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Penicillin G Potassium Biotika Inj. Sicc. 1mio, 5mio units

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