AZACTAM. 1 g. 1 flacon
AZACTAM. 1 g. 1 flacon
QUALITATIVE AND QUANTITATIVE COMPOSITION
Azactam lg powder for injection Each vial contains lg aztreonam
3 . PHARMACEUTICAL FORM
A sterile powder for injection .
AZACTAM powder for injection (Aztreonam) is indicated for the treatment of the following infections caused by susceptible gram- negative organisms .
In the case of infections suspected or , isolated Gram- positive or anaerobic pathogens , AZACTAM should be used in combination with another antibiotic to cover the microbial spectrum.
Urinary tract infections ( complicated and uncomplicated ), including pyelonephritis and cystitis ( appearing for the first time or recurring ) and asymptomatic bacteriuria .
Infections of the lower respiratory tract , including pnivmoniya and bronchitis. In the treatment of acute pulmonary exacerbations in patients with cystic fibrosis are usually clinically podobronie .
Bacteremia / C eptitsemiya
Meningitis caused by Haemophilus influenzae and Neisseria meningitidis.
Infections of the bones and connections ( joints)
Infections of the skin and subcutaneous ( soft ) tissues , including those associated with postoperative wounds, ulcers and burns.
Intra - abdominal infections, including peritonitis .
Gynecological infections, including pelvic inflammatory disease , endometriosis and pelvic tselulit.Gonoreya (acute uncomplicated urogenital or ano - rectal infection caused by beta- lactamase -producing or non-producing strains of N. gonorrhoeae).
AZACTAM (aztreonam) used as adjunctive therapy to surgery for treatment of infections caused by susceptible microorganisms, including abscesses , infections following perforation of internal hollow organs , skin and serosal surfaces. AZACTAM is effective against the most common Gram- negative aerobic pathogens encountered in common hipurgiya .
4.2 Posology and method of administration
AZACTAM (aztreonam) injections may be administered by intravenous or intramuscular injection. The dose and route of administration should be determined depending on the sensitivity of the causative organism , the severity and location of the infection and the patient's condition .
Dosage in adults
Urinary tract infections 500 mg or 1 g 8 or 12 pm
Moderate systemic infections 1 g or 2 g 8 or 12 pm
Severe systemic or life-threatening infections 2g 6 or 8 pm
* The maximum recommended dose is 8 g daily.
Single dose of 1 g AZACTAM, given intramuscularly is effective in the treatment of acute uncomplicated gonorrhea or acute uncomplicated cystitis .
Intravenous route recommended in patients , who require administration of a single dose of greater than lg , or those with bacterial septicemia localized parenchymal abscess (e.g., intra - abdominal abscess ) , peritonitis , or other severe or life-threatening systemic infection .
Because of the severity of infection caused by Pseudomonas aeruginosa, a dose of 2 g every 6 or 8 hours, at least at the beginning of the treatment , in the event of systemic infection caused by these microorganisms.
The usual dose in patients older than 1 week is 30 mg / kg every 6 or 8 chasa.Pri severe infections in patients aged 2 years or more recommended dose of 50 mg / kg every 6 to 8 hours.
The recommended dosage for the treatment of infections caused by P. aeruginosa was 50 mg / kg every 6 or 8 hours in all patients.
The maximum daily dose in pediatric patients should not exceed the maximum recommended dose in adults.
Azactam in children should be administered intravenously , as there is not enough experience with intramuscular administration in childhood.
Prolonged detention serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. Therefore, after applying the usual starting dose , the dose of AZACTAM should be reduced by half in patients with creatinine clearance between 10 and 30 mL/min/1.73 m2.
In patients with severe renal impairment (creatinine clearance less than 10 mL/min/1.73 m2), and in those on hemodialysis , at initiation of treatment should be given the usual dose . The maintenance dose should be one -quarter of the usual starting right dose , administered in usual fixed interval of 6 , 8 or 12 hours. For severe or life-threatening infections , in addition to the maintenance dose after each hemodialysis session should be administered one-eighth of the initial dose.
