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Bitammon plo. jof. 1,5g


                                            BITAMMON 1 g/0.5 g
Powder for solution for injection or infusion

Drug substances:          ampicillinum natricum 1.063 g (responds to ampicillinum 1.0 g) and
                                   sulbactamum natricum 0.547 g (responds to sulbactamum 0.5 g) in 1 injection vial.
                                  The medicinal product contains 115 mg of sodium (5 mmol Na+).

Complete list of excipients, see the Part 6.1.

Powder for solution for injection or infusion.
Description: white to cream powder of characteristic odour, well soluble in water.


4.1. Therapeutic indications 
BITAMMON is indicated for treatment of infections of upper and lower airways, including sinusitis, otitis media, epiglottitis, bacterial pneumonia and bronchitis; infections of gastrointestinal tract (peritonitis, cholecystitis); infections of bones and joints, skin and soft tissues; gynecologic infections; urinary infections: pyelonephritis and cystitis, gonorrhea and non-gonococcal urethritis, bacterial septicemia.
BITAMMON may be applied prophylactically before surgery major in the area of peritoneum and pelvis in order to prevent early postoperative infection. BITAMMON may be used also in obstetrics for prevention of sepsis after termination of pregnancy by cesarean section. 

4.2. Posology and method of administration 
BITAMMON may be applied intravenously or intramuscularly.
Usual dosage to adults moves between 1.5 to 12 g daily applied in partial doses in the interval 6 to 8 hours. Less serious infections may be treated with the doses applied IN 12-hour intervals. The total daily dose of BITAMMON is 12 g (4 g of sulbactam), if the condition of the patient requires the higher doses of antibiotic, ampicillin may be added.
Children from infant age are applied usually 150 mg/kg/day (what responds 100 mg of ampicillin and 50 g of sulbactam) divided into 3 – 4 partial doses. In newborns in the first week of life, especially in preterm born babies, the usual dosing is each 12 hours. Dosing must be adapted to severity of the infection and maturity of renal functions of a newborn.
Patients with serious impairment of renal functions (creatinine clearance 30 ml.s-1) should get modified doses. As the kinetics of elimination of both components is the same and their mutual ratio in plasma remains constant, proceed according to practice established in case of ampicillin.
The treatment takes usually 5 to 14 days, in necessary cases also longer, however it has to be continued at least 48 hours after temperature drop and extinction of clinical symptoms of disease.
In prophylaxis of infections in surgery it is necessary to apply 1.5 – 3 g of BITAMMON i.v. together with introduction to anesthesia. The dose can be repeated every 6 to 8 hours. If another application is not indicated therapeutically, in most surgical interventions the application is terminated within 24 hours.
In treatment of uncomplicated gonorrhea BITAMMON can be applied as a single dose of 1.5 g. If 1.0 g of probenecid p.o. is applied concomitantly, the higher plasmatic levels and prolonged biological half-life are reached in patient. 

4.3. Contraindications 
Hypersensitivity to penicillins, hypersensitivity to cephalosporins; in patients with allergy, asthma, hay fever or urticaria in anamnesis. 
Allergic reaction is indication for discontinuation of application of BITAMMON.

4.4. Special warnings and special precautions for use 
Because of possible development of hypersensitivity the relative contraindications are hypersensitivity to cephalosporins, any allergy, bronchial asthma, hay fever or urticaria in anamnesis. In renal insufficiency with prolonged elimination half-life the doses have to be decreased accordingly. Similarly as by use of other antibiotics it is necessary to monitor constantly the symptoms of excessive reproduction of resistant micro-organisms including mycotic flora. In case that this superinfection occurs, it is necessary to discontinue the treatment by BITAMMON and start with adequate therapy. 

4.5. Interaction with other medicinal products and other forms of interaction 
In concomitant application of BITAMMON with other medicinal products the mutual affection of effect of these medicaments. In concomitant application with allopurinol there increases the risk of skin reactions. Probenecid decelerates the tubular secretion what leads to increased plasmatic level and prolongation of elimination half-life of BITAMMON.

4.6. Pregnancy and lactation 
Reproduction studies in animals revealed no evidence of impaired fertility or fetal defect after application of ampicillin/sulbactam combination. At application it is necessary to consider the ratio of expected therapeutic benefit and possible risk. 
In application of BITAMMON to breast-feeding mothers, the incidence of diarrhea and sensibilization risk in breast-fed baby is possible.

4.7. Effects on ability to drive and use machines 
No effect on ability to drive and use machines is assumed.

4.8. Undesirable effects
General disorders and reactions in application site: like in other parenterally applied antibiotics pain in injection site, especially after intramuscular application. After i.v. application phlebitis may occur.
Disorders of gastro-intestinal tract: most commonly nausea, vomiting and diarrhea.
Skin and subcutaneous tissue disorders: rash, itching eventually other skin reactions like in other penicillins.
Blood and lymphatic system disorders: during treatment by ampicillin/sulbactam combination anemia, thrombocytopenia, eosinophilia and leukopenia may occur. These reactions disappear usually spontaneously after termination of treatment. 
Disorders of liver and biliary tract: temporary the AST, ALT and ALP values may be increased.

