INSTRUCTIONS FOR MEDICAL USE PARMAZON-S PARMAZONE-S
Trade name of the drug:PARMAZON-S Active substances (INN):cefoperazone, sulbactam Dosage form:powder for the preparation of an injectable solution for intramuscular and intravenous administration. Composition: 1 bottle in grams contains: active substances: cefoperazone sodium salt (in terms of cefoperazone) – 1000mg; sulbactam sodium salt (in terms of sulbactam) – 500 mg. Description:White or almost white crystalline powder. After dissolution: pure, light yellow, transparent solution. Pharmacotherapeutic group:Antibiotic (gr. cephalosporins). Pharmacological properties Cephalosporin III generation in combination with a beta-lactamase inhibitor. Cefoperazone sodium is a semi-synthetic cephalosporin broad-spectrum antibiotic intended only for parenteral use. It acts on sensitive microorganisms during their active reproduction by inhibiting the biosynthesis of the mucopeptide of the cell wall. Sulbactam is a stable irreversible inhibitor of various beta-lactamases secreted by microorganisms resistant to beta-lactam antibiotics. Sulbactam expands the spectrum of activity of the drug against resistant strains, without changing the activity (against sensitive strains, binding to some penicillin-binding proteins of bacteria) shows synergism when used simultaneously with beta-lactam antibiotics. Sulbactam has no clinically significant antibacterial activity of its own (with the exception of Neisseriaceae and Acinetobacter). PARMAZONE-C is active against all microorganisms sensitive to cefoperazone. In addition, it has synergism (a decrease in BMD when using PARMAZONE-Sdo 4 times compared to those when using both components separately) against various microorganisms, primarily the following: Haemophilusinfluenzae, Bacteroidesspp., Staphylococcusspp., Acinetobactercalcoaceticus, Enterobacteraerogenes, Escherichiacoli, Proteusmirabilis, Klebsiellapneumoniae, Morganellamorganii, Citrobacterfreundii, Enterobactercloacae, Citrobacterdiversus. PARMAZONE-C is active in vitro against a wide range of clinically significant microorganisms. Gram-positive microorganisms:Staphylococcus aureus, producing and not producing penicillinase, Staphylococcusepidermidis, Streptococcuspneumoniae, Streptococcuspyogenes (beta-hemolytic streptococcus group A), Streptococcusagalactiae (beta-hemolytic streptococcus group B), most other strains of beta-hemolytic streptococci, many strains of Streptococcusfaecalis (Enterococcus). Gram-negative microorganisms:Escherichiacoli, r^pbsiellaspp., Enterobacterspp., Citrobacterspp., Haemophilusinfluenzae, Proteusmirabilis, Proteusvulgaris, Morganellamorganii (old name Proteusmorganii), Providenciarettgeri (old name Proteusrettgeri), Providenciaspecies, Serratiaspp. (including S.marcescens), Salmonella and Shigellaspp., Pseudomonasaeruginosa and some other Pseudomonasspp., Acinetobactercalcoaceticus, Neisseriagonorrhoeae, Neisseriameningitidis, Bordetellapertussis, Yersiniaenterocolitica. Anaerobic microorganisms: Gram-negative bacilli (including Bacteroidesfragilis, other Bacteroidesspp. and Fusobacteriumspp.).Gram-positive and gram-negative cocci (including Peptococcus, Peptostreptococcus and Veillonellaspecies). Gram-positive papillae (including Clostridium, Eubacterium and Lactobacillusspp.). Pharmacokinetics Both sulbactam and cefoperazone are well distributed in various tissues and body fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovaries, uterus. There is no data on the presence of any pharmacokinetic interaction between sulbactam and cefoperazone when PARMAZONE-C is administered. A certain portion of the dose of sulbactam and cefoperazone is excreted by the kidneys. The rest of cefoperazone is excreted mainly with bile.
