Phagocef

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PHAGOCEF (PHAGOCEF)

Composition:

Active substance: cefotaxime;

One vial contains sodium cefotaxime equivalent to cefotaxime 1000 mg;

Dosage form. Powder for solution for injection.

Main physicochemical properties: white or yellowish powder.

Pharmacotherapeutic group.
Antibacterial agents for systemic use. β-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D01.

Pharmacological Properties

Pharmacodynamics

Phagocef is a semi-synthetic third-generation cephalosporin antibiotic intended for parenteral administration. It exerts a bactericidal effect and has a broad spectrum of activity. Sensitive to the drug are: Streptococcus (except group D), including Streptococcus pneumoniae; Staphylococcus aureus, including strains producing and not producing penicillinase; Bacillus subtilis and Mycoides; Neisseria gonorrhoeae (strains producing and not producing penicillinase), Neisseria meningitidis, other Neisseria species, Escherichia coli, Klebsiella sp., including Klebsiella pneumoniae; Enterobacter spp. (some strains are resistant); Serratia spp., Proteus (both indole-positive and indole-negative species), Salmonella, Citrobacter spp., Providencia, Shigella, Yersinia, Haemophilus influenzae and Parainfluenzae (strains producing and not producing, including ampicillin-resistant strains), Bordetella pertussis, Moraxella, Aeromonas hydrophila, Veillonella, Clostridium perfringens, Eubacterium, Propionibacterium, Fusobacterium, Bacteroides spp., and Morganella. Variable sensitivity to the drug is observed in: Pseudomonas aeruginosa, Acinetobacter, Helicobacter pylori, Bacteroides fragilis, and Clostridium difficile. Resistant to the drug are: group D Streptococcus, Listeria, and methicillin-resistant staphylococci.

Pharmacokinetics

Absorption. Five minutes after a single intravenous administration of 1 g of cefotaxime, its serum concentration reaches 100 mcg/mL. After intramuscular administration of cefotaxime at the same dose, maximum blood concentration is achieved within 0.5 hours and reaches 24 mcg/mL. Bactericidal concentrations in blood are maintained for up to 12 hours.

Distribution. Plasma protein binding averages 25–40%. Cefotaxime penetrates well into tissues and biological fluids of the body. It reaches effective concentrations in pleural, peritoneal, and synovial fluids. It crosses the blood-brain barrier. It undergoes biotransformation to form an active metabolite.

Elimination. Approximately 60–70% of the administered dose is excreted unchanged in urine, and the remainder is excreted as metabolites. It is partially excreted in bile. The elimination half-life is about 1 hour after intravenous administration and 1–1.5 hours after intramuscular administration. In patients with renal impairment and in elderly patients, the elimination half-life is approximately doubled. In newborns, the half-life ranges from 0.75 to 1.5 hours, and in premature infants, from 1.4 to 6.4 hours.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• infections of the ear, nose, and throat organs (tonsillitis, otitis);
• respiratory tract infections (bronchitis, pneumonia, pleurisy, abscesses);
• urinary and genital system infections;
• septicemia, bacteremia;
• intra-abdominal infections (including peritonitis);
• skin and soft tissue infections;
• bone and joint infections;
• meningitis (except listeriosis) and other central nervous system infections.

Prophylaxis of infections following surgical procedures on the gastrointestinal tract, urological, and obstetric-gynecological surgeries.

Contraindications.

Hypersensitivity to cephalosporin antibiotics, hypersensitivity to other β-lactam antibiotics, to lidocaine (for intramuscular administration), bleeding, enterocolitis in history (especially ulcerative colitis); atrioventricular block without a cardiac pacemaker, severe heart failure.

Special safety precautions.

Do not use Phagocef if you have ever experienced severe skin rash, skin peeling, blistering and/or ulceration of mucous membranes of the mouth, throat, nose, genital organs, and eyes after taking cefotaxime or other cephalosporins.

Severe skin adverse reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), drug reaction with eosinophilia and systemic symptoms, which may be life-threatening or fatal, have been reported in the post-marketing period associated with cefotaxime therapy.

Patients should be informed about the signs and symptoms of skin reactions when prescribing.

If signs or symptoms suggesting these reactions occur, cefotaxime should be discontinued immediately. If a patient develops acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms during cefotaxime treatment, cefotaxime therapy must not be resumed and should be permanently discontinued.

In children, rash may be mistaken for the underlying infection or an alternative infectious process; physicians should consider the possibility of a reaction to cefotaxime in children who develop rash and fever during cefotaxime therapy.

Do not use Phagocef and inform your doctor if any of the above applies to you.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with nephrotoxic medicinal products (aminoglycosides) and potent diuretics (ethacrynic acid, furosemide), colistin, polymyxin, the risk of developing renal failure increases.

During cefotaxime treatment, the effectiveness of oral contraceptives may be reduced; therefore, additional contraception should be used during this period. Cefotaxime should not be used together with bacteriostatic antibiotics (e.g., tetracyclines, erythromycin, chloramphenicol) due to the possibility of an antagonistic effect.

