SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE
MEDICINAL PRODUCT
PENICILIN G 1,0
DRASELNÁ SOĽ BIOTIKA
PENICILIN G 5,0 DRASELNÁ
SOĽ BIOTIKA
2. QUALITATIVE AND QUANTITATIVE
COMPOSITION
Benzylpenicillinum kalicum , 1 000 000
IU or 5 000 000 IU in injection vial
For the full list of excipients, see
section 6.1.
3. pharmaceutical
form
Powder for solution for injection
White or almost white
micro-crystalline powder, freely soluble in water, practically insoluble in fatty
oils and in liquid paraffin.
4. Clinical
particulars
4.1. Therapeutic indications
Application
of benzylpenicillin potassium salt is indicated at the beginning of treatment
of severe injections induced by penicillin-sensitive pathogens (later the
therapy can continue with application of procaine benzylpenicillin). It is a
first choice drug in pneumonias and other infections induced by pneumococci (except
enterococci), in pneumococcal meningitides (combined with sulfonamides),
infections induced by pyogenic streptococci, sensitive golden staphylococci,
gonococci and meningococci (in combination with sulfonamides), further in
treatment of anthrax, diphtheria, lues, listeriosis, actinomycosis. It is
effective in infections induced by clostridia and corynebacteria and in
treatment of other infections induced by etiological agents sensitive to
penicillin. Mega-doses of benzylpenicillin are indicated in treatment of
subacute bacterial endocarditis and bacterial meningitis, if the tests show a
good susceptibility. Penicillin G is highly effective in treatment of various
stages of lues also in patients with HIV and lues.
Treatment
of hepatotoxic poisonings of 1st type (poisonings by green amanita
and other 27 mushrooms species containing amatoxins.
4.2. Posology and method of
administration
From pharmacokinetic data there is
resulting that benzylpenicillin potassium salt must be applied each 4th
or at the latest each 6th hour therefore this medicinal product is
suitable for hospital treatment only. Dosage depends on kind and localization
of infectious process, on susceptibility of etiological agent and age of patient.
In treatment of current infections 25 000 – 100 000 IU/kg/day divided
into 4 – 6 partial doses are applied.
The usual daily doses are as follows:
Children up to 1 year 100
000 IU
Children from 1 to 6 years 400
000 to 1 000 000 IU
Children from 6 years and
adults 800
000 to 2 400 000 IU
These doses are administered further
at least 3 days after fever has subsided and clinical symptoms of disease have
disappeared. To finish the treatment of streptococcal infections it is
necessary to apply the Pendepon injection or Pendepon Compositum injection. In
treatment of subacute bacterial endocarditis and in bacterial meningitis the
mega-doses are applied, that means 15 – 30 – 60, maximum of 80 million IU
daily. In application of mega-doses the individual dose should not exceed 10
million IU and is to be applied as intravenous infusion over at least 1 hour.
In case of doses exceeding 5 million IU, the control of renal function from the
second day of the treatment at the latest is necessary. At a daily dose
exceeding 20 million IU the occurrence of neurotoxic reactions can be expected which
appear if the penicillin level is higher than 12 IU/mL of liquor. In the next
increase of doses it is necessary to monitor also the levels of penicillin in
blood and cerebrospinal fluid. Children can be applied also the mega-doses of
0.5 – 1.0 million IU per kg of body weight daily, but an increased intake of
potassium must be taken into account. By symptoms of CNS irritation the
application must be discontinued, or anticonvulsive must be applied. In
treatment of subacute bacterial endocarditis the mega-doses of benzylpenicillin
are to be applied for 4 – 6 weeks. In application of mega-doses of benzylpenicillin
potassium salt it is necessary to check kaliemia. This treatment can be
therefore performed only in the medical centers where their continuous control
is possible.
In local application (instillation and
mucosa lavage) penicillin is to be applied concomitantly parenterally or per
orally.
In ophthalmology for treatment of
infections induced by sensitive microbes subconjunctivally 200 000 IU
dissolved in 1 mL of physiological solution. This application must be combined
with parenteral application.
For treatment of mushroom poisonings
(hepatotoxic poisonings) it is necessary to apply the mega-doses of Penicillin
G, i.e. 300 000 up to 2 000 000 IU per kg of body weight and day
i.v. during 3 days to adults, children and pregnant women. It is suitable to
combine the treatment with the application of silymarine at a dose of 20 mg per
kg of body weight and day in i.v. infusion for 3 to 4 days.
4.3. Contraindications
Absolute contraindication is
hypersensitivity to penicillin and cephalosporins.
Special care is necessary in
application to the patients having allergy, bronchial asthma, hay fever and
urticaria in anamnesis. Extraordinary caution is necessary in application of
mega-doses to children up to 6 weeks and to patients older than 60 years with
impaired tubular renal function. Administration of benzylpenicillin is not
contraindicated in pregnancy, puerperium, in lactation and neither in the patients
with renal insufficiency (as long as mega-doses are not applied).
