CLARITHROMYCIN
Please note clarithromycin is not licensed for the treatment of tuberculosis in the UK.
Clarithromycin is not usually recommended for the treatment of MDRTB. When it is used, it should be counted as half a drug in a treatment regimen.
DOSAGE
For all patients over 12 years old:
By intravenous infusion:
· 500mg twice a day given through a large proximal vein.
By mouth:
· 500mg twice a day.
Paediatric doses: [NOTE: Limited data on evidence for dosing in TB. These doses are based on clarithromycin dosing for respiratory tract infections in the latest BNF for children 2012-2013.]
By intravenous infusion into large proximal vein
· Child 1 month–12 years: 7.5 – 15 mg/kg twice a day
· Child 12–18 years: 500 mg twice a day
By mouth:
Child 1 month – 12 years:
· body-weight under 8 kg: 7.5 mg/kg twice a day
· 8–11 kg: 62.5 mg twice a day
· 12–19 kg, 125 mg twice a day
· 20–29 kg, 187.5 mg twice a day
· 30–40 kg, 250 mg twice a day
Child 12 – 18 years: 500mg twice a day
PREPARATIONS
Oral: 250mg, 500mg tablets.
125mg/5mL, 250mg/5mL suspension.
Parenteral: 500mg powder for solution for injection
DRUG LEVEL MONITORING
· Drug levels need not be routinely measured.
ADVERSE EFFECTS
COMMON:
Gastrointestinal: Abdominal pain (2%), diarrhoea (3-6%), nausea (3%), vomiting (6%) and taste perversion (3-19%).
Neurological: Headache (2%).
SERIOUS:
Cardiovascular: QTc prolongation (very rare)
Dermatological (rare): Anaphylaxis, leukocytoclastic vasculitis, toxic epidermal necrolysis, and Stevens-Johnson syndrome.
Hepatic: Hepatomegaly, hepatic dysfunction & hepatic failure (rare).
Immunological: Anaphylaxis.
Infective: Clostridium difficile-associated diarrhoea and colitis.
Ototoxicity: Hearing loss and tinnitus reported in association with long-term use.
ADVERSE EFFECTS: MONITORING
ECG: Baseline, 2 weeks then every 3 months and after the addition of any new medication that is known to prolong QT.
Audiometry: Baseline and repeat if symptomatic.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Use with caution with antivirals:
· Increased plasma concentrations of: atazanavir, etravirine, nevirapine, telaprevir, tipranavir, and possibly maraviroc, rilpivirine.
· Increased clarithromycin concentrations with: atazanavir, ritonavir, telaprevir, tipranavir.
· Reduced clarithromycin concentrations with: atravirine, nevirapine.
· Increased risk of ventricular arrhythmias with saquinavir and telaprevir.
Increased plasma concentrations of:
· Antiepileptics: carbamazepine, phenytoin (monitor plasma concentrations).
· Ciclosporin (avoid clarithromycin, or monitor ciclosporin plasma concentrations).
· Coumarins e.g. warfarin (increased anticoagulant effect).
· Ivabradine (avoid use).
· Linezolid (consider drug level monitoring)
· Rifabutin (requires rifabutin dose reduction).
· Sirolimus (avoid clarithromycin, or monitor sirolimus plasma concentrations).
· Statins (avoid use).
· Tacrolimus (avoid clarithromycin, or monitor tacrolimus plasma concentrations).
· Theophylline (reduce theophylline dose and monitor plasma concentrations).
· Ticagrelor (avoid use).
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To macrolides.
Use of other drugs that may prolong the QT interval.
Renal & liver disease: Avoid in patients with both severe renal and liver disease.
Cautions:
Pregnancy & Breast-feeding.
Renal Disease: Use with caution. Reduce the dose.
Myasthenia Gravis: Macrolides may aggravate myasthenia gravis.
Cardiovascular Disease: 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.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
Clarithromycin is not usually recommended for the treatment of MDRTB. When it is used, it should be counted as half a drug in a treatment regimen.
DOSAGE
For all patients over 12 years old:
By intravenous infusion:
· 500mg twice a day given through a large proximal vein.
By mouth:
· 500mg twice a day.
Paediatric doses: [NOTE: Limited data on evidence for dosing in TB. These doses are based on clarithromycin dosing for respiratory tract infections in the latest BNF for children 2012-2013.]
By intravenous infusion into large proximal vein
· Child 1 month–12 years: 7.5 – 15 mg/kg twice a day
· Child 12–18 years: 500 mg twice a day
By mouth:
Child 1 month – 12 years:
· body-weight under 8 kg: 7.5 mg/kg twice a day
· 8–11 kg: 62.5 mg twice a day
· 12–19 kg, 125 mg twice a day
· 20–29 kg, 187.5 mg twice a day
· 30–40 kg, 250 mg twice a day
Child 12 – 18 years: 500mg twice a day
PREPARATIONS
Oral: 250mg, 500mg tablets.
125mg/5mL, 250mg/5mL suspension.
Parenteral: 500mg powder for solution for injection
DRUG LEVEL MONITORING
· Drug levels need not be routinely measured.
ADVERSE EFFECTS
COMMON:
Gastrointestinal: Abdominal pain (2%), diarrhoea (3-6%), nausea (3%), vomiting (6%) and taste perversion (3-19%).
Neurological: Headache (2%).
SERIOUS:
Cardiovascular: QTc prolongation (very rare)
Dermatological (rare): Anaphylaxis, leukocytoclastic vasculitis, toxic epidermal necrolysis, and Stevens-Johnson syndrome.
Hepatic: Hepatomegaly, hepatic dysfunction & hepatic failure (rare).
Immunological: Anaphylaxis.
Infective: Clostridium difficile-associated diarrhoea and colitis.
Ototoxicity: Hearing loss and tinnitus reported in association with long-term use.
ADVERSE EFFECTS: MONITORING
ECG: Baseline, 2 weeks then every 3 months and after the addition of any new medication that is known to prolong QT.
Audiometry: Baseline and repeat if symptomatic.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Use with caution with antivirals:
· Increased plasma concentrations of: atazanavir, etravirine, nevirapine, telaprevir, tipranavir, and possibly maraviroc, rilpivirine.
· Increased clarithromycin concentrations with: atazanavir, ritonavir, telaprevir, tipranavir.
· Reduced clarithromycin concentrations with: atravirine, nevirapine.
· Increased risk of ventricular arrhythmias with saquinavir and telaprevir.
Increased plasma concentrations of:
· Antiepileptics: carbamazepine, phenytoin (monitor plasma concentrations).
· Ciclosporin (avoid clarithromycin, or monitor ciclosporin plasma concentrations).
· Coumarins e.g. warfarin (increased anticoagulant effect).
· Ivabradine (avoid use).
· Linezolid (consider drug level monitoring)
· Rifabutin (requires rifabutin dose reduction).
· Sirolimus (avoid clarithromycin, or monitor sirolimus plasma concentrations).
· Statins (avoid use).
· Tacrolimus (avoid clarithromycin, or monitor tacrolimus plasma concentrations).
· Theophylline (reduce theophylline dose and monitor plasma concentrations).
· Ticagrelor (avoid use).
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To macrolides.
Use of other drugs that may prolong the QT interval.
Renal & liver disease: Avoid in patients with both severe renal and liver disease.
Cautions:
Pregnancy & Breast-feeding.
Renal Disease: Use with caution. Reduce the dose.
Myasthenia Gravis: Macrolides may aggravate myasthenia gravis.
Cardiovascular Disease: 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.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
