Nefazol

Package leaflet: Information for the patient

NEFAZOL

1 g / 4 ml powder and solvent for injectable solution for intramuscular use
Cefazolin sodium
Generic medicine
Please read this leaflet carefully before using this medicine because it contains impor-
tant information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What NEFAZOL is and what it is used for
2. What you need to know before using NEFAZOL
3. How to use NEFAZOL
4. Possible side effects
5. How to store NEFAZOL
6. Package contents and other information

1. What NEFAZOL is and what it is used for

NEFAZOL contains the active substance cefazolin sodium, a substance belonging to a class of medicines called cephalosporins, beta-lactam antibiotics used to treat infections caused by bacteria sensitive to this active ingredient.
NEFAZOL is used in the treatment of the following infections:

• Respiratory tract infections,
• Ear and throat infections,
• Stomach and intestinal infections (gastroenterological),
• Liver and biliary tract infections (hepatobiliary),
• Genitourinary tract infections,
• Skin, soft tissue, bone, and joint infections,
• Obstetric and gynaecological infections,
• Eye infections,
• Inflammation of the membrane lining the internal abdominal walls (peritoneum), of the blood (septicaemia), and of the tissue lining the internal cavities and heart valves (endocardium) caused by bacteria.

Cefazolin is also indicated before, during, and after surgical procedures (perioperative prophylaxis) to prevent infections (see section 3).

2. What you need to know before taking NEFAZOL

Do not take NEFAZOL if:

• You are allergic (hypersensitive) to cefazolin sodium, to other similar substances (beta-lactam antibiotics such as other cephalosporins and penicillins), or to any of the other ingredients of this medicine (listed in section 6).
• You are allergic to lidocaine or to other similar local anesthetics of the amide type.
• Do not administer NEFAZOL to premature infants or children under one month of age.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using NEFAZOL.
If you experience any allergic-type reaction after receiving NEFAZOL, stop treatment immediately and contact your doctor or go to the nearest hospital; severe allergic reactions, and particularly anaphylaxis, may require emergency medical treatment.
Pay special attention and inform your doctor:

• If you have previously had an allergy to cefazolin, cephalosporins, penicillins, or other antibiotics that work by the same mechanism of action (beta-lactams), or to other drugs. Patients allergic to antibiotics of the cephalosporin class may also be allergic to penicillins. Severe reactions (including anaphylaxis) to both classes of drugs have been reported.
• If you are allergic to lidocaine or other amide-type local anesthetics, as you may also be allergic to NEFAZOL (risk of severe anaphylactic-type reactions) (see "Do not take NEFAZOL").
• If you have had or currently suffer from gastrointestinal disorders, particularly colitis (inflammation of the colon).
• If you develop diarrhea during treatment. Contact your doctor immediately, as use of NEFAZOL may lead to the overgrowth of bacteria not sensitive to the medicine, resulting in disruption of the normal colonic flora, potentially leading to a serious condition called pseudomembranous colitis.

Concomitant use of medicines that promote fecal accumulation (fecal stasis) must be strictly avoided.

• If you have kidney problems, as careful evaluation of renal function by your doctor is required both before and during treatment with NEFAZOL. This medicine may cause kidney damage, and such effects are more likely if you are over 50 years of age, already have kidney problems, or are taking other medicines that may harm the kidneys (see "Other medicines and NEFAZOL"). Your doctor may reduce the dose of NEFAZOL depending on your condition.

If you have high blood pressure (hypertension) or heart problems (heart failure), because this medicine contains sodium (see "NEFAZOL contains sodium").

• If you are being treated with blood-thinning medicines due to the risk of coagulation disorders. Your doctor will monitor your therapy and may recommend dose adjustments (see "Other medicines and NEFAZOL").

Laboratory tests
Inform your doctor if you are being treated with NEFAZOL and need to undergo laboratory tests, as this medicine may interfere with the results of certain tests (false positive Coombs test, even in newborns whose mothers received NEFAZOL before delivery; false positive urinary glucose test with Benedict, Fehling, or Clinitest methods).

• NEFAZOL must not be administered directly into the intrathecal space, where fluid circulates around the spinal cord.

Children
NEFAZOL must not be administered to premature infants or newborns under one month of age (see section "Do not take NEFAZOL"). In early infancy, the product should only be used when strictly necessary and under direct medical supervision.

Other medicines and NEFAZOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, contact your doctor if you are taking:

• Probenecid (a medicine used in the treatment of gout to reduce uric acid levels). Concomitant use may increase blood levels of NEFAZOL.
• Medicines that cause kidney damage (such as aminoglycosides, colistin, polymyxin B, or vancomycin). Concomitant administration should be avoided.
• Penicillins or chloramphenicol (antibiotics).
• Oral anticoagulants (medicines that inhibit blood clot formation). If co-administration with oral anticoagulants or high-dose heparin is necessary, your doctor will determine appropriate therapy by adjusting the dose of cefazolin and/or anticoagulants and will monitor your coagulation parameters (see "Warnings and precautions").
• Oral contraceptives, as NEFAZOL may reduce their effectiveness. Therefore, alternative contraceptive methods are recommended in addition to hormonal contraceptives during treatment with cefazolin.

