Nacef^® (Powder) Instructions for Use

Marketing Authorization Holder

PFC Prebend, LLC (Russia)

ATC Code

J01DB04 (Cefazolin)

Active Substance

Cefazolin (Rec.INN registered by WHO)

Dosage Forms

	Nacef®	Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1 or 5 pcs. in a set with solvent or without it
		Powder for preparation of solution for intravenous and intramuscular administration 500 mg: vial 1 or 5 pcs. in a set with solvent or without it

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Solvent water for injections (5 ml).

Glass vials with a capacity of 10 ml (1) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (2) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Solvent water for injections (5 ml).

Glass vials with a capacity of 10 ml (1) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (2) – cardboard packs.

Clinical-Pharmacological Group

First generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin antibiotic of the first generation for parenteral use. It acts bactericidally by disrupting the synthesis of the microbial cell wall. It has a broad spectrum of action, active against gram-positive (Staphylococcus spp., Staphylococcus aureus (non-penicillinase-producing and penicillinase-producing; including Streptococcus pneumoniae), Corynebacterium diphtheriae, Bacillus anthracis) and gram-negative (Neisseria meningitidis, Neisseria gonorrhoeae, Shigella spp., Salmonella spp., Escherichia coli, Klebsiella spp., Treponema spp., Leptospira spp.) microorganisms.

Active against Haemophilus influenzae, some strains of Enterobacter and Enterococcus.

Ineffective against Pseudomonas aeruginosa, indole-positive strains of Proteus spp., Mycobacterium tuberculosis, Serratia spp., anaerobic microorganisms, methicillin-resistant strains of Staphylococcus spp.

Pharmacokinetics

The time to reach C_max after intramuscular administration in doses of 500 and 1000 mg respectively is 2 and 1 hour. C_max is 38 and 64 µg/ml; after intravenous administration, the time to reach C_max is at the end of the infusion, after intravenous administration of 1000 mg C_max is 180 µg/ml.

It penetrates into joints, tissues of the cardiovascular system, into the abdominal cavity, kidneys and urinary tract, placenta, middle ear, respiratory tract, skin and soft tissues. It is excreted in small amounts with breast milk. The concentration in the gallbladder tissue and bile is significantly higher than in the blood serum. In case of gallbladder obstruction, the concentration in bile is lower than in plasma. V_d is 0.12 l/kg. Plasma protein binding is 85%. T_1/2 after intramuscular administration is 1.8 hours, after intravenous administration is 2 hours. In case of renal impairment T_1/2 is 20-40 hours.

It is excreted mainly by the kidneys unchanged: within the first 6 hours – 60-90%, after 24 hours – 70-95%. C_max in urine is 1000 µg/ml and 4000 µg/ml after intramuscular administration in doses of 500 mg and 1000 mg respectively.

Indications

• Bacterial infections of the upper and lower respiratory tract, urinary and biliary tract, pelvic organs, skin and soft tissues, bones and joints;
• Endocarditis, sepsis, peritonitis, otitis media, osteomyelitis, mastitis;
• Wound, burn and postoperative infections;
• Other infectious diseases caused by microorganisms sensitive to cefazolin.
• Prevention of surgical infections in the pre- and postoperative period.

ICD codes

Dosage Regimen

Intramuscularly, intravenously (bolus and drip).

The average daily dose for adults is 1 g; frequency of administration is 2 times/day. The maximum daily dose is 6 g (in rare cases – 12 g); the frequency of administration can be increased to 3-4 times/day.

The average duration of treatment is 7-10 days.

For prevention of postoperative infection 1 g – 30 minutes before surgery, 0.5-1 g – during surgery and 0.5-1 g every 6-8 hours for 24 hours after surgery.

