Oropod 100 mg/40 mg/5 mL Film-Coated Tablets

Adults: OROPOD 100 film-coated tablets are indicated for short-term treatment of upper and lower respiratory tract infections due to susceptible microorganisms:

• Acute bronchitis, relapses or acute exacerbations of chronic bronchitis and bacterial pneumonia
• Pharyngitis and tonsillitis
• Community-acquired bronchopneumonia
• Acute sinusitis

Use in children: OROPOD 40 mg/5 mL suspension is indicated for short-term treatment of infections due to susceptible microorganisms: Upper and lower respiratory tract infections:

• Otitis media
• Tonsillitis and pharyngitis
• Pneumonia

Tonsillitis, pharyngitis and acute bronchitis: One tablet (100 mg) every 12 hours with meals (200 mg/day). In the treatment of beta-haemolytic streptococcal infections, the dose has to be administered for at least 10 days.

Acute sinusitis, acute exacerbations of chronic bronchitis, pneumonia: Two tablets (200 mg) every 12 hours with meals (400 mg/day).

Elderly patients: Dosage adjustment is not necessary where renal function is normal.

Renal insufficiency in adults and children: The following dosing schedule is proposed:

Creatinine clearance Dosage

• > 40 mL / minute No change
• < 40 mL / minute u2212 10 to 39 mL /minute u2212 < 10 mL /minute u03a9 (50 mg) tablet daily
• u03a9 (50 mg) tablet every second day

For patients undergoing haemodialysis the dosage should be administered after each dialysis session.

In children: The dosage depends on the weight of the child being treated. The average dose is 8 mg/kg/day administered in two doses at 12 hourly intervals with meals. The following table may be used as a dosage guide:

Weight (kg) Dose

• Between 10 and 15 kg 5 mL (40 mg) every 12 hours
• u2265 15 kg 10 mL (80 mg) every 12 hours

There is insufficient experience with OROPOD 40 mg/5 mL to make dosage recommendations for children less than 1 year of age.

• Hypersensitivity to cephalosporin antibiotics (see section 4.4).
• OROPOD 40 mg/5 mL must not be given to children with phenylketonuria, since the formulation contains aspartame (25 mg/5 mL).
• Children below 1 year of age (see section 4.2).

Hypersensitivity reactions: Before initiating therapy with OROPOD careful enquiry should be made concerning previous hypersensitivity reactions to penicillins and other beta-lactams as cross sensitivity occurs between penicillins and cephalosporins (see section 4.3). Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on OROPOD. If an allergic reaction occurs, OROPOD should be discontinued.

Renal impairment: OROPOD should be used with care in 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 medicines such as aminoglycosides and/or potent diuretics. In such cases renal function should be monitored.

Gastrointestinal disease: Caution should be exercised in patients with a history of gastrointestinal disease, especially ulcerative colitis, regional enteritis or antibiotic associated colitis.

Clostridium difficile u2013 associated disease: Severe and persistent watery diarrhoea which occurs during treatment or the first weeks after treatment may be a result of antibiotic related pseudomembranous enterocolitis caused by Clostridium difficile. The diagnosis of this rare and possibly fatal condition should be confirmed by colonoscopy or histology. OROPOD should be discontinued if symptoms suggestive of pseudomembranous enterocolitis arise and appropriate antibiotic therapy should be initiated.

Interactions with laboratory tests: Positive Coombsu2019 test: OROPOD may be absorbed onto the surface of red cell membranes and react with antibiotics directed against the medicine. This can produce a positive antiglobulin (Coombsu2019) test and haemolytic anaemia. Jaffu00cb method interference: Cefpodoxime may interfere with Jaffu00cb method of measuring creatinine concentrations and may produce falsely high values.

