Dynacef Suspension 5 ml Powder for oral suspension

In Children: DYNACEF SUSPENSION is indicated for use in the short-term treatment of upper and lower respiratory tract infections caused by susceptible micro-organisms:

• Acute otitis media due to: Haemophilus influenzae (non-typeable), Streptococcus pneumoniae, Moraxella catarrhalis
• Tonsillitis and pharyngitis due to: Streptococcus pyogenes
• Pneumonia due to: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis.

Paediatric population

The dosage depends on the weight of the child being treated. The average dose is 8 mg/kg/day. The following may be used as a dosage guide:

• Children weighing between 10 and 15 kg the dose is 5 mL (40 mg) every 12 hours.
• Children weighing 15 kg or more, the dose is 10 mL (80 mg) every 12 hours.

The use of DYNACEF SUSPENSION in children under one year of age has not been established (see section 4.3). DYNACEF SUSPENSION must not be given to children with phenylketonuria, since the formulation contains aspartame (see section 4.3). Refer to section 6.6 for reconstitution instructions.

Special populations

Renal Insufficiency in children: When the creatinine clearance is above 40 mL/min, it is not necessary to adjust the dose. For values below 40 mL/min, the daily dosage regimen should be reduced by half. For values 10 - 39 mL/min DYNACEF SUSPENSION should be administered as a single daily dose and every second day for values below 10 mL/min. DYNACEF SUSPENSION should be administered after each dialysis session for haemodialysis patients.

Hepatic insufficiency in children: No dosage adjustment necessary.

Method of administration

Oral use. DYNACEF SUSPENSION is administered in two doses at 12 hourly intervals with meals. Shake the bottle before use. Refer to section 6.6. for reconstitution instructions. Missed dose: Doctors should advise patients who forget to take DYNACEF SUSPENSION to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• Known sensitivity to cephalosporin antibiotics, penicillinu2019s, any other beta-lactam class of antibiotics, or to any of the ingredients of DYNACEF SUSPENSION (see section 6.1)
• DYNACEF SUSPENSION must not be given to children with phenylketonuria since the formulation contains aspartame.
• Children below 1 year of age (see section 4.2).

Hypersensitivity reactions: Before initiating therapy with DYNACEF SUSPENSION, careful enquiry should be made concerning an allergic diathesis and previous hypersensitivity reactions to penicillin and other beta-lactam antibiotics. The use of DYNACEF SUSPENSION is strictly contraindicated in subjects with a previous history of immediate type hypersensitivity to cephalosporins (see section 4.3). There have been reports of serious and occasionally fatal hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arterio-spasm that can result in myocardial infarction) (see section 4.8). If an allergic reaction occurs, treatment should be stopped immediately.

Clostridium difficile u2013 associated disease: Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous colitis may develop. It is important to consider its diagnosis in patients who develop diarrhoea, particularly if severe and/or persistent in association with the use of DYNACEF SUSPENSION. Such colitis may range in severity from mild to life threatening. Treatment should be discontinued if symptoms suggestive of pseudomembranous colitis arise. Mild cases of pseudomembranous colitis usually respond to discontinuance of the medicine alone. The diagnosis of this possibly fatal condition is confirmed by endoscopy and/or histology. Screening of faeces for this pathogen, and its cytotoxin is the best way to diagnose Clostridium difficile - associated disease. When the colitis or suspected pseudomembranous colitis, does not improve after the medicine has been discontinued, or when it is severe, oral vancomycin or metronidazole therapy should be started without delay. Clostridium difficile -associated disease can be favoured by faecal stasis.

Renal impairment: DYNACEF SUSPENSION should be given with caution to patients with renal impairment. In patients with severe renal failure, it may be necessary to adjust the daily dose based on creatinine clearance (see section 4.2). Changes in renal function have been observed with antibiotics of the same class and particularly when given concurrently with potentially nephrotoxic agents such as aminoglycosides and/or potent diuretics. In such cases renal function should be monitored.

Interactions with laboratory tests: DYNACEF SUSPENSION may interfere with Jaffu00e8 method of measuring creatinine concentrations and may produce falsely high values. Positive Coombsu2019 test: DYNACEF SUSPENSION may be absorbed onto the surface of red cell membranes and react with antibiotics directed against the medicine. This can produce a positive antiglobulin test and haemolytic anaemia. Cross-reactivity may occur with penicillin for this reaction.

Superinfection: The use of DYNACEF SUSPENSION, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken (see section 4.8).

Encephalopathy: Beta-lactam antibiotics, including cefpodoxime (as in DYNACEF SUSPENSION), predispose patients to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness or movement disorders), particularly in case of overdose or if they have impaired renal function.

