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药品详细

Clarithromycin(克拉霉素)

化学结构式图
中文名
克拉霉素
英文名
Clarithromycin
分子式
C38H69NO13
化学名
(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-12,13-dihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
分子量
Average: 747.9534
Monoisotopic: 747.476891299
CAS号
81103-11-9
ATC分类
J01F 未知
药物类型
small molecule
阶段
approved
商品名
Biaxin;Biaxin XL;Klacid;Klaricid;Macladin;Naxy;Veclam;Zeclar;
同义名
CLA;Clarithromycine;Clathromycin;
基本介绍

Clarithromycin, a semisynthetic macrolide antibiotic derived from erythromycin, inhibits bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit. Binding inhibits peptidyl transferase activity and interferes with amino acid translocation during the translation and protein assembly process. Clarithromycin may be bacteriostatic or bactericidal depending on the organism and drug concentration.

生产厂家
  • Abbott laboratories
  • Abbott laboratories pharmaceutical products div
  • Apotex corp
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc florida
  • Wockhardt ltd
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H: Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 2007 Feb 10;369(9560):482-90. Pubmed
  2. Zuckerman JM, Qamar F, Bono BR: Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline. Infect Dis Clin North Am. 2009 Dec;23(4):997-1026, ix-x. Pubmed
  3. Piscitelli SC, Danziger LH, Rodvold KA: Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm. 1992 Feb;11(2):137-52. Pubmed
  4. Peters DH, Clissold SP: Clarithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic potential. Drugs. 1992 Jul;44(1):117-64. Pubmed
  5. Clarithromycin. Tuberculosis (Edinb). 2008 Mar;88(2):92-5. Pubmed
  6. Stephenson GA, Stowell JG, Toma PH, Pfeiffer RR, Byrn SR: Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity. J Pharm Sci. 1997 Nov;86(11):1239-44. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
antibacterials 抗细菌;
药理
Indication An alternative medication for the treatment of acute otitis media caused by H. influenzae, M. catarrhalis, or S. pneumoniae in patients with a history of type I penicillin hypersensitivity. Also for the treatment of pharyngitis and tonsillitis caused by susceptible Streptococcus pyogenes, as well as respiratory tract infections including acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, mild to moderate community-acquired pneuomia, Legionnaires' disease, and pertussis. Other indications include treatment of uncomplicated skin or skin structure infections, helicobacter pylori infection, duodenal ulcer disease, bartonella infections, early Lyme disease, and encephalitis caused by Toxoplasma gondii (in HIV infected patients in conjunction with pyrimethamine). Clarithromycin may also decrease the incidence of cryptosporidiosis, prevent the occurence of α-hemolytic (viridans group) streptococcal endocarditis, as well as serve as a primary prevention for Mycobacterium avium complex (MAC) bacteremia or disseminated infections (in adults, adolescents, and children with advanced HIV infection).
Pharmacodynamics Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, some mycobacteria, and some other organisms including Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. Other aerobic bacteria that clarithromycin has activity against include C. pneumoniae and M. pneumoniae. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.
Mechanism of action Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.
Absorption Clarithromycin is well-absorbed, acid stable and may be taken with food.
Volume of distribution Not Available
Protein binding ~ 70% protein bound
Metabolism
Hepatic - predominantly metabolized by CYP3A4 resulting in numerous drug interactions.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Clarithromycin
14-hydroxyclarithromycin Details
Clarithromycin
N-desmethylclarithromycin Details
Route of elimination After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is somewhat greater, approximately 30%.
Half life 3-4 hours
Clearance Not Available
Toxicity Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort. Transient hearing loss with high doses has been observed. Pseudomembraneous colitis has been reported with clarithromycin use. Allergic reactions ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis and Stevens-Johnson syndrome have also occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually reversible, but fatalities have been reported. Clarithromycin may also cause tooth decolouration which may be removed by dental cleaning. Fetal abnormalities, such as cardiovascular defects, cleft palate and fetal growth retardation, have been observed in animals. Clarithromycin may cause QT prolongation.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00248 Clarithromycin Pathway SMP00248
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 220 dec °C PhysProp
water solubility 0.33 mg/L Not Available
logP 3.16 MCFARLAND,JW ET AL. (1997)
pKa 8.99 (at 25 °C) MCFARLAND,JW ET AL. (1997)
Predicted Properties
Property Value Source
water solubility 2.17e-01 g/l ALOGPS
logP 3.18 ALOGPS
logP 3.24 ChemAxon
logS -3.5 ALOGPS
pKa (strongest acidic) 12.46 ChemAxon
pKa (strongest basic) 8.38 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 13 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 182.91 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 190.79 ChemAxon
polarizability 82.03 ChemAxon
药物相互作用
Drug Interaction