When used in combination therapy, cefotaxime solutions should not be mixed with solutions of aminoglycosides – they should be administered separately.

Concomitant use of nifedipine increases cefotaxime bioavailability by 70%.

Probenecid blocks tubular secretion of cefotaxime and prolongs its elimination half-life.

Cefotaxime should not be used together with lidocaine:

• for intravenous administration;
• in children under 30 months of age;
• in patients with a history of hypersensitivity to lidocaine;
• in patients with heart block.

Special precautions for use.

Do not use Phagocef if you have ever experienced a severe skin rash, skin peeling, blistering and/or ulceration of mucous membranes of the mouth, throat, nose, genital organs, or eyes after taking cefotaxime or other cephalosporins.

Be especially cautious with Phagocef if serious skin reactions associated with cefotaxime treatment have been previously recorded, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), or acute generalized exanthematous pustulosis. Discontinue cefotaxime use and immediately contact your doctor if you notice any symptoms related to these serious skin conditions.

Exercise caution when administering the drug to patients with impaired kidney or liver function, or with a history of hypersensitivity to penicillins. In patients with impaired renal function, the drug dosage should be reduced according to the severity of renal impairment and pathogen sensitivity. During prolonged treatment, renal function should be monitored and dysbiosis prevented. It is advisable to regularly monitor peripheral blood cell counts and liver function. A false-positive Coombs test result may occur during drug administration.

Anaphylactic reactions. The use of cephalosporins requires careful assessment of allergic history (allergic diathesis, hypersensitivity reactions to β-lactam antibiotics). If a hypersensitivity reaction develops in a patient, treatment should be discontinued. Cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins. In case of any doubts, the presence of a physician during the first administration of the drug is mandatory due to the possible development of an anaphylactic reaction. Cross-allergy between cephalosporins and penicillins is known to occur in 5–10% of cases. The drug should be used with particular caution in patients with a history of penicillin allergy.

Pseudomembranous colitis. Pseudomembranous colitis, manifested by severe and persistent diarrhea, may develop within the first weeks of treatment. Diagnosis is confirmed by colonoscopy and/or histological examination. These complications are considered serious—immediately discontinue administration of the drug and initiate appropriate therapy, including oral vancomycin or metronidazole. Concurrent use of cefotaxime with nephrotoxic drugs requires monitoring of renal function; treatment lasting more than 10 days requires monitoring of blood parameters. Elderly and debilitated patients should be given vitamin K (to prevent hypocoagulation).

As with other broad-spectrum antibiotics, prolonged use of cefotaxime may lead to overgrowth of non-susceptible microorganisms, necessitating discontinuation of therapy. If superinfection occurs during treatment, appropriate antimicrobial therapy should be initiated. False-positive results may occur when measuring urinary glucose by reduction methods. To avoid this, an enzymatic test should be used.

Alcohol consumption is prohibited during treatment, as disulfiram-like effects may occur (facial flushing, abdominal and epigastric cramps, nausea, vomiting, headache, hypotension, tachycardia, breathing difficulties).

1 g of powder for injection solution contains 2.2 mmol (50.5 mg) of sodium. The amount of sodium at the maximum daily dose exceeds 8.7 mmol (200 mg). This should be taken into account when prescribing Phagocef to patients requiring sodium restriction.

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy is contraindicated.

Breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

Due to the possibility of adverse reactions affecting the nervous system, driving or operating machinery should be avoided during treatment.

Method of Administration and Dosage.

The drug should be administered by intravenous bolus, intravenous infusion, and intramuscular injection.

When using lidocaine as a solvent, safety information regarding lidocaine should be taken into account.

The prepared solution should be stored in a refrigerator at a temperature of (2–8 °C) for 24 hours.

For intravenous bolus injection, dissolve 1 g of powder in 8 mL of sterile water for injection. Administer slowly over 3–5 minutes.

For intravenous infusion, dissolve 1 g of powder in 50 mL of 0.9% sodium chloride solution or 5% glucose solution. The duration of intravenous infusion is 50–60 minutes.

For intramuscular injection, dissolve 1 g of powder in 4 mL of sterile water for injection or 1% lidocaine solution and administer deeply into the gluteal muscle.

The duration of treatment should be determined individually.

Adults and children with body weight over 50 kg should be administered Phagoccef at a dose of 1 g every 12 hours. In severe cases, the drug should be administered at a dose of 1 g 3–4 times daily. The maximum daily dose is 12 g.

For uncomplicated infections, as well as urinary tract infections, administer intramuscularly or intravenously at a dose of 1 g every 12 hours; for uncomplicated acute gonorrhea, administer 1 g (1 vial) intramuscularly once daily or intravenously; for moderate infections, administer the drug at a dose of 1–2 g every 12 hours; for severe infections (meningitis), administer 2 g of the drug intravenously every 6–8 hours. For prophylaxis of infections before surgical intervention, administer 1 g of Phagoccef as a single dose at the time of anesthesia induction. If necessary, repeat the dose after 6–12 hours. In case of impaired renal function, the dose should be reduced. When creatinine clearance is 10 mL/min or less, reduce the daily dose by half.