4.4. Special warnings and precautions
for use
In application of mega-doses of benzylpenicillin
potassium salt a significant intake of potassium into the body has to be counted
on, and therefore the mega-doses must not be administered in system
neurological diseases, in hyperkaliemia and in the states inducing it.
Penicillin G may be administered also to people with allergy to penicillin, if
the disease requires the treatment by penicillin and namely after
desensitization by application of progressively increasing doses of penicillin.
Desensitization may be performed only at Intensive Care Unit, because this
procedure bears a life-threatening risk.
4.5. Interaction with other medicinal
products and other forms of interaction
In concomitant administration with
bacteriostatic antibiotics (tetracyclines, chloramphenicol, erythromycin)
occurs the mutual decrease of action. Benzylpenicillin reduces the efficacy of
per oral anticoagulants. Chlorpromazine reduces efficacy of benzylpenicillin.
Concomitant application of probenecid induces a mutual increase of plasmatic
levels. Penicillin level in blood is increased by concomitant application of
salicylates, aminophenazone and vitamin C. Benzylpenicillin increases
hyperkalemic effect of other substances, induces false positivity of tests on
presence of proteins and sugar in urine.
4.6. Pregnancy and lactation
Long-time experiences with
administration of benzylpenicillin have confirmed the safety for a fetus. In
usual doses the medicinal product is not contraindicated. Penicillin is
excreted into breast milk and may cause sensibilization and allergic reactions.
Therefore during administration of penicillin it is better to interrupt the
breast-feeding.
4.7. Effects on ability to drive and
use machines
The medicinal product is safe and the
influence on ability to drive and use machines is not assumed.
4.8. Undesirable effects
The most
serous and the most frequent undesirable effect are allergic reactions which
occur more often in people with allergic disposition (1 – 10 % of patients).
The most serious symptom is anaphylactic reaction which occurs in 1 – 2 minutes
after application (sometimes within half an hour, rarely also later) as
collapse or even cardio-respiratory failure with potential lethal ending. The
other allergic symptoms are: urticaria, fever, pain of joints, angioneurotic
edema. A serious complication may be Lyell´s or Stevens-Johnson syndrome.
Occurrence of nausea, vomiting, diarrhea; hemorrhage, hemolytic anemia,
eosinophilia, thrombocytopenia, rarely cholestatic jaundice and development of
lupus erythematodes. In treatment of syphilis even in 50 % of cases
Jarisch-Herxheimer reaction occurs which is shown by fever, sweating, headaches
up to collapse. The reason is release of endotoxins. In cardiovascular syphilis
this reaction can have a very heavy development (primary atrophy n. optici,
nervous deafness) and may be finished also lethally.
Administration
of mega-doses induces a higher occurrence of undesirable effects. Disorders of
function of kidneys, liver, hematopoiesis and CNS may occur. After the
application of mega-doses of benzylpenicillin, the most frequent is occurrence
of temporary bitterness in mouth, headache, sometimes vomiting or also the
symptoms of CNS irritation: localized cramps of facial muscles or limbs,
epileptiform attacks up to generalized tonic-clonic cramps eventually coma. In
anaphylactic shock after application of benzylpenicillin it is necessary to get
under control the failure of blood circulation or potential respiratory
failures by adrenaline, noradrenaline, hydrocortisone, to apply antihistamines
and calcium. Proceed according to the principles of how to overcome these
reactions.
4.9. Overdose
Benzylpenicillin is antibiotic with
very low toxicity. LD50 in
mice and rats is higher than 5 000 mg/kg, what can be considered
practically to be non-toxicity.
Indirect toxicity: after application
of high doses of benzylpenicillin potassium salt, in patients with reduced
renal function the cumulative poisoning by potassium may appear. Other symptoms
of indirect toxicity are the changes of normal bacterial flora with
over-reproduction of penicillin-resistant flora and the super-infection symptoms.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: antibiotic
ATC Code: J01CE01
Penicillin G is the first antibiotic
introduced in clinical practice. It acts on the base of mechanism common for
all beta-lactam antibiotics, by inhibition of synthesis of bacterial cell wall.
Through binding to proteins of cell wall it inhibits the transpeptidation of
peptidoglycan, inhibits synthesis of murein. Subsequently the autolytic enzymes
are activated and cell wall is destructed. Benzylpenicillin potassium salt for
parenteral application is basic bactericidal antibiotic of middle-wide spectrum
with short-time action. It is very well soluble in water.
A n t i m i c r o b i a l s p e c t r u m : it has a very good action
against pyogenic and other hemolytic streptococci, pneumococci, gonococci and
meningococci, corynebacteria, listeria, Erysipelothrix
insidiosa, bacillus of anthrax, actinomyces, Clostridium tetani and clostridia of anaerobic traumatosis; as well
as against moraxella, Treponema pallidum
and most leptospira strains. It has a lower action against viridating
streptococci (on about 70 – 80 % of strains), against enterococci (only 20 – 40
% of strains) and from staphylococci only on the penicillinase non-producing
strains (about 15 % of strains). If the higher concentrations are reached (in
serum by application of high doses, in urine also by usual doses),
benzylpenicillin acts also on some gram-negative intestinal sticks, e.g. on Escherichia coli, suspiginous forms of
proteus and salmonella. This effect can be used clinically, for example in some
infections of urinary tract. Insensitive are pseudomonades, brucella,
francisela, bordetella, haemophili (except Haemophilus
hemolyticus) and mycobacteria, but also mycoplasma, rickettsias, bedsonias,
fungi and protozoa.
