Orelox Range 100 mg/200 mg/40 mg/5 ml Film-Coated Tablets

In adults ORELOX 100 and ORELOX 200 are indicated for use in the short-term treatment of upper and lower respiratory tract infections due to susceptible micro-organisms (sensitivity tests must be performed):

• Acute bronchitis due to: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis.
• Pharyngitis and tonsillitis due to: Streptococcus pyogenes.
• Acute exacerbations of chronic bronchitis due to: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis.
• Bacterial pneumonia and community-acquired bronchopneumonia due to: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis.
• Acute sinusitis due to: Haemophilus influenzae (non-typeable), Streptococcus pneumoniae, Methicillin-sensitive Staphylococcus aureus, Moraxella catarrhalis.

In children ORELOX JUNIOR is indicated for use in the short-term treatment of infections due to susceptible micro-organisms: Upper and lower respiratory tract infections:

• 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.

Posology In adults Each film-coated tablet contains 100 mg or 200 mg of cefpodoxime. The dosage depends on the condition being treated.

Tonsillitis, pharyngitis and acute bronchitis One ORELOX 100 tablet (100 mg) every 12 hours with meals (200 mg/day). As is the case with all beta-lactam antibiotics in the treatment of beta-haemolytic streptococcal infections, a therapeutic dose has to be administered for at least 10 days.

Acute sinusitis, acute exacerbations of chronic bronchitis, pneumonia One ORELOX 200 tablet (200 mg) every 12 hours with meals (400 mg/day).

Elderly patients Where renal function is normal, it is not necessary to adjust the dose.

Hepatic insufficiency in adults and children No dosage adjustment necessary.

Renal insufficiency in adults and 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 and administered as a single daily dose for values 10 u2013 39 mL/min, every second day for values below 10 mL/min and after each dialysis session for haemodialysis patients.

In children ORELOX JUNIOR must not be given to children with phenylketonuria, since the formulation contains aspartame (see section 4.3). 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. Shake the bottle before use.

The following table may be used as a dosage guide:

The use of ORELOX JUNIOR in children under one year of age is currently not indicated since insufficient clinical data is available at present (see section 4.3).

• Known sensitivity to cephalosporin antibiotics (see section 4.4).
• Safety of use in pregnancy and lactation has not been established.
• ORELOX JUNIOR must not be given to children with phenylketonuria, since the formulation contains aspartame (20 mg/5 mL).
• Children below 1 year of age (see section 4.2).

Anaphylactic reactions Preliminary enquiry as to an allergic diathesis and particularly hypersensitivity of beta-lactam antibiotics should precede treatment with ORELOX. The use of ORELOX is strictly contraindicated in subjects with a previous history of immediate type hypersensitivity to cephalosporins. ORELOX should be used with extreme caution in patients sensitive to penicillin and other u00df-lactam antibiotics as cross-allergy may develop. Strict medical supervision is required throughout the treatment.

Hypersensitivity reactions (anaphylaxis) observed with ORELOX can be serious and occasionally fatal. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic arteriospasm that can result in myocardial infarction, see section 4.8). Treatment should be stopped immediately, should an allergic reaction occur.

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 generalized 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, ORELOX 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, as in ORELOX, treatment with cefpodoxime must not be restarted in this patient at any time.

Clostridium difficile u2013 associated disease Diarrhoea, particularly if severe and/or persistent, occurring during treatment or in the initial weeks following treatment with ORELOX, may be symptomatic of Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. 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.

Renal impairment Use with care in patients with renal impairment. Changes in renal function have been observed with antibiotics of the same class as ORELOX, particularly when given concurrently with potentially nephrotoxic agents such as aminoglycosides and/or potent diuretics. In such cases, renal function should be monitored.

Positive Coombsu2019 test ORELOX 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 ORELOX, 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, Infections and Infestations).

Encephalopathy Beta-lactams, including cefpodoxime, predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment.

Aspartame ORELOX JUNIOR must not be given to children with phenylketonuria, since the formulation contains aspartame (20 mg/5 mL) (see section 4.3).

Lactose/sucrose Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take ORELOX 100 or ORELOX 200, as the tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance e.g. galactosemia, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take ORELOX JUNIOR, as it contains lactose and sucrose.

The bioavailability of ORELOX is increased if the product is administered during meals (acid pH). Histamine H2 antagonists (such as ranitidine) and antacids reduce the bioavailability of ORELOX. Probenecid reduces the excretion of ORELOX. ORELOX potentially enhances the anticoagulant effect of warfarin and reduces the contraceptive effect of oestrogens. Cases showing development of a positive Coombsu2019 test have been reported (see section 4.4). A false positive reaction for glucose in the urine may occur with Benedictu2019s or Fehlingu2019s solution or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.

Pregnancy Safety of ORELOX in pregnant women has not been established, it is therefore advisable not to administer ORELOX during pregnancy (see section 4.3).

Lactation Since ORELOX is excreted in human breast milk, either breastfeeding or treatment of the mother should be discontinued in mothers who are breastfeeding their infants.

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.

The following side effects have been reported:

Infections and Infestations Frequent: superinfections, overgrowth of non-susceptible organisms (see section 4.4).

Blood and lymphatic system disorders Less frequent: reduction of haemoglobin, thrombocytosis, thrombocytopenia, leucopenia, haemolytic anaemia and eosinophilia. Neutropenia and agranulocytosis may occur during treatment with ORELOX.

Immune system disorders Less frequent: anaphylactic reactions: e.g. angioedema, bronchospasm, malaise, possibly culminating in shock may occur (see section 4.4).

Nervous system disorders Less frequent: headache, dizzy sensations, paraesthesia. Beta-lactams, including cefpodoxime proxetil, predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness or movement disorders), particularly in case of overdose or renal impairment.

Ear and labyrinth disorders Less frequent: tinnitus.

Cardiac disorders Frequency unknown: Kounis syndrome.

Gastrointestinal disorders Frequent: diarrhoea, nausea, vomiting, abdominal pains. Less frequent: diarrhoea may sometimes be a symptom of enterocolitis, which may, in some cases, be accompanied by blood in stools. A particular form of enterocolitis than can occur with antibiotics is pseudomembranous colitis (in most cases due to Clostridium difficile) (see section 4.4).

Hepato-biliary disorders Less frequent: increases in liver enzymes (AST, ALT and alkaline phosphatase), and/or bilirubin. These laboratory abnormalities exceed twice the upper limit of the normal range and elicit a pattern of drug induced hepatitis, usually cholestatic.

Skin and subcutaneous tissue disorder Less frequent: cutaneous eruptions, rash, pruritus, urticaria and purpura. Cases of bullous eruptions (erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis) have been reported. Frequency unknown: acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), linear IgA disease.

Renal and urinary disorders Less frequent: increase of blood urea and creatinine. Changes in renal function have been observed with antibiotics from the same group as ORELOX, particularly when co-prescribed with aminoglycosides and/or potent diuretics (see section 4.4).

General disorders and administration site conditions Less frequent: asthenia.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of ORELOX is important. It allows continued monitoring of the benefit/risk balance of ORELOX. Healthcare providers are asked to report any suspected adverse reactions to [SAHPRA via the MedSafety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

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