Children. For children with body weight under 50 kg, the drug should be administered at a dose of 50–100 mg/kg body weight per day, divided into 3–4 intramuscular or intravenous injections. In severe infections (including meningitis), increase the daily dose to 100–200 mg/kg body weight, divided into 4–6 intravenous or intramuscular injections. For premature infants and children up to 1 week of age, the daily dose is 50 mg per 1 kg body weight, divided into two equal doses administered intravenously. For children aged 1–4 weeks, the daily dose is 50–100 mg per 1 kg body weight, divided into three equal doses administered intravenously.

Children.

The medicinal product should not be administered intramuscularly to children under 2.5 years of age.

Overdose.

Symptoms: possible fever, leukopenia, thrombocytopenia, acute hemolytic anemia, skin, gastrointestinal reactions, and hepatic reactions, dyspnea, renal failure, stomatitis, anorexia, temporary hearing loss, disorientation, encephalopathy (especially in case of renal failure). In isolated cases, seizures and exacerbation of adverse effects may occur.

Treatment. No specific antidote is available. Serum levels of cefotaxime can be reduced by hemodialysis or peritoneal dialysis. Symptomatic therapy should be administered if necessary. In case of anaphylactic shock, appropriate measures should be taken immediately. If signs of hypersensitivity reaction occur (skin rash, urticaria, headache, nausea, loss of consciousness), administration of cefotaxime should be discontinued. In case of severe hypersensitivity reaction or anaphylactic reaction, appropriate therapy should be initiated (administration of epinephrine and/or glucocorticoids). Additional measures may be required in other clinical conditions, such as artificial ventilation, use of histamine receptor antagonists. In case of circulatory failure, resuscitation measures should be taken.

Side effects

Gastrointestinal system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, dysbacteriosis, flatulence, stomatitis, glossitis, pseudomembranous colitis.

Hepatobiliary system: hepatitis, liver function disorders, acute liver failure, jaundice, cholestasis.

Cardiac disorders: arrhythmia after rapid bolus infusion via central venous catheter.

Immune system: anaphylactic reactions, angioneurotic edema, bronchospasm, Jarisch-Herxheimer reaction; rarely – anaphylactic shock.

Skin and subcutaneous tissue: hypersensitivity reactions including erythema, rash, skin itching, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), fever; very rarely – acute generalized exanthematous pustulosis; frequency "not known" – drug reaction with eosinophilia and systemic symptoms (DRESS).

Renal and urinary system: renal function disorders, increased creatinine (especially when used concomitantly with aminoglycosides), oliguria, interstitial nephritis, increased blood urea nitrogen.

Laboratory findings: increased blood urea nitrogen and creatinine, hypocoagulation, positive Coombs test, elevated levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase) and/or bilirubin.

Blood and lymphatic system: neutropenia, granulocytopenia, transient leukopenia, anisocytosis, hypocoagulation, thrombocytopenia, agranulocytosis, hypoprothrombinemia, hemolytic anemia, eosinophilia, autoimmune hemolytic anemia.

Central nervous system: headache, reversible encephalopathy (e.g. altered consciousness, gait disturbances), dizziness, seizures, increased fatigue, weakness.

Local reactions: fever, injection site reactions including pain and infiltration at intramuscular injection site, pain along the vein, tissue inflammation, phlebitis/thrombophlebitis.

Effects due to biological activity: possible development of superinfection (including candidiasis, vaginitis).

Other: hemorrhages and bleeding.

Jarisch-Herxheimer reaction

During treatment of borreliosis, the Jarisch-Herxheimer reaction may develop within the first days of therapy. The appearance of one or more of the following symptoms has been reported after several weeks of treatment for borreliosis: skin rash, itching, fever, leukopenia, elevated liver enzymes, dyspnea, joint discomfort.

Hepatobiliary disorders

Elevations in liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase) and/or bilirubin have been observed.

These laboratory findings rarely exceed twice the upper limit of normal range and may indicate liver dysfunction, usually cholestatic and most often asymptomatic.

During treatment of infections caused by spirochetes, a complication similar to the Herxheimer reaction may occur, leading to fever, chills, headache, and joint pain.

Reporting suspected adverse reactions

After marketing authorization of a medicinal product, it is very important to report suspected adverse reactions. This allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach of children.

Incompatibilities.

The solution of the medicinal product Fagocef is incompatible with solutions of other antibiotics in the same syringe or infusion solution, and with aminoglycoside solutions in the same syringe or infusion. For dilution, use only the solutions specified in the section "Administration and dosage".

Packaging.

Powder for injection solution 1000 mg, 1 vial in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

BROS LTD.

Manufacturer's address and place of business.

Augis & Galinis 15, Nea Kifisia (Attiki) 145 64, Greece.