Klaricid
Klaricid - General Information
A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [PubChem]
Pharmacology of Klaricid
Klaricid, a macrolide antibiotic similar to erythromycin and azithromycin, is effective against Mycobacterium avium complex (MAC) and is used for the treatment of Helicobacter pylori-associated peptic ulcer disease, community-acquired pneumonia, sinusitis, and chronic bronchitis. Klaricid is also used to treat respiratory tract, sexually transmitted, otitis media, and AIDS-related infections.
Klaricid for patients
Clarithromycin is an antibiotic used to treat infections such as sinus infections, throat infections, tonsil infections and other lung related infections. It can be used by some patients to prevent infections. It is important that you take this medication for the full period of time your doctor has prescribed it, even if you feel better after a day or two. This medication should not be taken by those with an allergy to erythromycin. There are several significant drug interactions with clarithromycin. Make sure to have your doctor or pharmacist fully evaluate all medications you might be taking and ask them about drug interactions. The most common side effects reported include taste disturbances, diarrhea and nausea, occurring in approximately 3% of patients. Clarithromycin can be taken with or without food. Unlike other suspensions (liquid forms), this suspension should not be refrigerated.
Klaricid Interactions
Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range. In two studies in which theophylline was administered with clarithromycin (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg q12h clarithromycin), the steady-state levels of Cmax, Cmin, and the area under the serum concentration time curve (AUC) of theophylline increased about 20%.
Concomitant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered.
When clarithromycin and terfenadine were coadministered, plasma concentrations of the active acid metabolite of terfenadine were threefold higher, on average, than the values observed when terfenadine was administered alone. The pharmacokinetics of clarithromycin and the 14-hydroxy-clarithromycin were not significantly affected by coadministration of terfenadine once clarithromycin reached steady-state conditions. Concomitant administration of clarithromycin with terfenadine is contraindicated.
Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24, and T½ increases of 30%, 89%, and 34%, respectively), by the concomitant administration of clarithromycin. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when co-administered with clarithromycin.
Co-administration of clarithromycin with ranitidine bismuth citrate resulted in increased plasma ranitidine concentrations (57%), increased plasma bismuth trough concentrations (48%), and increased 14-hydroxy-clarithromycin plasma concentrations (31%). These effects are clinically insignificant.
Simultaneous oral administration of clarithromycin and zidovudine to HIV-infected adult patients resulted in decreased steady-state zidovudine concentrations. When 500 mg of clarithromycin were administered twice daily, steady-state zidovudine AUC was reduced by a mean of 12% (n=4). Individual values ranged from a decrease of 34% to an increase of 14%. Based on limited data in 24 patients, when clarithromycin was administered two to four hours prior to oral zidovudine, the steady-state zidovudine Cmax was increased by approximately 2-fold, whereas the AUC was unaffected.
Simultaneous administration of clarithromycin and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics.
Concomitant administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers led to increases in the mean steady-state clarithromycin Cmin and AUC of 33% and 18%, respectively. Steady-state concentrations of 14-OH clarithromycin were not significantly affected by concomitant administration of fluconazole.
Concomitant administration of clarithromycin and ritonavir (n=22) resulted in a 77% increase in clarithromycin AUC and a 100% decrease in the AUC of 14-OH clarithromycin. Clarithromycin may be administered without dosage adjustment to patients with normal renal function taking ritonavir. However, for patients with renal impairment, the following dosage adjustments should be considered. For patients with CLCR 30 to 60 mg/min, the dose of clarithromycin should be reduced by 50%. For patients with CLCR < 30 ml/min, the dose of clarithromycin should be decreased by 75%.
Spontaneous reports in the post-marketing period suggest that concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously.
Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have also been reported in post-marketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin levels should be carefully monitored while patients are receiving digoxin and clarithromycin simultaneously.
The following drug interactions, other than increased serum concentrations of carbamazepine and active acid metabolite of terfenadine, have not been reported in clinical trials with clarithromycin; however, they have been observed with erythromycin products and/or with clarithromycin in post-marketing experience.
Concurrent use of erythromycin or clarithromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
Erythromycin has been reported to decrease the clearance of triazolam and, thus, may increase the pharmacologic effect of triazolam. There have been post-marketing reports of drug interactions and CNS effects (e.g., somnolence and confusion) with the concomitant use of clarithromycin and triazolam.
There have been reports of an interaction between erythromycin and astemizole resulting in QT prolongation and torsades de pointes. Concomitant administration of erythromycin and astemizole is contraindicated. Because clarithromycin is also metabolized by cytochrome P450, concomitant administration of clarithromycin with astemizole is not recommended.
As with other macrolides, clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin), through inhibition of cytochrome P450 metabolism of these drugs. Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly.
The use of erythromycin and clarithromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin and/or clarithromycin with carbamazepine, cyclosporine, tacrolimus, hexobarbital, phenytoin, alfentanil, disopyramide, lovastatin, bromocriptine, valproate, terfenadine, cisapride, pimozide, rifabutin, and astemizole. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving these drugs.
Klaricid Contraindications
Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibiotics.