NEFAZOL contains sodium
This medicine contains 50.5 mg of sodium (the main component of table salt) per vial. This corresponds to 2.5% of the maximum daily dietary intake recommended for an adult.
In patients with hypertension or heart failure, the sodium content of the injectable solution should be taken into account.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You should take NEFAZOL during pregnancy only if specifically instructed by your doctor, who will assess whether the potential benefits outweigh any possible risks to you and your baby.
If cefazolin is administered before a caesarean section, it may pass into the fetal bloodstream in variable amounts, lower than those in the mother's blood. However, although cefazolin does not appear to cause adverse effects on the fetus, it should only be administered after clamping of the umbilical cord.

Breastfeeding
This medicine is excreted in very low concentrations in breast milk; however, you should still consult your doctor and exercise caution during breastfeeding. If diarrhea or candidiasis occurs in the newborn during breastfeeding, the mother should either stop breastfeeding or discontinue treatment with cefazolin.

Driving and using machines
No effects on the ability to drive or use machinery have been reported.

3. How to take NEFAZOL

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Adults
The recommended dose of cefazolin is 1–3 g/day, divided into 2–3 equal doses depending on the type and severity of the infection, as shown in the following table:

• In exceptional cases, doses of cefazolin up to 12 g/day have been used.
  Use in children
  NEFAZOL must not be administered to premature infants and newborns under 1 month of age (see
  section "When you must not take NEFAZOL").
  The recommended total daily dose is 25–50 mg/kg body weight, to be divided into 3–4 equal
  doses. Depending on the severity of the infection, the physician may increase the dose up to
  100 mg/kg body weight.
  In very early infancy, NEFAZOL should be administered only when strictly necessary and under
  direct medical supervision.
  Use in patients with renal impairment
  If you suffer from renal impairment, your doctor will reduce the dose according to renal function tests as reported in the following table:

N.B. In particularly severe infections, it is recommended to administer an appropriate loading dose before proceeding to reduce the dosage as indicated above.
Use in patients undergoing peritoneal dialysis (physical therapy used for the treatment of chronic
renal failure)
If undergoing peritoneal dialysis (2 L/h), after instillation for 24 hours of a dialysate solution containing 50 mg/L and 150 mg/L of the drug, respectively, cefazolin blood concentrations averaged 10 and 30 mg/L. Peak blood levels were 29 mg/L (range 13 to 44 mg/L) with 50 mg/L (3 patients) and 72 mg/L (range 26 to 142 mg/L) with 150 mg/L (6 patients).
Use in perioperative prophylaxis
If you are scheduled to undergo surgery, you may be administered a 1 g intramuscular dose 30 to 60 minutes before surgery. For prolonged procedures (e.g., 2 hours or longer), an additional dose of 0.5 to 1 g may be administered during surgery (adjusted according to the duration of the operation).
Treatment with NEFAZOL may continue every 6–8 hours for 24 hours after surgery to prevent the risk of infections.
It is important that:

1. the initial dose is administered between half an hour and one hour before the start of surgery, to ensure adequate blood and tissue levels of the antibiotic at the time of incision;
2. if there is a high likelihood of exposure to pathogens, cefazolin is administered at regular intervals during surgery to maintain constant blood levels;
3. the use of cefazolin for prophylactic purposes ends within 24 hours after surgery;
4. in surgical procedures where infection could be particularly devastating (e.g., open-heart surgery, joint prosthesis implantation), prophylaxis with cefazolin may continue for 3–5 days after surgery.
   Method of administration
   The reconstituted cefazolin solution, prepared using the vial of solvent containing lidocaine supplied
   in the package, may be administered by intramuscular injection. After adding the solvent, the vial should be shaken until the powder is completely dissolved.
   Caution: the 4 ml solvent vial supplied with the 1 g pack, containing 0.5% lidocaine hydrochloride, is intended for intramuscular use only.
   The solution should be used immediately after reconstitution.
   Cefazolin should be reconstituted by dissolving the contents of the vial with the solvent vial supplied in the package.
   If you take more NEFAZOL than you should
   If you are administered an excessive amount of cefazolin, stop taking the medicine immediately and inform your doctor or go to the nearest hospital.
   Symptoms and signs of an overdose of cefazolin include pain, inflammation and phlebitis at the injection site, faintness, numbness in the limbs, and headache. Occasionally, an overdose may trigger seizures, particularly in patients with kidney problems, in whom drug accumulation may occur. Laboratory test abnormalities: increased blood creatinine and nitrogen levels (creatininemia and azotemia), increased liver enzymes and bilirubin, positive Coombs test (a test used in the diagnosis of anemia), changes in blood cell counts, and prolonged prothrombin time (a parameter assessing blood clotting ability).
   If you experience any of the above symptoms, your doctor or the hospital physician will provide the most appropriate therapeutic treatment based on your symptoms.
   If you forget to take NEFAZOL
   If a dose of NEFAZOL is not administered, inform your doctor, who will advise you on how to continue the treatment.
   If you miss an injection, it should be administered as soon as possible. However, if it is almost time for the next scheduled injection, skip the missed dose.
   Do not administer a double dose to make up for a forgotten dose.
   If you stop taking NEFAZOL
   Do not stop taking this medicine without first consulting your doctor.
   If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

