Newceph 1g 1 vial

NEWCEPH (NEWCEPH) International Nonproprietary Name: Ceftriaxone Dosage Form: Powder for solution for intravenous and intramuscular injection Composition of one vial: Ceftriaxone 1.0 g Active substance: Ceftriaxone sodium trisodium sesquihydrate 1.193 g (calculated as ceftriaxone) 1.0 g See also: Peo - Peo with Lidocaine 1g. 1 vial Description: Crystalline powder from almost white to yellowish-white. Pharmacological group: Antibiotic-cephalosporin. ATX code: J01DD04 Pharmacological action Pharmacodynamics Broad-spectrum third-generation cephalosporin antibiotic for parenteral administration. Bactericidal activity is due to inhibition of bacterial cell wall synthesis. Resistant to β-lactamases produced by most Gram-positive and Gram-negative microorganisms. Active against Gram-positive aerobic microorganisms - Staphylococcus aureus (including penicillinase-producing), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. (viridans group) Gram-negative aerobic microorganisms - Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Borrelia burgdorferi, Acinetobacter calcoaceticus, Haemophilus influenzae (including ampicillin-resistant and β-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii, Neisseria meningitidis, Neisseria gonorrhoeae (including penicillin-producing strains), Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa many strains, Bacteroides fragilis, Clostridium spp. anaerobic microorganisms (most strains of Clostridium difficile are resistant), Peptostreptococcus spp., Peptococcus spp. In vitro activity against most strains of the following microorganisms, but the safety and efficacy of ceftriaxone in the treatment of diseases caused by these microorganisms have not been clinically established: aerobic Gram-negative microorganisms - Citrobacter diversus, Citrobacter freundii, Providencia spp. (including Providencia rettgeri), Salmonella spp. (including Salmonella typhi), Shigella spp., aerobic Gram-positive microorganisms - Streptococcus agalactiae, anaerobic microorganisms - Prevotella (Bacteroides) bivius, Porphyromonas (Bacteroides) melaninogenicus. Methicillin-resistant Staphylococcus spp. strains, many strains of group D streptococci and Enterococcus spp. (Enterococcus faecalis), Clostridium difficile, Bacteroides spp. strains (β-lactamase-producing) are resistant to the drug. Methicillin-resistant staphylococci are resistant to cephalosporins, including ceftriaxone, as are enterococci, including Enterococcus faecalis, which are also resistant to ceftriaxone. Pharmacokinetics Absorption After intramuscular administration, ceftriaxone is rapidly and completely absorbed into the systemic circulation. It penetrates well into the body's tissues and fluid compartments: respiratory tract, bones, joints, urinary tract, skin, subcutaneous tissue, and abdominal organs. In case of meningitis, it penetrates well into the cerebrospinal fluid. The bioavailability of ceftriaxone after intramuscular administration is 100%. Distribution After intramuscular administration of ceftriaxone at doses of 0.5 g and 1.0 g, the maximum concentration (Cmax) in blood plasma is 38 mcg/mL and 76 mcg/mL, respectively; after intravenous administration of doses of 0.5 g, 1.0 g, and 2.0 g - 82 mcg/mL, 151 mcg/mL, and 257 mcg/mL, respectively. In adults, 2-24 hours after administration of the drug at a dose of 50 mg/kg, the concentration in the cerebrospinal fluid many times exceeds the minimum inhibitory concentrations for the most common causative agents of meningitis. Steady state is reached within 4 days of drug administration. Reversible binding to plasma proteins (albumin) is 83-95%. The volume of distribution (Vd) is 5.78-13.5 L (0.12-0.14 L/kg), in children - 0.3 L/kg. It crosses the placental barrier in small amounts. Elimination The half-life is 6-9 hours, which allows for once-daily administration of the drug. Plasma clearance - 0.58-1.45 L/h, renal clearance - 0.32-0.73 L/h. It is excreted unchanged in 33-67% by the kidneys; 40-50% is excreted with bile into the intestines, where it is biotransformed into an inactive metabolite. Approximately 50% is excreted within 48 hours. Pharmacokinetics in special clinical cases In newborns, approximately 70% of the drug is excreted by the kidneys. In newborns and elderly patients (over 75 years of age), as well as in patients with impaired renal and liver function, the half-life is significantly increased. In patients undergoing hemodialysis with creatinine clearance of 0-5 mL/min, the half-life is 14.7 hours; with creatinine clearance of 5-15 mL/min - 15.7 hours; with creatinine clearance of 16-30 mL/min - 11.4 hours; with creatinine clearance of 31-60 mL/min - 12.4 hours. In children with meningitis, the half-life after intravenous administration at a dose of 50-75 mg/kg is 4.3-4.6 hours. Ceftriaxone is not removed by hemodialysis. Indications for use Infectious and inflammatory diseases caused by ceftriaxone-sensitive microorganisms: intra-abdominal infections, including peritonitis, inflammatory diseases of the gastrointestinal tract, biliary tract (including cholangitis, gallbladder empyema), upper and lower respiratory tract and ENT infections (including acute and complicated chronic bronchitis, pneumonia, lung abscess, pleural empyema), epiglottitis, bone and joint infections, skin and soft tissue infections, genitourinary tract infections (including pyelitis, acute and chronic pyelonephritis, cystitis, prostatitis, epididymitis), infected wounds