4.9. Overdose 
In application of high doses of BITAMMON, particularly for a longer time, it is necessary to control the liver function, particularly the changes of AST, ALT and ALP.
In high doses, similarly as penicillins, it can induce epileptiform spasms through CNS irritation.
Spasms induced by overdose are treated with sedation by diazepam. 
Allergic reaction is indication for discontinuation of BITAMMON application. In anaphylactic shock it is necessary to handle the failure of blood circulation and breathing disorders by adrenalin, noradrenalin, hydrocortisone, to apply calcium and antihistamines; proceed according to the principles for managing these reactions. 


5.1. Pharmacological properties
Pharmacotherapeutic group:     antibiotic drug (combination of antibiotic with inhibitor of beta-lactamases). 
ATC code:                              J01CR01

Mechanism of action:
BITAMMON is combination of beta-lactam antibiotic ampicillin and inhibitor of beta-lactamases sulbactam. Ampicillin acts on sensitive micro-organisms with the same mechanism as other penicillins; it blocks synthesis of cell wall of micro-organisms. Ampicillin acts on all streptococci species (including streptococci of A and B group), on viridating streptococci, pneumococci and enterococci (80 – 98 %), on corynebacteria, listeria, Erysipelothrix insidiosa, bacillus of anthrax and also on actinomyces, less on clostridia. From staphylococci, it acts only on the strains, which do not create beta-lactamase, i.e. on about 10 – 20 % of strains. From gram-negative bacteria, it has a good effect on gonococci and meningococci, on salmonellas (about 90 % of strains). Less sensitive are haemophili and bordetella (about 60 – 70 % of strains), Escherichia coli (60 %), shigella (40 – 90 %), Klebsiella and enterobacteria (15 %), providence and citrobacter (30 %), from protea is acts on about 60 % of Proteus mirabilis strains, but only on 5 – 20 % of strains of other biotypes (Proteus vulgaris, morganii and rettgeri). From other strains, sensitive are brucella, leptospira and treponema. 
From anaerobes, sensitive are most gram-positive cocci and bacteria except B. fragilis. It does not act on yersinia, francisela, pseudomonades, mycobacteria, mycoplasma, rickettsias, bedsonias, fungi and protozoa. 
Sulbactam is irreversible inhibitor of beta-lactamases, structurally similar to penicillin. Its own antimicrobial activity is low. It has a significant efficiency only against Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides sp, Moraxella catarrhalis and Pseudomonas cephacia. Thanks its presence it protects ampicillin against destruction by beta-lactamases produced by gram-positive or gram-negative bacteria. As it is bound also to penicillin binding proteins, some strains are more sensitive to this combination than to the treatment by beta-lactam antibiotic alone. 

5.2. Pharmacokinetic properties
Biological availability of BITAMMON is high. Ampicillin reaches after i.m./i.v. application the maximal blood concentrations up to 30 minutes. It penetrates quickly the tissues, a little penetrates brain and cerebrospinal fluid, in inflammations (meningitis) it crosses well also through cerebrospinal barrier. It is almost completely excreted by urine. Biological half-life in normal renal function is about 1 – 1.3 hours, in serious renal insufficiency it is prolonged even to 21 hours.
Sulbactam has similar pharmacokinetic properties as ampicillin. It is eliminated especially by urine by glomerular filtration. Biological half-life of sulbactam in normal function is about 1 – 2 hours, in heavy renal insufficiency the biological half-life is prolonged up to 9 hours.

5.3. Preclinical safety data
For the ampicillin/sulbactam combination in the ratio 1:2 the LD50 in mice was determined on 5.9 (5.5 – 6.4) g/kg. In application of the dose of 900 mg/kg of sulbactam intraperitoneally to experimental rats, in animals occurred tonic spasm in abdominal cavity, rapid breathing, increased motion activity and aggressiveness. These symptoms disappeared within 3 minutes after application. In experimental animals after the repeated application occurred also the increased values of ALP, AST and ALT. Within two weeks after termination of application these values were normalized. 


6.1. List of excipients

6.2. Incompatibilities
Sodium salt of ampicillin is incompatible with adrenalin, noradrenalin, atropine sulfate, calcium chloride and gluconate, chlorpromazine chloride, chlortetracycline, oxytetracycline, tetracycline, gentamicin sulfate, kanamycin sulfate, sodium salt of phenobarbital, hydrolysates of amino acids, sodium salt of hydrocortisone hydrogen succinate. BITAMMON should also not be mixed with blood preparations and hydrolysates of proteins.

6.3. Shelf life
2 years

6.4. Special precautions for storage 
Store in original package in order to protect from light and moisture.

6.5. Nature and contents of container
Vial with crimp of colorless glass, rubber stopper, aluminium crimp cap, box.
Package size: 1x1.5g; 10x1.5g; 50x1.5g

Not all package sizes have to be introduced on the market. 

6.6. Instructions for use and other handling
BITAMMON is not determined for immediate use and must be dissolved before application.
To be applied as intravenous injection, the solution is prepared by dissolving of 1.5 g of BITAMMON in 3.2 mL of aqua pro injectione or other suitable compatible solvent. To be applied as infusion, it is further dissolved with suitable infusion solution. It is necessary to wait after dissolution until the foaming disappears and to check visually the dissolving and compatibility. Intravenously the dose may be applied as bolus (with duration minimum 3 minutes), or in intravenous infusion within 15 to 30 minutes. BITAMMON may be applied also deep intramuscularly. 
If a pain appears during application, a local anesthetic may be added (e.g. lidocaine hydrochloride).

BB Pharma a.s., Pod Višňovkou, Prague 4, Czech Republic
15/0284/98-S, 15/747/10-C
September 2013