Indications for use Infectious and inflammatory diseases caused by microorganisms sensitive to the drug: - upper and lower respiratory tract infections; - infections of the upper and lower urinary tract; - intraabdominal infections (including peritonitis, cholecystitis, cholangitis); - septicemia; - meningitis; - skin and soft tissue infections; - infections of bones and joints; - inflammatory diseases of the pelvic organs; - endometritis; - gonorrhea. Given the wide spectrum of action of PARMAZON-C, monotherapy with this drug is effective for most infections. However, if necessary, PARMAZONE-C can be used in combination with other antibiotics (with simultaneous use of aminoglycosides, kidney function should be monitored). Method of administration and dosage In adults, Parmazone-C is recommended to be used in the following daily doses: The ratio of cefoperazone/ sulbactam PARMAZONE-C (g) Cefoperazone (g) Sulbactam(g) 1:2 1.5 1 0.5
In severe or refractory infections, the daily dose of PARMAZON-C can be increased to 8 g with a 1:1 component ratio (i.e. 4 g of cefoperazone). Patients receiving PARMAZONE-C in a 1:1 ratio may require additional administration of cefoperazone. The dose should be divided into equal parts and administered every 12 hours. The recommended maximum daily dose of sulbactam is 4 g. In children, Parmazone-C is recommended to be used in the following daily doses:
PARMAZONE-C Ratio of Cefoperazone Sulbactam 1 cefoperazone / sulbactam (mg/kg/day) (mg/kg/day) (mg/kg/day) 1:2 60 to 120 20 to 40 40 to 80
In case of serious or refractory infections, doses can be increased to 160 mg / kg / day with a component ratio of 1:1. The daily dose is divided into 2-4 equal parts.Newborns during the first week of life, the drug should be administered every 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg / kg / day. In patients with severe renal insufficiency (CC less than 3 ml / min), the dose of PARMAZON-C is changed to compensate for the decrease in clearance of sulbactam. In patients with CC (creatinine clearance) of 15-30 ml /min, the maximum dose of sulbactam is 1 g every 12 hours (the maximum daily dose of sulbactam is 2 g), and in patients with CC <15 ml/ min, the maximum dose of sulbactam is 500 mg every 12 hours (the maximum daily dose of sulbactam is 1 g). In severe infections, additional administration of cefoperazone may be required. Since the pharmacokinetics of sulbactam changes significantly during hemodialysis, and the half-life of cefoperazone from blood plasma decreases somewhat, the administration of PARMAZONE-C should be planned after dialysis. Rules for the preparation and application of the solution for intravenous administration, for repeated infusions, the contents of each vial of PARMAZON-C are dissolved in an adequate volume of 5% dextrose solution, 0.9% sodium chloride solution and / or sterile water for injection, and then diluted to 20 ml with the same solvent. The infusion is carried out for 15-20 minutes . To prepare a solution for intravenous infusion, a Ringer's lactated solution can be used, however, it cannot be used for initial dissolution. For intravenous injection, the contents of each vial should be dissolved as indicated above and administered for at least 3 minutes. Rules for the preparation of a solution for intravenous administration:
Total Equivalent Dose Volume Maximum Final dose (g) cefoperazone+sulbactam (g) solvent (ml) concentration (mg/ml) 1.5 0.5+1.0 3.2 125+250
PARMAZONE-C is compatible with water for injection, 5% dextrose solution, saline solution and 5% dextrose solution in saline solution in concentrations from 10 mg/ml of cefoperazone and 10 mg/ml of sulbactam to 250 mg/ml and 250 mg/ml, respectively. When diluted with Ringer's lactated solution, the solution is prepared in 2 stages: first, sterile water is used for injection, then the resulting solution is diluted with Ringer's lactated solution to a sulbactam concentration of 5 mg / ml (2 ml of the initial solution is diluted with 50 ml of Ringer's lactated solution or 4 ml of 100 ml of Ringer's lactated solution). When diluting with lidocaine, sterile water for injection should be used to dissolve the powder. A solution containing cefoperazone at a concentration of 250 mg/ml or more is prepared in 2 stages: first, sterile water is used for injection, and then diluted with a 2% lidocaine solution to obtain a solution containing up to 250 mg/ml of cefoperazone 250 mg/ml of sulbactam in approximately 0.5% lidocaine hydrochloride solution.
Side effects From the digestive system: disorders of the gastrointestinal tract were most often noted - diarrhea, less often - nausea and vomiting; pseudomembranous colitis. Allergic reactions: there were macular-papular rash, urticaria, the risk of their occurrence is higher in patients with allergic reactions (especially to penicillin in the anamnesis). Anaphylactoid reactions (including shock), Stevens-Johnson syndrome From the body as a whole: headache, fever, injection pain, chills. From the laboratory parameters: transient increase in liver function indicators - ACT, ALT, alkaline phosphatase, bilirubin. From the cardiovascular system: arterial hypotension, vasculitis. From the hematopoietic system: leukopenia. Local reactions: sometimes transient pain is observed after intravenous injection. With intravenous administration of PARMAZON-C (as well as other cephalosporins and penicillins) with the help of a catheter, phlebitis may develop at the site of infusion. Dermatological reactions: itching. From the urinary system: hematuria.
Contraindications Hypersensitivity to cephalosporins and other beta-lactam antibiotics. With caution, it is used during pregnancy, during breastfeeding, with hepatic and renal insufficiency.
Drug interactions Pharmaceutical interaction Solutions of PARMAZON-C and aminoglycosides should not be mixed in the same syringe or in the system for intravenous infusions, given the physical incompatibility between them. If combined therapy with PARMAZON-C and aminoglycosides is carried out, then two drugs are administered by successive infusions using separate secondary catheters, and the primary catheter is washed with an adequate solution between the administration of doses of drugs. The intervals between the administration of PARMAZONE-C and aminoglycoside during the day should be as long as possible. It is not necessary to use the Ringer's lactated solution for the initial dissolution of the powder, given the incompatibility of this mixture. However, compatibility can be achieved by two-stage preparation of the solution - initially, the powder is dissolved in water for injection, and then diluted with a lactated Ringer solution. It is not recommended to use a 2% lidocaine hydrochloride solution for the initial dissolution of the powder, given their incompatibility. However, compatibility can be achieved by two-step preparation of the solution - initially the powder is dissolved in water for injection, and then diluted with a 2% lidocaine hydrochloride solution.
