Clarithromycin absorption

Amsden GW, Cheng KL, Peloquin CA, Nafziger AN, Oral cimetidine prolongs clarithromycin absorption, Antimicrob Agents Chemother ( 99S) 42,1578-80,... 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

Clarithromycin is derived from erythromycin by addition of a methyl group and has improved acid stability and oral absorption compared with erythromycin. Its mechanism of action is the same as that of erythromycin. Clarithromycin and erythromycin are virtually identical with respect to antibacterial activity except that clarithromycin is more active against Mycobacterium avium complex (see Chapter 47). Clarithromycin also has activity against M leprae and Toxoplasma gondii. Erythromycin-resistant streptococci and staphylococci are also resistant to clarithromycin. 

Azithromycin is rapidly absorbed and well tolerated orally. It should be administered 1 hour before or 2 hours after meals. Aluminum and magnesium antacids do not alter bioavailability but delay absorption and reduce peak serum concentrations. Because it has a 15-member (not 14-member) lactone ring, azithromycin does not inactivate cytochrome P450 enzymes and therefore is free of the drug interactions that occur with erythromycin and clarithromycin. 

Fluconazole, probenecid and atovaquone increase the risk of myelotoxicity by zidovudine. This may be attributed to an increased plasma concentration of zidovudine in the presence of these drugs, perhaps through their inhibitory effects on glucuronose transferase. Rifabutin and rifampin decrease plasma concentrations, and clarithromycin decreases the absorption of zidovudine. Zidovudine and stavu-dine should not be used in combination because they compete for intracellular phosphorylation. 

Administration The erythromycin base is destroyed by gastric acid thus either enteric coated tablets or esterified forms are administered. All are adequately absorbed on oral administration. Clarithromycin and azithromycin are stable to stomach acid and are readily absorbed. Food interferes with the absorption of erythromycin and azithromycin but can increase that of clarithromycin. Intravenous administration of erythromycin is associated with a high incidence of thrombophlebitis. 

GRAPEFRUIT JUICE ANTIBIOTICS - CLARITHROMYCIN, ERYTHROMYCIN Significant delay in onset of action of clarithromycin (t from 82 to 148 minutes), t plasma concentrations of erythromycin (maximum concentration t, AUC 11,5-fbld) Due to inhibition of absorption attributed to effect on P-gp The interaction is unlikely to cause clinically relevant 1 antimicrobial activity of clarithromycin Telithromycin is unlikely to be affected by grapefruit juice. Be aware... 

Clarithromycin reduced the peak concentration and AUC of zidovudine at steady state by about 12% (32), possibly as a result of reduced zidovudine absorption (62). However, if the two drugs were taken at least 2 hours apart, the pharmacokinetics of zidovudine were unaffected. 

Clarithromycin has an unpredictable effect on the absorption of zidovudine blood concentrations may rise or fall (40,41). 

Aluminium/magnesium hydroxide antacids may reduce the peak levels of azithromycin. Mylanta can prolong the absorption of erythromycin, but this is unlikely to be clinically important Aluminium/magnesium hydroxide antacids do not appear to significantly alter the pharmacokinetics of clarithromycin, roxithromycin or telithromycin. 

The pharmacokinetics of azithromycin were not affected by a single 800-mg dose of cimetidine in one study, and although cimetidine prolongs the absorption of clarithromycin, this is unlikely to be of clinical significance. ... 

A single-dose study in 9 healthy subjects found that clarithromycin 250 mg increased the rate of absorption of tolbutamide 500 mg by about 20% and increased its bioavailability by 26%. Hypoglycaemia, reported as... 

Caleium-ehaimel bloekers are metabolised in the gut wall and liver by the eytoehrome P450 CYP3A subfamily of isoenzymes, which are inhibited by erythromycin, clarithromycin, and telithromycin, so that in their presence a normal oral dose becomes in effect an overdose with its attendant adverse effects. Verapamil, erythromycin and possibly clarithromycin are also P-glycoprotein inhibitors, which may contribute to the pharmacokinetic interaction by reducing the elimination of the calcium-channel blocker, or by increasing macrolide absorption. ... 

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