Patients with impaired renal function require a change in the dosing regimen according to the values of creatinine clearance (CrCl). With CrCl 55 ml/min and above or with plasma creatinine content of 1.5 mg% and less, the full dose can be administered. With CrCl 54-35 ml/min or with plasma creatinine content of 3-1.6 mg% – the full dose can be administered, but the intervals between injections should be increased to 8 hours. With CrCl 34-11 ml/min or plasma creatinine content of 4.5-3.1 mg% – 1/2 dose with 12-hour intervals. Patients with CrCl 10 ml/min and less or with plasma creatinine content of 4.6 mg% and above – 1/2 of the average dose every 18-24 hours. All recommended doses are administered after an initial loading dose.

The average daily dose for children is 20-50 mg/kg; in severe infections the dose can be increased to 100 mg/kg/day. Frequency of administration is 3-4 times/day. In children with impaired renal function, the dosing regimen is adjusted depending on the CrCl values. With CrCl 70-40 ml/min – 60% of the average daily dose administered every 12 hours. With CrCl 40-20 ml/min – 25% of the average daily dose with a 12-hour interval. Children with CrCl 5-20 ml/min – 10% of the average daily dose every 24 hours. All recommended doses are administered after an initial loading dose.

Preparation of solutions

For intramuscular administration, the drug is dissolved in 4-5 ml of water for injections, isotonic sodium chloride solution or 0.25-0.5% procaine solution.

For intravenous drip administration, the drug is dissolved in 100-250 ml of isotonic sodium chloride solution or 5% glucose solution; the injection is carried out over 20-30 minutes (infusion rate 60-80 drops per minute).

For intravenous bolus administration, a single dose of the drug is diluted in 10 ml of isotonic sodium chloride solution and administered slowly over 3-5 minutes.

During dilution, the vials are shaken vigorously until complete dissolution.

Adverse Reactions

Allergic reactions hyperthermia, skin rash, urticaria, skin itching, bronchospasm, eosinophilia, angioedema, arthralgia, anaphylactic shock, multiforme erythema, malignant exudative erythema (Stevens-Johnson syndrome).

From the central nervous system convulsions.

From the urinary system in patients with kidney diseases when treated with large doses (6 g) – impaired renal function (in these cases the dose is reduced and treatment is carried out under control of the dynamics of blood urea nitrogen and creatinine).

From the digestive system nausea, vomiting, diarrhea, abdominal pain, pseudomembranous enterocolitis, rarely – cholestatic jaundice, hepatitis.

From the hematopoietic organs leukopenia, neutropenia, thrombocytopenia, thrombocytosis, hemolytic anemia.

With prolonged treatment – dysbacteriosis, superinfection caused by antibiotic-resistant strains, candidiasis (including candidal stomatitis).

Laboratory parameters positive Coombs test, increased activity of “hepatic” transaminases, hypercreatininemia, increased prothrombin time.

Local reactions with intramuscular administration – pain (at the injection site), with intravenous administration – phlebitis.

Contraindications

• Hypersensitivity to drugs of the cephalosporin group and other beta-lactam antibiotics.
• Pregnancy and lactation. If it is necessary to use the drug, breastfeeding should be discontinued.
• Not prescribed to newborns (up to 1 month).

With caution renal/hepatic insufficiency, pseudomembranous enterocolitis.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

The safety of use in premature infants and children of the first year of life has not been established.

Special Precautions

Patients with a history of allergic reactions to penicillins, carbapenems may have increased sensitivity to cephalosporin antibiotics.

During treatment with cefazolin, positive direct and indirect Coombs tests, as well as a false-positive urine reaction for sugar, may be obtained.

When prescribing the drug, exacerbation of gastrointestinal diseases, especially colitis, is possible.

Use in pediatrics

The safety of use in premature infants and children of the first year of life has not been established.

Drug Interactions

Simultaneous administration with anticoagulants and diuretics is not recommended. With simultaneous use of cefazolin and “loop diuretics”, blockade of its tubular secretion occurs.

Aminoglycosides increase the risk of kidney damage. Pharmaceutically incompatible with aminoglycosides (mutual inactivation).

Drugs that block tubular secretion increase the concentration in the blood, slow down excretion and increase the risk of toxic reactions.

Storage Conditions

List B. In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life 3 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.