Ificef^® (Powder) Instructions for Use

Marketing Authorization Holder

Unique Pharmaceutical Laboratories (India)

ATC Code

J01DD04 (Ceftriaxone)

Active Substance

Ceftriaxone

Dosage Forms

	Ificef®	Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1 pc.
		Powder for preparation of solution for intravenous and intramuscular administration 250 mg: vial 1 pc.
		Powder for preparation of solution for intravenous and intramuscular administration 500 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration crystalline, from white to yellowish color.

Vials with a volume of 5 ml (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration crystalline, from white to yellowish color.

Vials with a volume of 5 ml (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration crystalline, from white to yellowish color.

Vials with a volume of 10 ml (1) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Ceftriaxone is a third-generation cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits the synthesis of the cell membrane, and in vitro suppresses the growth of most gram-positive and gram-negative microorganisms. Ceftriaxone is resistant to beta-lactamase enzymes (both penicillinases and cephalosporinases produced by most gram-positive and gram-negative bacteria).

It is effective against the following microorganisms.

Gram-positive

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus V(Str.agalactiae), Streptococcus viridans, Streptococcus bovis.

Staphylococcus spp., resistant to methicillin, are also resistant to cephalosporins, including ceftriaxone. Most strains of enterococci (e.g., Streptococcus faecalis) are also resistant to ceftriaxone.

Gram-negative

Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including K.pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are resistant), Salmonella spp. (including S.typhi), Serratia spp. (including S. marcescens), Shigella spp., Vibrio spp. (including V.cholerae), Yersinia spp. (including Y.enterocolitica).

Note: Many strains of the listed microorganisms, which multiply stably in the presence of other antibiotics, such as penicillins, first-generation cephalosporins, and aminoglycosides, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data, ceftriaxone shows good efficacy in primary and secondary syphilis.

Anaerobic

Bacteroides spp. (including some strains of B. fragilis), Clostridium spp. (including C.difficile), Fusobacterium spp. (except F.mostiferum. F.varium), Peptococcus spp., Peptostreptococcus spp.

Note: Some strains of many Bacteroides spp. (e.g., B.fragilis) that produce beta-lactamase are resistant to ceftriaxone. To determine the sensitivity of microorganisms, it is necessary to use discs containing Ceftriaxone, as it has been shown that in vitro certain strains of pathogens may be resistant to classical cephalosporins.

Pharmacokinetics

When administered parenterally, Ceftriaxone penetrates well into tissues and body fluids.

The AUC after intravenous and intramuscular administration coincide. This means that the bioavailability of ceftriaxone with intramuscular administration is 100%. When administered intravenously, Ceftriaxone rapidly diffuses into the interstitial fluid, where it retains its bactericidal effect against pathogens sensitive to it for 24 hours.

Ceftriaxone reversibly binds to albumin and this binding is inversely proportional to concentration: for example, when the drug concentration in blood serum is less than 100 mg/L, the binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg/L – only 85%. Due to the lower albumin content in the interstitial fluid, the concentration of ceftriaxone in it is higher than in the blood serum.

T_1/2 in healthy adult subjects is about 8 hours. In newborns up to 8 days old and in elderly people over 75 years old, the average T_1/2 is approximately 2 times longer. In adults, 50-60% of ceftriaxone is excreted unchanged in the urine, and 40-50% – also unchanged in the bile. Under the influence of intestinal flora, Ceftriaxone is converted into an inactive metabolite. In newborns, approximately 70% of the administered dose is excreted by the kidneys. In renal failure or liver pathology in adults, the pharmacokinetics of ceftriaxone hardly changes, T_1/2 lengthens insignificantly. If kidney function is impaired, excretion with bile increases, and if there is liver pathology, then the excretion of ceftriaxone by the kidneys increases.

Penetration into cerebrospinal fluid: In newborns and children with meningeal inflammation, Ceftriaxone penetrates into the cerebrospinal fluid, and in the case of bacterial meningitis, an average of 17% of the drug concentration in the blood serum diffuses into the cerebrospinal fluid, which is approximately 4 times more than in aseptic meningitis. 24 hours after intravenous administration of ceftriaxone at a dose of 50-100 mg/kg body weight, the concentration in the cerebrospinal fluid exceeds 1.4 mg/L. In adult patients with meningitis, 2-25 hours after administration of ceftriaxone at a dose of 50 mg/kg body weight, the concentration of ceftriaxone many times exceeded the minimum inhibitory dose necessary to suppress the pathogens most commonly causing meningitis.

