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1-Chemistry
Amikacin Sulfate- C22H43N5O13.2H2SO4
2- Pharmacology
Lorikacin® is active against a wide range of aerobic Gramnegative
bacilli. Lorikacin® binds irreversibly to the 30s
subunit of the bacterial ribosome, blocking protein synthesis
by inhibiting the movement of peptidyl-t RNA associated
with translocation as well as increasing the frequency of
misreading of the genetic code owing to incorrect codonanticodon
interaction. The effect is bactericidal.
3- Toxicology
Studies on mutagenic, carcinogenic or teratogenic effects
have not been carried out. Reproductive studies in rats and
mice have not demonstrated effects on fertility.
4- Clinical pharmacology
Most aerobic and facultative Gram-negative bacilli are
inhibited by 3-6 mg.1-1 Lorikacin®. Among Gram-positive
bacteria, streptococci and Listeria monocytogenes are usually
resistant and staphylococci, although sensitive in vitro, tend
to be clinically resistant. Lorikacin® is also active in vitro
against diphtheroids, gonococci, meningococci, Haemophilus
species, mycoplasma, and Legionella pneumophila. Lorikacin®
is also active against the “higher” mycolic acid-containing
bacteria. Activity against Mycobacterium tuberculosis has
been demonstrated in experimental infections.
5- Pharmacokinetics
Absorption from sites of intramuscular injection leads to peak
serum levels in 60-90 min. In adults, intravenous infusion of
500 mg Lorikacin® over 20-30 min yields peak levels of about
25-30 mg.1-1.
Oral absorption negligible
Presystemic metabolism nil
Plasma half- life
range 2.2-2.5h
mean 2.3 h
Volume of distribution 0.2-0.25 1.kg-1
Plasma protein binding minimal (<10%)
Levels of aminoglycosides in interstitial fluid are 17-30% of
simultaneously measured serum levels and therapeutic levels
are achieved in ascitic, peritoneal, pleural, and synovial fluids.
Lorikacin® is excreted only by glomerular filtration.
More than 90% of the drug is recovered unchanged in the
urine over 24 h.
6- Metabolism
Despite previous suggestions that there is some metabolism
of aminoglycosides, there is no current evidence that this is
so. More than 40% of the dose is excreted unchanged in the
urine.
7- Therapeutic use
Mode of use
Lorikacin® is used almost exclusively for the systemic
treatment of suspected or proven infections caused by aerobic
Gram-negative organisms , especially in hospitals where
resistance to earlier aminoglycosides such as kanamycin,
gentamicin, and tobramycin has become frequent. Lorikacin®
is given intramuscularly or intravenously, the latter being
preferred if there is circulatory collaps associated with Gram-
negative septicemia.The recommended dose is 15 mg. kg-1
daily divided in two or, less commonly, three equal doses.
This is usually achieved in adults of 60-70 kg by giving 500
mg every 12h as a 30 min intravenous infusion in a diluent
such as 100-200ml of normal saline or 5% dextrose in water.
Newborn infants less than 1 week of age and those less than
2000g could receive 7.5 mg.kg-1every 12 h while more mature
infants could receive as much as 10 mg.kg-1 every 12 h.
Indications
1. Gram - negative sepsis
a. Urinary tract. Lorikacin® is the drug of choice when
Amikacin
LORIKACIN
gentamicin resistance has been demonstrated. Cystitis can be
cured by a single dose of aminoglycosides.
b. Peritoneal cavity. Lorkacin is frequently used in combination
to treat the component of sepsis caused by facultative Gramnegative
rods (mostly Escherichia coli) and thereby
complement chemotherapeutic agents, such as metronidazole
or clindamycin, with a narrower or essentially antianaerobic
spectrum of action.