Information on excipients of DYNACEF SUSPENSION: DYNACEF SUSPENSION contains aspartame (20 mg/5 mL), and sucrose. Excessive use of aspartame should be avoided by patients with phenylketonuria since one of its metabolic products is phenylalanine (see section 4.3). Sucrose: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

• Probenecid slows tubular excretion of DYNACEF SUSPENSION and increases serum levels thereof
• the bioavailability increases if DYNACEF SUSPENSION is administered during meals (acid pH)
• absorption of DYNACEF SUSPENSION is decreased by concurrent ingestion of antacids or histamine H2-receptor antagonists such as ranitidine. Therefore, mineral antacids (aluminium hydroxide, sodium bicarbonate) and histamine blocking H2 blockers, which cause an increase in gastric pH, should be taken 2 or 3 hours after DYNACEF SUSPENSION administration. In contrast, a decrease in gastric pH (pentagastrin) will increase bioavailability
• enhanced nephrotoxicity with a loop diuretic (e.g. furosemide) may occur
• changes in renal function have been observed with antibiotics of the same class, particularly when given concurrently with potentially nephrotoxic medicines such as aminoglycosides (e.g. gentamicin) and/or potent diuretics. In such cases, renal function should be monitored (see section 4.2)
• as with other cephalosporins, isolated cases showing development of a positive Coombsu2019 test have been reported (see section 4.4)

In patients treated with DYNACEF SUSPENSION, a false positive reaction for glucose in the urine may occur with Benedictu2019s or Fehlingu2019s solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.

Concurrent use with anticoagulants, such as warfarin, may increase the risk of bleeding. Special INR imbalance issues: Numerous cases of increased oral anticoagulant activity have been reported in patients receiving antibiotics. The severity of the infection or inflammation, age and general health status of the patient appear to be risk factors. Under these circumstances, it seems difficult to determine to what extent the infection itself or its treatment play a role in the INR imbalance. However, certain classes of antibiotics are more involved, particularly fluoroquinolones, macrolides, cyclines, cotrimoxazole and certain cephalosporins.

Not applicable.

If adverse effects occur, such as dizziness or encephalopathy (which can include seizure, confusion, consciousness disorders or abnormal movements), (see sections 4.4, 4.8, 4.9), patients should not drive or use machines.

Summary of the safety profile

Tabulated list of adverse effects

System Organ Class Frequency Side effects

Infections and Infestations Frequent Oral and vaginal candidiasis, superinfections, overgrowth of non-susceptible organisms

Blood and lymphatic system disorders Less frequent Thrombocytopenia, leucopenia, neutropenia, hypoprothrombinaemia, haemolytic anaemia, reduction of haemoglobin, thrombocytosis and agranulocytosis, aplastic anaemia, pancytopenia, eosinophilia, lymphocytosis, anaemia, leukocytosis eosinophilia

Immune system disorders Less frequent Hypersensitivity reactions, anaphylactic reactions, angioedema, bronchospasm, malaise, shock

Metabolism and nutrition disorders Frequent Appetite loss

Nervous system disorders Frequent Less frequent Headache Dizziness, paraesthesia, asthenia, seizures, CNS toxicity

Ear and labyrinth disorders Less frequent Tinnitus, hearing loss

Cardiac disorders Frequency unknown Kounis syndrome

Gastrointestinal disorders Frequent Less frequent Diarrhoea, nausea, vomiting and abdominal pain Dyspepsia, flatulence, pseudomembranous colitis, blood in stools, acute pancreatitis, fever

Hepato-biliary disorders Less frequent Hepatic dysfunction including cholestasis, elevated liver enzymes (elevations of AST, ALT and alkaline phosphatase), bilirubinaemia, liver injury, hepatitis, cholestatic jaundice

Skin and subcutaneous tissue disorders Less frequent Pruritus and urticaria, toxic epidermal necrolysis, erythema multiforme, rash, Stevens-Johnson syndrome, bullous eruptions, cutaneous eruptions, purpura, Linear IgA bullous dermatosis (LABD)

Renal and urinary disorders Less frequent Renal dysfunction, toxic nephropathy, increase in blood urea and creatinine

General disorders and administrative site conditions Less frequent Fatigue and asthenia

Investigations Less frequent Positive response to the Coombs' test

a. Description of selected adverse reactions

Beta-lactam antibiotics, including cefpodoxime (as in DYNACEF SUSPENSION, predispose patients to encephalopathy (which can include seizure, confusion, consciousness disorders or abnormal movements), particularly if they have had an overdose or if they have renal failure.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected], to ensure safety of the product.

Signs and symptoms: Overdosage with DYNACEF SUSPENSION may manifest in any of the symptoms described under section 4.8. Convulsions and other signs of CNS toxicity have been associated with high doses, especially in patients with severe renal impairment. There is a risk of encephalopathy, particularly in patients with renal insufficiency.

Management of overdose: There is no specific antidote for DYNACEF SUSPENSION. Treatment is symptomatic and supportive.