Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections.[3] This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others.[3] Clarithromycin can be taken by mouth as a pill or liquid.[3]
Common side effects include nausea, vomiting, headaches, and diarrhea.[3] Severe allergic reactions are rare.[3] Liver problems have been reported.[3] It may cause harm if taken during pregnancy.[3] It is in the macrolide class and works by slowing down bacterial protein synthesis.[3]
Safety and effectiveness of clarithromycin in treating clinical infections due to the following bacteria have not been established in adequate and well-controlled clinical trials:[8]
Clarithromycin has been researched as a potential treatment for idiopathic hypersomnia (IH) in adults, but the evidence is limited. A 2021 Cochrane study determined that the evidence is inadequate to definitively determine the efficacy of clarithromycin in the management of idiopathic hypersomnia.[9] The American Academy of Sleep Medicine's 2021 clinical practice guidelines conditionally suggested its use, especially for those who don't respond to other therapies.[10][11]
Contraindications
Clarithromycin should not be taken by people who are allergic to other macrolides or inactive ingredients in the tablets, including microcrystalline cellulose, sodium croscarmellose, magnesium stearate, and povidone[citation needed]
Clarithromycin should not be used by people with a history of cholestatic jaundice and/or liver dysfunction associated with prior clarithromycin use.[8]
The most common side effects are gastrointestinal: diarrhea (3%), nausea (3%), abdominal pain (3%), and vomiting (6%). It also can cause headaches, insomnia, and abnormal liver function tests. Allergic reactions include rashes and anaphylaxis. Less common side effects (<1%) include extreme irritability, hallucinations (auditory and visual), dizziness/motion sickness, and alteration in senses of smell and taste, including a metallic taste. Dry mouth, panic attacks, and nightmares have also been reported, albeit less frequently.[12]
Cardiac
In February 2018, the FDA issued a Safety Communication warning with respect to an increased risk for heart problems or death with the use of clarithromycin, and has recommended that alternative antibiotics be considered in those with heart disease.[13]
Clarithromycin can lead to a prolonged QT interval. In patients with long QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threatening arrhythmias.[14]
In one trial, the use of short-term clarithromycin treatment was correlated with an increased incidence of deaths classified as sudden cardiac deaths in stable coronary heart disease patients not using statins.[15]
Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can cause ototoxicity, delirium and mania.[citation needed]
Clarithromycin should not be used in pregnant women except in situations where no alternative therapy is appropriate.[8] Clarithromycin can cause potential hazard to the fetus hence should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[8] For lactating mothers it is not known whether clarithromycin is excreted in human milk.[8]
Interactions
Clarithromycin inhibits a liver enzyme, CYP3A4, involved in the metabolism of many other commonly prescribed drugs. Taking clarithromycin with other medications that are metabolized by CYP3A4 may lead to unexpected increases or decreases in drug levels.[17][18]
A few of the common interactions are listed below.
Colchicine
Clarithromycin has been observed to have a dangerous interaction with colchicine as the result of inhibition of CYP3A4 metabolism and P-glycoprotein transport. Combining these two drugs may lead to fatal colchicine toxicity, particularly in people with chronic kidney disease.[8]
Statins
Taking clarithromycin concurrently with certain statins (a class of drugs used to reduce blood serum cholesterol levels) increases the risk of side effects, such as muscle aches and muscle break down (rhabdomyolysis).[19]
Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments.[22] For example, clarithromycin may lead to decreased zidovudine concentrations.[23]
Unlike erythromycin, clarithromycin is acid-stable, so can be taken orally without having to be protected from gastric acids. It is readily absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, clarithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of clarithromycin are released; its concentration in the tissues can be over 10 times higher than in plasma. Highest concentrations are found in liver, lung tissue, and stool.
Metabolism
Clarithromycin has a fairly rapid first-pass metabolism in the liver. Its major metabolites include an inactive metabolite, N-desmethylclarithromycin, and an active metabolite, 14-(R)-hydroxyclarithromycin. Compared to clarithromycin, 14-(R)-hydroxyclarithromycin is less potent against mycobacterial tuberculosis and the Mycobacterium avium complex. Clarithromycin (20%-40%) and its active metabolite (10%-15%) are excreted in urine. Of all the drugs in its class, clarithromycin has the best bioavailability at 50%, which makes it amenable to oral administration.