Special instructions In patients receiving beta-lactam antibiotics, including cephalosporins, cases of severe hypersensitivity reactions (anaphylactic) have been described, which sometimes led to death. The risk of developing such reactions is higher in patients who have a history of hypersensitivity reactions to various allergens. if an allergic reaction occurs, it is necessary to cancel the drug and prescribe adequate therapy. In case of serious anaphylactic reactions, urgent administration of adrenaline is necessary. According to the indications, oxygen is prescribed, steroids are administered intravenously and ensure the patency of the respiratory tract, including intubation. With complete obstruction of the biliary tract, severe liver diseases, as well as renal dysfunction combined with any of these conditions, it may be necessary to adjust the dosage regimen of the drug. In patients with impaired liver function and concomitant renal impairment, it is necessary to monitor the serum concentration of cefoperazone and adjust its dose if necessary. If regular monitoring of the serum concentration of cefoperazone is not carried out in such cases, then its daily dose should not exceed 2 g. When treated with cefoperazone, as with other antibiotics, vitamin K deficiency has developed in rare cases. The reason for it is probably the suppression of the normal intestinal microflora that synthesizes this vitamin. The risk group includes patients receiving poor nutrition, patients with malabsorption (for example, cystic fibrosis) and long-term on / in artificial nutrition. In such cases, as well as in patients receiving anticoagulants, it is necessary to monitor prothrombin time and, if indicated, prescribe vitamin K. With prolonged treatment with PARMAZON-C (as with other antibiotics), excessive growth of insensitive microorganisms may be observed. Patients should be carefully monitored during treatment. With long-term therapy with PARMAZON-C, it is recommended to periodically monitor the indicators of the function of internal organs, including the kidneys, liver and hematopoiesis system. When drinking alcohol during treatment with cefoperazone and for up to 5 days after its administration, reactions characterized by hot flashes, sweating, headache and tachycardia were recorded. Similar reactions have been observed with the use of some other cephalosporins, therefore, patients should be warned about the possibility of their occurrence when drinking alcoholic beverages against the background of PARMAZON-C treatment. In patients who need artificial nutrition (orally or parenterally), the use of solutions containing ethanol should be avoided. When using Benedict's or Fehling's solution in the test, a false positive reaction to glucose in the urine may be observed against the background of the use of the drug. Cefoperazone does not displace bilirubin from binding to plasma proteins. Use in pediatrics When conducting long-term therapy with the drug in children, it is recommended to periodically monitor the indicators of kidney function, liver, hematopoiesis, especially in newborns, especially premature babies, and young children. Pregnancy and lactation Sulbactam and cefoperazone penetrate through the placenta. Adequate and strictly controlled studies of the safety of PARMAZON-C during pregnancy have not been conducted, therefore, the drug should be used during pregnancy only if absolutely necessary. Sulbactam and cefoperazone are excreted in very small amounts in breast milk. Although both components do not penetrate well into breast milk, nevertheless, caution should be exercised when using PARMAZON-C during lactation (breastfeeding). About the effect on the reaction speed when driving vehicles or working with other mechanisms. There are no messages at the moment.
Overdose Information on the acute toxicity of cefoperazone sodium and sulbactam sodium in humans is limited. Symptoms: in case of overdose, you can expect the appearance of undesirable effects recorded when using the drug. It is necessary to take into account the fact that a high concentration of beta-lactam antibiotics in the cerebrospinal fluid can lead to neurological disorders, including seizures. Treatment: both cefoperazone and sulbactam are removed from the blood during hemodialysis, so this method of treatment can contribute to the elimination of the drug from the body in case of overdose in patients with impaired renal function.
Release form 1.5 g of the drug in glass vials, hermetically sealed with rubber stoppers, compressed with aluminum caps with the control of the first hiding (flip-off). A self-adhesive label is pasted on the bottle. One bottle together with the instructions for use is placed in a cardboard box.
Storage conditions Store in a dry and protected from light place, at a temperature not higher than 250C.The drug should be stored out of the reach of children.
Expiration date 2 years. Do not use after the expiration date.
Conditions of release from pharmacies By prescription.
Manufacturer: MAXMED LIFE SCIENCES PVT LTD PLOT NO. 54, SECTOR IIDC, PANTNAGAR, RUDRAPUR, UTTARAKHAND, INDIA 263153.
Name and address of the organization accepting claims (proposals) on the quality of medicines in the territory of the Republic of Uzbekistan Manoj Kumar FUTURE-WORLD GROUP Tashkent, Chilanzarsky district, 13A Sanat str. +99891 134 94 14 info.fwg@yandex.com
