Clarithromycin: Difference between revisions

{{Short description|Antibiotic medication}}

{{Use dmy dates|date=March 2024}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 457457495

| alt =

| image2 = Clarithromycin-from-xtal-3D-bs-17.png

| alt2 =

| tradename = Biaxin, others

| DailyMedID = Clarithromycin

| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Oral administration|By mouth]], [[intravenous]]

| ATC_prefix = J01

| ATC_suffix = FA09

| legal_AU = S4

| legal_US = Rx-only

| legal_EU = Rx-only

| legal_EU_comment = <ref name="List of nationally authorised medicinal products-2020">{{cite web | title = Active substance: clarithromycin | work = List of nationally authorised medicinal products | publisher = European Medicines Agency | date = 10 December 2020 | url = https://www.ema.europa.eu/documents/psusa/clarithromycin-list-nationally-authorised-medicinal-products-psusa/00000788/202004_en.pdf }}</ref>

| legal_status = Rx-only

| metabolism = [[Liver]]

| elimination_half-life = 3–4 h

| PubChem = 84029

| ChemSpiderID = 10342604

| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEMBL = 1741

<!--Chemical data-->

| IUPAC_name = (3''R'',4''S'',5''S'',6''R'',7''R'',9''R'',11''S'',12''R'',13''S'',14''R'')-6-<nowiki/>{[(2''S'',3''R'',4''S'',6''R'') -4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy} -14-ethyl-12,13-dihydroxy-4-<nowiki/>{[(2''R'',4''R'',5''S'',6''S'')-5-hydroxy -4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7 -methoxy-3,5,7,9,11,13-hexamethyl -1-oxacyclotetradecane-2,10-dione

| C=38 | H=69 | N=1 | O=13

| smiles = CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C38H69NO13/c1-15-26-38(10,45)31(42)21(4)28(40)19(2)17-37(9,47-14)33(52-35-29(41)25(39(11)12)16-20(3)48-35)22(5)30(23(6)34(44)50-26)51-27-18-36(8,46-13)32(43)24(7)49-27/h19-27,29-33,35,41-43,45H,15-18H2,1-14H3/t19-,20-,21+,22+,23-,24+,25+,26-,27+,29-,30+,31-,32+,33-,35+,36-,37-,38-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = AGOYDEPGAOXOCK-KCBOHYOISA-N

| class = [[Macrolides]]

| synonyms = 6-''O''-methylerythromycin A

<!-- Definition and medical uses -->

'''Clarithromycin''', sold under the brand name '''Biaxin''' among others, is an [[antibiotic]] used to treat various [[bacterial]] infections.<ref name=AHFS2015>{{cite web|title=Clarithromycin|url=https://www.drugs.com/monograph/clarithromycin.html|publisher=The American Society of Health-System Pharmacists|access-date=4 September 2015|url-status=live|archive-url=https://web.archive.org/web/20150903071907/http://www.drugs.com/monograph/clarithromycin.html|archive-date=3 September 2015}}</ref> This includes [[strep throat]], [[pneumonia]], skin infections, ''[[Helicobacter pylori|H. pylori]]'' infection, and [[Lyme disease]], among others.<ref name=AHFS2015/> Clarithromycin can be taken by mouth as a tablet or liquid or can be infused intravenously.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->

Common side effects include nausea, vomiting, headaches, and diarrhea.<ref name=AHFS2015/> Severe [[allergic reaction]]s are rare.<ref name=AHFS2015/> Liver problems have been reported.<ref name=AHFS2015/> It may cause harm if taken during [[pregnancy]].<ref name=AHFS2015/> It is in the [[macrolide]] class and works by slowing down bacterial [[protein synthesis]].<ref name=AHFS2015/> Clarithromycin resistance is already a major challenge to healthcare systems and such resistance is spreading, leading to recommendations to test the susceptibility of pathogenic organisms to the antibiotic before commencing clarithromycin therapy.<ref> {{cite journal | vauthors = Mommersteeg MC, Nieuwenburg SA, Wolters LM, Roovers BH, van Vuuren HA, Verhaar AP, Bruno MJ, Kuipers EJ, Peppelenbosch MP, Spaander MC, Fuhler GM | title = The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance. | journal = United European Gastroenterol J | volume = 11 | issue = 9 | pages = e894-903| date = November 2023 | pmid = 37854002 | pmc = 10637120 | doi = 10.1002/ueg2.12473 | doi-access = free}}</ref>