Indications

Infections caused by pathogens sensitive to ceftriaxone

• Sepsis;
• Meningitis;
• Abdominal infections (peritonitis, inflammatory diseases of the gastrointestinal tract, biliary tract);
• Infections of bones, joints, connective tissue, skin;
• Infections in patients with reduced immunity;
• Kidney and urinary tract infections;
• Respiratory tract infections (including pneumonia);
• ENT organ infections;
• Urogenital infections (including gonorrhea).

Prevention of infections in the postoperative period.

ICD codes

Dosage Regimen

The drug is administered intramuscularly and intravenously.

For adults and children over 12 years old the average daily dose is 1-2 g of ceftriaxone once a day or 0.5-1 g every 12 hours. In severe cases or in cases of infections caused by moderately sensitive pathogens, the daily dose can be increased to 4 g.

For newborns with a single daily dosage, the following scheme is recommended

1. For newborns (up to two weeks of age): 20-50 mg/kg body weight/day (a dose of 50 mg/kg body weight is not recommended to be exceeded due to the immature enzyme system of newborns).
2. For infants and children under 12 years old: the daily dose is 20-75 mg/kg body weight.

In children with a body weight of 50 kg and above, the dosage for adults should be followed. A dose of more than 50 mg/kg body weight must be administered as an intravenous infusion, for at least 30 minutes.

The duration of therapy depends on the course of the disease.

For bacterial meningitis in newborns and children the initial dose is 100 mg/kg body weight once a day (maximum 4 g). Once the pathogenic microorganism has been isolated and its sensitivity determined, the dose must be reduced accordingly. The best results were achieved with the following therapy durations

For treatment of gonorrhea, caused by both penicillinase-producing and non-penicillinase-producing strains, the recommended dose is 250 mg as a single intramuscular injection.

Before infected or presumably infected surgical interventions to prevent postoperative infections, depending on the risk of infection, a single administration of ceftriaxone at a dose of 1-2 g is recommended 30-90 minutes before surgery.

In patients with impaired renal function, provided liver function is normal, it is not necessary to reduce the dose of ceftriaxone. Only in pre-terminal stage renal failure (creatinine clearance below 10 ml/min) is it necessary that the daily dose of ceftriaxone does not exceed 2 g.

In patients with impaired liver function, provided renal function is preserved, it is also not necessary to reduce the dose of ceftriaxone.

In cases of simultaneous presence of severe liver and kidney pathology, the concentration of ceftriaxone in the blood serum must be regularly monitored. In patients on hemodialysis, it is necessary to monitor the concentration of ceftriaxone in the plasma, because the rate of its excretion may decrease in them.

Rules for using the drug

For intramuscular injection, 1 g of the drug must be dissolved in 3.5 ml of a 1% lidocaine solution and injected deep into the gluteal muscle; it is recommended to inject no more than 1 g of the drug into one buttock. Lidocaine solution should never be administered intravenously.

For intravenous injection, 1 g of the drug must be dissolved in 10 ml of sterile distilled water and administered intravenously slowly over 2-4 minutes.

The duration of intravenous infusion is at least 30 minutes. For intravenous infusion, 2 g of powder must be dissolved in approximately 40 ml of a calcium-free solution, for example: in 0.9% sodium chloride solution, in 5% dextrose solution, in 10% dextrose solution, 5% fructose solution.

Adverse Reactions

Allergic reactions urticaria, chills or fever, rash, itching; rarely – bronchospasm, eosinophilia, polymorphic exudative erythema (including Stevens-Johnson syndrome), serum sickness, angioedema, anaphylactic shock.

From the digestive system nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, taste disturbance, stomatitis, glossitis, pseudomembranous enterocolitis, impaired liver function (increased activity of hepatic transaminases, less often – alkaline phosphatase or bilirubin, cholestatic jaundice), pseudocholelithiasis of the gallbladder (‘sludge’ syndrome), dysbacteriosis.

From the hematopoietic organs anemia, leukopenia, leukocytosis, neutropenia, granulocytopenia, lymphopenia, thrombocytosis, thrombocytopenia, hemolytic anemia, hypocoagulation, decreased concentration of plasma coagulation factors (II, VII, IX, X), prolonged prothrombin time, basophilia.