Dosage in the elderly
Kidney condition is the main factor determining the dose in these patients ; these patients tend to have decreased renal function. Serum creatinine can not determine exactly the status of the kidney. Therefore, as with all antibiotics leaking through the kidneys is necessary evaluation of creatinine clearance and dosage adjusted accordingly in the event of nuzhda.Prodalzhitelnostta of treatment depends on the severity of the infection , but generally Azactam should be administered at least 48 hours after resolution of symptoms or the occurrence of microbiological eradication . In persistent infections may need administration for several weeks.
This product is contraindicated in patients with known hypersensitivity to aztreonam or any of the other ingredients.
Special warnings and special precautions for use
In patients with impaired renal or hepatic function , close monitoring during treatment with Azactam.
Antibiotics and other drugs should be given with caution in all patients with a history of allergic reaction to substances with similar structure. If an allergic reaction is necessary to stop the drug and , if necessary, institute supportive therapy . Severe hypersensitivity reactions may require administration of epinephrine and other emergency merki.Pri nearly all antibacterial agents , including aztreonam, there is evidence of pseudomembranous colitis with severity ranging from mild to life threatening .
The use of antibiotics may result in the overgrowth of nonsusceptible organisms , including Gram- positive organisms and fungi. If superinfection occurs during therapy, appropriate measures are taken .
Data on safety and effectiveness in infants aged one week node are limited; use in this group requires careful consideration (see Dosage and method of administration ) .
AZACTAM contain arginine. Studies in Infants with low body weight, show that the use of arginine in the composition of AZACTAM, may lead to increases in serum arginine , insulin, and indirect bilirubin . The effects of exposure to this amino acid during treatment have not been fully elucidated.
Co-administration of probenecid or furosemide and AZACTAM leads to clinically insignificant increases in serum levels of aztreonam. Pharmacokinetic studies of single doses showed no significant interactions between somehow aztreonam and gentamicin, nafcillin sodium, cephradine, clindamycin or metronidazole. He reported disulfiram -like reactions with alcohol intake . This is not unusual since aztreonam does not contain methyl- tetrazole side chain.
Aztreonam is incompatible with nafcillin sodium, cephradine and metronidazole.
4.6 Pregnancy and lactation
Aztreonam crosses the placenta and enters the fetal circulation . Studies in pregnant rats and rabbits at daily doses up to 15 and 5 times the maximum human dose proparachvani showed no evidence of embryo- or fetotoksichnist and teratogenicity. When rats were administered doses of aztreonam, 15 times the maximum recommended human during pregnancy and lactation has not been observed associated with taking the drug observed changes in the parameters of both the mother and the fetus and newborn .
There are no adequate comparative studies in pregnant women. Since studies on reproductive function in animals do not always correspond to those in humans , aztreonam should be used during pregnancy only if strictly necessary (need ) .
KarmachkiAztreonam are secreted in milk at concentrations of less than 1% of those obtained with the simultaneous definitions in maternal serum , requiring temporary interruption of the feeding during the treatment with AZACTAM.
4.7 Effects on ability to drive and use machines
No data available.
4.8 Undesirable effects
In clinical trials , adverse reactions are infrequent , and in 2% of patients had treatment interruptions .
The adverse reactions considered related to treatment or those with uncertain relationship to treatment with Azactam are:
Hypersensitivity: anaphylaxis, angioedema , bronchospasm .
Skin: Rash , pruritus, petechiae , purpura , diaphoresis , flushing , urticaria, erythema multiforme, toxic epidermal necrolysis and exfoliative dermatitis.
Hematologic : Rare cases of eosinophilia , elevated prothrombin and partial thromboplastin time , thrombocytosis , thrombocytopenia , neutropenia , anemia , pancytopenia , leukocytosis , bleeding and positive test of Coombs.