C. Female genital tract. Lorikacin® is frequently used in
serious infections to treat the associated (mostly Escherichia
coli) aerobic Gram-negative component of puerperal sepsis
associated with endometritis.
d. Burns. Plasmid - determined gentamicin resistance is a
common finding in strains of Ps. aeruginosa in burns units
where Lorikacin®, together with antipseudomonal penicillins
such as ticarcillin, piperacillin or azlocillin, becomes the drug
of choice for empirical treatment of sepsis.
e. Biliary tree. Lorikacin® in combination with ampicillin or
other ?-lactam antibiotics is frequently ( and apparently
effectively) used in the treatment of cholangitis and
cholecystitis.
f. Neonates. Lorikacin® becomes the aminoglycoside of
choice for the empirical treatment of sepsis in neonatal
intensive care units harboring kanamycin and gentamicin -
resistant Gram - negative bacteria.
g. Neutropenia. Lorikacin® is as effective as other
aminoglycosides in empirical combination therapy of fever
in the neutropenic host. It becomes the aminoglycoside of
choice for treatment of genamicin- resistant bacteremia.
h. Respiratory tract. Lorikacin® combined with
antipseudomonal ?- lactams such as ticarcillin produces
clinical improvement in exacerbations of bronchial infection
caused by Pseudomonas aeruginosa in patients with cystic
fibrosis.
i. Meningitis. Even in the presence of inflamed meninges,
aminoglycoside levels in CSF are unlikely to be thrapeutic
. Direct administration into the CSF using repeated lumbar
punctures or preferably into the lateral ventricle using a drain,
shunt, or Ommaya reservoir is therefore the only way to
achieve adequate levels. Lorikacin® used in this way has been
given in doses of 4 -10 mg daily.
2. Infections caused by mycobacteria and Nocardia
asteroides
There are reports of the successful use of Lorikacin® in the
treatment of these infections.
Contraindications
Provided blood levels can be measured during the courses of
treatment, there are no absolute contraindications to the use
of Lorikacin® in the presence of life -threatening septicemia.
The drug should be used cautiously and preferably for less
than 2 weeks in the elderly, and in patients with myasthenia
gravis only in an intensive care setting.
8- Adverse reactions
Potentially life- threatening effects
Large doses of aminoglycosides cause neuromuscular
blockade, the effect being potentiated by anesthesia, muscle
relaxants, and myasthenia gravis and antagonized by calcium
and neostigmine. Initial and potentially reversible symptoms
include tinnitus, mild high frequency loss detected by
audiogram, vertigo, and ataxia. Overt deafness, should it
occur,usaully appears suddenly during therapy but occasionally
it may appear and progress after its cessation.
Symptomatic adverse effects
Tinnitus and a sens of fullness in the ears may follow bolus
injection of Lorikacin® and are an occasional prelude to
serious ototoxicity. Circumoral parasthesia may occur.
Interferance with clinical pathology tests
No interference with clinical pathology tests has been recorded.
9- High risk groups
Nonates
Doses of Lorikacin® should take into account gestational age
at birth and body surface area (as an estimate of extracellular
fluid volume) but frequent monitoring of blood levels is
imperative.
Breast milk. Information concerning the appearance of
Lorikacin® in breast milk is not available.
Children
Lorikacin® may be used in the management of neutropenic
infection, cystic fibrosis and urinary tract infection.
Pregnant women
Lorikacin® crosses the placental barrier, yielding peak fetal
serum levels of about 16% of the maternal level and a half
- life of about 3.7h.
The elderly
Special care is required when using Lorikacin® in the elderly
in whom renal function may be impaired, as old age appears
to be an independent risk factor for ototoxicity and
nephrotoxicity.
Concurrent disease
The elimination of Lorikacin® is delayed in patients with
reduced renal function. Therefore, special care is required
during treatment.
10-Drug interactions
Potentially hazardous interactions
Neuromuscular blocking agents may be potentiated by
Lorikacin®, the effect being reversed by use of intravenous
calcium salts. Lorikacin® should not be given concurrently
with potent diuretics, such as ethacrynic acid and furosemide
because these enhance its nephrotoxicity.
Potentially useful interactions
The synergy that can frequently be demonstrated between
Lorikacin® and penicillins or cephalosporins in vitro is the
rationale for the use of these combinations in the management
of Gram-negative infections in febrile neutropenic patients,
and of infections caused by difficult organisms such as
Pseudomonas aeruginosa.
Storage
Store below 30ºC. Protect from light and freezing.
Packaging
Boxes of 10 Ampoules of 2 ml
58
R
Amikacin (as Sulfate) Amp.
100 mg/2 ml, 500 mg/2 ml
LORIKACIN
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