and burns, gonorrhea without complications, including those caused by penicillinase-producing microorganisms, sepsis and bacterial septicemia, bacterial meningitis and endocarditis, Lyme disease (tick-borne borreliosis), infections in immunocompromised patients, prevention and treatment of postoperative infectious complications. Contraindications Hypersensitivity to ceftriaxone and other cephalosporins, penicillins, carbapenems; first trimester of pregnancy, lactation; hyperbilirubinemia in newborns and premature infants; administration with intravenous calcium-containing solutions in newborns. Precautions Premature infants, renal and/or hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with antibacterial drug use, second and third trimesters of pregnancy. Use during pregnancy and lactation The drug can be used during pregnancy (II and III trimesters) only if the expected benefit to the mother outweighs the potential risk to the fetus (ceftriaxone crosses the placental barrier). If the drug needs to be used during lactation, breastfeeding should be discontinued (it is excreted in breast milk). Method of administration and dosage The drug is administered intramuscularly or intravenously (bolus or infusion). In adults or children over 12 years of age, 1-2 g is administered once daily. The maximum daily dose is not more than 4 g. In newborns up to 14 days of age, 20-50 mg/kg/day is administered. The maximum daily dose is not more than 50 mg/kg. In infants and young children (15 days to 12 years of age), 20-80 mg/kg body weight is administered once daily. In children weighing ≥50 kg, adult doses are used. Doses of 50 mg/kg and higher for intravenous administration should be given by infusion over at least 30 minutes. The total daily dose in children should not exceed 2 g. The course of treatment for infections caused by Streptococcus pyogenes should be at least 10 days. In patients with renal and hepatic insufficiency, the daily dose of the drug should not exceed 2 g without monitoring ceftriaxone concentration in the blood. Elderly patients should receive the usual adult doses without age adjustment. The duration of the course is usually 4-14 days; longer administration may be necessary for complicated infections. Administration of the drug should be continued for 2-3 days after the disappearance of symptoms and signs of infection. In bacterial meningitis in infants and young children, it is 100 mg/kg once daily. The maximum daily dose is 4 g. The duration of therapy depends on the type of pathogen and can range from 4 days for meningitis caused by Neisseria meningitidis to 10-14 days for meningitis caused by susceptible strains of Enterobacteriaceae. In Lyme disease: in adults and children over 12 years of age, 50 mg/kg is administered once daily, the maximum daily dose is 2 g. The duration of treatment is 14 days. In acute uncomplicated gonorrhea, the drug is administered intramuscularly once at a dose of 250 mg. For the prevention of postoperative complications - once, 1.0 g, 30-60 minutes before surgery. During surgery on the colon and rectum - simultaneous (but separate) administration of NEWCEPH and a drug from the 5-nitroimidazole group is effective. In patients with impaired renal function, dose adjustment is not required if liver function remains normal. In cases of severe terminal renal failure with creatinine clearance less than 10 mL/min, the daily dose of the drug should not exceed 2 g. In patients with impaired liver function, dose adjustment is not required if kidney function remains normal. In case of combined severe renal and hepatic insufficiency, ceftriaxone concentration in plasma should be regularly monitored, and the dose should be adjusted if necessary. Additional administration of the drug after dialysis is not required for patients on hemodialysis. The rate of ceftriaxone excretion may be reduced in such patients, so the drug concentration in blood plasma should be monitored to adjust the dose in a timely manner. Preparation and administration of solutions Only freshly prepared solutions should be used. For intramuscular injection, dissolve 1.0 g of the drug in 3.5 mL of water for injection. To reduce pain during intramuscular injections, administer the drug with a 1% lidocaine solution. Inject deep into the gluteal muscle or thigh muscle. Do not inject more than 1.0 g of the drug into one muscle. Lidocaine solution cannot be administered intravenously. For intravenous injection, dissolve 1.0 g of the drug in 10 mL of water for injection. Administer the solution over 2-4 minutes. For intravenous infusion, dissolve 2.0 g of the drug in 40 mL of water for injection or one of the solutions that do not contain calcium (0.9% sodium chloride solution; 0.45% sodium chloride solution + 2.5% dextrose solution; 5% dextrose solution; 10% dextrose solution; 6% dextran solution in 5% dextrose solution; 6-10% hydroxyethyl starch solution). Administer the solution over 30 minutes. Side effects Allergic reactions: rash, itching, fever, chills, urticaria, edema, allergic dermatitis, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome. Nervous system: headache, dizziness. Gastrointestinal tract: diarrhea, nausea, vomiting, taste disturbance, flatulence, pseudomembranous colitis, stomatitis, glossitis. Hematopoietic organs: with prolonged use at high doses, changes in peripheral blood count (anemia, including hemolytic), eosinophilia, thrombocytosis, leukopenia, neutropenia, lymphopenia, thrombocytopenia, granulocytopenia