Garamycin

Garamycin

Garamycin* injection
40 mg per ml & 80 mg per 2 ml. Brand of gentamicin sulfate injection, aqueous solution
FDR PARENTRAL ADMINISTRATION (intramuscular and Intravenous)
Description: Each ml of Garamycln injection contains the aminoglycoslde antibiotic gentamicin sulfate. equivalent to 40 mg gentamicin base,
methylparoben and propytparaben as preservatives sodium bisuiitte and disodlum edetale.
Actions: Microbiologyzin vrlro tests have demonstrated that gentamicin is a bactericidal antibiotic which acts by inhibiting protein synthesis in
susceptible microorganisms. it is active against a wide variety of pathogenic Gram-negative and Gram-positive bacteria, including Escherichia coll,
Proteus sp. [lhdole - positive and lhdoie - negative]. Pseudomonas aeruglnosa. species of the Klebsiella -Ehterabacter - Serralia group, Cltrobacter
sp., Prowdencia sp.. Staphylococcus sp. [coogulase-positive and cooguiase-negative, including penicillin and methlclllin - resistant strains], and
Nelssella gonorrhoeae. Gentamlcln is also active in vttro against species oi Salmonella and Shigello. in vltro studies have shown that an
“aminoglycoslde combined with an antibiotic that interferes with cell wall synthesis may act synerglstlcally against some group D streptococcal
strains. The combination of gentamicin and penicillin G has
a synergistic bactericidal effect against virtually all strains of Streptococcus faecolis and its varieties [S. faecalls var.liquifaciens. S. faecatis var.
zymogenes]. S. faeclum and S.durans. Ah enhanced killing effect against many of these strains also has been shown in vllro wth combinations of
gentamicin and amplcmin, carbeniclmn. hafcillin or oxacllllnfihe combined eflect of gentamicin and corbenlclliln is synergistic for many strains of
Pseudomonas aeruginosa. in vltro synergism against other Gram-negative organisms has been shown with combinations of gentamicin and
cephalosporins. Genfamicin may be active against clinical isolates of bacteria resistant to other aminogiycosides. Bacteria resistant lo one
aminoglycoslde may be resistant to one or more other aminogiycosides. Bacterial resistance to gentamicin is generally developed slowly.
indications and Usage: Garamycln injection is indicated in the treatment of infections caused by susceptible strains of the following
microorganisms: Pseudomonas aeruginosa. Proteus sp. [indole-positive and ihdole-negative], Escherichia coli. Klebslella-Enterobacter -Serrotia Sp.
Providehcia sp., Staphylococcus sp. [coaguiase-positive and coagulase-negative. including penicillin and methicillin -resistant strains], and Neisselia
gonorrhoeae. Clinical studies have shown Garamycln injection to be effective in:
- Sepiicemio. bacteremio [including neonatal sepsis].
- Serious infections of the central nervous system [CNS] [including meningitis].
- infections of the kidney and genito - urinary tract {including pelvic]. '
- Respiratory tract infections. - - infections of the gastrointestinal tract.
- Skin, bone or salt tissue infections [including infected bums and wounds]. =
- lntra-abdominal infections [including peritonitis] - Ocular infections.
Garamycin injection may be considered as initial therapy in suspected or conflrrhed Gram-negative infections. in suspected Gram-negative
infections, the decision to continue therapy with Garamycin injection should be based on results of susceptibility tests and the patients clinical
response and tolerance to the drug. in serious infections, when the causative microorganisms are unknown. Garamycln injection may be
adminbtered as initial therapy in conjunction with a penicillin or cephalosparin type drug before obtaining results of susceptibility testing. if
anaerobic micro-organisms are suspected. suitable antimicrobial therapy in conjunction with Garamycln lniectlon or other appropriate antibiotic
therapy should then be continued. Garamycin injection has been used effectively in combination with corbenlclliln or ticarcillin for the treatment of
life-threatening infections caused by Pseudomonas oeruginosa. it has also been found effective when used in conjunction with a penicillin-type
drug for the treatment of endocarditis caused by group D streptococci. in the neonate with suspected sepsis or staphylococci pneumonia. a
penicillin-type drug is also usually indicated as concomitant therapy with gentamlcin.Garamycin injection has been shown to be effective in the
treatment of serious staphylococcal infections. in the pert-operative period, Garamycln injection may be started preoperahreiy and continued
pastoperativeiy for treatment of suspected or proven infection due to susceptible microorganisms. Subconjunctival administration of gentamicin is
recommended for treatment of endophlhaimitis caused by sensitive microorganisms. ll may be used prophylaclically in patients undergoing high
risk intraocular Surgery, especially if preoperative cultures or smears contain Gram-negative microorganisms. Garamycin injection may also be
administered by _
direct endotracheal instillation or by hebuilzatlonosan adlunct to systemic therapy in the treatment of serious pulmonary infections. Garamycin
lntrathecai injection is indicated as an adjunct to systemic therapy in the treatment of serious CNS infections, such as meningitis and ventrlcuiitis
caused by susceptible Gram-negative microorganisms. A preservative free intralhecai presentation is available.
