29 Mar 2012

Klaricid Paediatric (Clarithromycin) - United Kingdom

Updated: 29 Mar 2012

Klaricid Paediatric Suspension 125mg/5ml

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension is indicated in children 6 months to 12 years.

Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension is indicated for the treatment of infections caused by susceptible organisms. Indications include:

Lower respiratory tract infections.

Upper respiratory tract infections.

Skin and skin structure infections.

Acute otitis media.

Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension is usually active against the following organisms in vitro:

Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-haemolytic streptococci); alpha-haemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes.

Gram-negative Bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae; Legionella pneumophila, Bordetella pertussis, Helicobacter pylori; Campylobacter jejuni.

Mycoplasma: Mycoplasma pneumoniae; Ureaplasma urealyticum.

Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae; Chlamydia pneumoniae.

Anaerobes: Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes.

Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension has bactericidal activity against several bacterial strains. These organisms include H. influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Helicobacter pylori and Campylobacter species.

The activity of clarithromycin against H. pylori is greater at neutral pH than at acid pH.

Klaricid Paediatric Description, Presentation and Dosage

Klaricid Paediatric Description

Klaricid Paediatric Drug Class Description

Anti-infectious - ATC code: J01FA09

Klaricid Paediatric Drug Description

Clarithromycin: 125mg/mL

Klaricid Paediatric Generic Name

Clarithromycin

Klaricid Paediatric Presentation

Klaricid Paediatric Presentation

White to off - white granules for reconstitution.

Klaricid Paediatric Manufacturer

Abbott Healthcare Products Limited

Free Medical Education Resources

Klaricid Paediatric Dosage

Klaricid Paediatric Adult Dosage

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. The recommended daily dosage of Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension in children is given in the following table and is based on a 7.5mg/kg b.i.d. dosing regime. Doses up to 500mg b.i.d. have been used in the treatment of severe infections.

KLARICID PAEDIATRIC SUSPENSION OR CLARITHROMYCIN 125 MG/5ML GRANULES FOR ORAL SUSPENSION DOSAGE IN CHILDREN

Dosage Based on Body Weight (kg)
Weight*(kg) Approx Age (yrs) Dosage (ml bid Dosage per 5ml teaspoonful twice daily
8-11 1 - 2 2.50 1/2
12-19 3 - 6 5.00 1.00
20-29 7 - 9 7.50 1 1/2
30-40 10 - 12 10.00 2.00

* Children < 8 kg should be dosed on a per kg basis (approx. 7.5 mg/kg bid)

Preparation for use:140ml bottle: 74ml of water should be added to the granules in the bottle and shaken to yield 140ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

100 ml bottle:

53ml of water should be added to the granules in the bottle and shaken to yield 100ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

70 ml bottle:

37ml of water should be added to the granules in the bottle and shaken to yield 70ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

50 ml bottle:

27ml of water should be added to the granules in the bottle and shaken to yield 50ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

Sachet: After cutting along the dotted line, empty contents of sachet into a glass, half fill the sachet with cold water. Add to glass and stir thoroughly before taking.

Klaricid Paediatric Child Dosage

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. The recommended daily dosage of Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension in children is given in the following table and is based on a 7.5mg/kg b.i.d. dosing regime. Doses up to 500mg b.i.d. have been used in the treatment of severe infections.

KLARICID PAEDIATRIC SUSPENSION OR CLARITHROMYCIN 125 MG/5ML GRANULES FOR ORAL SUSPENSION DOSAGE IN CHILDREN

Dosage Based on Body Weight (kg)

Weight*

(kg)

Approx Age

(yrs)

Dosage

(ml)

bid

Dosage per 5ml

teaspoonful

twice daily

8-11

1 - 2

2.50

1/2

12-19

3 - 6

5.00

1.00

20-29

7 - 9

7.50

1 1/2

30-40

10 - 12

10.00

2.00

* Children < 8 kg should be dosed on a per kg basis (approx. 7.5 mg/kg bid)

Preparation for use:

140 ml bottle: 74ml of water should be added to the granules in the bottle and shaken to yield 140ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

100 ml bottle: 53ml of water should be added to the granules in the bottle and shaken to yield 100ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

70 ml bottle: 37ml of water should be added to the granules in the bottle and shaken to yield 70ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

50 ml bottle: 27ml of water should be added to the granules in the bottle and shaken to yield 50ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125mg per 5ml.

Sachet: After cutting along the dotted line, empty contents of sachet into a glass, half fill the sachet with cold water. Add to glass and stir thoroughly before taking.

Klaricid Paediatric Precautions, Reactions and Contraindications

Klaricid Paediatric Special Precautions

Klaricid Paediatric Special Precautions

The physician should not prescribe clarithromycin to pregnant women without carefully weighing the benefits against risk, particularly during the first three months of pregnancy.

Caution is advised in patients with severe renal insufficiency.

Clarithromycin is principally excreted by the liver. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function. Caution should also be exercised when administering clarithromycin to patients with moderate to severe renal impairment.

Cases of fatal hepatic failure 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. Clostridium 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.