may occur. Genitourinary system: vaginal candidiasis, vaginitis, oliguria. Local reactions: with intravenous administration - phlebitis, pain, induration along the vein; with intramuscular administration - pain, sensation of heat, tension, or induration at the injection site. Laboratory parameters: increased (decreased) prothrombin time, increased activity of liver transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased urea concentration, presence of sediment in urine. Other: increased sweating, facial flushing, precipitation of ceftriaxone calcium salts in the gallbladder with corresponding symptoms, pancreatitis, formation of kidney stones. Adverse reactions with a frequency of less than 0.1%: abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, cholelithiasis, bronchospasm, colitis, dyspepsia, epistaxis, abdominal distension, bile stasis (sludge syndrome), glucosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, seizures, serum sickness. Overdose To date, there have been no reports of NEWCEPH overdose. Symptoms of overdose - intensification of dose-dependent side effects - see above. Treatment: symptomatic. There is no specific antidote. Hemodialysis and peritoneal dialysis are ineffective. Interaction with other medicinal products Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone. Ceftriaxone and aminoglycosides have synergy against many Gram-negative bacteria (including Pseudomonas aeruginosa); the drugs should be administered separately at recommended doses. Ceftriaxone, by suppressing intestinal flora, inhibits vitamin K synthesis. Concomitant administration with platelet aggregation inhibitors (non-steroidal anti-inflammatory drugs, salicylates, sulfinpyrazone) increases the risk of bleeding. Concomitant administration with anticoagulants enhances anticoagulant effect. Concomitant use with loop diuretics and other nephrotoxic drugs increases the risk of nephrotoxic effects. Does not interact with probenecid. Pharmaceutical interactions Mixing ceftriaxone with solutions containing calcium (including Hartmann's and Ringer's solutions) is not allowed. It is pharmaceutically incompatible with solutions containing other antibiotics, including amsacrine, vancomycin, fluconazole, and aminoglycosides. Special instructions During prolonged treatment, regular monitoring of peripheral blood count, liver and kidney function indicators is necessary. In rare cases, opacities (precipitates of ceftriaxone calcium salt) are observed during ultrasound examination of the gallbladder, which disappear after discontinuation of the drug. If symptoms or signs indicating possible gallbladder disease or ultrasound signs of "sludge phenomenon" develop, it is recommended to discontinue administration of the drug. Rare cases of pancreatitis have been described with the use of the drug, possibly due to obstruction of the bile ducts. Most patients had risk factors for bile duct stasis (prior therapy with the drug, concomitant severe diseases, total parenteral nutrition); however, the role of ceftriaxone in the formation of precipitates in the bile ducts cannot be excluded. Ceftriaxone does not contain the N-methylthiotetrazole group, which causes disulfiram-like effects with simultaneous use of ethanol and bleeding, which is characteristic of some cephalosporins. Rare cases of prothrombin time changes have been described with the use of the drug. In patients with vitamin K deficiency (impaired synthesis, nutritional disorders), prothrombin time monitoring and administration of vitamin K (10 mg/week) may be necessary if prothrombin time increases before or during therapy. Fatal reactions have been described due to the accumulation of ceftriaxone-Ca2+ precipitates in the lungs and kidneys of newborns. Theoretically, the possibility of interaction between ceftriaxone and intravenous solutions containing Ca2+ exists in patients of other age groups, therefore ceftriaxone should not be mixed with Ca2+-containing solutions (including for parenteral nutrition), nor should they be administered simultaneously, including through separate access for infusion at different sites. There are no reports of possible interactions between ceftriaxone and oral calcium-containing preparations, as well as intramuscular ceftriaxone calcium-containing preparations (intravenous and oral). With ceftriaxone treatment, false positive results of Coombs test, galactosemia test, glucose determination in urine (glucose determination is recommended only by enzymatic method) may be observed. Despite a thorough collection of anamnesis, the development of anaphylactic shock cannot be ruled out, which requires immediate therapy: first, epinephrine is administered intravenously, and then - glucocorticosteroids. Effect on ability to drive and operate machinery During treatment, exercise caution when driving vehicles and performing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. Dosage form Powder for solution for intravenous and intramuscular injection 1.0 g. 1.0 g ceftriaxone in colorless glass vials. Vial hermetically sealed with a rubber stopper and crimped aluminum cap with a plastic cover. 1 vial with instructions for use in a cardboard box. Storage conditions Store in a protected place from light at a temperature not exceeding 25 0 C. Keep out of reach of children. Shelf life 2 years. Do not use after the expiry date. Dispensing conditions: Pharmaceutical product group - II, dispensed by prescription form №3