Information about some of the excipients of OROPOD: OROPOD contains sugar, which may have an effect on the glycaemic control of patients with diabetes mellitus. OROPOD 100 contains lactose monohydrate. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take OROPOD 100. OROPOD 40 mg/5 mL contains sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose mal-absorption or sucrase-isomaltase insufficiency should not take OROPOD 40 mg/5 mL. OROPOD 40 mg/5 mL contains artificial sweetener (aspartame 25 mg/5 mL). Caution is advised in patients with phenylketonuria.

Superinfections: The use of cefpodoxime, 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 OROPOD), 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 impaired renal function.

Severe cutaneous adverse reactions (SCARs): Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with unknown frequency in association with cefpodoxime treatment. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cefpodoxime should be withdrawn immediately, and an alternative treatment considered. If the patient has developed a serious reaction such as SJS, TEN, DRESS or AGEP with the use of cefpodoxime, treatment with cefpodoxime must not be restarted in this patient at any time.

• Absorption of OROPOD 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 H 2 blockers, which cause an increase in gastric pH, should be taken 2 or 3 hours after OROPOD administration. In contrast, a decrease in gastric pH (pentagastrin) will increase bioavailability.
• Probenecid reduces the renal excretion of SANDOZ CEFPODOXIME and increases serum levels thereof.
• The bioavailability increases if SANDOZ CEFPODOXIME is administered during meals (acid pH).
• 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 Coombs test have been reported (see section 4.4).
• In patients treated with OROPOD, a false positive reaction for glucose in the urine may occur with Benedicts or Fehlings 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.

Safety and efficacy have not been established in pregnancy and lactation.

Dizziness has been reported during treatment with cefpodoxime and may affect patientsu2019 ability to drive or operate machinery.

The following side effects have been reported:

Infections and Infestations

• Frequent: Oral and vaginal candidiasis, superinfections, overgrowth of non-susceptible organisms

Blood and lymphatic system disorders

• Frequent: Thrombocytosis, leucopenia and eosinophilia, reduction of haemoglobin.
• Less frequent: Thrombocytopenia, neutropenia, agranulocytosis, haemolytic anaemia, hypoprothrombinaemia, aplastic anaemia, pancytopenia, lymphocytosis, anaemia, leucocytosis, lymphocytosis, leukocytosis.

Immune system disorders

• Less frequent: Hypersensitivity reactions, anaphylactic reactions, angioedema, bronchospasm, malaise, shock

Metabolism and nutrition disorders

• Frequent: Appetite loss

Nervous system disorders

• Less frequent: Headache, dizzy sensations, paraesthesia, asthenia, seizures, CNS toxicity

Ear and labyrinth disorders

• Less frequent: Tinnitus, hearing loss

Gastrointestinal disorders:

• Frequent: Nausea, vomiting, flatulence, abdominal pains and diarrhoea.
• Less frequent: Dyspepsia, flatulence, pseudomembranous colitis, blood in stools, acute pancreatitis, fever

Hepatobiliary disorders:

• Less frequent: Hepatic dysfunction including cholestasis, elevated liver enzymes (elevations of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase), bilirubinaemia, liver injury, hepatitis, cholestatic jaundice.

Skin and subcutaneous tissue disorders

• Frequent: Skin rashes, urticaria, pruritus, purpura, reactions resembling serum sickness, cutaneous eruptions. Cases of bullous eruptions have been reported.
• Less frequent: Erythema multiforme or Stevens-Johnson syndrome, toxic epidermal necrolysis

Frequency unknown: Acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS)

Renal and urinary disorders:

• Less frequent: Increase in blood urea and creatinine, renal dysfunction, toxic nephropathy

General disorders and administrative site conditions

• Less frequent: Fatigue

Investigations:

• Less frequent: A positive Coombs test may occur.

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. Health care providers are requested to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Suspected adverse reactions can also be reported directly to the HCR via https://pvi1j.solutions.iqvia.com or the e-mail address, [email protected].

In cases of overdosage, particularly in patients with renal insufficiency, there is a risk of reversible encephalopathy for several cephalosporins. Convulsions have also been reported with very high doses especially in patients with renal impairment. Treatment is symptomatic and supportive.