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Pendepon Compositum Inj. Sicc.

SUMMARY OF PRODUCT CHARACTERISTICS

 

1. NAME OF THE MEDICINAL PRODUCT

PENDEPON COMPOSITUM


2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Benzathini benzylpenicillinum                         1 200 000 IU,

Procaini benzylpenicillinum monohydricum      300 000 IU in injection vial.

Complete list of excipients, see the Part 6.1.

 

3. PHARMACEUTICAL FORM

Powder for suspension for injection

White or almost white micro-crystalline powder without odour or of light characteristic odour. It is sparingly soluble in water, sparingly soluble in 96% alcohol and practically insoluble in chloroform. It is freely soluble in dimethylformamide.

 

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

Prevention of streptococcal infestations of people threatened with rheumatic fever. Sanation of germ-carriers of beta-hemolytic streptococcus. Lues.

4.2. Posology and method of administration

For prevention of streptococcal infestations and regressions of rheumatic fever the dose of 1 500 000 IU is applied always after 14 – 18 days. If during long-time prevention the acute streptococcal disease is developed, it is necessary to start immediately the treatment with short-term penicillins lasting 7 days. In sanation of germ-carriers of beta-hemolytic streptococci one injection of the medicinal product is applied each 14 days.

Lues: treatment of early states in adults (primary, secondary and latent phase lasting shorter than year) as a single dose 3 000 000 IU. Treatment of later states (latent phase lasting longer than year, cardio-vascular syphilis) 3 000 000 IU weekly during three weeks (totally 9 mil. IU).

Pendepon compositum is applied as suspension with thicker intramuscular needle deep intragluteally into external upper quadrant M. glutaeus maximus. Children are applied into M. femoris lateralis. Before application of injection it is recommended with aspiration to check the correct location of cannula in muscle.

4.3. Contraindications

Absolute: hypersensitivity to penicillin and procaine or other components of the medicinal product.

Relative contraindication is application of the medicinal product to patients with any allergy, hay fever and urticaria in anamnesis and in bronchial asthma.

The medicinal product is not suitable for treatment of acute infections.

Intravenous application of Pendepon compositum is absolutely prohibited!

4.4. Special warnings and special precautions for use

The medicinal product is not suitable for treatment of acute infections. Caution is necessary, if the medicinal product is administered to the patients with any allergy, hay fever, urticaria and in bronchial asthma also in anamnesis. In anaphylactic shock it is necessary to get the circulation failure and potential breathing disorders under control using adrenaline, noradrenaline, hydrocortisone, to apply antihistamines and calcium. Further it is necessary to follow the principles of how to overcome these reactions.

4.5. Interaction with other medicinal products and other forms of interaction

In concomitant application of bacteriostatic antibiotics (tetracyclines, chloramphenicol, erythromycin etc.) the mutual antagonism occurs. Pendepon compositum decreases the effect of per oral anticoagulants; chlorpromazine decreases effect of penicillin. Level of penicillin in blood is increased by concomitant application of salicylates, aminophenazone and vitamin C. In order to reach high serum concentrations it is possible to use probenecid which reduces tubular secretion of penicillin and thus increases its plasmatic level. The medicinal product causes false positive tests for proteins and sugar in urine.

4.6. Pregnancy and lactation

Benzylpenicillin passes placenta and the level in serum of fetus reaches the levels close to the levels in serum of mother. Present experiences with application to pregnant women and also testing in rats, rabbits and monkeys have not proven any evidence of teratogenicity. In current doses the medicinal product is not contraindicated. In first trimester however it is applied only if it is necessary. Penicillin is excreted into breast milk, the levels in milk reach 2 – 15 % of serum concentration. This can be a reason of sensibilization (allergic reaction), more often however it is influence of physiological intestinal flora.

4.7. Effects on ability to drive and use machines

The medicinal product is safe and an effect on ability to drive and use machines is not assumed.

4.8. Undesirable effects

Allergic reactions occur much more often in persons with allergic disposition. The most serious is anaphylactic reaction which appears 1 – 2 minutes after application (sometimes also within half an hour or even later) as collapse or even cardio-respiratory failure which could lead up to a lethal ending. Other allergic symptoms are urticaria, fever, pain in joist, angioneurotic edema, Lyell´s or Stevens-Johnson syndrome. Occurrence of nausea, vomiting, diarrhea; hemorrhage, hemolytic anemia, eosinophilia, thrombocytopenia; very rarely cholestatic jaundice and lupus erythematodes is possible. In treatment of syphilis even in 50 % of cases occurs Jarisch-Herxheimer reaction, which is shown by fever, sweating, headache up to collapse (consequence of endotoxins release). In cardio-vascular syphilis this reaction can have a very heavy running (primary atrophy n. optici, nervous deafness) and may be finished also lethally. If in parenteral application the suspension of benzathine benzyl penicillin penetrates into blood, Hoigne´s syndrome, which has a rapid start, but a benign process. It is shown mostly by psychic experiences (fear of death, auditory and visual color hallucinations, confusion, disorientation), dizziness, taste disorders, tachycardia, palpitation of heart. Complications usually disappear within 30 minutes and are treated symptomatically. After intravasal injection in children Nicolaus syndrome can occur. Early symptoms: sudden skin ischemia distally from injection site, partially with livid coloration and pain. Late symptoms: slight paralysis, ischemic necrosis, intestinal and renal bleeding. Besides local findings conditioned by ischemia (e.g. pain, paleness, formation of edema and pustules with subsequent necrotization) it is not possible to exclude a more difficult process demonstrated by shock and coagulopathy. Without any delay 300 IU/kg of heparin has to be applied i.v., or i.m. if necessary. Thrombolytic therapy has to be initiated at specialized workstation. In prevention of both symptoms it is necessary to apply the correct application procedure (change of injection site, needle with sufficiently big lumen, aspiration and fixation in injection site). Patient should be kept under medical supervision at least 30 minutes after the application. After intramuscular application a local painful reaction, necrosis and abscess may occur.