• Positive direct and indirect Coombs test (laboratory test used to detect the presence of autoimmune diseases);
• Severe allergic reaction (anaphylactic reaction) presenting as shortness of breath, often followed by serious circulatory problems (cardiovascular collapse) or shock, skin manifestations (mainly itching and urticaria, with or without swelling of the skin and mucous membranes), and gastrointestinal symptoms (nausea, vomiting, abdominal pain with cramps, and diarrhoea);
• Mild and transient blood abnormalities, for example: increased platelet count (thrombocytosis), reduced white blood cell count (neutropenia, leucopenia, agranulocytosis) or reduced platelet count (thrombocytopenia), reduced red blood cell count (anaemia, haemolytic anaemia), reduced count of all blood cells (aplastic anaemia, pancytopenia), and bleeding;
• Impaired kidney function (acute renal failure) associated with kidney inflammation (interstitial nephritis);
• Severe inflammation of the colon associated with antibiotic use (pseudomembranous colitis), potentially fatal. Colitis may also occur after treatment has been discontinued;
• Urticaria, itching, various types of skin rash (maculopapular, erythematous or morbilliform);
• Fever and chills;
• Serum sickness-like reactions (fever, urticaria, joint pain, swelling and lymph node enlargement);
• Increased white blood cell count (eosinophilia);
• Joint pain;
• Swelling;
• Skin redness;
• Anal and genital itching;
• Swelling of the skin and mucous membranes (angioedema);
• Severe, potentially fatal skin allergic reactions (Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis);
• Skin peeling (exfoliative dermatitis). Hypersensitivity reactions are more likely to occur in patients who have previously shown allergic reactions, particularly to penicillin.
• Increased liver function test values indicating liver dysfunction, such as transaminases (AST/SGOT, ALT/SGPT), alkaline phosphatase, lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGTP), or bilirubin, or liver disorders including impaired bile excretion (cholestasis). These effects are generally mild and resolve upon discontinuation of therapy;
• Transient increase in blood values indicating kidney dysfunction, such as azotemia and creatininemia;
• Nausea, vomiting, and diarrhoea;
• Oral thrush (oral candidiasis);
• Abdominal pain;
• Frequent urge to urinate/defecate;
• Indigestion;
• Inflammation of the tongue;
• Stomach burning;
• Injection site reactions, such as pain, tissue hardening, swelling;
• Vein inflammation (phlebitis) following intravenous administration;
• Chest tightness;
• Dizziness, headache;
• Malaise, fatigue;
• Fungal infection and vaginal inflammation, with genital and anal itching.

These side effects require appropriate therapeutic measures and careful evaluation by the physician, who may decide whether treatment should be discontinued.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly through the national reporting system at the following address:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store NEFAZOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp.". The expiry date refers to the last day of that month and to the product in its original, intact packaging stored under proper conditions.
From a microbiological standpoint, the product after reconstitution with its solvent should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2° - 8° C, unless reconstitution has taken place under controlled, validated aseptic conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What NEFAZOL contains
The active substance is cefazolin.
One vial of NEFAZOL lyophilisate contains 1048 mg of cefazolin sodium equivalent to 1000 mg of
cefazolin.
One 4 ml solvent ampoule for intramuscular use contains lidocaine hydrochloride monohydrate and
water for injections.

Description of the appearance of NEFAZOL and package contents
NEFAZOL is available as a powder and solvent for injectable solution for intramuscular use.
Carton pack containing one 1 g glass vial of powder and one 4 ml glass ampoule containing the solvent.

Marketing Authorization Holder and Manufacturer
MARKETING AUTHORIZATION HOLDER
NEW RESEARCH S.r.l.
Via Tiburtina, 1143 00156 Rome
Italy

MANUFACTURER
ESSETI Farmaceutici S.r.l.
Via Campobello, 15
00040 Pomezia (RM)
Italy