Prednisone Clarithromycin

Clarithromycin inhibits CYP3A4, which is responsible for the metabolic clearance of prednisolone, the biologically active metabolite of prednisone. Clarithromycin (500 mg bd for 2 days) reduced the clearance of methylpredniso-lone by 65% and significantly increased its plasma concentrations clarithromycin did not influence the clearance or plasma concentrations of prednisone (488). Acute mania has been reported to be related to inhibition of the metabolic clearance of prednisone by clarithromycin (SEDA-22, 444 489). 

Finkenbine R, Gill HS. Case of mania due to prednisone-clarithromycin interaction. Can J Psychiatry 1997 42(7) 778. 

Finkenbine RD, Frye MD. Case of psychosis due to prednisone-clarithromycin interaction. Gen Hosp Psychiatry 1998 20(5) 325-6. 

Henoch-Schdnlein purpura developed in an 84-year-old Indian woman 10 days after she started to take clarithromycin (250 mg bd) for pneumonia (52). She was otherwise healthy and taking no regular medications. Histology confirmed a leukocytoclastic vasculitis of superficial vessels, with extravasation of erythrocytes, and direct immunofluorescence showed immunoglobulin A in superficial dermal vessels. Treatment with prednisone (1 mg/kg/day) was required. Most of the symptoms and signs resolved within a few days, but renal function remained impaired. 

In an open study in six adults with mild to moderate asthma, clarithromycin significantly reduced methylprednisolone clearance, thereby increasing the risk of steroid-induced adverse effects (160). In contrast, prednisolone clearance and mean prednisolone plasma concentrations were unaffected. Frank psychosis due to combined therapy with prednisone and clarithromycin has been reported (161). 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Troleandomycin and, to a lesser extent, clarithromycin and erythromycin can reduce the clearance of methylprednisolone, thereby increasing both its therapeutic and adverse effects. A patient receiving long-term clarithromycin developed Cushing s syndrome after starting treatment with inhaled budesonide. There appears to be no pharmacokinetic interaction between erythromycin and inhaled ciclesonide. Similarly, prednisolone appears not to be affected by macrolides, except possibly in those also taking enzyme-inducers such as phenobarbital. Isolated case reports describe the development of acute mania and psychosis in two patients, apparently due to an interaction between prednisone and clarithromycin. 

A study in 6 asthmatic patients found that clarithromycin 500 mg twice daily for 9 days had no significant effect on prednisone pharmacokinetics." ... 

The evidence for the interaction leading to psychosis between prednisone and clarithromycin is limited and its general importance is uncertain, but prescribers should be aware of the reports of psychosis if both drugs are used together. Note that psychosis is a rare adverse effect of high-dose corticosteroids given alone. 

Some macrohdes have been found to have anti-inflammatory properties and are being used in airway diseases such as panbronchioUtis, cystic fibrosis, bronchiectasis, and asthma. The treatment of OP with erythromycin or clarithromycin has been reported in small series (121—124). After three months of therapy, full or partial remission was achieved in most patients, whereas others required addition of prednisone for disease control. Although their effect appears slower and less constant than with corticosteroids, macrolides might become a therapeutic option in OP, either alone or associated with corticosteroids. This issue requires further studies. 

---