KLARICID PAEDIATRIC

Paediatric patients under 12 years of age Clinical trials have been conducted using Klaricid Paediatric Suspension in children 6 months to 12 years of age. Therefore, children under 12 years of age should use Klaricid Paediatric Suspension.

Recommended doses and dosage schedules:

The usual duration of treatment is for 5 to 10 days depending on the pathogen involved and the severity of the condition. d. d.. The prepared suspension can be taken with or without meals, and can be taken with milk. 00 * Children < 8 kg should be dosed on a per kg basis (approx.

5mg/kg per day. Dosage should not be continued beyond 14 days in these patients. 6

a. Summary of the safety profile The most frequent and common adverse reactions related to clarithromycin therapy for both adult and paediatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion. 8). There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without pre- existing mycobacterial infections.

b. Tabulated summary of adverse reactions The following table displays adverse reactions reported in clinical trials and from post-marketing experience with clarithromycin immediate-release tablets, granules for oral suspension, powder for solution for injection, extended-release tablets and modified-release tablets.

The reactions considered at least possibly related to clarithromycin are displayed by system organ class and frequency using the following convention: very common (≥1/10), common (≥ 1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100) and not known (adverse reactions from post-marketing experience; cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness when the seriousness could be assessed. System Organ Class Very common ≥1/10 Common ≥ 1/100 to < 1/10 Uncommon ≥1/1,000 to < 1/100 Not Known* (cannot be estimated from the available data) Infections and infestations Cellulitis1, candidiasis, gastroenteritis2, infection3, vaginal infection Pseudomembranous colitis, erysipelas, Blood and lymphatic system Leukopenia, neutropenia4, thrombocythaemia3, eosinophilia4 Agranulocytosis, thrombocytopenia Immune system disorders Anaphylactoid reaction1, hypersensitivity Anaphylactic reaction.

g. Acute generalised exanthematous pustulosis (AGEP),Stevens- Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS)), acne Musculoskel etal and connective tissue disorders Muscle spasms3, musculoskeletal stiffness1, myalgia2 Rhabdomyolysis2,6, myopathy Renal and urinary disorders Blood creatinine increased1, blood urea increased1 Renal failure, nephritis interstitial General disorders and administratio n site conditions Injection site phlebitis1 Injection site pain1, injection site inflammation 1 Malaise4, pyrexia3, asthenia, chest pain4, chills4, fatigue4 Investigation s Albumin globulin ratio abnormal1, blood alkaline phosphatase increased4, blood lactate International normalised ratio increased, prothrombin time prolonged, urine colour abnormal dehydrogenase increased4 1 ADRs reported only for the Powder for Concentrate for Solution for Infusion formulation 2ADRs reported only for the Extended-Release Tablets formulation 3 ADRs reported only for the Granules for Oral Suspension formulation 4 ADRs reported only for the Immediate-Release Tablets formulation 5,6 See section c) * Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

6). Clarithromycin is principally metabolised by the liver. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function. 2). Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin.

This hepatic dysfunction may be severe and is usually reversible. 8) have been reported. Some patients may have had pre- existing hepatic disease or may have been taking other hepatotoxic medicinal products. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening. Clostridioides difficile- associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis.

Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Therefore, discontinuation of clarithromycin therapy should be considered regardless of the indication. Microbial testing should be performed and adequate treatment initiated. Drugs inhibiting peristalsis should be avoided. There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency.

5). 3). 5). 8). 3). 5). Furthermore, clarithromycin should be used with caution in the following: • Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia; • Patients concomitantly taking other medicinal products associated with QT prolongation other than those which are contraindicated Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results.

1. g. 5). 5). 5). 5). 5). Concomitant administration with ticagrelor, ivabradine or ranolazine is contraindicated. Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4, (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis.

5). 5). Clarithromycin should not be given to patients with electrolyte disturbances (hypokalaemia or hypomagnesaemia, due to the risk of prolongation of the QT interval). Clarithromycin should not be used in patients who suffer from severe hepatic failure in combination with renal impairment.