There is a risk of encephalopathy in cases of administration of beta-lactam antibiotics, including cefixime, particularly in case of overdose or renal impairment.
Adverse reactions seen at dose levels up to 2 g Denvar in normal subjects did not differ from the profile seen in patients treated at the recommended doses. Cefixime is not removed from the circulation in significant quantities by dialysis.
No specific antidote exists. General supportive measures are recommended
None.
Denvar is generally well tolerated. The majority of adverse reactions observed in clinical trials were mild and self-limiting in nature.
The following adverse reaction (Preferred term# or equivalent) will be considered listed:
| Blood and lymphatic system disorders: | Eosinophilia Hypereosinophilia Agranulocytosis Leucopenia Neutropenia Granulocytopenia Haemolytic anaemia Thrombocytopenia Thrombocytosis |
| Gastrointestinal: | Abdominal pain Diarrhoea* Dyspepsia Nausea Vomiting Flatulance |
| Hepatobiliary disorders: | Jaundice |
| Infections and infestations: | Pseudomembranous colitis |
| Investigations: | Aspartate aminotransferase increased Alanine aminotransferase increased Blood bilirubin increased Blood urea increased Blood creatinine increased |
| Nervous system disorders: | Dizziness Headache Cases of convulsions have been reported with cephalosporins including cefixime (frequency not known)** Beta-lactams, including cefixime, predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment (frequency not known)** |
| Respiratory, thoracic and mediastinal disorders: | Dyspnoea |
| Renal and urinary disorders: | Renal failure acute including tubulointerstitial nephritis as an underlying pathological condition |
| Immune System disorders, administrative site conditions, skin and subcutaneous tissue disorders: | Anaphylactic reaction Serum sickness-like reaction Drug rash with eaosinophilia and systemic symptoms (DRESS) Pruritus Rash Drug Fever Arthralgia Erythema multiforme Stevens-Johnson syndrome Toxic epidermal necrolysis Angio-oedema Urticaria Pyrexia Face oedema Genital pruritus Vaginitis |
The above mentioned listed adverse reactions have been observed during clinical studies and/or during marketed use.
# Preferred term in MedDRA (v.14.0)
*Diarrhoea has been more commonly associated with higher doses. Some cases of moderate to severe diarrhoea have been reported; this has occasionally warranted cessation of therapy. Denvar should be discontinued if marked diarrhoea occurs
** Cannot be estimated from available data
Reporting of suspected adverse reactions
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 via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms.
Clinical efficacy has been demonstrated in infections caused by commonly occurring pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. It is highly stable in the presence of beta-lactamase enzymes.
Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase positive and negative strains and meticillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to cefixime.
The absolute oral bioavailability of cefixime is in the range of 22-54%. Absorption is not significantly modified by the presence of food. Cefixime may therefore be given without regard to meals.
From in vitro studies, serum or urine concentrations of 1 mcg/mL or greater were considered to be adequate for most common pathogens against which cefixime is active. Typically, the peak serum levels following the recommended adult or paediatric doses are between 1.5 and 3 mcg/mL. Little or no accumulation of cefixime occurs following multiple dosing.
The pharmacokinetics of cefixime in healthy elderly (age > 64 years) and young volunteers (11-35) compared the administration of 400 mg doses once daily for 5 days. Mean Cmax and AUC values were slightly greater in the elderly. Elderly patients may be given the same dose as the general population.
Cefixime is predominantly eliminated as unchanged drug in the urine. Glomerular filtration is considered the predominant mechanism. Metabolites of cefixime have not been isolated from human serum or urine.
Serum protein binding is well characterised for human and animal sera; cefixime is almost exclusively bound to the albumin fraction, the mean free fraction being approximately 30%. Protein binding of cefixime is only concentration dependent in human serum at very high concentrations which are not seen following clinical dosing.
Transfer of 14C-labelled cefixime from lactating rats to their nursing offspring through breast milk was quantitatively small (approximately 1.5% of the mothers' body content of cefixime in the pup). No data are available on secretion of cefixime in human breast milk. Placetal transfer of cefixime was small in pregnant rats dosed with labelled cefixime.
In the case of side effects such as encephalopathy (which may include convulsion, confusion, impairment of consciousness, movement disorders), the patient should not operate machines or drive a vehicle.
None.
