF THIS LEAFLET:
October 1988

12-143/10-92