Dosage and Administration: The recommended dosage for intravenous and intramuscular administration is identical. Garamycin injection also
may be administered by subconjunctivol or subtenon injection, nebulization or direct endotrocheal lnstltialloh. The patient pretreatment body
weight should be obtained for calculation of correct dosage. Garamycin lniectlon shouki not be physically premixed with other drugs but should be
administered separately in accordance with the recommended route of administration and dosage schedule. it is deslralde to measure peak and
trough gentamicin serurh concentration to assure adequate, but not excessive levels. The peak concentration is expected to be in the range of 4
lo o mcgiml. Trough levels above 2 mcglml should be avoided. Determination of the adequacy of a serum level for a particular patient must take
into consideration susceptibility of the causative microorganism, severity of infection, and the status of the patients host-defense mechanisms. The
usual duration of treatment for all patients is seven to ten days. in complicated infections. a longer course of therapy may be necessary. in such
cases monitoring of renal, auditory and vesfibuiar functions is recommended, since toxicity is more likely to occur with treatment extended over ten
days. Dosage should be reduced if clinically indicated.
lntrarnuscular Administration: -
Patients with Normal Renal Function:
Adults: Recommended dosage of Garamycin injection for patients with serious infections and normal renal function is 3 mgii<g.iday, administered in
three equal doses every eight hours or two equal doses every l 2 hours. A simplified dosing may be used for adults weighing over 60 Kg, BU mg
three times daily or a dose of i 20 mg may be given every i2 hours, for adults vrleighlng 60 kg or less. 60 mg three limes daily. For very small or
very large adults. dosage should be calculated in milligram per kilogram of lean body weight. For patients with life-threatening infections.
dosages up to 5 mgikglday may be administered in three or four equal doses. This dosage should be reduced to 3 mglkglday as soon as clinically
indicated. When systemic or urinary tract infections are of moderate severity and the causative microorganism is likely to be highly responsive. a
dosage of 2 mglkglday administered in two equal doses may be considered. However. if prompt clinical response is not apparent, dosage should
be increased to 3 mg,l'kgr’doy administered in three equal doses. Gentamicin is highly concentrated in urine and renal tissue. in patients with urinary
tract infection, particularly if chronic or recurrent and without evidence of impairment of renal function, Garamycin injection may be administered
lniramuscularly in a dose of lse mg once a day for 7 to l0 days. For adults weighing less than 50 Kg the single daily dose should be 3 mgrkg of
body weight.
Pediatric Patients:
* Premature or full term neonates one week of age or less: 5 to 6 mgikgiday (2.5 to 3 mgrkg administered every 12 hours]
* Neonates aver one week or age and infants; 7.5 r-nglkglday [2.5 mg-‘kg administered every 8 hours]
* Children: o to 7.5 mgrkglday [2 to 2.5 mgfkg administered every B hours].A garamycih pediatric injection formulation is available.
Patients with impaired Renal function: Dosage must be adjusted in patients with impaired renal function. Whenever possible. serum
concentrations of gentamicin should be monitored. Dosage schedules are not intended as rigid recommendations. but are provided as guides to
dosage when the measurements ofgentamlcln serum levels is not feasible. One method of dosage adjustment is to increase the interval between
administration of the usual doses. Since the serum crealinine concentration has a high correlation with the serum half-life of gentamicin, this
laboratory fest may provide guidance for adjustment of the interval between doses. The interval between doses [in hours] may be approximated by
multiplying the serum crealinine level [mgli U0 ml] by 8 [Table i]. For example, a patient weighing so Kg with a serum crealinine level of 2 mgli O0
ml could be given 60 mg [I mg,iKg] every To hours [2 mgll U0 ml x B].
