Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: MIP Pharma GmbH, Kirkeler Str. 41, 66440, Blieskastel, Germany
Hypersensitivity to cefazolin.
Patients with known hypersensitivity to cephalosporin antibiotics.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
In case of any known hypersensitivity to penicillins or other beta-lactam antibiotics, attention is to be paid to a possible cross-sensitivity (see section 4.3).
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with cefazolin must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cefazolin, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if cefazolin is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Cefazolin should be administered only with special caution to patients with allergic reactivity (e.g. allergic rhinitis or bronchial asthma) as the risk for a serious hypersensitivity reaction is increased.
Antibacterial agent-associated pseudomembranous colitis has been reported with use of cefazolin and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhoea during or subsequent to the administration of cefazolin (see section 4.8). Discontinuation of therapy with cefazolin and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
As there are no sufficient experiences available so far, Cefazolin 2 g must not be applied to new-borns and babies in the first month of life.
In case of a renal insufficiency with a glomerular filtration rate under 55 ml/min, an accumulation of cefazolin must be taken into consideration. Therefore, the dosage has to be reduced accordingly or the dosage interval has to be prolonged (see section 4.2).
In patients with renal impairment the use of cefazolin may be associated with seizures.
Prolonged prothrombin time may occur in patients with renal or hepatic impairment or poor nutritional state, as well as in patients receiving a protracted course of antimicrobial therapy, and patients previously stabilised on anticoagulant therapy. In these patients the prolongation of prothrombin time has to be monitored under treatment with cefazolin since it can very rarely cause plasmatic blood coagulation diseases (see sections 4.5 and 4.8). Therefore, INT (International Normalised Ratio) has to be measured regularly in patients with diseases which can cause haemorrhages (e.g. gastro-intestinal ulcers) as well as in patients with coagulation defects (inherited: e.g. haemophilia; acquired: e.g. by parenteral feeding, malnutrition, disordered liver or renal function or thrombocytopenia; caused by drugs: e.g. by heparin or other oral anticoagulants). Vitamin K can be substituted (10 mg per week) if necessary.
Long-term and repeated administration can lead to overgrowth of resistant organisms. If superinfection occurs during therapy, appropriate measures should be taken.
In rare cases, the non-enzymatic urine sugar test and the Coombs test can show false positive results.
This medicinal product contains 4.2 mmol (or 96 mg) sodium per 2,000 mg dose. To be taken into consideration by patients on a controlled sodium diet.
Cephalosporins may very rarely cause bleeding disorders (see 4.4). During concomitant use with oral anticoagulants (for e.g. warfarin or heparin) in high doses, the coagulation parameters should be monitored.
Some cefalosporins such as cefamandol, cefazolin and cefotetan can cause interference in the metabolism of vitamin K1, especially in cases of vitamin K1 deficiency. This may require vitamin K1 supplementation.
Due to its inhibitory effect on the renal diuresis, the administration of probenicid induces a higher concentration and a longer retention time of cefazolin in the blood.
It cannot be excluded that cefazolin intensifies the nephrotoxic effect of aminoglycosides and quick-acting diuretics (e. g. Furosemid). Therefore, the renal function should be controlled during a concomitant therapy with these drugs.
Cefazolin reaches the embryo/fetus via the placenta. There is not sufficient experience in the human use of cefazolin. As a precautionary measure, cefazolin should only be used during pregnancy after careful benefit/risk assessment, especially during the first trimester of pregnancy.
Cefazolin is excreted in maternal milk at low concentrations and therefore it should only be used after careful benefit/risk assessment. Diarrhoea and fungus infection of the mucous membranes could occur in the breast-fed infant, so that nursing might have to be discontinued. The possibility of sensitisation should be borne in mind.
Cefazolin has no or negligible influence on the ability to drive and use machines.
Dependent on the dose and duration of the treatment, patients are expected to experience one or several of the adverse reactions mentioned below.
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)
Uncommon: Oral candidiasis (prolonged use).
Rare: Genital candidiasis (monoliasis), vaginitis.
Rare: Increase or decrease in blood glucose concentration (hyperglycemia or hypoglycemia). Leukopenia, granulocytopenia, neutropenia, thrombocytopenia, leukocytosis, granulocytosis, monocytosis, lymphocytopenia, basophilia and eosinophilia were observed in blood counts. These effects are rare and reversible.
Very rare: Coagulation (blood clotting) disorders and bleeding as a consequence. At risk for these side effects are patients with a deficiency of vitamin K or other blood clotting factors, or patients on artificial nutrition, inadequate diet, impaired liver and renal function, thrombocytopenia and patients with disorders or diseases that cause bleeding (e.g. haemophilia, stomach and duodenal ulcers). Also see sections 4.4 and 4.5. Decreased haemoglobin and/or hematocrit, anaemia, agranulocytosis, aplastic anaemia, pancytopenia and hemolytic anaemia.
Uncommon: Erythema, erythema multiforme, exanthema, urticaria, reversible local permeability of the blood vessels, joints, or mucous membranes (angioedema), drug-induced fever and interstitial pneumonia or pneumonitis.
Rare: Toxic epidermal necrolysis (Lyell’s syndrome), Stevens-Johnson syndrome.
Very rare: Anaphylactic shock, swelling of the larynx with narrowing of the airways, increased heart rate, shortness of breath, falling blood pressure, swollen tongue, anal pruritus, genital pruritus, face edema.
Uncommon: Seizures (in patients with renal dysfunction, with inappropriate high treated doses).
Rare: Dizziness, malaise, fatigue. Nightmares, vertigo, hyperactivity, nervousness or anxiety, insomnia, drowsiness, weakness, hot flushes, disturbed colour vision, confusion and epileptogenic activity.
Rare: Pleural effusion, chest pain, dyspnoea or respiratory distress, cough, rhinitis.
Common: Loss of appetite, diarrhoea, nausea and vomiting. These symptoms are usually moderate and often disappear during or after treatment.
Very rare: Pseudomembranous colitis (see section 4.4)
Rare: Temporary increase in serum concentrations of AST, ALT, gamma GT, bilirubin and/or LDH and alkaline phosphatase, transient hepatitis, transient cholestatic jaundice.
Rare: Nephrotoxicity, interstitial nephritis, undefined nephropathy, proteinuria, temporary increase in blood urea nitrogen (BUN) usually in patients treated concomitantly with other potential nephrotoxic medicines.
Common: Pain at the site of intramuscular injection, sometimes with induration
Uncommon: Intravenous administration may cause thrombophlebitis.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
Cefazolin is incompatible with amikacin disulfate, amobarbital-sodium, bleomycin sulphate, calcium gluceptate, calcium gluconate, cimetidin hydrochloride, colistin methat-sodium, erythromycin gluceptate, kanamycin sulphate, oxytetracyclin hydrochloride, pentobarbital-sodium, polymyxin-B-sulphate and tetracycline hydrochloride.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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