Exacerbation of symptoms of myasthenia gravis has been reported in patients receiving clarithromycin therapy.

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. Deaths have been reported in some such patients. If concomitant administration of colchicine and clarithromycin is necessary, patients should be monitored for clinical symptoms of colchicine toxicity.

Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and midazolam.

Caution is advised regarding concomitant administration of clarithromycin with other ototoxic drugs, especially with aminoglycosides. Monitoring of vestibular and auditory function should be carried out during and after treatment.

Due to the risk for QT prolongation, clarithromycin should be used with caution in patients with coronary artery disease, severe cardiac insufficiency, hypomagnesaemia, bradycardia (<50 bpm), or when co-administered with other medicinal products associated with QT prolongation. Clarithromycin must not be used in patients with congenital or documented acquired QT prolongation or history of ventricular arrhythmia.

Pneumonia: In view of the emerging resistance of Streptococcus pneumoniae to macrolides, it is important that sensitivity testing be performed when prescribing clarithromycin for community-acquired pneumonia. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.

Skin and soft tissue infections of mild to moderate severity: These infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Therefore, it is important that sensitivity testing be performed. In cases where beta–lactam antibiotics cannot be used (e.g. allergy), other antibiotics, such as clindamycin, may be the drug of first choice. Currently, macrolides are only considered to play a role in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum (erythrasma), acne vulgaris, and erysipelas and in situations where penicillin treatment cannot be used.

In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.

Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme.

HMG-CoA reductase inhibitors: Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated. As with other macrolides, clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors. Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Patients should be monitored for signs and symptoms of myopathy. Rare reports of rhabdomyolysis have also been reported in patients taking atorvastatin or rosuvastatin concomitantly with clarithromycin. When used with clarithromycin, atorvastatin or rosuvastatin should be administered in the lowest possible doses. Adjustment of the statin dose or use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin or pravastatin) should be considered.

Oral hypoglycaemic agents/Insulin: The concomitant use of clarithromycin and oral hypoglycaemic agents and/or insulin can result in significant hypoglycaemia. With certain hypoglycaemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycaemia when used concomitantly. Careful monitoring of glucose is recommended.

Oral anticoagulants: There is a risk of serious haemorrhage and significant elevations in International Normalized Ratio (INR) and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.

Use of any antimicrobial therapy, such as clarithromycin, to treat H. pylori infection may select for drug-resistant organisms.

Long-term use may, as with other antibiotics, result in colonisation with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted.

Attention should also be paid to the possibility of cross resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Klaricid Paediatric Adverse Reactions

Klaricid Paediatric Adverse Reactions

a. Summary of the safety profile

The most frequent and common adverse reactions related to clarithromycin therapy for both adult and peadiatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion. These adverse reactions are usually mild in intensity and are consistent with the known safety profile of macrolide antibiotics.

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 (GREATER-THAN OR EQUAL TO (8805)1/10), common (GREATER-THAN OR EQUAL TO (8805) 1/100 to < 1/10), uncommon (GREATER-THAN OR EQUAL TO (8805)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

GREATER-THAN OR EQUAL TO (8805)1/10

Common

GREATER-THAN OR EQUAL TO (8805) 1/100 to < 1/10

Uncommon

GREATER-THAN OR EQUAL TO (8805)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, erythrasma

Blood and lymphatic system

 

 

Leukopenia, neutropenia 4, thrombocythaemia3, eosinophilia4

Agranulocytosis, thrombocytopenia

Immune system disorders5

 

 

Anaphylactoid reaction1, hypersensitivity

Anaphylactic reaction

Metabolism and nutrition disorders

 

 

Anorexia, decreased appetite

Hypoglycaemia6

Psychiatric disorders

 

Insomnia

Anxiety, nervousness3, screaming3

Psychotic disorder, confusional state, depersonalisation, depression, disorientation, hallucination, abnormal dreams

Nervous system disorders

 

Dysgeusia, headache, taste perversion

Loss of consciousness1, dyskinesia1, dizziness, somnolence7, tremor

Convulsion, ageusia, parosmia, anosmia

Ear and labyrinth disorders

 

 

Vertigo, hearing impaired, tinnitus

Deafness

Cardiac disorders

 

 

Cardiac arrest1, atrial fibrillation1, electrocardiogram QT prolonged8, extrasystoles1, palpitations

Torsade de pointes8, ventricular tachycardia8

Vascular disorders

 

Vasodilation1

 

Haemorrhage 9

Respiratory, thoracic and mediastinal disorder

 

 

Asthma1, epistaxis2, pulmonary embolism1

 

Gastrointestinal disorders

 

Diarrhoea 10, vomiting, dyspepsia, nausea, abdominal pain

Oesophagitis 1, gastrooesophageal reflux disease2, gastritis, proctalgia2, stomatitis, glossitis, abdominal distension4, constipation, dry mouth, eructation, flatulence,

Pancreatitis acute, tongue discolouration, tooth discolouration

Hepatobiliary disorders

 