<!-- History, society and culture -->

Clarithromycin was developed in 1980 and approved for medical use in 1990.<ref name="Greenwood-2008">{{cite book | vauthors = Greenwood D |title=Antimicrobial drugs : chronicle of a twentieth century medical triumph|date=2008|publisher=Oxford University Press |location=Oxford |isbn=978-0-19-953484-5 |page=239 |edition=1 |url=https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA239 |url-status=live|archive-url=https://web.archive.org/web/20160305044428/https://books.google.ca/books?id=i4_FZHmzjzwC&pg=PA239|archive-date=5 March 2016}}</ref><ref name="Fischer-2006">{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=498 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA498 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO-2019">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Clarithromycin is available as a generic medication.<ref name=AHFS2015/> It is made from [[erythromycin]] and is chemically known as 6-O-methylerythromycin.<ref name="Kirst-2012">{{cite book| vauthors = Kirst HA |title=Macrolide Antibiotics|date=2012|publisher=Birkhäuser Basel |location=Basel |isbn=978-3-0348-8105-0 |page=53 |edition=2 |url=https://books.google.com/books?id=8Vn2BwAAQBAJ&pg=PA53 |url-status=live |archive-url= https://web.archive.org/web/20160305031148/https://books.google.ca/books?id=8Vn2BwAAQBAJ&pg=PA53 |archive-date=5 March 2016}}</ref>

==Medical uses==

===Antibiotic===

Clarithromycin is primarily used to treat a number of bacterial infections including [[pneumonia]], ''[[Helicobacter pylori]]'', and as an alternative to [[penicillin]] in [[strep throat]].<ref name=AHFS2015/> Other uses include [[cat scratch disease]] and other infections due to [[Bartonella]], [[cryptosporidiosis]], as a second line agent in [[Lyme disease]] and [[toxoplasmosis]].<ref name=AHFS2015/> It may also be used to prevent [[bacterial endocarditis]] in those who cannot take penicillin.<ref name=AHFS2015/> It is effective against upper and lower respiratory tract infections, skin and soft tissue infections and [[helicobacter pylori]] infections associated with duodenal ulcers.{{cn|date=March 2023}}

==== Spectrum of bacterial susceptibility ====

{{More citations needed|section|date=February 2018}}

Aerobic Gram-positive bacteria

* ''[[Staphylococcus aureus]]''

* ''[[Streptococcus pneumoniae]]''

* ''[[Streptococcus pyogenes]]''

Aerobic Gram-negative bacteria

* Haemophilus parainfluenzae&nbsp;

* ''[[Haemophilus influenzae]]''

* ''[[Moraxella catarrhalis]]''

Helicobacter

* [[Helicobacter pylori]]

Mycobacteria

[[Mycobacterium avium complex]] consisting of:

* [[Mycobacterium avium avium]]

* [[Mycobacterium intracellulare]]

Other bacteria

* ''[[Chlamydia pneumoniae]]''

* ''[[Mycoplasma pneumoniae]]''

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:<ref name="biaxin-filmtab" />

Aerobic Gram-positive bacteria

* [[Streptococcus agalactiae]]

* [[Streptococcus|Streptococcus (Groups C, F, G)]]

* Viridans group streptococci

Aerobic Gram-negative bacteria

* [[Bordetella pertussis]]

* [[Legionella pneumophila]]

* [[Pasteurella multocida]]

Anaerobic Gram-positive bacteria

* [[Clostridium perfringens]]

* Peptococcus Niger

* [[Cutibacterium acnes]]

Anaerobic Gram-negative bacteria

* Prevotella melaninogenica (formerly [[Bacteroides melaninogenicus]])