Abiraterone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
Acenocoumarol The macrolide, clarithromycin, may increase the anticoagulant effect of acenocoumarol.
Alprazolam The macrolide, clarithromycin, may increase the effect of the benzodiazepine, alprazolam.
Alvimopan Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Aminophylline Clarithromycin may increase the effect amd toxicity of aminophylline.
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Anisindione The macrolide, clarithromycin, may increase the anticoagulant effect of anisindione.
Aprepitant The CYP3A4 inhibitor, clarithromycin, may increase the effect and toxicity of aprepitant.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Atazanavir may increase serum level of clarithromycin.
Atorvastatin The macrolide, clarithromycin, may increase the toxicity of the statin, atorvastatin.
Bretylium Increased risk of cardiotoxicity and arrhythmias
Bromazepam Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if clarithromycin is initiated, discontinued or dose changed. Dosage adjustments may be required.
Buspirone Clarithromycin may increase the effect and toxicity of buspirone.
Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
Carbamazepine Clarithromycin may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic or adverse effects of carbamazepine if clarithromycin is initiated, discontinued or dose changed.
Cerivastatin The macrolide, clarithromycin, may increase the toxicity of the statin, cerivastatin.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Citalopram Possible serotoninergic syndrome with this combination
Colchicine Severe colchicine toxicity can occur
Cyclosporine The macrolide, clarithromycin, may increase the effect of cyclosporine.
Dabrafenib Strong CYP3A4 inhibitors may increase levels of dabrafenib. Consider alternate therapy.
Dantrolene Clarithromycin may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if clarithromycin is initiated, discontinued or dose changed.
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Darunavir Increased levels of clarithromycin
Diazepam The macrolide, clarithromycin, may increase the effect of the benzodiazepine, diazepam.
Dicumarol The macrolide, clarithromycin, may increase the anticoagulant effect of dicumarol.
Digoxin The macrolide, clarithromycin, may increase the effect of digoxin in 10% of patients.
Dihydroergotamine Risk of ergotism and severe ischemia with this association
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Dronedarone Clarithromycin is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
Dyphylline Increases the effect and toxicity of theophylline
Efavirenz Efavirenz decreases levels of clarithromycin
Eletriptan The macrolide, clarithromycin, may increase the effect and toxicity of eletriptan.
Eplerenone The macrolide, clarithromycin, may increase the effect and toxicity of eplerenone.
Ergotamine Risk of ergotism and severe ischemia with this association
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Etravirine Clarithromycin (and other macrolide antibiotics), when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to use alternative antibiotic agents if available. If concurrent therapy cannot be avoided, monitor for reduced effectiveness of clarithromycin.
Everolimus The macrolide, clarithromycin, may increase the serum concentration and toxicity of everolimus.
Fluoxetine Possible serotoninergic syndrome with this combination
Fosphenytoin Clarithromycin may increase the therapeutic and adverse effects of fosphenytoin.
Gefitinib This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Iloperidone Clarithromycin is a strong CYP3A4 inhibitor that increases serum concentration of iloperidone. Reduce dose of iloperidone by 50%
Imatinib The macrolide, clarithromycin, may increase the serum concentration of imatinib.
Indinavir Indinavir may decrease the effectiveness of clarithromycin by decreasing the formatin of the active metabolite, 14-hydroxy-clarithromycin. Clarithromycin may increase the serum concentration of indinavir. Indinavir may increase the serum concentration of clarithromycin. Consider alternate therapy or monitor the efficacy and adverse effects of both agents more closely during concomitant therapy.
Itraconazole The macrolide, clarithromycin, may increase the effect and toxicity of itraconazole.
Ivacaftor Strong CYP3A4 inhibitors may increase levels of ivacaftor. Monitor concomitant therapy closely.
Lovastatin The macrolide, clarithromycin, may increase the toxicity of the statin, lovastatin.
Lurasidone Concomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
Methylprednisolone The macrolide, clarithromycin, may increase the effect of corticosteroid, methylprednisolone.
Methysergide Risk of ergotism and severe ischemia with this association
Midazolam The macrolide, clarithromycin, may increase the effect of the benzodiazepine, midazolam.
Oxtriphylline Clarithromycin may increase the effect and toxicity of oxtriphylline.
Pazopanib Clarithromycin is a strong inhibitor of CYP3A4 thus increasing exposure of pazopanib.
Phenytoin Clarithromycin may increase the therapeutic and adverse effects of phenytoin.
Pimozide Increased risk of cardiotoxicity and arrhythmias
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Quetiapine The macrolide, clarithromycin, may increase the effect and toxicity of quetiapine.
Quinidine Increased risk of cardiotoxicity and arrhythmias
Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
Regorafenib Strong CYP3A4 inhibitors may increase levels of regorafenib.
Repaglinide Clarithromycin may increase the effect of repaglinide.
Rifabutin The rifamycin, rifabutin, may decrease the effect of the macrolide, clarithromycin.
Rifampin The rifamycin, rifampin, may decrease the effect of the macrolide, clarithromycin.
Saxagliptin Clarithromycin is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
Sertraline Possible serotoninergic syndrome with this combination
Sildenafil Increases the effect and toxicity of sildenafil
Simvastatin The macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin.
Sirolimus The macrolide, clarithromycin, may increase the serum concentration of sirolimus.
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Sotalol Increased risk of cardiotoxicity and arrhythmias
Sunitinib Possible increase in sunitinib levels
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, Clarithromycin, may also increase the blood concentration of Tacrolimus.
Tadalafil Clarithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Clarithromycin may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Tamsulosin Clarithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clarithromycin is initiated, discontinued, or dose changed.
Telithromycin Co-administration may result in altered plasma concentrations of Clarithromycin and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
Temsirolimus Clarithromycin may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Clarithromycin, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Clarithromycin is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Clarithromycin may increase the therapeutic and adverse effects of theophylline.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tiagabine The strong CYP3A4 inhibitor, Clarithromycin, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Clarithromycin is initiated, discontinued or dose changed.
Tipranavir The concentrations of Tipranavir and Clarithromycin increase during concomitant therapy. Dose adjustments are required for patients with renal impairment.
Tolterodine Clarithromycin may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Clarithromycin is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
Topotecan The p-glycoprotein inhibitor, Clarithromycin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol Clarithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Clarithromycin, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Clarithromycin is initiated, discontinued or dose changed.
Triazolam The macrolide, clarithromycin, may increase the effect of the benzodiazepine, triazolam.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Clarithromycin, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Concomitant therapy should be used with caution.
Valproic Acid The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Clarithromycin is initiated, discontinued or dose changed.
Vardenafil Clarithromycin, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Vemurafenib Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
Venlafaxine Clarithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Clarithromycin is initiated, discontinued, or dose changed.
Verapamil Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Clarithromycin is initiated, discontinued or dose changed.
Vilazodone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.
Vinblastine Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Clarithromycin is initiated, discontinued or dose changed.
Vincristine Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Clarithromycin is initiated, discontinued or dose changed.
Vinorelbine Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Clarithromycin is initiated, discontinued or dose changed.
Vismodegib P-glycoprotein inhibitors may increase the chance of adverse drug reactions.
Voriconazole Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of clarithromycin by decreasing its metabolism. Clarithromycin may increase the serum concentration of voriconazole by decreasing its metabolism. Consider alternate therapy or monitor for QTc prolongation and changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Warfarin The macrolide, clarithromycin, may increase the anticoagulant effect of warfarin.
Zidovudine Clarithromycin may decrease the serum concentration of zidovudine. Increased myelosuppression in mice has been observed. Consider staggering doses during concomitant therapy and closely monitor response to zidovudine therapy.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zolpidem Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if clarithromycin is initiated, discontinued or dose changed.
Zonisamide Clarithromcyin, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if clarithromycin is initiated, discontinued or dose changed.
Zopiclone Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if clarithromycin is initiated, discontinued or dose changed.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
食物相互作用
  • Biaxin - take without regard to meals (however absorption appears to be improved when drug is taken with food).
  • Biaxin XL - take with a meal, taking it on an empty stomach is associated with total product exposure 30% inferior to that observed when administered with food.

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