5.2. Pharmacokinetic properties
Benzylpenicillin is instable in acid
environment, hydrolysis of beta-lactam ring occurs. Absorption from
gastrointestinal tract is irregular and unreliable that is why it is applied
parenterally only. After intramuscular application benzylpenicillin potassium
salt is absorbed very quickly and maximal concentration in blood is reached
already in 15 – 30 minutes. Then the level decreases very quickly and already
in 4 hours it is decreased under the efficient concentration.
|
Dose mil. IU
|
Route
of administration
|
Serum
levels PNC G in IU /mL
|
|
|
|
0.5 h
|
1 h
|
4 h
|
6 h
|
8 h
|
|
0.6
|
i.m.
|
6 - 9
|
3 - 6
|
0.03 – 0.3
|
< 0.03
|
0
|
|
1
|
i.m.
|
20 - 28
|
18 - 24
|
1.5 - 3
|
0.2 – 0.6
|
0.08
|
|
5
|
i.v. infusion
|
60 - 120
|
-
|
-
|
6 – 12
|
3 - 9
|
|
10
|
i.v. infusion
|
80 - 300
|
-
|
-
|
10 – 30
|
2 - 15
|
Distribution into body liquids and
tissue in relation to serum:
Liquor <
5 %
CNS < 3
%
Bronchial secretion 15 - 50
%
Bones <
10%
Mother milk 3
-10 %
Passage through placenta 25 - 50 %
Pleural exudate 20
- 65 %
Peritoneal liquid 18
- 50 %
Synovial liquid 40
%
Tissues and organs 30 - 50
%
Bile 180 -
500 %
The medicinal product penetrates well
into most tissues, pericardial and pleural cavity, into bile, saliva, milk. It
crosses also placental barrier. It is present particularly in extracellular
liquid. On proteins is bound 40 – 50 % of a dose. Penetration to cerebro-spinal
liquor and chamber water of eye is very low. In inflammations (meningitis)
however it penetrates to cerebro-spinal liquor (and also to other body fluids)
in significantly higher extent and more quickly. The penetration to pyogenic focuses,
ischemic areas and necrotic tissues in not sufficient. Half-life in plasma is
0.4 – 0.65 h. It is excreted mostly by kidneys, by tubular secretion 80 %, by
glomerular secretion 20 %. Inhibitor of tubular secretion probenecid prolongs
half-life and increases plasmatic level what is also used therapeutically.
Biological half-life in anuria is prolonged to 7 – 10 hours. It is excreted
into breast milk and in infants it can induce exanthema and in lues congenital
the Jarisch-Herxheimer reaction.
1 million of units contains 65.7 mg
(1.68 mmol) of potassium.
6. pharmaceutic
particulars
6.1. List of excipients
None.
6.2. Incompatibilities
In infusion solutions benzylpenicillin
is incompatible with metaraminol, thiopental, amobarbital, ascorbic acid,
promethazin, oxytetracycline, tetracycline, vancomycin, chloramphenicol and
sulfadiazine.
6.3. Shelf life
3 years
6.4. Special precautions for
storage
Store below 25 °C, on dry place, protect
from light.
6.5. Nature and contents of
container
Injection vial with stuck
label, rubber stopper with aluminium crimp, box.
Package size:
1, 10 and 50 injection
vials with a content of 1 000 000 IU or 5 000 000 IU.
Not all pack sizes may be marketed.
6.6. Special
precautions for disposal and other handling
The medicinal product has to be dissolved before application.
Benzylpenicillin potassium salt is well soluble even in a small volume of a
liquid (water for injection, isotonic solution of sodium chloride, 5% glucose
solution) which is added to vial in the quantity calculated according to the
required concentration of solution. For application of mega-doses the
antibiotic is dissolved in 50 – 250 mL of water for injection. At preparation
of solution it is necessary to avoid a contact of benzylpenicillin solution
with skin or mucosa because of a high sensibilization risk. From this reason,
before application the drawn air must not be jetted from the injection syringe
into air, but always only back into empty vial.
Solution of benzylpenicillin potassium salt is applied
intramuscularly, intravenously, subcutaneously, subconjunctivally or also
locally (instillation and sinusitis lavage). In local application penicillin is
to be applied concomitantly parenterally or per orally.
7. MARKETING
AUTHORISATION HOLDEr
BB Pharma
a.s., Pod Višňovkou 1662/21, Prague, Czech Republic
8. MARKETING
AUTHORISATION NUMBER
15/0156/69-S, 15/0305/13-S,
15/156/69-A/C, 15/156/69-B/C
9. Date
of first authorisation/renewal of the authorisation
1969 /
10. date
of revision of the text
September 2013