=== Idopathic hypersomnia ===

Clarithromycin has been researched as a potential treatment for [[idiopathic hypersomnia]] (IH) in adults, but the evidence is limited. A 2021 [[Cochrane (organisation)|Cochrane]] study determined that the evidence is inadequate to definitively determine the efficacy of clarithromycin in the management of idiopathic hypersomnia.<ref name="pmid34031871">{{cite journal |vauthors=Trotti LM, Becker LA, Friederich Murray C, Hoque R |title=Medications for daytime sleepiness in individuals with idiopathic hypersomnia |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=5 |pages=CD012714 |date=May 2021 |pmid=34031871 |pmc=8144933 |doi=10.1002/14651858.CD012714.pub2 |quote=There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia.}}</ref> The [[American Academy of Sleep Medicine|American Academy of Sleep Medicine's]] 2021 clinical practice guidelines conditionally suggested its use, especially for those who don't respond to other therapies.<ref name="pmid34743789">{{cite journal |vauthors=Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF |title=Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline |journal=Journal of Clinical Sleep Medicine |volume=17 |issue=9 |pages=1881–1893 |date=September 2021 |pmid=34743789 |pmc=8636351 |doi=10.5664/jcsm.9328 |quote=Recommendation 9: We suggest that clinicians use clarithromycin (vs no treatment) for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL)}}</ref><ref name="AASM GAG">{{cite web |title=Treatment of Central Disorders of Hypersomnolence: An American Academy of Sleep Medicine Clinical Practice Guideline - Guidelines at a Glance |url=https://aasm.org/wp-content/uploads/2022/03/Treatment_Central_Disorders_Hypersomnolence_Guideline_at_a_Glance.pdf |publisher=American Academy of Sleep Medicine |access-date=25 February 2024 |archive-url=https://web.archive.org/web/20240225104203/https://aasm.org/wp-content/uploads/2022/03/Treatment_Central_Disorders_Hypersomnolence_Guideline_at_a_Glance.pdf |archive-date=25 February 2024 |date=2021 |url-status=live}}</ref>

== 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|date=February 2018}}

* Clarithromycin should not be used by people with a history of [[cholestatic jaundice]] and/or liver dysfunction associated with prior clarithromycin use.<ref name="biaxin-filmtab" />

* Clarithromycin should not be used in the setting of [[hypokalaemia]] (low blood potassium){{Citation needed|date=February 2018}}

* Use of clarithromycin with the following medications: [[cisapride]], [[pimozide]], [[astemizole]], [[terfenadine]], [[ergotamine]], [[ticagrelor]], [[ranolazine]] or [[dihydroergotamine]] is not recommended.<ref name="biaxin-filmtab" />

* It should not be used with [[colchicine]] in people with kidney or liver impairment.<ref name="biaxin-filmtab" />

* Concomitant use with cholesterol medications such as [[lovastatin]] or [[simvastatin]].<ref name="biaxin-filmtab" />

* [[Hypersensitivity]] to clarithromycin or any component of the product, erythromycin, or any [[macrolide]] antibiotics.<ref name="biaxin-filmtab" />

* [[QT prolongation]] or ventricular cardiac arrhythmias, including [[Torsades de pointes|torsade de pointes]].<ref name="biaxin-filmtab" />

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.<ref name="Drugs.com">{{cite web|url=https://www.drugs.com/sfx/clarithromycin-side-effects.html|title=Clarithromycin Side Effects in Detail |work=Drugs.com|access-date=18 August 2017|url-status=live|archive-url=https://web.archive.org/web/20170819021124/https://www.drugs.com/sfx/clarithromycin-side-effects.html|archive-date=19 August 2017}}</ref>

<!-- Clarithromycin may cause positive results on urine drug screens for cocaine.{{Citation needed|date=October 2013}} -->

===Cardiac===

In February 2018, the US [[Food and Drug Administration]] (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.<ref name="FDA">{{cite web|title=Safety Alerts for Human Medical Products - Clarithromycin (Biaxin): Drug Safety Communication - Potential Increased Risk of Heart Problems or Death in Patients With Heart Disease|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm597862.htm|website=U.S. [[Food and Drug Administration]] (FDA)|access-date=24 February 2018|archive-date=24 April 2018|archive-url=https://web.archive.org/web/20180424093508/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm597862.htm|url-status=dead}}</ref>

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 [[Heart arrhythmia|arrhythmia]]s.<ref name="Yamaguchi-2003">Yamaguchi S, Kaneko Y, Yamagishi T, et al. [Clarithromycin-induced torsades de pointes]. Nippon Naika Gakkai Zasshi. 2003;92(1):143–5.</ref>

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.<ref name="pmid21447948">{{cite journal | vauthors = Winkel P, Hilden J, Fischer Hansen J, Hildebrandt P, Kastrup J, Kolmos HJ, Kjøller E, Jespersen CM, Gluud C, Jensen GB | title = Excess sudden cardiac deaths after short-term clarithromycin administration in the CLARICOR trial: why is this so, and why are statins protective? | journal = Cardiology | volume = 118 | issue = 1 | pages = 63–7 | year = 2011 | pmid = 21447948 | doi = 10.1159/000324533 | s2cid = 11873791 }}</ref>