From the urinary system impaired renal function (azotemia, increased blood urea, hypercreatininemia, glucosuria, cylindruria, hematuria), oliguria, anuria.

Local reactions phlebitis, pain along the vein, pain and infiltration at the site of intramuscular injection.

Other headache, dizziness, nosebleeds, candidiasis, superinfection.

Contraindications

• First trimester of pregnancy;
• Hypersensitivity to cephalosporins, penicillins and carbapenems.

With caution – hyperbilirubinemia in newborns, premature infants, renal/hepatic impairment, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs, pregnancy II-III trimester, lactation period.

Use in Pregnancy and Lactation

With caution – pregnancy II-III trimester, lactation period. If prescribed during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution – hepatic impairment. In patients with impaired liver function, provided that renal function is preserved, there is also no need to reduce the dose of ceftriaxone.

In cases of simultaneous severe renal and hepatic impairment, the plasma concentration of the drug should be regularly determined.

Use in Renal Impairment

With caution – renal impairment.

In patients with impaired renal function, provided that liver function is normal, there is no need to reduce the dose of ceftriaxone. Only in pre-terminal renal failure (creatinine clearance below 10 ml/min) is it necessary that the daily dose of ceftriaxone does not exceed 2 g.

In cases of simultaneous presence of severe hepatic and renal pathology, the serum concentration of ceftriaxone must be regularly monitored.

Pediatric Use

For newborns with a single daily dosage, the following regimen is recommended

1. For newborns (up to two weeks of age): 20-50 mg/kg body weight/day (a dose of 50 mg/kg body weight is not recommended to be exceeded due to the immature enzyme system of newborns).
2. For infants and children under 12 years of age: the daily dose is 20-75 mg/kg body weight.

For children with a body weight of 50 kg and above, the dosage for adults should be followed. A dose of more than 50 mg/kg body weight must be administered as an intravenous infusion over at least 30 minutes.

The duration of therapy depends on the course of the disease.

For bacterial meningitis in newborns and children, the initial dose is 100 mg/kg body weight once/day (maximum 4 g). Once the pathogenic microorganism has been isolated and its sensitivity determined, the dose must be reduced accordingly. The best results were achieved with the following therapy durations

With caution – hyperbilirubinemia in newborns, premature infants.

Geriatric Use

Elderly and debilitated patients may require the prescription of vitamin K.

Special Precautions

In cases of simultaneous severe renal and hepatic impairment, the plasma concentration of the drug should be regularly determined.

In patients on hemodialysis, the plasma concentration of ceftriaxone should be monitored because its elimination rate may be reduced in them.

During long-term treatment, the peripheral blood picture, indicators of the functional state of the liver and kidneys should be regularly monitored.

In rare cases, ultrasound of the gallbladder reveals shadows that disappear after discontinuation (even if this phenomenon is accompanied by pain in the right hypochondrium, continuation of antibiotic prescription and symptomatic treatment are recommended).

During treatment, the consumption of ethanol is contraindicated – disulfiram-like effects are possible (facial flushing, stomach spasms, nausea, vomiting, headache, decreased blood pressure, tachycardia, shortness of breath).

Despite a detailed medical history, which is a rule for other cephalosporin antibiotics as well, the possibility of anaphylactic shock cannot be excluded, which requires immediate therapy – first epinephrine is administered intravenously, then corticosteroids.

In vitro studies have shown that, like other cephalosporin antibiotics, Ceftriaxone is able to displace bilirubin bound to serum albumin. Therefore, in newborns with hyperbilirubinemia and, especially, in premature newborns, the use of ceftriaxone requires even greater caution.

Elderly and debilitated patients may require the prescription of vitamin K.

Overdose

Excessively high plasma concentrations of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis. Symptomatic measures are recommended for the treatment of overdose cases.

Drug Interactions

Ceftriaxone and aminoglycosides have synergism against many gram-negative bacteria.

Incompatible with ethanol.

NSAIDs and other platelet aggregation inhibitors increase the likelihood of bleeding.

When used concomitantly with loop diuretics and other nephrotoxic drugs, the risk of nephrotoxic effects increases.

Pharmaceutically incompatible with solutions containing other antibiotics.

Storage Conditions

Store in a dry place, out of reach of children, at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.