Table T Dosage adjustment Guide For Patients With Renal impairment [ Interval of administration between usual doses is prolonged]
T __ ___
weight of 1
Adult l
Patients j
Dose
’ Ereellnlrre
clearance
rate
lL‘!."£"."l
‘ Greatlnlrre um
illilgflflfiml) 1 Nitrogen l
Blood .
rmr ran my _7 j
Frequency of
adlhinletrflflon
. r
Over 60
Ks
tllilmg I
{2mt}
Over 7'0
35-til
14- 34
15-23
10-15
5-O
1.4-1.!
2.0-Z.l
2.!-3.?
8.I~r5.3
5.4-7.2
Leeelhen 1.4 Leunnn la
ll-2!
30-30 ‘
Ml-ID
5|]-H
rs-100
Every 8 hours
Evlry 12 hour!
Every ti hour!
Every 2-I hours
Every 3! llourl ‘
Everydllmra [
l
lone
°°"il°' \ sr:rmgr1.smn
ebovo--
r hm‘ Samoan Semen
j - glsqyni " above ..abovre .
in patients with serious systemic infections and renal impairment, it may be desirable to administer the antibiotic more frequently but in reduced
dosage. in such patientsgehtamlctn serum concentrations should be measured. After the usual initial dose, a rough guide for determining reduced
dosage at eight-hour intervals is to divide the normally recommended dose by the serum crealinine level [ Table 2]. For example. after an initial
dose of so mg fl mg I kg ]. a patient weighing 60 kg with a serum crealinine level of 2.0 mgr 100 ml could be given 30 mg every eight hours
[60:21 . it should be noted that the status of renal function may be changing over the course of the infectious process.
Table 2 Dgwge adjustment Guide For Patlentstojjth Renal lmpalrrnentl Decreasedposage at Eight - Hour Intervals After the usual Initial Dose]
i
[ l mg  100
mil
_ (mli
Clearance Rate:
Serum C reatulinr: V ‘ Approximate Crcatiniru: Percent of usual dose l _
1-110
1.1-1.3
l.4-in
r.r-1.4
2.0-2.2
2.3-2.5
2.r>-3.0
3.1-3..-1
3.6-4.0
4.1-5.1
\ 5.2-6.6
l
mirj|i|.73 m2) ____
T r00
.-~r00
to-100
55-r0
45-55
40-45
35-40
30-35
25-30
20-2s
15-20
10-rs
<10”
80
65
55
SO
40
35
30
25
20
15
14
in adults with renal failure undergg nemodiaiysls. the amount of gentamicin removed from the blood may vary depending upon several factors
including the dialysis method used. A six-hour hemodialysis may reduce gentamicin serum concentrations by approximately 50 %.Shorter dialysis
sessions will remove less drug. Recommended dosage at the end of each dialysis period is l to i .7 mg l kg depending upon the severity of
infection. in children. a dose of 2.0 to 2.5 mg i kg may be administered. Amlhogiycosides are also removed by peritoneal dialysis but at a rate
considerably less than by hemadiatysis.
intravenous Administration: intravenous administration of gentamicin is useful for treating patients with septicemia or those in shock. ll may also be
the preferred route of administration for some patients mm congestive heart failure, hematologic disorders, severe bums, or those with reduced
muscle mass. For intravenous administration in adults. a single dose of Gararnycln injection may be diluted in 50 to 200 ml of sterile normal saline or
in a sterile solution of dextrose 5 % in water: in infants and children, the volume of diluent should be less. the solution may be infused over a period
of one half to two hours.ln certain circumstances a single dose of Garamycln injection may also be given directly lhta a vein or l.V. tubing slowly
over a period of 2 to 3 minutes.
Concomitant therapyrln combination wlh other antibiotics, the dosage of Garamycln injection must not be reduced.
Adverse reactions:
-Nephrotoxlcity : Adverse renal eliects occur more frequently in patients with a history of renal impairrnenl and in patients treated for longer periods
or with larger than recommended dosage.-Neurotoxicity : Adverse effects on both vestibular and
auditory branches of the eight cranial nerve have been reported primarily in patients with renal impairment and in patients on high doses ahdlor
prolonged therapy. symptoms include dizziness, vertigo. tinnitus, roaring in the ears and hearing loss. Hearing loss is usually manifested initially by
diminution of high lone ocully and may be irreversible. Other factors that may increase the risk of aminoglycoslde induced otoloxicily include
dehydration, concomitant administration of ethacryhic acid or furosemlde or previous exposure to other ototoxlc CltUgS.NUr‘i'rbf'l9SS, skin tingling.