Concomitant administration of clarithromycin with cisapride, pimozide, or terfenadine is contraindicated. There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with cisapride, pimozide, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of hepatic metabolism of these drugs by erythromycin and clarithromycin. Fatalities have been reported.
For information about contraindications of other drugs indicated in combination with clarithromycin, refer to the
Additional information about Klaricid
Klaricid Indication: For the treatment of bacterial infection of (pharyngitis/tonsillitis, sinusitis, bronchitis, pneumonia, uncomplicated skin and skin structure infections) caused by H. influenzae, M. catarrhalis, M. pneumoniae, S. pneumoniae, C. pneumoniae (TWAR), S. aureus, S. pyogenes, Mycobacterium avium and Mycobacterium intracellulare
Mechanism Of Action: Klaricid is first metabolized to 14-OH clarithromycin. Like other macrolides, it then binds to the 50 S subunit of the 70 S ribosome of the bacteria, blocking RNA-mediated bacterial protein synthesis. Klaricid also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.
Drug Interactions: Alprazolam The macrolide increases the effect of the benzodiazepine
Aminophylline Increases the effect and toxicity of theophylline
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Anisindione The macrolide increases the anticoagulant effect
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Atazanavir increases levels of clarithromycin
Atorvastatin The macrolide possibly increases the statin toxicity
Bretylium Increased risk of cardiotoxicity and arrhythmias
Buspirone Increases the effect and toxicity of buspirone
Carbamazepine The macrolide increases the effect of carbamazepine
Cerivastatin The macrolide possibly increases the statin toxicity
Cisapride Increased risk of cardiotoxicity and arrhythmias
Citalopram Possible serotoninergic syndrome with this combination
Colchicine Severe colchicine toxicity can occur
Cyclosporine The macrolide increases the effect of cyclosporine
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Darunavir Increased levels of clarithromycin
Diazepam The macrolide increases the effect of the benzodiazepine
Dicumarol The macrolide increases anticoagulant effect
Digoxin The macrolide increases the effect of digoxin in 10% of patients
Dihydroergotamine Risk of ergotism and severe ischemia with this association
Dyphylline Increases the effect and toxicity of theophylline
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Dyphylline Increases the effect and toxicity of theophylline
Efavirenz Efavirenz decreases levels of clarithromycin
Eletriptan This macrolide increases the effect and toxicity of eletriptan
Eplerenone This macrolide increases 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
Fluoxetine Possible serotoninergic syndrome with this combination
Fosphenytoin Increases the effect and toxicity of phenytoin
Gefitinib This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Imatinib The macrolide increases levels of imatinib
Indinavir Increases the effect and toxicity of indinavir
Itraconazole The macrolide increases the effect and toxicity of itraconazole
Lovastatin The macrolide possibly increases the statin toxicity
Methylprednisolone The macrolide increases the effect of corticosteroid
Methysergide Risk of ergotism and severe ischemia with this association
Midazolam The macrolide increases the effect of the benzodiazepine
Acenocoumarol The macrolide increases anticoagulant effect
Oxtriphylline Increases the effect and toxicity of theophylline
Phenytoin Increases the effect and toxicity of phenytoin
Pimozide Increased risk of cardiotoxicity and arrhythmias
Quetiapine This macrolide increases the effect/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 Increased levels of ranolazine- risk of toxicity
Repaglinide Increases the effect of repaglinide
Rifabutin The rifamycin decreases the effect of the macrolide
Rifampin The rifamycin decreases the effect of the macrolide
Sertraline Possible serotoninergic syndrome with this combination
Sildenafil Increases the effect and toxicity of sildenafil
Simvastatin The macrolide possibly increases the statin toxicity
Sirolimus The macrolide increases sirolimus levels
Sotalol Increased risk of cardiotoxicity and arrhythmias
Sunitinib Possible increase in sunitinib levels
Tacrolimus This antibiotic increases the effect and toxicity of tacrolimus
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Increases the effect and toxicity of theophylline
Triazolam The macrolide increases the effect of the benzodiazepine
Vardenafil Increases the effect and toxicity of vardenafil
Warfarin The macrolide increases anticoagulant effect
Everolimus The macrolide increases everolimus levels/toxicity
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Food Interactions: 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.
Generic Name: Clarithromycin
Synonyms: CLA; Clarithromycine; Clathromycin
Drug Category: Anti-Bacterial Agents; Other Macrolides
Drug Type: Small Molecule; Approved
Other Brand Names containing Clarithromycin: Biaxin; Biaxin XL; Klacid; Klaricid; Macladin; Naxy; Veclam; Zeclar;
Absorption: 50%
Toxicity (Overdose): Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort. 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 occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually reversible, but fatalities have been reported.
Protein Binding: Low protein binding
Biotransformation: Hepatic
Half Life: 3-4 hours
Dosage Forms of Klaricid: Tablet, extended release Oral
Tablet Oral
Chemical IUPAC Name: (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
Chemical Formula: C38H69NO13
Clarithromycin on Wikipedia: https://en.wikipedia.org/wiki/Clarithromycin
Organisms Affected: Enteric bacteria and other eubacteria
