SUPRAX Film-coated tablet Ref.[6586] Active ingredients: Cefixime

Encephalopathy

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.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in some patients on cefixime. When severe cutaneous adverse reactions occur, cefixime should be discontinued and appropriate therapy and/or measures should be taken.

Suprax should be given with caution to patients who have shown hypersensitivity to other drugs.

Hypersensitivity to penicillins

As with other cephalosporins, cefixime should be given with caution to patients with a history of hypersensitivity to penicillin, as there is some evidence of partial cross-allergenicity between the penicillins and cephalosporins.

Patients have had severe reactions (including anaphylaxis) to both classes of drugs. If an allergic effect occurs with Suprax, the drug should be discontinued and the patient treated with appropriate agents if necessary.

Haemolytic anaemia

Drug-induced haemolytic anaemia, including severe cases with a fatal outcome, has been described for cephalosporins (as a class). The recurrence of haemolytic anaemia after re-administration of cephalosporins in a patient with a history of cephalosporin (including cefixime) – associated haemolytic anaemia has also been reported.

Acute renal failure

As with other cephalosporins, cefixime may cause acute renal failure including tubulointerstitial nephritis as an underlying pathological condition. When acute renal failure occurs, cefixime should be discontinued and appropriate therapy and/or measures should be taken.

Renal impairment

Suprax should be administered with caution in patients with markedly impaired renal function (See section 4.2).

Paediatric use

Safety of cefixime in premature or newborn infant has not been established.

Treatment with broad spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated diarrhoea.

Pseudomembranous colitis is associated with the use of broad-spectrum antibiotics (including macrolides, semi-synthetic penicillins, lincosamides and cephalosporins); it is therefore important to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment.

Management of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriologic studies, fluids, electrolytes and protein supplementation. If the colitis does not improve after the drug has been discontinued, or if the symptoms are severe, oral vancomycin is the drug of choice for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be excluded.

Anticoagulants

In common with other cephalosporins, increases in prothrombin times have been noted in a few patients. Care should therefore be taken in patients receiving anticoagulation therapy.

Cefixime should be administered with caution to patients receiving coumarin-type anticoagulants, e.g. warfarin potassium. Since cefixime may enhance effects of the anticoagulants, prolonged prothrombin time with or without bleeding may occur.

Other forms of interaction

A false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.

A false positive direct Coombs test has been reported during treatment with cephalosporin antibiotics, therefore it should be recognised that a positive Coombs test may be due to the drug.

Reproduction studies have been performed in mice and rats at doses up to 400 times the human dose and have revealed no evidence of impaired fertility or harm to the foetus due to cefixime. In the rabbit, at doses up to 4 times the human dose, there was no evidence of a teratogenic effect; there was a high incidence of abortion and maternal death which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in the population of the microflora of the intestine. There are no adequate and well-controlled studies in pregnant women. Suprax should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.

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.

Suprax 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 disorders: 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. Suprax 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.

Not applicable.