ZEPILEN Powder for solution for injection/infusion Ref.[28167] Active ingredients: Cefazolin

• Before initiating Zepilen treatment, it should be determined whether the patient has a history of allergic reactions to cephalosporins, penicillins or other drugs.
• Zepilen should be administrated with caution in patients with penicillin allergy. There are findings that a partial cross-allergy between penicillins and cephalosporins can occur; also, some cases of serious hypersensitivity reactions (incl. anaphylaxis) were described to both classes. If allergic reactions are observed, Zepilen should be discontinued and the patient treated accordingly.
• Plasmatic coagulation disorders can rarely occur under cefazolin treatment. Patients at risk are the ones with risk factors that lead to a vitamin K deficiency or other coagulation problems (parenteral nutrition, malnutrition, impaired hepatic and renal function, thrombocytopenia). The same applies to co-morbidities (e.g. hemophilia, stomach and intestinal ulcers), that can exacerbate bleeding. Therefore, in these cases, the Quick time value should be monitored and Vitamin K (10 mg per week) should be used.
• Caution should be exercised when administering Zepilen in patients who have a history of gastrointestinal disease (ulcerative colitis).
• Special care is recommended in patients with allergic diathesis or bronchial asthma and hay fever.
• Severe and persistent diarrhea (pseudomembranous colitis) may occur and can be life-threatening. In these cases Zepilen should be immediately discontinued and appropriate therapy (e.g. oral vancomycin, 4 × 250 mg daily) should be initiated. Anti-peristaltic drugs are contraindicated.
• Prolonged use of Zepilen can cause overgrow of the non-susceptible organisms. A close observation of the patient is therefore essential. If suprainfections occur during treatment, appropriate action should be taken.
• In patients with low urinary output because of renal impairment, the dosage should be adjusted.
• Not for intrathecal use.
• The sodium content of the solution must be taken into account in hypertension and heart failure.

Zepilen 1g contains 2.2 mmol (50.72 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Zepilen 500 mg contains 1.1 mmol (25.36 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

• Co-administration of probenecid may reduce the tubular secretion of cephalosporins resulting in increased and prolonged cephalosporin effects.
• False-positive reactions with Benedict’s reagent, Fehling’s solution or Clinitest tablets may occur, but not when using Clinistix test strips and when using the paper Tes-Tape for urine sugar.
• False positive Coombs test can also occur, including in newborns whose mothers received cephalosporins before delivery.
• Cefazolin is incompatible with aminoglycosides, amobarbital-Na, ascorbic acid, bleomycin sulfate, calcium glucoheptonate, calcium gluconate, cimetidine, colistin methanesulfonate-Na, erythromycin glucoheptonat, lidocaine HCl, pentobarbital Na, polymyxin B sulfate, tetracyclines (see section 6.2).

Pregnancy

There is insufficient data about the use of cefazolin during pregnancy to assess the possible harmfulness during pregnancy.

Breast-feeding

Zepilen should be administered with caution in breast-feeding women as cefazolin is excreted in small amounts into breast milk.

There are no data available regarding cefazolin effects on the ability to drive and use machines.

The following undesirable effects may occur while using Cefazolin.

The frequency of each side-effect is given between parentheses, using the following category classification: Very common (1/10), Common (1/100 to <1/10), Uncommon (1/1,000 to <1/100), Rare (1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Very rare: during treatment with cefazolin extremely rare plasmatic coagulation disorders may occur. Patients at risk are the ones with risk factors and specific therapy, leading to a vitamin K deficiency.

Not known: eosinophilia, neutropenia, leukopenia, hemolytic anemia, thrombocytopenia and positive direct and indirect Coombs test.

Immune system disorders

Not known: Lyell syndrome and Stevens-Johnson syndrome, urticaria, anaphylaxis, angioneurotic edema.

Gastrointestinal disorders

Rare: nausea and vomiting.

Not known: pseudomembranous colitis symptoms during or after antibiotic treatment, loss of appetite, diarrhea and mouth thrush have been reported.

Hepatobiliary disorders

Rare: As with some penicillins and other cephalosporins, isolated cases of transient hepatitis and cholestatic jaundice have been reported.

Skin and subcutaneous tissue disorders

Very rare: anaphylactic shock. It can occur up to half an hour after application and requires immediate intensive medical care.

Not known: skin rash with flushing, pruritus, pruritus vulvae, genital pruritus, anal pruritus.

Renal and urinary disorders

Rare: interstitial nephritis and other kidney injuries have been reported. Most patients who had these side effects were seriously ill and received various drug therapies. Cefazolin function regarding kidney disease is still unclear.

Reproductive system and breast disorders

Not known: genital moniliasis and vaginitis.

General disorders and administration site conditions

Not known: drug fever, pain at the injection site, sometimes with induration, following intramuscular use, phlebitis at the injection site.

Investigations

Rare: transient increases in ALT, AST and alkaline phosphatase was observed.

Not known: transient increases in BUN without clinical evidence of renal impairment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicines.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Cefazolin is incompatible with aminoglycosides, amobarbital-Na, ascorbic acid, bleomycin sulfate, calcium glucoheptonate, calcium gluconate, cimetidine, colistin methanesulfonate-Na, erythromycin glucoheptonat, lidocaine HCl, pentobarbital Na, polymyxin B sulfate, tetracyclines (see section 4.5).