Hepatobiliary : Elevations of liver transaminases and alkaline phosphatase , usually reversible during treatment and no obvious signs or symptoms of hepatobliarna dysfunction. Rarely reported clinical diagnosis of jaundice or hepatitis.
Gastrointestinal : Diarrhea , nausea and / or vomiting, abdominal cramps , ulcers in the mouth and taste changes . Observed rare cases of C. difficile- associated diarrhea , including pseudomembranous colitis or bleeding from the gastrointestinal tract intestinlniya .
Local reactions : there is discomfort at the site of intravenous injection and phlebitis / thrombophlebitis ; mild discomfort at the site of intramuscular injection .
Other: There have been rare reports of the following side effects vaginitis , vaginal candidiasis , hypotension , pripdak , diplopia , weakness, paraesthesia , confusion , lightheadedness , dizziness , insomnia, ECG changes , tinnitus, headache, breast tenderness , bad breath , taste , muscle aches, fever, malaise , sneezing and nasal congestion , wheezing, dyspnea and chest pain . There are uncommon cases of elevated serum creatinine .
If necessary , aztreonam may be separated from the serum by means of hemodialysis and / or peritoneal dialysis . There was separation of aztreonam from serum by continuous arteriovenous hemofiltration .
5.1 Farmakodinomichni properties
AZACTAM a fully synthetic bactericidal antibiotic classified monobactam. It is active against a broad spectrum of Gram- negative aerobic pathogens mikroorganizmi.Aztreonam is active in vitro against most strains of the following organisms, including many that are multi - resistant to other antibiotics (such as certain cephalosporins , penicillins and aminoglycosides ):
Escherichia coli Enterobacter species Klebsiella species, including K. pneumoniae and K. oxytoca Proteus mirabilis Proteus vulgaris Morganella morganii ( before Proteus morganii) Providencia species, including P. stuartii and P. rettgeri before Proteus rettgeri) Pseudomonas species, including P. aeruginosa Serratia marcescens Neisseria gonorrhoeae ( including penicillinase -producing strains ) Haemophilus influenzae ( including ampicillin - rezstentni and penicillinase - producing strains ) Citrobacter species
Some strains of Acinetobacter calcoaceticus
Aztreonam is active in vitro against a variety of other gram-negative aerobic pathogens , although the clinical significance of this is unknown .
These organisms include:
In vitro aztreonam and aminoglycosides have shown synergistic activity against most strains of P. aeruginosa, many of the strains of the Enterobacteriaceae and other Gram- negative aerobic bacilli . Because the beta - lactamase induction , has been found that certain antibiotics ( taprimer , cefoxitin, imipenem) exhibit antagonizam against most beta- lactam antibiotics , including aztreonam, with respect to several Gram -negative aerobes , as strains of Enterobacter and Pseudomonas.
5.2 Pharmacokinetic properties
Pharmacokinetics in Adults
Single 30 -minute intravenous infusion of AZACTAM in doses of 500 mg, 1 g and 2 g of healthy subjects resulted in peak serum levels , respectively 54 , 90 and 204 mcg / mL, immediately after dosing ; as the eighth hour serum levels are respectively 1 , 3 and 6 mcg / mL. Single 3- minute intravenous injection of the same dose results in serum levels of 58 , 125 and 242 pg / mL, 5 minutes after completion of inzhektsiyata.Serumnite concentrations of aztreonam in healthy subjects after the intramuscular injection at doses of 500 mg and 1 g are measurable; peak serum levels occurred after about 1 hour. After identical single intravenous or intramuscular dose AZACTAM, serum concentrations of aztreonam comparable at 1 hour (1.5 hours after the start of the IV infusion ), with similar slopes of serum concentrations thereafter.
The half -life of the serum of aztreonam is about 1.7 hours ( 1.5 to 2.0) in subjects with normal renal function , irrespective of the dosage and mode of administration. In healthy subjects , with a weight of about 70 kg, serum clearance was 91 mL / min, and the renal 56 mL / min; average volume of razpredeelenie at steady state is about 12.6 1 , roughly equivalent to the volume in the extracellular fluid .