===Liver and kidney===

Clarithromycin has been known to cause [[jaundice]], [[cirrhosis]], and kidney problems, including [[kidney failure]].{{Citation needed|date=February 2018}} Some case reports suspect it of causing liver disease.<ref name="pmid12503933">{{cite journal | vauthors = Tietz A, Heim MH, Eriksson U, Marsch S, Terracciano L, Krähenbühl S | title = Fulminant liver failure associated with clarithromycin | journal = The Annals of Pharmacotherapy | volume = 37 | issue = 1 | pages = 57–60 | date = January 2003 | pmid = 12503933 | doi = 10.1345/1542-6270(2003)037<0057:flfawc>2.0.co;2 }}</ref>

===Central nervous system===

Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can cause [[ototoxicity]], delirium and mania.{{Citation needed|date=February 2018}}

===Infection===

A risk of [[oral candidiasis]] and [[vaginal candidiasis]], due to the elimination of the [[yeast|yeast's]] natural bacterial competitors by the antibiotic, has also been noted.{{Citation needed|date=February 2018}}

===Pregnancy and breastfeeding===

Clarithromycin should not be used in pregnant women except in situations where no alternative therapy is appropriate.<ref name="biaxin-filmtab" /> 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.<ref name="biaxin-filmtab" /> For lactating mothers it is not known whether clarithromycin is excreted in human milk.<ref name="biaxin-filmtab">{{cite web|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050662s044s050,50698s026s030,050775s015s019lbl.pdf|title = Biaxin Filmtab (clarithromycin tablets, USP) Biaxin XL Filmtab (clarithromycin extended-release tablets) Biaxin Granules (clarithromycin for oral suspension, USP)|date = 2 November 2015|access-date = 2 November 2015|url-status = live|archive-url = https://web.archive.org/web/20150824122417/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050662s044s050,50698s026s030,050775s015s019lbl.pdf|archive-date = 24 August 2015}}</ref>

== 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 [[CYP3A4#Ligands|drug]] levels.<ref name="pmid31628882">{{cite journal |vauthors=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 |title=Interaction potential between clarithromycin and individual statins-A systematic review |journal=Basic Clin Pharmacol Toxicol |volume=126 |issue=4 |pages=307–317 |date=April 2020 |pmid=31628882 |doi=10.1111/bcpt.13343 |url=}}</ref><ref name="pmid37874128">{{cite journal |vauthors=Herdegen T, Cascorbi I |title=Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs: Recommendations for Clinical Practice |journal=Dtsch Arztebl Int |volume= 120|issue=49 |pages= 833–840|date=December 2023 |pmid=37874128 |doi=10.3238/arztebl.m2023.0223 |pmc=10824494 |pmc-embargo-date=1 December 2024 |s2cid=264438050 |url=}}</ref>

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]].<ref name="biaxin-filmtab" />

===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]]).<ref name="pmid23778904">{{cite journal | vauthors = Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, Gomes T, Fleet J, Hwang YJ, Garg AX | title = Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study | journal = Annals of Internal Medicine | volume = 158 | issue = 12 | pages = 869–76 | date = June 2013 | pmid = 23778904 | doi = 10.7326/0003-4819-158-12-201306180-00004 | s2cid = 21222679 }}</ref>

===Calcium channel blockers===

Concurrent therapy with [[calcium channel blocker]] may increase risk of [[Hypotension|low blood pressure]], [[kidney failure]], and death, compared to pairing calcium channel blockers with [[azithromycin]], a drug similar to clarithromycin but without CYP3A4 inhibition.<ref name="pmid24346990">{{cite journal | vauthors = Gandhi S, Fleet JL, Bailey DG, McArthur E, Wald R, Rehman F, Garg AX | title = Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury | journal = JAMA | volume = 310 | issue = 23 | pages = 2544–53 | date = December 2013 | pmid = 24346990 | doi = 10.1001/jama.2013.282426 | doi-access = }}</ref> Administration of clarithromycin in combination with verapamil have been observed to cause [[Hypotension|low blood pressure]], [[Bradycardia|low heart rate]], and [[lactic acidosis]].<ref name="biaxin-filmtab" />

===Carbamazepine===

Clarithromycin may double the level of [[carbamazepine]] in the body by reducing its clearance, which may lead to toxic symptoms of carbamazepine, such as [[Diplopia|double vision]], [[Ataxia|loss of voluntary body movement]], and nausea, as well as [[hyponatremia]].<ref name="pmid18033049">{{cite journal | vauthors = Gélisse P, Hillaire-Buys D, Halaili E, Jean-Pastor MJ, Vespignan H, Coubes P, Crespel A | title = [Carbamazepine and clarithromycin: a clinically relevant drug interaction] | journal = Revue Neurologique | volume = 163 | issue = 11 | pages = 1096–9 | date = November 2007 | pmid = 18033049 | doi = 10.1016/s0035-3787(07)74183-8 }}</ref>