Its elimination half-life is about 3 to 4 hours with 250 mg administered every 12 h, but increased to 5 to 7 h with 500 mg administered every 8 to 12 h. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.[24]
History
Clarithromycin was invented by researchers at the Japanese drug company Taisho Pharmaceutical in 1980.[4] The product emerged through efforts to develop a version of the antibiotic erythromycin that did not experience acid instability in the digestive tract, causing side effects, such as nausea and stomachache. Taisho filed for patent protection for the drug around 1980 and subsequently introduced a branded version of its drug, called Clarith, to the Japanese market in 1991. In 1985, Taisho partnered with the American company Abbott Laboratories for the international rights, and Abbott also gained FDA approval for Biaxin in October 1991. The drug went generic in Europe in 2004 and in the US in mid-2005.[25]
Clarithromycin is available as a generic medication.[3] In the United States, clarithromycin is available as immediate-release tablets, extended-release tablets, and granules for oral suspension.[3]
Brand names
Clarithromycin is available under several brand names in many different countries, including Biaxin, Crixan, Claritron, Clarihexal, Clacid, Claritt, Clacee, Clarac, Clariwin, Claripen, Clarem, Claridar, Cloff, Fromilid, Infex, Kalixocin, Karicin, Klaricid, Klaridex, Klacid, Klaram, Klabax, Klerimed, MegaKlar, Monoclar, Resclar, Rithmo, Truclar, Vikrol and Zeclar.[citation needed]
Manufacturers
In the UK the drug product is manufactured in generic form by a number of manufacturers including Somex Pharma, Ranbaxy, Aptil and Sandoz.
^ abcdefghijklmn"Clarithromycin". The American Society of Health-System Pharmacists. Archived from the original on September 3, 2015. Retrieved September 4, 2015.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Yamaguchi S, Kaneko Y, Yamagishi T, et al. [Clarithromycin-induced torsades de pointes]. Nippon Naika Gakkai Zasshi. 2003;92(1):143–5.
^Winkel P, Hilden J, Fischer Hansen J, Hildebrandt P, Kastrup J, Kolmos HJ, et al. (2011). "Excess sudden cardiac deaths after short-term clarithromycin administration in the CLARICOR trial: why is this so, and why are statins protective?". Cardiology. 118 (1): 63–7. doi:10.1159/000324533. PMID21447948. S2CID11873791.
^Tietz A, Heim MH, Eriksson U, Marsch S, Terracciano L, Krähenbühl S (January 2003). "Fulminant liver failure associated with clarithromycin". The Annals of Pharmacotherapy. 37 (1): 57–60. doi:10.1345/1542-6270(2003)037<0057:flfawc>2.0.co;2. PMID12503933.
^Hougaard Christensen MM, Bruun Haastrup M, Øhlenschlaeger T, Esbech P, Arnspang Pedersen S, Bach Dunvald AC, Bjerregaard Stage T, Pilsgaard Henriksen D, Thestrup Pedersen AJ (April 2020). "Interaction potential between clarithromycin and individual statins-A systematic review". Basic Clin Pharmacol Toxicol. 126 (4): 307–317. doi:10.1111/bcpt.13343. PMID31628882.
^Herdegen T, Cascorbi I (December 2023). "Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs: Recommendations for Clinical Practice". Dtsch Arztebl Int. 120 (49): 833–840. doi:10.3238/arztebl.m2023.0223. PMC 10824494. PMID37874128. S2CID264438050.
^Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, et al. (June 2013). "Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study". Annals of Internal Medicine. 158 (12): 869–76. doi:10.7326/0003-4819-158-12-201306180-00004. PMID23778904. S2CID21222679.
^Gandhi S, Fleet JL, Bailey DG, McArthur E, Wald R, Rehman F, Garg AX (December 2013). "Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury". JAMA. 310 (23): 2544–53. doi:10.1001/jama.2013.282426. PMID24346990.
^Gélisse P, Hillaire-Buys D, Halaili E, Jean-Pastor MJ, Vespignan H, Coubes P, Crespel A (November 2007). "[Carbamazepine and clarithromycin: a clinically relevant drug interaction]". Revue Neurologique. 163 (11): 1096–9. doi:10.1016/s0035-3787(07)74183-8. PMID18033049.
^Sekar VJ, Spinosa-Guzman S, De Paepe E, De Pauw M, Vangeneugden T, Lefebvre E, Hoetelmans RM (January 2008). "Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers". Journal of Clinical Pharmacology. 48 (1): 60–5. doi:10.1177/0091270007309706. PMID18094220. S2CID38368595.
^Ferrero JL, Bopp BA, Marsh KC, Quigley SC, Johnson MJ, Anderson DJ, et al. (1990). "Metabolism and disposition of clarithromycin in man". Drug Metabolism and Disposition. 18 (4): 441–6. PMID1976065.
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