In patients with impaired renal function, the elimination half -life of aztreonam is prolonged (see Dosage and method of administration ) . In patients with hepatic impairment , the elimination half - elimirirane of aztreonam is prolonged slightly , as the liver is the major route of excretion .
Intravenous or intramuscular administration of a single dose of 500 mg or 1 g AZACTAM (aztreonam) every eight hours for seven days in healthy subjects resulted in pronounced accumulation of aztreonam or a change in its disposition ; serum protein binding is approximately 56% and is independent of dose . On average, about 6% of the intramuscular dose of lg is emitted as microbiologically inactive hydrolysis product of aztreonam, containing an open beta-lactam fingers in urine collected from 0 to eighth hour , the last day of repeated administration.
* Tissue penetration is related to therapeutic efficacy , but specific tissue levels do not meet the specific therapeutic effects.
** Concentrations in CSF ( cerebrospinal fluid) vary from 2.5 to 8.7 pg / mL. The concentrations in the CSF have 5 to 10% of the serum concentration measured in 30 minuti.Kontsentratsiite of aztreonam in the peritoneal fluid obtained from 1 to 6 hours after repeated intravenous administration of 2 g of ranging between 12 and 90 pg / mL in the majority of patients studied .
Pharmacokinetics in children:
The pharmacokinetics of aztreonam in children vary with age.
Note: Data on safety and efficacy in neonates less than 1 week are limited : the use in this group of patients requires careful consideration ( see Dosage and method of administration ) .
5.3 Preclinical safety data
Carcinogenicity . mutagenicity and impairment of fertility
No studies on animal carcinogenicity studies.
Conducted in vivo and in vitro genotoxicity studies with aztreonam in several standard laboratory models revealed no evidence of mutagenic potential of genetically nivo.Provedenite hramozomno or reproductive studies on two generations of rats at daily doses exceeding 20 times the maximum daily human dose , applied before and during pregnancy and lactation are not leprosy impairment of fertility .
6.1 List of excipients and their amounts
Aztreonam is incompatible with nafcillin sodium, cephradine and metronidazole Do not mix with other drugs , except as provided in Section 6.6 .
6.3 Shelf life
36 mesetsa.Srok life after reconstitution : 24 hours at a temperature below 25 ° C or 72 hours at a temperature of 2-8 ° C.
6.4 Special precautions for storage
Keep in the original container at room temreratura to avoid exposure to excessive heat.
6.5 Nature and contents of container
Azactam placed in glass vials or bottles with rubber stopper and aluminum foil.
6.6 Recommendations for use
Preparation of Parenteral solutions
After addition of the solvent , the content in the container ( vial or bottle ) , shake vigorously and immediately . The resulting solution is not for repeated administration ; if all contents not used in the form of a unit dose , the remaining unused solution should be discarded .
In zaviisimost the concentration of aztreonam and the solvent used , the resultant injection of AZACTAM (aztreonam) is a colorless to slightly straw - yellow , such as on standing may become lightly pink hue ( the activity is not disturbed ) . Products for parenteral use should be inspected visually for particulate matter and discoloration if the solution and container permit.
Each gram AZACTAM, dissolved in 3 mL of a suitable solvent (see Products for parenteral solutions) , provides 1 g AZACTAM in a total volume of about 4 mL.
Intramuscular (IM) administration
Sadarzhanieto vial AZACTAM (aztreonam) for injection must be diluted with at least 3 mL of a suitable solvent per gram of aztreonam. You can use the following solvents:
Sterile water for Injection USP
Bacteriostatic Water for Injection USP ( benzyl alcohol or with a methyl and propylparabens ) Sodium chloride for injection USP Bacteriostatic Sodium Chloride Injection USP ( with benzyl alcohol) .