Clarithromycin

Clarithromycin was synthesized by researchers at the Japanese company Taisho Pharmaceutical in the 1970s and approved by the FDA in 1991. Clarithromycin is not effective against TB when used by itself, but some evidence shows that the drug can work against MDR / XDR TB when used in combination with other anti-TB medications. Dosage ------ The optimal dosage for clarithromycin for treatment and prevention of TB in adults is 500 mg orally every 12 hours. How it works ------------ Clarithromycin interferes with bacterial growth by inhibiting the synthesis of bacterial proteins. It does so by binding to the bacterial ribosome, the enzyme that builds proteins from RNA transcripts. Side effects ------------ The most common side effects are abnormal taste, diarrhea, headache, indigestion, nausea, stomach pain, and vomiting. Less common side-effects include headaches, hallucinations, dizziness, and rash. In rare cases, the medication may cause jaundice or kidney problems. Clinical evidence and approval ----------------------------------- Clarithromycin is categorized by the WHO as a Group 5 medication with an “unclear role” in the treatment of drug-resistant TB.[^Truffot] Group 5 medications like clarithromycin should only be used after other drug options from Groups 1-4 have been exhausted or are unavailable. There is a lack of clinical studies establishing its effectiveness for TB treatment. TB treatment is therefore an “off-label” use of the medication. Multiple studies have demonstrated that Clarithromycin by itself is inactive against the bacteria that cause TB. However, the drug shows promise as a medication to be used synergistically, i.e. with other antibiotic medications. A 1995 in-vitro study at Creighton Univ. Medical Centre tested the effectiveness of Clarithromycin, when combined with other standard anti-TB drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), against 12 strains of drug-resistant tuberculosis. Results showed that combinations of clarithromycin with other anti-TB drugs can make resistant TB strains susceptible to drugs and eliminate TB bacteria. The study concluded that “the ability of clarithromycin…to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.”[^Cavaliere] Interestingly, a study published in 2000 found that certain drugs that inhibit the synthesis of bacterial cell walls can successfully reverse resistance to clarithromycin in strains of TB bacteria, making these bacteria once again susceptible to treatment.[^Bosne-David] This finding could have practical applications for the treatment of MDR / XDR TB. Pricing (per lowest unit, i.e. single tablet or injection) ----------------------------------------------------------- • 500 mg tablet, 14 tablets: R30.01 • 125 mg/5 ml suspension, 50 ml bottle: R16.31 Advocacy issues ---------------- - Further studies are needed to establish the effectiveness of clarithromycin in the treatment of TB. - No pediatric formulation is available, and more research is needed to determine the safety and efficacy in children. - Using the medication for an “off-label” purpose such as TB treatment poses liability issues that may become a problem for healthcare providers if patients experience complications. [^Truffot]: C. Truffot-Pernot et al. Clarithromycin Is Inactive against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995; 39(12): 2827 [^Cavaliere]: S. Cavaliere et al. Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995; 39(7): 1542-1545. [^Bosne-David]: S. Bosne-David et al. Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors. Journal of Antimicrobial Chemotherapy. 2000; 46(3): 391-395.