Clarithromycin

Question 1

What is clarithromycin?

Answer 1

semisynthetic macrolide antibiotic derived from erythromycin

Question 2

What class of drugs does clarithromycin belong to?

Answer 2

macrolide antibiotics

Question 3

What are other drugs in the same class as clarithromycin?

Answer 3

erythromycin
roxithromycin
azithromycin

Question 4

What is clarithromycin indicated for?

Answer 4

respiratory tract infections
mild to mod skin/soft tissue infections
otitis media
mycobacterium infections
endocarditis
prophlaxis in dental surgery in patients with penicillin allergy
H. pylori eradication

Question 5

What is the dose of clarithromycin given for H. pylori eradication?

Answer 5

Oral:
250mg/12 hours for 7 days.
NB: this is increased in penumonia or severe infections to 500mg/12 hours for up to 14 days.

Question 6

What is the mechanism of action of clarithromycin?

Answer 6

Macrolides bind to the 50S ribosomal subunits of susceptible bacteria to suppress protein synthesis.

Potent against wide variety of aerobic and anaerobic G+ and G- organisms.
It also has excellent activity against H. pylori (campylobacter)

Question 7

What are the main PK/PD parameters associated with Clarithromycin use?

Answer 7

PK:
Readily and rapid absorption
absolute bioavailability: 50%

protein binding average~ 70%

Predominantly hepatically metabolised by CYP3A4: numerous drug interactions

~20% is eliminated in urine.

Half life of 3-4 hours

Question 8

What are the precautions associated with clarithromycin use?

Answer 8

Patients predisposed to QT interval prolongation, neonate risk
Compatible with breastfeeding but may cause diarrhoea in infant.

Question 9

What are the contraindications with clarithromycin use?

Answer 9

history of QT prolongation or ventricular arrhythmia; concomitant administration with cisapride or pimozide concomitant administration with ergotamine or dihydroergotamine (risk of toxicity);
concomitant administration with lovastatin or simvastatin (risk of myopathy and rhabdomyolysis); concomitant use of colchicine in patients with renal or hepatic impairment (increased risk of colchicine toxicity)

Question 10

What are the adverse effects with clarithromycin use?

Answer 10

nausea, vomiting, abdominal discomfort, diarrhoea, dyspepsia
tooth and tongue discolouration, smell and taste disturbances, stomatitis, glossitis, headache.

Less common: hepatotoxicity (cholestatic jaundice), cardiac arrest, QT interval prolongation, arrhythmias, athralgia, myalgia, rash

Question 11

What are the drug interactions associated with clarithromycin use?

Answer 11

Cisapride and Pimozide: elevated Cisapride levels when adminsitered concomitantly, resulting in GT prolongation and cardiac arrhthmias.

Terfenadine: reported to alter metabolism of terfenadine resulting in increased levels of terfenadine, assoc. with arrhthmias etc.

Ergotamine: postmarketing reports indicate co-admin assoc. with acute ergot toxicity characterised by vasospasm and ischemia of extremeities

Rifampicin, Nevirapine,
Fluconazole
Ritonavir
antiarrhythmias,
HMGCoA reductase inhibitors
Omeprazole: increased ss plasma concentrations of Omeprazole
etc.

Question 12

What are the alarm bells associated with clarithromycin use?

Answer 12

Do not give in patients susceptible to cardiac arrhythmias, QT prolongation
do not give in neonates under 2 weeks of age

hearing loss (very very rare adverse effect) is reversible.

Question 13

What monitoring is required in clarithromycin use?

Answer 13

Hepatic function? (cholestatic jaundice and other dysfunction have been reported)