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
