Dr Sharon Rees @reesprescribe
Day 1: The first macrolide antibiotic, erythromycin, was isolated from streptomyces erythraeus in 1952. #clarithromycin is a semi-synthetic derivative, marketed in the 90s, with increased bioavailability, longer t½ and a superior adverse drug reaction (ADR) profile, especially re Gastrointestinal (GI) issues.
Dr Sharon Rees @reesprescribe
(cont) #clarithromycin has greater lipophilicity allowing increased penetration into lung tissue, and enhanced treatment of intracellular pathogens such H. influenzae.
Dr Sharon Rees @reesprescribe
Day 2: Indications #clarithromycin include upper & lower RTIs, H. pylori, penicillin alternative for conditions such as otitis media, strep throat, skin and soft tissue infections, and Lyme disease. Adult dose range oral 250-500 mg x2 daily. Children > 1 month weight-dependent dose.
Dr Sharon Rees @reesprescribe
(cont) Bacterial resistance to second generation macrolides such as #clarithromycin is increasing; common mechanisms are up regulation of bacterial efflux pumps and reduced drug binding affinity; an example would be because of bacterial modification of the target ribosome unit.
Dr Sharon Rees @reesprescribe
Day 3: #clarithromycin kinetics; stable orally, good absorption, hepatic metabolism, renal excretion, t½ 3-7 hrs, depending on dose.
Dr Sharon Rees @reesprescribe
#clarithromycin is more lipophilic compared to erythromycin and has an increased volume of distribution. Inhibition CYP3A4 liver enzymes and p-glycoprotein, leads to multiple drug-drug interactions (DDIs).
Dr Sharon Rees @reesprescribe
Day 4: #clarithromycin and active metabolite 14-OH clarithromycin interfere with bacterial protein synthesis. They bind to a part of the ribosome which inhibits peptide translation. Classed as bacteriostatic, can be bactericidal depending on bacteria such as S.pyogenes and drug concentration.
Dr Sharon Rees @reesprescribe
Day 5: Common ADRs #clarithromycin; insomnia, headache, GI disturbance, rash. Serious; hepatitis, Stevens-Johnson syndrome, DRESS (drug rash with eosinophilia and systemic symptoms). Contraindications: hypokalaemia, history cholestatic jaundice, QT prolongation (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 6: #clarithromycin DDIs; CYP3A4 inducers such rifampicin can cause sub-therapeutic levels and increased effects of midazolam and warfarin.
Dr Sharon Rees @reesprescribe
(cont) #clarithromycin can inhibit statin breakdown, increasing risk of serious ADRs such as myopathy. Can also cause more exposure to digoxin (inhibits P-glycoprotein) plus several other serious DDIs.
Dr Sharon Rees @reesprescribe
Day 7: Interesting fact: neutrophils and macrophages have transporters, which take up #clarithromycin.
Dr Sharon Rees @reesprescribe
(cont) These phagocytes carry the antibiotic to the site of infection, which is thought to enhance tissue concentration of the drug. Also potentially useful for intracellular pathogens such as S. aureus.
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
Complete the additional reading suggested below and then answer the eight questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve six or more out of eight on the questions, a CPD certificate will be emailed to you.
Further reading on #clarithromycin
- Macrolides: https://bnf.nice.org.uk/treatment-summary/macrolides.html
- Clarithromycin: https://bnf.nice.org.uk/drug/clarithromycin.html
- Clarithromycin 500mg Tablets: https://www.medicines.org.uk/emc/product/6094/smpc
- Clarithromycin is usually better tolerated than erythromycin TRUE or FALSE?
- Macrolide antibiotics are all associated with which effect?
- A narrow spectrum of activity
- A poor tissue concentration
- Hydrophilic (water-loving) properties
- Inhibition of liver enzyme activity
- Macrolides including clarithromycin are known to be very nephrotoxic TRUE or FALSE?
- The mechanism of action of macrolides such as clarithromycin is to
- Inhibit the growth of a peptide chain in the ribosome, interrupting bacterial protein formation
- Suppress mitochondrial action and therefore bacterial cell respiration
- Punch holes in the bacterial cell wall
- Thin the bacterial cell membrane so the cell bursts
- Clarithromycin inhibits P-glycoprotein (P-gp), which means that drugs normally expelled from the cell, are able to exert a greater action, such as digoxin. TRUE or FALSE?
- Antibiotic-associated colitis is a common adverse drug reaction (ADR) for clarithromycin TRUE or FALSE?
- Which of the following is TRUE?
- Clarithromycin is active against several anaerobic organisms such as Bacteroides fragilis
- Clarithromycin has poor Gram-negative activity
- Clarithromycin must not be taken with food
- Clarithromycin is a prodrug
- Clarithromycin is commonly used as an alternative antibiotic in cases of penicillin allergy TRUE or FALSE?