Midixime®  is  an  orally  active  cephalosporin   antibiotic   which   has   marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms. ATC code: J01DD08

It is indicated for the treatment of the following acute infections when caused by susceptible micro-organisms:

Upper Respiratory Tract Infections (URTI): e.g. otitis media; and other URTI where the causative organism is known or suspected to be resistant to other commonly used antibiotics, or where treatment failure may carry significant risk.

Lower Respiratory Tract Infection: e.g. bronchitis.

Urinary Tract Infections: e.g. cystitis, cystourethritis, uncomplicated pyelonephritis. Clinical efficacy has been demonstrated in infections caused by commonly occuring pathogens                         including Streptococcus      pneumoniae, Streptococcus pyogenes,

Escherichia coli, Proteus mirabilis, Kliebsiella species, Haemophilus influenzae(beta- lactamase positive and negative), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacterspecies. Midixime® 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    Midixime®.    In    addition,    most    strains of Pseudomonas, Bacteriodes fragalis, Listeria monocytogenes and Clostridia are resistant to Midixime®.

Absorption of Midixime® is not significantly modified by the presence of food. The usual course of treatment is 7 days. This may be continued for up to 14 days if required.

Adults and Children over 10 Years: The recommended adult dosage is 200-400 mg daily according to the severity of infection, given either as a single dose or in two divided doses.

The Elderly: Elderly patients may be given the same dose as recommended for adults. Renal function should be assessed and dosage should be adjusted in severe renal impairment

Children (Use Paediatric Oral Suspension): The recommended dosage for children is 8 mg/kg/day administered as a single dose or in two divided doses. As a general guide for prescribing  in children the following daily  doses  in  terms  of volume  of Paediatric Oral Suspension are suggested:

6 months up to 1 year:            3.75 ml daily

Children 1-4 years:                  5 ml daily

Children 5-10 years:                10 ml daily

Children weighing more than 50 kg or older than 10 years should be treated with the recommended adult dose (200 - 400 mg daily depending on the severity of infection). The safety and efficacy of cefixime has not been established in children less than 6 months.

Dosage in Renal Impairment: Midixime® may be administered in the presence of impaired renal function. Normal dose and schedule may be given in patients with creatinine clearances of 20 ml/min or greater. In patients whose creatinine clearance is less than 20 ml/min, it is recommended that a dose of 200 mg once daily should not be exceeded. The dose and regimen for patients who are maintained on chronic ambulatory peritoneal dialysis or haemodialysis should follow the same recommendation as that for patients with creatinine clearances of less than 20 ml/min.

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.

Midixime® 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 Midixime®, 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.

Renal failure acute

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

Midixime® should be administered with caution in patients with markedly impaired renal function.

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.

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. Midixime® should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.

None.

Midixime® is generally well tolerated. The majority of adverse reactions observed in clinical trials were mild and self-limiting in nature.

The following adverse reaction will be considered listed:

The above mentioned listed adverse reactions have been observed during clinical studies and/or during marketed use.

*Diarrhea has been more commonly associated with higher doses. Some cases of moderate to severe diarrhea have been reported; this has occasionally warranted cessation of therapy. Midixime® should be discontinued if marked diarrhea occurs

To report any side effect(s):

•  Saudi Arabia:

The National Pharmacovigilance Center (NPC): SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa

•  Other GCC States:

Please contact the relevant competent authority.

There is no experience with overdoses with Midixime®.

Adverse reactions seen at dose levels up to 2 g Cefixime 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

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 Enterobacterspecies. 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.

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.

The other ingredients are Microcrystalline cellulose,   sodium lauryl    sulphate, magnesium stearate, croscarmellose sodium, hydrogenated vegetable oil.

Not applicable.

Store below 30°C.

Store in the original package in order to protect from moisture.

Midixime® 200 mg Hard gelatin capsules with orange cap printed PhI/orange body printed Cefix 200mg, size 1, packed in PVC/TE/PVDC-Alu blisters, intended for oral use.

Pack size:

8 Capsules.

Midixime®  400 mg Hard gelatin capsules with blue cap printed PhI/Blue body printed Cefix 400mg, size OE, packed in PVC/TE/PVDC-Alu blisters, intended for oral use.

Pack size:

6 Capsules.

No special requirements.