4.9. Overdose

Benzathin penicillin is a depot drug; it is almost excluded to reach toxic serum level after intramuscular application (LD50 of benzylpenicillin in mice and rats is higher than 5 000 mg/kg). Procaine is contained in the medicinal product in the volume of 120 mg, it is also not probable to reach a toxic level.


5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:  antibiotics

ATC code:  J01CE30

5.1. Pharmacodynamic properties

Pendepon compositum is a mixture of little and very little soluble benzyl penicillin salt with long-term effect, suitable particularly for prevention to streptococcal infection in patients threatened with rheumatic fever. Penicillin inhibits competitively the bacterial transaminasis which act in building of cell wall and thus inhibits the synthesis of murein. It activates autolytic enzymes with subsequent lesion of cell wall what results in killing of bacterial cell.

A n t i m i c r o b i a l   s p e c t r u m : is identical with spectrum of benzyl penicillin. It acts very well on pyogenic and other hemolytic streptococci, pneumococci, gonococci and meningococci, corynebacteria, listeria, Erysipelothrix insidiosa, bacillus of anthrax, actinomyces, clostridia of tetanus and anaerobic traumatosis, moraxella, Treponema pallidum and on most leptospira strains.

5.2. Pharmacokinetic properties

Mixture of two depot penicillins with different release kinetics.

Benzathin penicillin is stable in acid stomach environment. However, its absorption from GIT is not regular and not reliable. Therefore benzathine penicillin is applied intramuscularly only. After i.m. application it is slowly absorbed from the depot created in muscle. By hydrolysis of benzathine penicillin molecule benzylpenicillin is released. Release kinetics is close to zero order kinetics. Benzathine penicillin ensures after application of a dose of 600 000 IU the therapeutically efficient level for more than one week. Maximum serum levels are reached in adults within 13 to 24 hours, in small children and in newborns later. After a single dose application of 600 000 IU to adults the levels on 12th day reached 0.02 µg/mL. After the dose of 1 200 000 IU the average levels made 0.15 µg/mL on the 1st day, 0.03 µg/mL on 14th day and 0.003 µg/mL on 32nd day. In newborns after the dose of 50 000 IU/kg made the levels were 0.38 – 2.1 µg/mL after 24 hours and 0.07 – 0.09 µg/mL after 12 days. After application of 600 000 IU to children (27 kg) after 24 hours reached the levels 0.11 – 0.21 µg/mL.

Procaine penicillin is instable in acid stomach environment, hydrolysis of beta-lactam occurs. Absorption from gastrointestinal tract is not regular, therefore it is applied intramuscularly only. After intramuscular application it is absorbed slowly from muscle and maximum plasma level is reached in about 2 hours (1 – 4), then it decreases slowly. Effective level may be proved even 24 hours after application.

After application benzyl penicillin is released from procaine penicillin. It is distributed to the whole body, penetrates into pericardial and pleural cavity, bile and saliva. It passes through placental barrier and into breast milk. It penetrates primary to the places where the inflammatory processes are running and here the higher concentrations are reached than in the places without inflammation. In meningitis the high concentrations are reached in brain. Passage through non-flamed meninges is very low, in order to reach therapeutic concentrations in cerebrospinal liquor at the treatment of lues it is therefore combined with probenecid. It does not penetrate into bones. It penetrates insufficiently into purulent foci, into ischemic areas and necrotic tissues. Procaine benzyl penicillin is not soluble in lipids, therefore it does not enter the cells. 50 – 65 % is bound to plasmatic proteins. From an organism it is excreted by kidneys, mostly by tubular secretion, but more slowly than potassium salt of benzyl penicillin. Inhibitor or tubular secretion probenecid prolongs half-life and increases plasmatic level, what is also used therapeutically. In lower extent it is excreted also in bile. In liver penicillin is biotransformed about in 20 % to inactive metabolite.


6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Polysorbatum 80, lecithinum

6.2. Incompatibilities

In injection suspensions it is incompatible with procaine, thiopental, amobarbital, vitamin C, prometazine, oxytetracycline, tetracycline chloramphenicol, vancomycin and sulfadiazine.

The medicinal product causes the false positive tests for proteins and sugar in urine.

6.3. Shelf life

3 years

6.4. Special precautions for storage

Store below 25 ºC, on dry place, protect from light.

6.5. Nature and contents of container

Injection vial with stuck label, rubber stopper with aluminium cap, box, package leaflet: information for the user, carton.

Package size: 1 and 10 injection vials of 1 500 000 IU.

Not all pack sizes may be marketed.

6.6. Special precautions for disposal and other handling

The medicinal product must be suspended before application. Content of injection vial is shaken to side wall of the vial, then 4.5 mL of water for injection is injected into vial and under slight circular motion the suspension is prepared which contains about 300 000 IU in 1 mL. Homogenity is reached in 2 – 3 minutes. The vial should not be shaken because the foamed suspension is difficult to be applied. The prepared suspension is applied deep intragluteally into outside upper quadrant M. glutaeus maximus, in children into m. femoris lateralis using a stronger needle for application into muscle.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.


7. MARKETING AUTHORISATION HOLDER

BB Pharma a.s., Pod Višňovkou 1662/21, Prague, Czech Republic

8. MARKETING AUTHORISATION NUMBER

15/0155/69-S, 15/155/69-S/C

9. DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION 

1969 /

10. DATE OF REVISION OF THE TEXT

September 2013