Liver function test abnormal

Cholestasis4, hepatitis4, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased4

Hepatic failure11, jaundice hepatocellular

Skin and subcutaneous tissue disorders

 

Rash, hyperhidrosis

Dermatitis bullous1, pruritus, urticaria, rash maculo-papular3

Stevens-Johnson syndrome5, toxic epidermal necrolysis5, drug rash with eosinophilia and systemic symptoms (DRESS), acne

Musculoskeletal and connective tissue disorders

 

 

Muscle spasms3, musculoskeletal stiffness1, myalgia2

Rhabdomyolysis2,12, myopathy

Renal and urinary disorders

 

 

Blood creatinine increased1, blood urea increased1

Renal failure, nephritis interstitial

General disorders and administration site conditions

Injection site phlebitis1

Injection site pain1, injection site inflammation1

Malaise4, pyrexia3, asthenia, chest pain4, chills4, fatigue4

 

Investigations

 

 

Albumin globulin ratio abnormal1, blood alkaline phosphatase increased4, blood lactate dehydrogenase increased4

International normalised ratio increased9, prothrombin time prolonged9, urine color abnormal

1 ADRs reported only for the Powder for Solution for Injection 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

5,8,10,11,12See section a)

6,7,9See section c)

c. Description of selected adverse reactions

Injection site phlebitis, injection site pain, vessel puncture site pain, and injection site inflammation are specific to the clarithromycin intravenous formulation.

In very rare instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications.

A special attention to diarrhoea should be paid as Clostridium 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.

In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome and toxic epidermal necrolysis, clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.

As with other macrolides, QT prolongation, ventricular tachycardia, and torsade de pointes have rarely been reported with clarithromycin.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.

In some of the reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol.

There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in elderly and/or patients with renal insufficiency, some with a fatal outcome.

There have been rare reports of hypoglycaemia, some of which have occurred in patients on concomitant oral hypoglycaemic agents or insulin.

There have been post-marketing reports of drug interactions and central nervous system (CNS) effects (e.g. somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.

There is a risk of serious haemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.

There have been rare reports of clarithromycin ER tablets in the stool, many of which have occurred in patients with anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times. In several reports, tablet residues have occurred in the context of diarrhoea. It is recommended that patients who experience tablet residue in the stool and no improvement in their condition should be switched to a different clarithromycin formulation (e.g. suspension) or another antibiotic.

Special population: Adverse Reactions in Immunocompromised Patients (see section e)

d. Paediatric populations

Clinical trials have been conducted using clarithromycin paediatric suspension in children 6 months to 12 years of age. Therefore, children under 12 years of age should use clarithromycin paediatric suspension. There are insufficient data to recommend a dosage regimen for use of the clarithromycin IV formulation in patients less than 18 years of age.

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

e. Other special populations

Immunocompromised patients

In AIDS and other immunocompromised patients treated with the higher doses of clarithromycin over long periods of time for mycobacterial infections, it was often difficult to distinguish adverse events possibly associated with clarithromycin administration from underlying signs of Human Immunodeficiency Virus (HIV) disease or intercurrent illness.

In adult patients, the most frequently reported adverse reactions by patients treated with total daily doses of 1000 mg and 2000mg of clarithromycin were: nausea, vomiting, taste perversion, abdominal pain, diarrhoea, rash, flatulence, headache, constipation, hearing disturbance, Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) elevations. Additional low-frequency events included dyspnoea, insomnia and dry mouth. The incidences were comparable for patients treated with 1000mg and 2000mg, but were generally about 3 to 4 times as frequent for those patients who received total daily doses of 4000mg of clarithromycin.

In these immunocompromised patients, evaluations of laboratory values were made by analysing those values outside the seriously abnormal level (i.e. the extreme high or low limit) for the specified test. On the basis of these criteria, about 2% to 3% of those patients who received 1000mg or 2000mg of clarithromycin daily had seriously abnormal elevated levels of SGOT and SGPT, and abnormally low white blood cell and platelet counts. A lower percentage of patients in these two dosage groups also had elevated Blood Urea Nitrogen levels. Slightly higher incidences of abnormal values were noted for patients who received 4000mg daily for all parameters except White Blood Cell.

Klaricid Paediatric Contraindications

Klaricid Paediatric Contraindications

Klaricid Paediatric Suspension or Clarithromycin 125 mg/5ml Granules for Oral Suspension is contra-indicated in patients with known hypersensitivity to macrolide antibiotic drugs or to any of its excipients.

Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated, as this may result in ergot toxicity.

Concomitant administration of clarithromycin and any of the following drugs is contraindicated: astemizole, cisapride, pimozide and terfenadine as this may result in QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointe.

Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointe.

Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins), lovastatin or simvastatin, due to the risk of rhabdomyolysis. Treatment with these agents should be discontinued during clarithromycin treatment.

Clarithromycin should not be given to patients with hypokalaemia (risk of prolongation of QT-time).

Clarithromycin should not be used in patients who suffer from severe hepatic failure in combination with renal impairment.

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