Macrolide antibiotics adverse effects

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. 

Rapamycin (sirolimus), a macrolide antibiotic, has been used recently in organ transplantation for its potent immunosuppressive actions by inhibiting both cytokine mediated and growth factor mediated proliferation of smooth muscle cells and lymphocytes [55, 56]. In the RAVEL trial of non-acute single vessel lesions, the Sirolimus-eluting stent was compared to bare metal stent (BMS) in a 1 1 fashion [57]. One-year major adverse cardiovascular events and 6 month neointimal proliferation as assessed by late luminal loss (-0.01 0.33 mm in Sirolimus stent versus 0.80 0.53 mm in BMS) were improved. The Sirolimus-eluting stent thus virtually eliminated in-stent restenosis with no evidence of edge effect, dissection, or in-stent thrombosis. 

Adverse effects include abdominal cramps, diarrhoea, headache, convulsions and extrapyramidal effects. When used with imidazole antifungals/macrolide antibiotics, it may lead to Q-T prolongation and ventricular arrhythmias. 

CIMETIDINE MACROLIDES- ERYTHROMYCIN t efficacy and adverse effects of erythromycin, including hearing loss t bioavailability Consider an alternative antibiotic, e.g. clarithromycin. Deafness has been reversible with cessation of erythromycin... 

Macrolide antibiotics are contraindicated in patients with known hypersensitivity or intolerance to any macrolide. Because clarithromycin can have adverse effects on embryo-fetal development in animals, this drug should be avoided in pregnant women unless no other therapy is appropriate. Concurrent administration of the macrolides and astemizole or terfenadine can cause elected antihistamine levels, resulting in life-threatening cardiac arrhythmias, and should be avoided. 

Two other agents show promise in treatment of ocular toxoplasmosis. Atovaquone, primarily used for mild to moderate episodes of Pneumocystis carinii pneumonia, has been effective in small series of patients with toxoplasmosis. It appears to have activity against both tachy-zoites and tissue cysts. More recent studies on atovaquone in toxoplasmosis are limited to murine models, and no further reports on this drug therapy in humans have been published. Azithromycin, a macrolide antibiotic, is efficacious against T. gondii and can also kill tissue cysts. A randomized study of 46 patients compared the combinations of azithromycin plus pyrimethamine versus pyrimethamine plus sulfadiazine in treatment of ocular toxoplasmosis efficacy was similar, but the azithromycin/ pyrimethamine regimen caused less adverse effects. 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

Some of the macrolide antibiotics have been reported to inhibit the clearance of disopyramide (SEDA-21, 200) (SEDA-22, 207), resulting in serious dysrhythmias or hypoglycemia. The mechanism of this interaction is presumed to be inhibition of dealkylation of disopyramide to its major metabolite, mono-A-dealkyldisopyramide. For example, in human liver microsomes the macrolide antibiotic troleandomycin significantly inhibited the mono-A-dealkylation of disopyramide enantiomers by inhibition of CYP3A4 (34). This interaction can result in serious dysrhythmias or other adverse effects of disopyramide. 

The gastrointestinal adverse effects are the most common untoward effects of the macrolides (Table 2). Nausea and vomiting associated with abdominal pain and occasionally diarrhea can be minor and transitory or, in a small percentage of patients, become severe enough to result in premature withdrawal. The rate of these adverse effects varies among the different antibiotics. In general, newer macrolides, such as azithromycin, clarithromycin, or roxithromycin, are better tolerated and cause fewer adverse effects than erythromycin. 

Erythromycin can cause two different types of liver damage (36,37), benign increases in serum transaminases, which may or may not recur on rechallenge, and cholestatic hepatitis. Reports of intrahepatic cholestasis with azithromycin (38), clarithromycin (39,40), and josamycin (41) suggest that the newer macrolides are not free of this adverse effect, although the relative risks compared with erythromycin are unclear. Similar involvement of the liver has been seen with the ester of triacetyloleandomycin, but not with the unesterified antibiotic. 

The patient must be instructed to Provide their healthcare provider with a complete history of over-the-counter medications, prescribed medications, and herbal therapies to identify contraindications for macrolides. Explain that there might be a chance of hearing loss as an adverse side effect of macrolides. Monitor for adverse effects (see 13.21 Macrolide Antibiotics), and call the healthcare provider immediately if one is present. Macrolide Antibiotics Pregnancy Category B ... 

Sturgill, M. G., and Rapp, R. P. (1992). Clarithromycin Review of a new macrolide antibiotic with improved microbiological spectrum and favorable pharmacokinetic and adverse effect profiles. Ann. Pharmacother. 26, 1099-1108. 

Adverse effects tend to be mild GI effects—dyspepsia, constipation and flatulence. More serious effects, such as renal tubular obstruction, rhabdomyolysis and myopathy, have been reported. These are most likely to occur with concurrent therapy of other drugs that inhibit the metabolism of the drug (e.g., systemic anti-fungals or macrolide antibiotics) or with consumption of grapefruit. Elevated liver enzymes (e.g., transaminase) may also be present. 

Macrolides antibiotics have some side effects that adversely affect the patient. The most common side effects are nausea, vomiting, stomach pain, and cramps. These occur with azithromycin, clarithromycin, erythromycin, and dirithromycin. Troleandomycin causes stomach cramps and discomfort. 

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