muscle twitching, convulsions and myasthenia gravis like syndrome also have been reported.Olher reported adverse reactions possibly related to
gentamicin include:respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight lass, hypotehslon.
hypertension, rash. itching, urticaria. generalized buming. lOl\fflg9O| edema. anaphylactoid reactions, fever. and headache. nausea. vomiting,
increased satlvalion, slorhaiitls. purpura, pseudotumor cerebri, acute organic brain syndrome. pulmonary fibrosis. alopecio, joint pain, transient
_..*
hepatomegaly. and spleenomegaiy. Laboratory abnormalities possibly related to gentamicin include: increased serum iransaminose [ SGOT , SGPT
], and increased serum lactic dehydrogenase [LDH ] and blllrubin, decreased serum calcium, magnesium. sodium and potassium. anemia.
ieukopenla, granuiocviopehia, transient agranuiocytasla. eosinophilia, increased and decreased reticuiocyte counts, and thrombocytopenia. While
clinical laboratory tests abnormalities may be isolated findings they may be associated with clinically related signs and syrhptomswhile local
tolerance to Garamycin injection is generally excellent. there has been an occasional report of pain at the injection site. Subcutaneous atrophy or
fat necrosis suggesting local irritation has been reported rarely. .
Contraindications: Hypersensitivity or serious toxic reactions to gentamicin or other aminogiycosides controindicates its use.
Precautions:
- Neurotoxlc and nephrotoxic antibiotics may be absorbed from body surface after local irrigation or application. the potential
toxic effect of antibiotics administered in this fashion should be considered. increased nephrotoxlclty has been reported following -concomitant
administration of aminoglycoslde antibiotics and some cephaiasparins.-Neuromuscular blockade and respiratory paralysis have been reported in
the cat receiving high doses [ 40 mglkg] of gentamicin. the possibility of these phenomena occurring in man should be considered if gentamicin is
administered to patients receiving neuromuscular blocking agents, such as succlnylchollhe, tubocurarine or decamethonium; anesthetics or
massive transfusions of citrate-anlicoagulated blood. if blockade occurs. calcium salts may reverse these phenomena.~Eiderly patients may have
reduced renal function which may not be evident in the results of routine screening tests. such as BUN or serum crealinine .A crealinine clearance
determination may be more useful. Monitoring of renal function during gentamicin treatment , as with other aminogiycosides is particularly
ifTtDOt’l’Cll'l‘i it'l 5UCh
patients.
A Fanconi-like syndrome with amlnoaclduria and metabolic acidosis has been reported in some adults and infants treated with gentamicin.
Crass allergehicity among aminogiycosides has been demonstrated.
-Patients should be well hydrated during treatment.
-in vltro mixing of an aminoglycoslde with beta-lactam type antibiotics [penicillins or cephatosporins] may result in significant mutual inactivation .
Even when an aminoglycoslde and a penicillin - type drug are administered separately by different routes of reduction in aminogiycosides serum
half-life or serum levels h been reported in patients with impaired renal function and in some patients with l"tOlTl"'lO| renal function. A reduction in
gentamicin serum half-itfe has been reported in patients with severe renal impairment who received corbenlclliln concomitantly with gentamicin
Usually, such inactivation of the aminoglycoslde is clinically significant only in patients with severely impaired renal function.
-Treatment with gentamicin may result in overgrowth of hon- susceptible microorganisms. if this occurs. appropriate therapy is indicated.
-Garamycin injection contains 3.2 mgiml sodium blsultite , a sulttte that may cause allergic type reactions including anaphyloctlc symptoms and
life-threatening or less severe asthmatic episodes in susceptible people.
-Amlnogiycoslde antibiotics cross the placenta and may cause fetal harm when administered to pregnant women. ll is not
known whether gentamicin sulphate can cause fetal harm when administered to pregnant women or can affect reproduction _
CCiDCICl'|Y.
-Because of the potential tor serious adverse reactions from aminoglycoslde in nursing infants. o decision should be made to
discontinue nursing or therapy taking into account the importance of the dug to the mother. -
-in the event of overdose or toxic reactions, hemodialysts will aid in the removal of gentamicin from the blood. The rate of removal of gentamicin is
considerably less by peritoniai dialysis than it is by hemodlalysis. in the newborn infants, exchange transfusions may be considered. These
procedures are of particular importance for patients with impaired renal function.
AMKB-B0-3140-6-ln -1 1 B