===HIV medications===

Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments.<ref name="pmid18094220">{{cite journal | vauthors = Sekar VJ, Spinosa-Guzman S, De Paepe E, De Pauw M, Vangeneugden T, Lefebvre E, Hoetelmans RM | title = Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers | journal = Journal of Clinical Pharmacology | volume = 48 | issue = 1 | pages = 60–5 | date = January 2008 | pmid = 18094220 | doi = 10.1177/0091270007309706 | s2cid = 38368595 }}</ref> For example, clarithromycin may lead to decreased [[zidovudine]] concentrations.<ref name="pmid9257746">{{cite journal | vauthors = Polis MA, Piscitelli SC, Vogel S, Witebsky FG, Conville PS, Petty B, Kovacs JA, Davey RT, Walker RE, Falloon J, Metcalf JA, Craft C, Lane HC, Masur H | title = Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection | journal = Antimicrobial Agents and Chemotherapy | volume = 41 | issue = 8 | pages = 1709–14 | date = August 1997 | pmid = 9257746 | pmc = 163990 | doi = 10.1128/AAC.41.8.1709 }}</ref>

== Mechanism of action ==

Clarithromycin prevents [[bacteria]] from multiplying by acting as a [[protein synthesis inhibitor]]. It binds to 23S rRNA, a component of the 50S subunit of the bacterial [[ribosome]], thus inhibiting the [[Translation (biology)|translation]] of [[peptide]]s.{{Citation needed|date=February 2018}}

== Pharmacokinetics ==

{{More citations needed|section|date=February 2018}}

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 [[phagocyte]]s. 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, {{chem name|14-(''R'')-hydroxyclarithromycin}}. Compared to clarithromycin, {{chem name|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&nbsp;mg administered every 12 h, but increased to 5 to 7 h with 500&nbsp;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.<ref name="pmid1976065">{{cite journal | vauthors = Ferrero JL, Bopp BA, Marsh KC, Quigley SC, Johnson MJ, Anderson DJ, Lamm JE, Tolman KG, Sanders SW, Cavanaugh JH | title = Metabolism and disposition of clarithromycin in man | journal = Drug Metabolism and Disposition | volume = 18 | issue = 4 | pages = 441–6 | year = 1990 | pmid = 1976065 }}</ref>

== History ==

Clarithromycin was invented by researchers at the Japanese drug company [[Taisho Pharmaceutical]] in 1980.<ref name="Greenwood-2008"/> 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 drug|generic]] in Europe in 2004 and in the US in mid-2005.<ref name="pmid25165548">{{cite journal | vauthors = Vieweg WV, Hancox JC, Hasnain M, Koneru JN, Gysel M, Baranchuk A | title = Clarithromycin, QTc interval prolongation and torsades de pointes: the need to study case reports | journal = Therapeutic Advances in Infectious Disease | volume = 1 | issue = 4 | pages = 121–138 | date = August 2013 | pmid = 25165548 | pmc = 4040724 | doi = 10.1177/2049936113497203 }}</ref>

==Society and culture==

[[image:Clarith-200.jpg|thumb|150px|A pack of clarithromycin tablets manufactured by [[Taisho Pharmaceutical]]]]

=== Available forms ===

Clarithromycin is available as a generic medication.<ref name=AHFS2015/> In the United States, clarithromycin is available as immediate-release tablets, extended-release tablets, and granules for oral suspension.<ref name="AHFS2015" />

=== 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.{{cn|date=March 2023}}

=== Manufacturers ===

In the UK the drug product is manufactured in generic form by a number of manufacturers including Somex Pharma, Ranbaxy, Aptil and Sandoz.

{{clear}}

== References ==

{{Reflist}}

== External links ==

* {{ cite patent | country = US | title = Novel erythromycin compounds | number = 4331803 | status = patent | inventor = Watanabe Y, Morimoto S, Omura S | assign1 = Taisho Pharmaceutical | gdate = 1981-05-19 }}

{{Portal bar|Medicine}}

{{Authority control}}

[[Category:CYP3A4 inhibitors]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Drugs developed by AbbVie]]

[[Category:World Health Organization essential medicines]]

[[Category:Dimethylamino compounds]]